Child maltreatment has well-documented long-term, adverse effects on mental health, but it is not clear whether there are gender differences in these effects. We conducted a systematic review to ...investigate whether there are gender differences in the effects of maltreatment on adult depression and anxiety. Medline, PsycINFO, Web of Science, and Lilacs were searched for relevant studies published up to May 2016. Eligible studies included population-based studies (with a cohort, case-control or cross-sectional design) which assessed maltreatment during childhood or adolescence (≤18 years) and its association with major depression or generalized anxiety disorder (DSM/ICD diagnostic criteria) in adulthood (>18 years) separately for females and males. Meta-analysis was performed to estimate the association between each exposure and outcome using fixed and random effects models. Pooled odds ratios (OR) were estimated separately for women and men and compared. Five studies of physical and sexual abuse were included in the meta-analyses. These provided twenty-two effects sizes estimates (11 for men, 11 for women) for associations between physical/sexual abuse and depression/anxiety. Exposure to each kind of abuse increased the odds of depression/anxiety. Associations were larger for women than for men, however, these gender differences were not statistically significant. Physical and sexual abuse in childhood/adolescence are risk factors for depression/anxiety in adulthood and the effect could be larger for women; however, currently there is insufficient evidence to definitively identify gender differences in the effects of maltreatment.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by a combination of airways disease (bronchiolitis) and parenchymal destruction (emphysema), whose ...relative proportion varies from patient to patient.
To explore and contrast the molecular pathogenesis of emphysema and bronchiolitis in COPD.
We used network analysis of lung transcriptomics (Affymetrix arrays) in 70 former smokers with COPD to compare differential expression and gene coexpression in bronchiolitis and emphysema.
We observed that in emphysema (but not in bronchiolitis) (1) up-regulated genes were enriched in ontologies related to B-cell homing and activation; (2) the immune coexpression network had a central core of B cell-related genes; (3) B-cell recruitment and immunoglobulin transcription genes (CXCL13, CCL19, and POU2AF1) correlated with emphysema severity; (4) there were lymphoid follicles (CD20(+)IgM(+)) with active B cells (phosphorylated nuclear factor-κB p65(+)), proliferation markers (Ki-67(+)), and class-switched B cells (IgG(+)); and (5) both TNFRSF17 mRNA and B cell-activating factor protein were up-regulated. These findings were by and large reproduced in a group of patients with incipient emphysema and when patients with emphysema were matched for the severity of airflow limitation of those with bronchiolitis.
Our study identifies enrichment in B cell-related genes in patients with COPD with emphysema that is absent in bronchiolitis. These observations contribute to a better understanding of COPD pathobiology and may open new therapeutic opportunities for patients with COPD.
Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking. Yet, how do immune cells relate within and between these two ...biological compartments, how the pulmonary infiltrate influences the lung transcriptome, and what is the role of active smoking vs. presence of disease is unclear.
To investigate these questions, we simultaneously collected lung tissue and blood from 65 individuals stratified by smoking habit and presence of the disease. The immune cell composition of both tissues was assessed by flow cytometry, whole lung transcriptome was determined with Affymetrix arrays, and we used Weighted Gene Co-expression Network Analysis (WGCNA) to integrate results.
Main results showed that: (1) current smoking and the presence of COPD were both independently associated with a reduction in the proportion of lung T cells and an increase of macrophages, specifically those expressing CD80 + CD163+; (2) changes in the proportion of infiltrating macrophages, smoking status or the level of airflow limitation were associated to different WGCNA modules, which were enriched in iron ion transport, extracellular matrix and cilium organization gene ontologies; and, (3) circulating white blood cells counts were correlated with lung macrophages and T cells.
Mild-moderated COPD lung immune infiltrate is associated with the active smoking status and presence of disease; is associated with changes in whole lung tissue transcriptome and marginally reflected in blood.
Previous use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease has been associated with increased risk of community-acquired pneumonia. However, ICS have been ...associated with fewer pneumonia complications and decreased risk of pneumonia-related mortality.
The objective of the study was to assess the influence of previous use of ICS on the incidence of parapneumonic effusion in patients with different baseline respiratory disorders.
We conducted a single-center cohort study of 3,612 consecutively collected patients diagnosed with community-acquired pneumonia. We assessed clinical, radiographic, and pleural-fluid chemistry and microbiologic variables. Patients were classified according to whether or not they received prior ICS treatment.
A total of 633 patients (17%) were treated with corticosteroids before the diagnosis of pneumonia (chronic obstructive pulmonary disease, 54%; asthma, 13%). Incidence of parapneumonic effusion was lower in patients with ICS use compared with non-ICS patients (5% vs. 12%; P < 0.001). After matching according to propensity scores (n = 640), prior treatment with corticosteroids was still significantly associated with a lower incidence of parapneumonic effusion (odds ratio, 0.40; 95% confidence interval, 0.23-0.69; P = 0.001) compared with patients without ICS treatment. Prior ICS treatment was associated with higher levels of glucose (P = 0.003) and pH (P = 0.02), and lower levels of protein (P = 0.01) and lactic acid dehydrogenase (P = 0.007) in the pleural fluid.
Prior treatment with ICS in a population of patients with different respiratory chronic disorders who develop pneumonia is associated with lower incidence of parapneumonic effusion.
A Citizen Science initiative by the Westerdijk Fungal Biodiversity Institute and the Utrecht University Museum gave rise to a project where fungal and yeast isolates were obtained and identified from ...Dutch soil samples. During the current study, 386 yeast strains were isolated from 157 different locations in the Netherlands. These strains were identified using sequence data of the large-subunit rRNA gene (D1/D2 region) and the internal transcribed spacer 1 and 2 regions. A total of 53 different yeast species were found as well as 15 potentially novel species. Six novel ascomycetous species are described during this study that include Hanseniaspora mollemarum sp. nov., Ogataea degrootiae sp. nov., Pichia gijzeniarum sp. nov., Saccharomycopsis oosterbeekiorum sp. nov., Trichomonascus vanleenenius sp. nov. and Zygoascus flipseniorum sp. nov. This study made it possible to incorporate numerous yeast isolates into the CBS collection without any restrictions, which make these isolates readily available for use by others. Many of the isolates represented species of which only a few isolates or even only a single ex-type strain were available. Therefore, it is a clear indication that such biodiversity-orientated Citizen Science projects can enrich the pool of available yeasts for future research projects.
Noncommunicable diseases, including cardiovascular, metabolic and respiratory diseases, among others, are the major medical challenge of the 21st century. Most noncommunicable diseases are related to ...the ageing process and often co-occur in the same individual. However, it is unclear whether the index disease is somehow influencing the development of the other ones (comorbidity) or whether all of them (including the index disease) simply represent the clinical expression of pathological ageing (multimorbidity). The pathobiology of ageing, chronic obstructive pulmonary disease (COPD) and concomitant disorders is complex. A new field of research, known as systems biology if applied to model systems or network medicine if applied to human beings, has emerged over the past decade or so, to address biological complexity in a holistic, integrated way. It offers, therefore, great potential to decipher the relationship between ageing, COPD and comorbidities/multimorbidities. In this State of the Art review we present the basic concepts of systems biology, use some examples to illustrate the potential of network medicine to address complex medical problems, and review some recent publications that show how a systems-based research strategy can contribute to improve our understanding of multimorbidity and age-related respiratory diseases.
Tobacco smoking is the main environmental risk factor for chronic obstructive pulmonary disease (COPD), but not all smokers develop the disease. A population of lung-resident mesenchymal stem cells ...(LR-MSCs) exist in healthy lungs, but how tobacco smoking affects them and their role in COPD have not been assessed yet. Using a sphere-based culture technique, we isolated LR-MSCs from lung tissue obtained from nonsmokers and current and former smokers with and without COPD (
= 53). The cells were characterized by flow cytometry and Affymetrix arrays. Their immunomodulatory capacity was assessed
using cocultures with T cells and after preincubation with 2.5% and 5% cigarette smoke extract. We were able to isolate LR-MSCs expressing similar phenotypic markers in all of the study groups. LR-MSCs from current smokers with COPD expressed different levels of CX3CL1 and CCL5 cytokines, and were unable to modulate CD8
T-cell proliferation. Preincubation of LR-MSCs with cigarette smoke extract reduced their immunomodulatory capacity. In conclusion,
) LR-MSCs can be isolated in similar amounts from never-smokers and smokers with and without COPD;
) their immunomodulatory capacity is impaired in current smokers with COPD, but not in those with normal lung function; and
) this is reversible after smoking cessation and is reproducible
.
Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have ...developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.
Previous studies have identified lung, sputum or blood transcriptomic biomarkers associated with the severity of airflow limitation in COPD. Yet, it is not clear whether the lung pathobiology is ...mirrored by these surrogate tissues. The aim of this study was to explore this question.
We used Weighted Gene Co-expression Network Analysis (WGCNA) to identify shared pathological mechanisms across four COPD gene-expression datasets: two sets of lung tissues (L1 n = 70; L2 n = 124), and one each of induced sputum (S; n = 121) and peripheral blood (B; n = 121).
WGCNA analysis identified twenty-one gene co-expression modules in L1. A robust module preservation between the two L datasets was observed (86%), with less preservation in S (33%) and even less in B (23%). Three modules preserved across lung tissues and sputum (not blood) were associated with the severity of airflow limitation. Ontology enrichment analysis showed that these modules included genes related to mitochondrial function, ion-homeostasis, T cells and RNA processing. These findings were largely reproduced using the consensus WGCNA network approach.
These observations indicate that major differences in lung tissue transcriptomics in patients with COPD are poorly mirrored in sputum and are unrelated to those determined in blood, suggesting that the systemic component in COPD is independently regulated. Finally, the fact that one of the preserved modules associated with FEV1 was enriched in mitochondria-related genes supports a role for mitochondrial dysfunction in the pathobiology of COPD.
Purpose
This study aimed to review evidence on the prevalence of and risk factors for conduct problems in Brazil.
Methods
We searched electronic databases and contacted Brazilian researchers up to ...05/2012. Studies were included in the review if they reported the prevalence of or risk factors for conduct problems, conduct disorder, or oppositional defiant disorder for 100 + Brazilian children aged ≤18 years, systematically sampled in schools or the community. Prevalence rates and sex differences were meta-analysed. Risk factor studies were reviewed one by one.
Results
The average prevalence of conduct problems in screening questionnaires was 20.8 %, and the average prevalence of conduct disorder/oppositional defiant disorder was 4.1 %. There was systematic variation in the results of screening studies according to methodology: recruitment location, informants, instruments, impairment criterion for case definition, and response rates. Risk factors previously identified in high-income countries were mainly replicated in Brazil, including comorbid mental health problems, educational failure, low religiosity, harsh physical punishment and abuse, parental mental health problems, single parent family, and low socioeconomic status. However, boys did not always have higher risk for conduct problems than girls.
Conclusions
Studies using screening questionnaires suggest that Brazilian children have higher rates of conduct problems than children in other countries, but diagnostic studies do not show this difference. Risk factors in Brazil were similar to those in high-income countries, apart from child sex. Future research should investigate developmental patterns of antisocial behaviour, employ a variety of research designs to identify causal risk mechanisms, and examine a broader range of risk factors.