There is controversy regarding the use of blood eosinophil levels as a biomarker of exacerbation risk and responsiveness of patients to inhaled corticosteroids (ICS).
Patients in stable COPD with ...Gold Initiative for Chronic Obstructive Lung Disease airflow obstruction grades II to IV were enrolled in an observational multicenter trial. Concordance was defined as blood eosinophil values persistently lower than or persistently higher than the absolute cutoff points of 150 cells/μL and 300 cells/μL, or the percentage cutoff points of 2%, 3%, and 4%. Discordance was obtained when the blood eosinophil values varied between any two visits. ICS treatment data were recorded at one time point at the inclusion of the study.
A total of 210 patients with 2,059 visits were included in the study. Seventy percent of the patients were male, and 36% were current smokers; their average age was 67.7 ± 9.4 years, and 81% were receiving ICS at the start of the study. Assessing eosinophil levels over time (median, 7 days 4; 12), irrespective of exacerbation or hospitalization, there was a discordance of 77%, 60%, and 42% when using the 2%, 3% and 4% cutoffs, respectively. This outcome changed to 34.5%, 24%, and 17.2% discordance when only using two visits for the analysis. The discordance was similar when using absolute eosinophil values. Patients in a stable state had higher discordant values than patients with mild/moderate exacerbations. The same was seen in patients hospitalized for other illnesses compared with patients hospitalized for severe exacerbation of COPD. Discordancy was high regardless of whether patients were taking ICS at the beginning of the study period.
These study data suggest that blood eosinophil levels present significant variability throughout the course of COPD, and a single measurement may therefore not be a reliable predictor of ICS response.
Purpose
The aim of this systematic review is to assess the effect of different types of exercise on breast cancer-related lymphedema (BCRL) in order to elucidate the role of exercise in this patient ...group.
Methods
A systematic data search was performed using PubMed (December 2016). The review is focused on the rehabilitative aspect of BCRL and undertaken according to the PRISMA statement with Levels of Evidence (LoE) assessed.
Results
11 randomized controlled trials (9 with LoE 1a and 2 with LoE 1b) that included 458 women with breast cancer in aftercare were included. The different types of exercise consisted of aqua lymph training, swimming, resistance exercise, yoga, aerobic, and gravity-resistive exercise. Four of the studies measured a significant reduction in BCRL status based on arm volume and seven studies reported significant subjective improvements. No study showed adverse effects of exercise on BCRL.
Conclusion
The evidence indicates that exercise can improve subjective and objective parameters in BCRL patients, with dynamic, moderate, and high-frequency exercise appearing to provide the most positive effects.
Cross-sectional magnetic resonance imaging (MRI) studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early ...overgrowth; however, this has never been confirmed by a longitudinal study. We performed the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent using structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of autistic disorder at approximately 48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter were significantly enlarged in toddlers with autistic disorder, with the most severe enlargement occurring in frontal, temporal, and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with autistic disorder that was mainly characterized by a quadratic age effect. Females with autistic disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers to determine the underlying neuropathological processes causing the onset of autistic symptoms.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous in aetiology and accelerate disease progression. Here, we aimed to investigate the association of fractional ...exhaled nitric oxide (FeNO) and its variability with AECOPD of different aetiology.
FeNO was determined in 2157 visits (1697 stable, 133 AECOPD and 327 follow-up) of 421 COPD patients from the PREVENT study, an investigator-initiated, longitudinal and interventional study, who were on daily treatment with inhaled corticosteroids/long-acting β2-agonists.
Longitudinal measurements of FeNO revealed an intra-subject variability of FeNO that was significantly higher in exacerbators compared to non-exacerbators (p < 0.001) and positively associated with the number of AECOPD. As FeNO variability increased, the probability of patients to remain AECOPD-free decreased. In patients included in the highest FeNO variability quartile (≥15.0 ppb) the probability to remain free of AECOPD was only 35% as compared to 80% for patients included in the lowest FeNO variability quartile (0.50-4.39 ppb). The change of FeNO from the last stable visit to AECOPD was positively associated with the probability of viral infections and this association was stronger in current smokers than ex-smokers. In contrast, the change in FeNO from the last stable visit to an AECOPD visit was inversely associated with the probability of bacterial infections in ex-smokers but not in current smokers.
FeNO variability was associated with the risk and aetiology of AECOPD differentially in current and ex-smokers.
The amygdala undergoes aberrant development in autism spectrum disorder (ASD). We previously found that there are reduced neuron numbers in the adult postmortem amygdala from individuals with ASD ...compared to typically developing controls. The current study is a comprehensive stereological examination of four non-neuronal cell populations: microglia, oligodendrocytes, astrocytes, and endothelial cells, in the same brains studied previously. We provide a detailed neuroanatomical protocol for defining each cell type that may be applied to other studies of the amygdala in neurodevelopmental and psychiatric disorders. We then assess whether cell numbers and average volumes differ between ASD and typically developing brains. We hypothesized that a reduction in neuron numbers in ASD might relate to altered immune function and/or aberrant microglial activation, as indicated by increased microglial number and cell body volume. Overall, average non-neuronal cell numbers and volumes did not differ between ASD and typically developing brains. However, there was evident heterogeneity within the ASD cohort. Two of the eight ASD brains displayed strong microglial activation. Contrary to our original hypothesis, there was a trend toward a positive correlation between neuronal and microglial numbers in both ASD and control cases. There were fewer oligodendrocytes in the amygdala of adult individuals with ASD ages 20 and older compared to typically developing controls. This finding may provide a possible sign of altered connectivity or impaired neuronal communication that may change across the lifespan in ASD.
Autism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ...ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons from 59 postmortem human brains (27 ASD and 32 controls) in the superior temporal gyrus (STG) of individuals ranging from 2 to 73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways, and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in gamma aminobutyric acid (GABA) (
and
) and glutamate (
) signaling pathways. In LCM neurons, AP-1-mediated neuroinflammation and insulin/IGF-1 signaling pathways were upregulated in ASD, while mitochondrial function, ribosome, and spliceosome components were downregulated. GABA synthesizing enzymes
and
were both downregulated in ASD neurons. Mechanistic modeling suggested a direct link between inflammation and ASD in neurons, and prioritized inflammation-associated genes for future study. Alterations in small nucleolar RNAs (snoRNAs) associated with splicing events suggested interplay between snoRNA dysregulation and splicing disruption in neurons of individuals with ASD. Our findings supported the fundamental hypothesis of altered neuronal communication in ASD, demonstrated that inflammation was elevated at least in part in ASD neurons, and may reveal windows of opportunity for biotherapeutics to target the trajectory of gene expression and clinical manifestation of ASD throughout the human lifespan.
Introduction
High-intensity interval training (HIIT) is an appropriate training modality to improve endurance and therefore contributes to physical performance. This review investigates the effect of ...HIIT on functional performance in cancer patients. We reviewed the relative peak oxygen uptake (relV̇O
2PEAK
) and meta-analytical compared HIIT with moderate intensity continuous training (MICT). Furthermore, we took various training parameters under consideration.
Methods
A systematic literature search was conducted in Scopus, PubMed, and Cochrane Library databases. For the review, we included randomized controlled trials containing HIIT with cancer patients. From this, we filtered interventions with additional MICT for the meta-analysis. Outcomes of interest were various functional performance assessments and V̇O
2MAX
.
Results
The research yielded 584 records which fit the inclusion criteria, of which 31 studies with
n
=1555 patients (57.4±8.6 years) could be included in the overall review and 8 studies in the meta-analysis (
n
=268, 59.11±5.11 years) regarding relV̇O
2PEAK
. Different functional outcomes were found, of which walking distance (+8.63±6.91% meters in 6-min walk test) and mobility (+2.7cm in sit and reach test) improved significantly due to HIIT. In terms of relV̇O
2PEAK
, the performance of cancer patients was improved by HIIT (10.68±6.48%) and MICT (7.4±4.29%). HIIT can be favored to increase relV̇O
2PEAK
(SMD 0.37; 95% CI 0.09–0.65;
I
2
=0%;
p
=0.009). Effect sizes for relV̇O
2PEAK
improvements correlate moderately with total training volume (Spearman’s ρ=0.49;
p
=0.03), whereas percentage increases do not (Spearman’s ρ=0.24;
p
=0.14).
Conclusion
Functional and physical outcomes were positively altered by different HIIT protocols and forms of implementation, whereas a tendency toward more effectiveness of HIIT vs. MICT was found for relV̇O
2PEAK
. Future studies should include functional parameters more often, to finally allow a comparison between both training protocols in this regard.
The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and ...into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7–46 years of age) were stained using a Golgi‐Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age‐matched TD controls (<18 years old) and (b) decreases in the amygdala as people with ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age‐matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD.
Here we demonstrate the density of spines in the amygdala is greater in young children with ASD than typically developing peers. This phenomenon normalizes with age such that there is no difference in spine density between adults with ASD and typically developing adults.
A decrease in the number of functional insulin-producing beta-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in ...beta-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of beta-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-kappaB, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of beta-cell secretory function and cell turnover. Thus, the mechanisms regulating beta-cell proliferation, apoptosis, and function are inseparable processes.
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