•Low and medium CRF are associated with a greater risk of common mental health disorders.•CRF appears to have a dose-dependent relationship with common mental health disorders.•CRF could be useful ...for predicting and preventing common mental health disorders.
Physical activity is associated with a lower incidence of common mental health disorder, but less is known about the impact of cardiorespiratory fitness (CRF).
In this review, we systematically evaluated the relationship between CRF and the incidence of common mental health disorders in prospective cohort studies. We systematically searched six major electronic databases from inception to 23rd of May 2019. We assessed study quality using the Newcastle–Ottawa scale.
We were able to pool the hazard ratios (HRs) and 95% confidence intervals (CIs) of four studies including at least 27,733,154 person-years of data. We found that low CRF (HR = 1.47, 95% CI 1.23 – 1.76 p < 0.001 I2 = 85.1) and medium CRF (HR = 1.23, 95% CI 1.09 – 1.38 p < 0.001 I2 = 87.20) CRF are associated with a 47% and 23% greater risk of a common mental health disorders respectively, compared with high CRF. We found evidence to suggest a dose-response relationship between CRF and the risk of common mental health disorders.
We were only able to identify a small number of eligible studies from our search and heterogeneity was substantial in the subsequent meta-analysis.
Our findings indicate that there is a longitudinal association between CRF levels and the risk of a common mental health disorder. CRF levels could be useful for identifying and preventing common mental health disorders at a population-level.
The multifunctional profibrotic cytokine TGF-β2 is implicated in the pathophysiology of primary open angle glaucoma (POAG). While the underlying cause of POAG remains unclear, TGF-β2 dependent ...remodeling of the extracellular matrix (ECM) within the trabecular meshwork (TM) microenvironment is considered an early pathologic consequence associated with impaired aqueous humor (AH) outflow and elevated IOP. Mitochondrial-targeted antioxidants have been recently shown by our group to markedly attenuate TGF-β2 profibrotic responses, strongly implicating oxidative stress as a key facilitator of TGF-β2 signaling in human TM cells. In this study, we determined the mechanism by which oxidative stress facilitates TGF-β2 profibrotic responses in cultured primary human TM cells.
Semiconfluent cultures of primary or transformed human TM cells were conditioned overnight in serum-free media and subsequently challenged without or with TGF-β2 (5 ng/mL). Relative changes in the mRNA content of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) isoforms, connective tissue growth factor (CTGF), collagen 1α1 and 4α1 isoforms or relative changes in the protein content of Nox4, phospho- and total-Smad2 and -Smad3, collagens I and IV were determined in the absence or presence of GKT137831, a Nox1-Nox4 dual enzyme inhibitor, and quantified by real-time qPCR or by immunoblot, respectively. Relative in situ changes in collagens I and IV and in alpha smooth muscle actin (αSMA) were semiquantified by immunocytochemistry, whereas relative changes in filamentous actin stress fiber formation was semiquantified by phalloidin staining.
Quiescent primary human TM cells cultured in the presence of TGF-β2 exhibited a marked selective increase in endogenous Nox4 mRNA and Nox4 protein expression. Actinomycin D prevented TGF-β2 mediated increases in Nox4 mRNA expression. TM cells reverse transfected with siRNA against Smad3 prevented TGF-β2 mediated increases in Nox4 mRNA expression. Pre-incubating TM cells with GKT137831 attenuated TGF-β2 mediated increases in intracellular reactive oxygen species (ROS), in COL1A1, COL4A1, and CTGF mRNA expression, in Smad3 protein phosphorylation, in collagens I, collagens IV, and αSMA protein expression, and in filamentous actin stress fiber formation.
TGF-β2 promotes oxidative stress in primary human TM cells by selectively increasing expression of NADPH oxidase 4. Dysregulation of redox equilibrium by induction of NADPH oxidase 4 expression appears to be a key early event involved in the pathologic profibrotic responses elicited by TGF-β2 canonical signaling, including ECM remodeling, filamentous actin stress fiber formation, and αSMA expression. Selective inhibition of Nox4 expression/activation, in combination with mitochondrial-targeted antioxidants, represents a novel strategy by which to slow the progression of TGF-β2 elicited profibrotic responses within the TM.
Background Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent. To assess the associations of sedentary behaviour ...with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviours with sleep, light, or moderate to vigorous physical activity, using compositional data analysis methods. Methods We conducted a prospective cohort study in 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour and physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow-up. Results Replacing 60 min of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1.3% (95% CI, 0.4-2.1%), 12.5% (95% CI, 11.4-13.5%), and 7.6% (95% CI, 6.9-8.4%), and lower odds of possible depression by 0.95 (95% CI, 0.94-0.96), 0.75 (95% CI, 0.74-0.76), and 0.90 (95% CI, 0.90-0.91) at follow-up. Replacing 60 min of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6.6% (95% CI, 5.5-7.6%) and 4.5% (95% CI, 3.7-5.2%), and lower odds of meeting the threshold for a possible anxiety disorder by 0.90 (95% CI, 0.89-0.90) and 0.97 (95%CI, 0.96-0.97) at follow-up. However, replacing 60 min of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4.5% (95% CI, 3.7-5.3%) and higher odds of a possible anxiety disorder by 1.07 (95% CI, 1.06-1.08). Conclusions Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults. Replacing sedentary behaviour with moderate-to-vigorous activity may reduce mental health risks, but more work is necessary to clarify the role of light activity. Keywords: Sedentary behaviour, Depression, Anxiety, Compositional, Physical activity, MVPA
Objective
Cardiorespiratory fitness (CRF) is a major modifiable risk factor for cardiovascular disease (CVD). We conducted a clinical overview to highlight the reduced CRF expressed as maximal oxygen ...uptake (VO2max) (or predicted) or peak oxygen uptake (VO2peak) in people with schizophrenia compared to the general population. We also aimed to identify correlates of and clinical strategies to improve CRF.
Method
We systematically searched major electronic databases from inception until November 2014. A meta‐analysis calculating the standardised mean difference (SMD) was employed.
Results
CRF was significantly reduced in people with schizophrenia (n = 154) with a SMD of −0.96 (95% CI −1.29 to −0.64) (N = 5) compared to controls (n = 182). Negative symptoms, increased body mass index and female gender were negatively associated with CRF. Promoting physical activity may improve CRF in people with schizophrenia by up to 4–4.5 ml/kg/min following a 6–8 weeks programme (N = 4, n = 98).
Conclusion
People with schizophrenia have a large and significantly reduced CRF. Given the overwhelming evidence for physical activity as the cornerstone of preventing and managing CVD in the general population, incorporating such interventions in the treatment of people with schizophrenia is justified and urgently required. We present clear practical strategies of how this can be achieved within clinical settings.
Abstract
Animal weapons are diverse and often exaggerated structures associated with sexual selection and male–male combat. Despite their diversity, our knowledge of these structures comes primarily ...from studies that focus on the size of the weapons and neglect other components, such as their shape or performance. Furthermore, weapons can exhibit species-level plasticity based on nutrition and other ecological variables, but few studies have documented seasonal variation in weapon plasticity. Here, we investigate how weapon size, shape and performance differ across adult male reproductive and non-reproductive Allegheny crayfish, Faxonius obscurus. Given that F. obscurus and other cambarid crayfishes exhibit cyclical moulting between reproductive and non-reproductive states, they provide an ideal system in which to investigate such questions. We found that claws of reproductive and non-reproductive male F. obscurus differ in all three weapon components we investigated; claws from reproductive males were longer, stronger and different in shape compared with claws from non-reproductive males. Wielding longer and stronger claws is likely to confer greater competitive success during the mating season, which demonstrates an unexplored pattern of seasonal weapon plasticity. We discuss these results considering our knowledge of the seasonality of weapon phenotypes and propose several avenues of future research using cambarid crayfish as a model system.
Abstract Introduction Data about the prevalence of borderline personality (BPD) and bipolar (BD) disorders comorbidity are scarce and the boundaries remain controversial. We conducted a systematic ...review and meta-analysis investigating the prevalence of BPD in BD and BD in people with BPD. Methods Two independent authors searched MEDLINE, Embase, PsycINFO and the Cochrane Library from inception till November 4, 2015. Articles reporting the prevalence of BPD and BD were included. A random effects meta-analysis and meta-regression were conducted. Results Overall, 42 papers were included: 28 considering BPD in BD and 14 considering BD in BPD. The trim and fill adjusted analysis demonstrated the prevalence of BPD among 5273 people with BD (39.94±11.78 years, 44% males) was 21.6% (95% CI 17.0–27.1). Higher comorbid BPD in BD were noted in BD II participants (37.7%, 95% CI 21.9–56.6, studies=6) and North American studies (26.2%, 95% CI 18.7–35.3, studies=11). Meta regression established that a higher percentage of males and higher mean age significantly (p<0.05) predicted a lower prevalence of comorbid BPD in BD participants. The trim and fill adjusted prevalence of BD among 1814 people with BPD (32.22±7.35 years, 21.5% male) was 18.5% (95% CI 12.7–26.1). Limitations Paucity of longitudinal/control group studies and accurate treatment records. Conclusions BPD-BD comorbidity is common, with approximately one in five people experiencing a comorbid diagnosis. Based on current diagnostic constructs, and a critical interpretation of results, both qualitative and quantitative syntheses of the evidence prompt out the relevance of differences rather similarities between BD and BPD.
•Few studies have examined associations between physical multimorbidity and sedentary behaviour in older adults.•We analysed cross-sectional data from a large population-based sample of adults aged ...≥50 years.•Sedentary behaviour increased with the number of chronic physical conditions.•People with ≥4 conditions had greater odds of high sedentary behavior.•Prospective studies are needed to clarify the directionality and potential underlying mechanisms.
Physical multimorbidity, defined as the presence of two or more chronic physical conditions, is widespread and reduces life expectancy and quality of life in older adults. Sedentary behavior (SB) is increasingly identified as a risk factor for a range of chronic physical conditions, independent of physical activity.
To investigate associations between physical multimorbidity and SB in older adults.
We used cross-sectional data from a population-based sample of 6903 adults aged ≥50 years who participated in the Irish Longitudinal Study on Ageing (TILDA) in 2009-2011. We conducted multivariable linear and logistic regression analyses to assess associations between multimorbidity and SB.
Self-reported minutes/day of SB and high SB (≥ 8 h/day).
We found that most of the 14 individual chronic physical conditions included here were associated with greater SB. Those with stroke (OR = 2.63, 95 % CI = 1.69, 4.10) and cirrhosis (OR = 2.53, 95 %CI = 1.19, 5.41) were the most likely to be classified with high SB. Time spent in SB and the prevalence of high SB increased linearly with number of chronic conditions. Multivariable regression models adjusting for sociodemographic and psychological factors, disability, social network, and physical activity showed that, compared with people with none, those with ≥4 chronic physical conditions had 1.45 times greater odds (OR = 1.45, 95 % CI = 1.09, 1.93) of high SB and higher mean minutes/day of SB (β = 21.37, 95 % CI = 5.53, 37.20).
Our results suggest that physical multimorbidity is associated with SB and highlight the need for prospective research to examine the directionality and mechanisms of these associations.
This study investigated the association between sedentary behavior (SB) and anxiety, and explored factors that influence this relationship in six low- and middle-income countries.
Cross-sectional ...data were analyzed from the World Health Organization's Study on Global Ageing and Adult Health. Multivariable linear and logistic regression analyses were conducted to assess the association between anxiety and self-reported SB. Potentially influential factors were examined with mediation analysis.
The sample consisted of 42,469 adults aged≥18years (50.1% female; mean age 43.8years). After adjusting for sociodemographics and country, people with anxiety engaged in 24 (95%CI=7–41) more minutes per day of SB than non-anxious individuals; the corresponding figure for the elderly (≥65years) was much higher (55min; 95% CI=29–81). Anxiety was associated with a 2.0 (95%CI=1.5–2.7) times higher odds for high SB (i.e., ≥8h/day). Overall, the largest proportion of the high SB-anxiety relationship was explained by mobility limitations (46.8%), followed by impairments in sleep/energy (44.9%), pain/discomfort (31.7%), disability (27.0%), cognition (13.3%), and physical activity levels (6.3%).
Anxiety was significantly associated with high SB, particularly among older adults. Future longitudinal studies are warranted to disentangle the potentially complex interplay of factors that may influence the anxiety-SB relationship.
•People with anxiety have a two-fold higher odds for being sedentary (+8 hours/day).•Mobility problems, pain and disability should be considered.•Cognitive problems influenced the relation between sedentary behavior and anxiety.
Chemical warfare nerve agent exposure leads to status epilepticus that may progress to epileptogenesis and severe brain pathology when benzodiazepine treatment is delayed. We evaluated the ...dose−response effects of delayed midazolam (MDZ) on toxicity induced by soman (GD) in the plasma carboxylesterase knockout (Es1−/−) mouse, which, similar to humans, lacks plasma carboxylesterase. Initially, we compared the median lethal dose (LD50) of GD exposure in female Es1−/− mice across estrous with male mice and observed a greater LD50 during estrus compared with proestrus or with males. Subsequently, male and female GD‐exposed Es1−/− mice treated with a dose range of MDZ 40 min after seizure onset were evaluated for survivability, seizure activity, and epileptogenesis. GD‐induced neuronal loss and microglial activation were evaluated 2 weeks after exposure. Similar to our previous observations in rats, delayed treatment with MDZ dose‐dependently increased survival and reduced seizure severity in GD‐exposed mice, but was unable to prevent epileptogenesis, neuronal loss, or gliosis. These results suggest that MDZ is beneficial against GD exposure, even when treatment is delayed, but that adjunct therapies to enhance protection need to be identified. The Es1−/− mouse GD exposure model may be useful to screen for improved medical countermeasures against nerve agent exposure.
In the present work, we expand our previous studies and report on the dose−response effects of delayed midazolam (MDZ) treatment in male and female Es1−/− mice when MDZ is administered at 40 min after the onset of status epilepticus. The extended treatment time point is to model a more realistic therapeutic window for first responders in the event of civilian casualties following chemical warfare nerve agent exposure. Results from this study provide the groundwork for a human‐relevant mouse model to use to identify adjunct therapies that enhance or complement the effectiveness of benzodiazepines against CWNA exposure.
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