Effects of an online mindfulness-based program for parents of children with attention deficit/hyperactivity disorder: a pilot, mixed methods study.

Objectives: Online mindfulness-based program (MBP) for parents and families especially in clinical population is limited. Engagement and significant dropout are major issues in MBP implementation. This pilot study examined the effects of an online mindfulness-based program (MBP) on parents of children with Attention Deficit/Hyperactivity Disorder (ADHD). Methods: A mixed methods study was applied to evaluate the effects of the MBP. A total of 43 parents were recruited and were randomly assigned into intervention group and waitlist control group. The online MBP lasted for 28 days, including 20 psychoeducation videos, homework audio guidance, and four instructor-led online group meetings. Purposive sampling was used to recruit parents who completed the program to share their experiences and suggestions for improving the program in semi-structured online interviews. Results: Quantitative data showed that participants from the online MBP reported a medium to large effect on the reduction of child ADHD symptoms. In semi-structured interviews, participants reported positive experiences in their help seeking intention, and personal changes, such as emotion regulation and quality attention to their children. Participants further made suggestions for improvement. Conclusions: The effect of online MBP is promising, and the program should be conducted. A large scale randomized controlled trial should be conducted to investigate the effects of MBP in clinical populations. Clinical trial registration: ClinicalTrials.gov NCT05480423.

Musculoskeletal crosstalk in chronic obstructive pulmonary disease and comorbidities: Emerging roles and therapeutic potentials.

Chronic Obstructive Pulmonary Disease (COPD) is a multifaceted respiratory disorder characterized by progressive airflow limitation and systemic implications. It has become increasingly apparent that COPD exerts its influence far beyond the respiratory system, extending its impact to various organ systems. Among these, the musculoskeletal system emerges as a central player in both the pathogenesis and management of COPD and its associated comorbidities. Muscle dysfunction and osteoporosis are prevalent musculoskeletal disorders in COPD patients, leading to a substantial decline in exercise capacity and overall health. These manifestations are influenced by systemic inflammation, oxidative stress, and hormonal imbalances, all hallmarks of COPD. Recent research has uncovered an intricate interplay between COPD and musculoskeletal comorbidities, suggesting that muscle and bone tissues may cross-communicate through the release of signalling molecules, known as "myokines" and "osteokines". We explored this dynamic relationship, with a particular focus on the role of the immune system in mediating the cross-communication between muscle and bone in COPD. Moreover, we delved into existing and emerging therapeutic strategies for managing musculoskeletal disorders in COPD. It underscores the development of personalized treatment approaches that target both the respiratory and musculoskeletal aspects of COPD, offering the promise of improved well-being and quality of life for individuals grappling with this complex condition. This comprehensive review underscores the significance of recognizing the profound impact of COPD on the musculoskeletal system and its comorbidities. By unravelling the intricate connections between these systems and exploring innovative treatment avenues, we can aspire to enhance the overall care and outcomes for COPD patients, ultimately offering hope for improved health and well-being.

The Effects of Mindfulness for Youth (MYmind) versus Group Cognitive Behavioral Therapy in Improving Attention and Reducing Behavioral Problems among Children with Attention-Deficit Hyperactivity Disorder and Their Parents: A Randomized Controlled Trial.

INTRODUCTION: There is a lack of studies evaluating mindfulness-based interventions for children with attention-deficit hyperactivity disorder (ADHD) compared with an evidence-based control. This randomized controlled trial (RCT) evaluated the effects of mindfulness for youth (MYmind) in improving children's attention, behavior, and parent-related outcomes versus cognitive behavioral therapy (CBT). METHODS: A total of 138 families of children with ADHD aged 8-12 years were recruited from the community with 69 randomized to MYmind and 69 to CBT. Participants were assessed at baseline, immediately after intervention, at 3 months and 6 months. The primary outcome was the attention score of the Sky Search subtest of the Test of Everyday Attention for Children (TEA-Ch). Secondary outcomes were child behavior and parent-related assessments. Linear mixed models were used to assess the efficacy of MYmind compared with CBT. RESULTS: Both MYmind and CBT significantly improved children's attention score at 6 months (MYmind: ß = 1.48, p = 0.013, Cohen's d = 0.32; CBT: ß = 1.46, p = 0.008, d = 0.27). There were significant within-group improvements in most secondary outcomes. No significant difference was shown for both primary or secondary outcomes between the two arms at any time point. CONCLUSIONS: Both MYmind and CBT appeared to improve children's attention and behavior outcomes, although no difference was found between these two interventions. This is the largest RCT so far comparing MYmind and CBT although there was loss of follow-up assessments during the pandemic. Further RCTs adopting a non-inferiority design are needed to validate the results.

DROID: Driver-Centric Risk Object Identification.

Identification of high-risk driving situations is generally approached through collision risk estimation or accident pattern recognition. In this work, we approach the problem from the perspective of subjective risk. We operationalize subjective risk assessment by predicting driver behavior changes and identifying the cause of changes. To this end, we introduce a new task called driver-centric risk object identification (DROID), which uses egocentric video to identify object(s) influencing a driver's behavior, given only the driver's response as the supervision signal. We formulate the task as a cause-effect problem and present a novel two-stage DROID framework, taking inspiration from models of situation awareness and causal inference. A subset of data constructed from the Honda Research Institute Driving Dataset (HDD) is used to evaluate DROID. We demonstrate state-of-the-art DROID performance, even compared with strong baseline models using this dataset. Additionally, we conduct extensive ablative studies to justify our design choices. Moreover, we demonstrate the applicability of DROID for risk assessment.

A promising new oral delivery mode for insulin using lipid-filled enteric-coated capsules.

The treatment of diabetes requires daily administration of the peptide insulin via subcutaneous (SC) injection due to poor stability following oral administration. Enteric capsules, designed to protect against low pH conditions in the stomach by providing a polymeric coating which only breaks down in the small intestine, have failed to significantly increase oral bioavailability for insulin. In parallel, amphiphilic lipid mesophases are versatile carrier materials which can protect encapsulated proteins and peptides from undesirable enzymatic degradation. Here we show the combined delivery capacity of a hydrated bicontinuous cubic lipid mesophase embedded within an enteric capsule. Animal studies demonstrated that the lipid filled enteric capsules could deliver insulin with bioavailabilities (relative to SC injection) as high as 99 % and 150 % for fast and slow acting insulin, respectively. These results provide a promising starting point towards further trials to develop an alternative, non-invasive mode for the delivery of insulin.

Inhibition of oxidative stress by apocynin attenuated chronic obstructive pulmonary disease progression and vascular injury by cigarette smoke exposure.

BACKGROUND AND PURPOSE: Cardiovascular disease affects up to half of the patients with chronic obstructive pulmonary disease (COPD), exerting deleterious impact on health outcomes and survivability. Vascular endothelial dysfunction marks the onset of cardiovascular disease. The present study examined the effect of a potent NADPH Oxidase (NOX) inhibitor and free-radical scavenger, apocynin, on COPD-related cardiovascular disease. EXPERIMENTAL APPROACH: Male BALB/c mice were exposed to either room air (Sham) or cigarette smoke (CS) generated from 9 cigarettes·day-1 , 5 days a week for up to 24 weeks with or without apocynin treatment (5 mg·kg-1 ·day-1 , intraperitoneal injection). KEY RESULTS: Eight-weeks of apocynin treatment reduced airway neutrophil infiltration (by 42%) and completely preserved endothelial function and endothelial nitric oxide synthase (eNOS) availability against the oxidative insults of cigarette smoke exposure. These preservative effects were maintained up until the 24-week time point. 24-week of apocynin treatment markedly reduced airway inflammation (reduced infiltration of macrophage, neutrophil and lymphocyte), lung function decline (hyperinflation) and prevented airway collagen deposition by cigarette smoke exposure. CONCLUSION AND IMPLICATIONS: Limiting NOX activity may slow COPD progression and lower cardiovascular disease risk, particularly when signs of oxidative stress become evident.

Cigarette smoke-induced pulmonary impairment is associated with social recognition memory impairments and alterations in microglial profiles within the suprachiasmatic nucleus of the hypothalamus.

Chronic obstructive pulmonary disease (COPD) is a major, incurable respiratory condition that is primarily caused by cigarette smoking (CS). Neurocognitive disorders including cognitive dysfunction, anxiety and depression are highly prevalent in people with COPD. It is understood that increased lung inflammation and oxidative stress from CS exposure may 'spill over' into the systemic circulation to promote the onset of these extra-pulmonary comorbidities, and thus impacts the quality of life of people with COPD. The precise role of the 'spill-over' of inflammation and oxidative stress in the onset of COPD-related neurocognitive disorders are unclear. The present study investigated the impact of chronic CS exposure on anxiety-like behaviors and social recognition memory, with a particular focus on the role of the 'spill-over' of inflammation and oxidative stress from the lungs. Adult male BALB/c mice were exposed to either room air (sham) or CS (9 cigarettes per day, 5 days a week) for 24 weeks and were either daily co-administered with the NOX2 inhibitor, apocynin (5 mg/kg, in 0.01 % DMSO diluted in saline, i.p.) or vehicle (0.01 % DMSO in saline) one hour before the initial CS exposure of the day. After 23 weeks, mice underwent behavioral testing and physiological diurnal rhythms were assessed by monitoring diurnal regulation profiles. Lungs were collected and assessed for hallmark features of COPD. Consistent with its anti-inflammatory and oxidative stress properties, apocynin treatment partially lessened lung inflammation and lung function decline in CS mice. CS-exposed mice displayed marked anxiety-like behavior and impairments in social recognition memory compared to sham mice, which was prevented by apocynin treatment. Apocynin was unable to restore the decreased Bmal1-positive cells, key in cells in diurnal regulation, in the suprachiasmatic nucleus of the hypothalamus to that of sham levels. CS-exposed mice treated with apocynin was associated with a restoration of microglial area per cell and basal serum corticosterone. This data suggests that we were able to model the CS-induced social recognition memory impairments seen in humans with COPD. The preventative effects of apocynin on memory impairments may be via a microglial dependent mechanism.

Enhancing Parental Well-being: Initial Efficacy of a 21-Day Online Self-help Mindfulness-Based Intervention for Parents.

Objectives: Parental self-care is extremely important in the face of stress throughout parenthood. A 21-day online mindfulness-based intervention was developed that was aimed at enhancing parental well-being. The present study evaluated this intervention by examining its initial efficacy on parents' mindfulness, parenting stress, subjective well-being, and symptoms of depression and anxiety. Methods: Participants were 273 parents (90.11% mothers) who were randomly assigned to the 21-day mindfulness-based intervention group (n = 136) or waitlist control group (n = 137). Pre-intervention assessment, immediate post-intervention assessment, and 30-day follow-up assessment were conducted to assess parents' mindfulness, parenting stress, subjective well-being, and symptoms of depression and anxiety. Results: Linear mixed models indicated that the group × time effects on subjective well-being, anxiety symptoms, and mindfulness were significant, after controlling for sex, age, education, income, habit of mindfulness practice, hours of weekly mindfulness practice, and diagnostic history of psychiatric disorder. Follow-up analyses indicated that compared to baseline, participants from the intervention group reported significantly greater subjective well-being and mindfulness, and fewer symptoms of anxiety than did those from the waitlist control group. The group × time effects on parenting stress and depressive symptoms were non-significant. Exploratory findings further suggested practicality and perceived acceptability of the intervention. Conclusions: This study showed initial efficacy of a 21-day online mindfulness-based intervention on parents' subjective well-being, anxiety symptoms, and mindfulness. The findings inform researchers and practitioners about the utility of a brief mindfulness-based intervention in promotion parental well-being. Other areas of feasibility warrant future investigation.

Graph-Based Depth Denoising & Dequantization for Point Cloud Enhancement.

A 3D point cloud is typically constructed from depth measurements acquired by sensors at one or more viewpoints. The measurements suffer from both quantization and noise corruption. To improve quality, previous works denoise a point cloud a posteriori after projecting the imperfect depth data onto 3D space. Instead, we enhance depth measurements directly on the sensed images a priori, before synthesizing a 3D point cloud. By enhancing near the physical sensing process, we tailor our optimization to our depth formation model before subsequent processing steps that obscure measurement errors. Specifically, we model depth formation as a combined process of signal-dependent noise addition and non-uniform log-based quantization. The designed model is validated (with parameters fitted) using collected empirical data from a representative depth sensor. To enhance each pixel row in a depth image, we first encode intra-view similarities between available row pixels as edge weights via feature graph learning. We next establish inter-view similarities with another rectified depth image via viewpoint mapping and sparse linear interpolation. This leads to a maximum a posteriori (MAP) graph filtering objective that is convex and differentiable. We minimize the objective efficiently using accelerated gradient descent (AGD), where the optimal step size is approximated via Gershgorin circle theorem (GCT). Experiments show that our method significantly outperformed recent point cloud denoising schemes and state-of-the-art image denoising schemes in two established point cloud quality metrics.

Glycolysis and the Pentose Phosphate Pathway Promote LPS-Induced NOX2 Oxidase- and IFN-ß-Dependent Inflammation in Macrophages.

Macrophages undergo a metabolic switch from oxidative phosphorylation to glycolysis when exposed to gram-negative bacterial lipopolysaccharide (LPS), which modulates antibacterial host defence mechanisms. Here, we show that LPS treatment of macrophages increased the classical oxidative burst response via the NADPH oxidase (NOX) 2 enzyme, which was blocked by 2-deoxyglucose (2-DG) inhibition of glycolysis. The inhibition of the pentose phosphate pathway with 6-aminonicotinamide (6-AN) also suppressed the LPS-induced increase in NOX2 activity and was associated with a significant reduction in the mRNA expression of NOX2 and its organizer protein p47phox. Notably, the LPS-dependent enhancement in NOX2 oxidase activity was independent of both succinate and mitochondrial reactive oxygen species (ROS) production. LPS also increased type I IFN-ß expression, which was suppressed by 2-DG and 6-AN and, therefore, is dependent on glycolysis and the pentose phosphate pathway. The type I IFN-ß response to LPS was also inhibited by apocynin pre-treatment, suggesting that NOX2-derived ROS promotes the TLR4-induced response to LPS. Moreover, recombinant IFN-ß increased NOX2 oxidase-dependent ROS production, as well as NOX2 and p47phox expression. Our findings identify a previously undescribed molecular mechanism where both glycolysis and the pentose phosphate pathway are required to promote LPS-induced inflammation in macrophages.

Factors Influencing Pap Smear Screening Uptake among Women Visiting Outpatient Clinics in Johor.

Introduction: Despite the benefits of cervical cancer screening, Pap smear uptake remains variable in Malaysia, with Johor previously reported as the state with the lowest uptake. This study aims to fill the gap in epidemiological knowledge and assess factors affecting the uptake of Pap smear screening among women in Johor. Methods: A cross-sectional study was conducted in several government and private clinics across Johor, including Pagoh, Muar, Batu Pahat, Kulai, and Johor Bahru districts. Data was collected from 452 women using self-administered questionnaires, and logistic regression was performed to determine factors associated with Pap smear uptake. Results: Findings showed that 48.5% of the women reported having undergone Pap smear screening in the previous 3 years, and 40.0% and 51.3% of respondents accurately answered questions on symptoms and risk factors of cervical cancer, respectively. Increasing age (ORad. 2.322, 95% CI 1.708-3.158), being married (ORadj 4.860, 95% CI 1.100-21.476), parity of ≥5 (ORadj 8.381, 95% CI 1.326-52.958), young age at first pregnancy (ORadj 0.932, 95% CI 0.877-0.991), knowledge of cervical cancer symptoms (ORadj. 1.745, 95% CI 1.065-2.857), support from family (ORadj 3.620, 95% CI 2.081-6.298), and contraception use (ORadj 2.220, 95% CI 1.314-3.750) were significantly associated with increased Pap smear uptake among women visiting outpatient clinics in Johor. Conclusion: Pap smear uptake remains suboptimal in Johor, and broad-based awareness campaigns tailored towards improving knowledge of cervical cancer with family involvement are crucial to improving uptake among women in Johor.

Cigarette Smoke Exposure Induces Neurocognitive Impairments and Neuropathological Changes in the Hippocampus.

Background and Objective: Neurocognitive dysfunction is present in up to ∼61% of people with chronic obstructive pulmonary disease (COPD), with symptoms including learning and memory deficiencies, negatively impacting the quality of life of these individuals. As the mechanisms responsible for neurocognitive deficits in COPD remain unknown, we explored whether chronic cigarette smoke (CS) exposure causes neurocognitive dysfunction in mice and whether this is associated with neuroinflammation and an altered neuropathology. Methods: Male BALB/c mice were exposed to room air (sham) or CS (9 cigarettes/day, 5 days/week) for 24 weeks. After 23 weeks, mice underwent neurocognitive tests to assess working and spatial memory retention. At 24 weeks, mice were culled and lungs were collected and assessed for hallmark features of COPD. Serum was assessed for systemic inflammation and the hippocampus was collected for neuroinflammatory and structural analysis. Results: Chronic CS exposure impaired lung function as well as driving pulmonary inflammation, emphysema, and systemic inflammation. CS exposure impaired working memory retention, which was associated with a suppression in hippocampal microglial number, however, these microglia displayed a more activated morphology. CS-exposed mice showed changes in astrocyte density as well as a reduction in synaptophysin and dendritic spines in the hippocampus. Conclusion: We have developed an experimental model of COPD in mice that recapitulates the hallmark features of the human disease. The altered microglial/astrocytic profiles and alterations in the neuropathology within the hippocampus may explain the neurocognitive dysfunction observed during COPD.

Influenza A Virus-Driven Airway Inflammation may be Dissociated From Limb Muscle Atrophy in Cigarette Smoke-Exposed Mice.

Limb muscle dysfunction is a hallmark of Chronic Obstructive Pulmonary Disease (COPD) which is further worsened following a viral-induced acute exacerbation of COPD (AECOPD). An amplified airway inflammation underlies the aggravated respiratory symptoms seen during AECOPD, however, its contributory role to limb muscle dysfunction is unclear. The present study examined the impact of influenza A virus (IAV)-induced exacerbation on hind limb muscle parameters. Airway inflammation was established in male BALB/c mice by exposure to cigarette smoke (CS) for 8 weeks. Exacerbation was then induced via inoculation with IAV, and various lung and muscle parameters were assessed on day 3 (peak of airway inflammation) and day 10 (resolution phase) post-infection. IAV infection exacerbated CS-induced airway inflammation as evidenced by further increases in immune cell counts within bronchoalveolar lavage fluid. Despite no significant impact on muscle mass, IAV exacerbation worsened the force-generating capacity of the tibialis anterior (TA) muscle. Protein oxidation and myogenic disruption was observed in the TA following CS exposure, however, IAV exacerbation did not augment these detrimental processes. To further explore the contributory role of airway inflammation on myogenic signaling, cultured myotubes were exposed to conditioned medium (CM) derived from bronchial epithelial cells stimulated with polyinosinic:polycytidylic acid and cigarette smoke extract (CSE). Despite an amplified inflammatory response in the lung epithelial cells, the CM derived from these cells did not potentiate myogenic disruption in the C2C12 myotubes. In conclusion, our data suggest that certain parameters of limb muscle dysfunction seen during viral-induced AECOPD may be independent of airway inflammation.

Ebselen prevents cigarette smoke-induced cognitive dysfunction in mice by preserving hippocampal synaptophysin expression.

BACKGROUND: Cigarette smoking (CS) is the leading cause of chronic obstructive pulmonary disease (COPD). The "spill-over" of pulmonary inflammation into the systemic circulation may damage the brain, leading to cognitive dysfunction. Cessation of CS can improve pulmonary and neurocognitive outcomes, however, its benefit on the neuroinflammatory profile remains uncertain. Here, we investigate how CS exposure impairs neurocognition and whether this can be reversed with CS cessation or an antioxidant treatment. METHODS: Male BALB/c mice were exposed to CS (9 cigarettes/day for 8 weeks) followed by 4 weeks of CS cessation. Another cohort of CS-exposed mice were co-administrated with a glutathione peroxidase mimetic, ebselen (10 mg/kg) or vehicle (5% CM-cellulose). We assessed pulmonary inflammation, spatial and working memory, and the hippocampal microglial, oxidative and synaptic profiles. RESULTS: CS exposure increased lung inflammation which was reduced following CS cessation. CS caused spatial and working memory impairments which were attributed to hippocampal microglial activation and suppression of synaptophysin. CS cessation did not improve memory deficits or alter microglial activation. Ebselen completely prevented the CS-induced working and spatial memory impairments, which was associated with restored synaptophysin expression without altering microglial activation. CONCLUSION: We were able to model the CS-induced memory impairment and microglial activation seen in human COPD. The preventative effects of ebselen on memory impairment is likely to be dependent on a preserved synaptogenic profile. Cessation alone also appears to be insufficient in correcting the memory impairment, suggesting the importance of incorporating antioxidant therapy to help maximising the benefit of cessation.

The alternative splicing landscape of a coral reef fish during a marine heatwave.

Alternative splicing is a molecular mechanism that enables a single gene to encode multiple transcripts and proteins by post-transcriptional modification of pre-RNA molecules. Changes in the splicing scheme of genes can lead to modifications of the transcriptome and the proteome. This mechanism can enable organisms to respond to environmental fluctuations. In this study, we investigated patterns of alternative splicing in the liver of the coral reef fish Acanthochromis polyacanthus in response to the 2016 marine heatwave on the Great Barrier Reef. The differentially spliced (DS; n = 40) genes during the onset of the heatwave (i.e., 29.49°C or +1°C from average) were related to essential cellular functions such as the MAPK signaling system, Ca(2+) binding, and homeostasis. With the persistence of the heatwave for a period of one month (February to March), 21 DS genes were detected, suggesting that acute warming during the onset of the heatwave is more influential on alternative splicing than the continued exposure to elevated temperatures. After the heatwave, the water temperature cooled to ~24.96°C, and fish showed differential splicing of genes related to cyto-protection and post-damage recovery (n = 26). Two-thirds of the DS genes detected across the heatwave were also differentially expressed, revealing that the two molecular mechanisms act together in A. polyacanthus to cope with the acute thermal change. This study exemplifies how splicing patterns of a coral reef fish can be modified by marine heatwaves. Alternative splicing could therefore be a potential mechanism to adjust cellular physiological states under thermal stress and aid coral reef fishes in their response to more frequent acute thermal fluctuations in upcoming decades.

Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice.

People with chronic obstructive pulmonary disease (COPD) are susceptible to respiratory infections which exacerbate pulmonary and/or cardiovascular complications, increasing their likelihood of death. The mechanisms driving these complications remain unknown but increased oxidative stress has been implicated. Here we investigated whether influenza A virus (IAV) infection, following chronic cigarette smoke (CS) exposure, worsens vascular function and if so, whether the antioxidant ebselen alleviates this vascular dysfunction. Male BALB/c mice were exposed to either room air or CS for 8 weeks followed by inoculation with IAV (Mem71, 1 × 104.5 pfu). Mice were treated with ebselen (10 mg/kg) or vehicle (5% w/v CM-cellulose in water) daily. Mice were culled 3- and 10-days post-infection, and their lungs lavaged to assess inflammation. The thoracic aorta was excised to investigate endothelial and smooth muscle dilator responses, expression of key vasodilatory and oxidative stress modulators, infiltrating immune cells and vascular remodelling. CS increased lung inflammation and caused significant vascular endothelial dysfunction, which was worsened by IAV infection. CS-driven increases in vascular oxidative stress, aortic wall remodelling and suppression of endothelial nitric oxide synthase (eNOS) were not affected by IAV infection. CS and IAV infection significantly enhanced T cell recruitment into the aortic wall. Ebselen abolished the exaggerated lung inflammation, vascular dysfunction and increased T cell infiltration in CS and IAV-infected mice. Our findings showed that ebselen treatment abolished vascular dysfunction in IAV-induced exacerbations of CS-induced lung inflammation indicating it may have potential for the treatment of cardiovascular comorbidities seen in acute exacerbations of COPD (AECOPD).

Exposure to cigarette smoke precipitates simple hepatosteatosis to NASH in high-fat diet fed mice by inducing oxidative stress.

Consumption of diet rich in fat and cigarette smoking (CS) are independent risk factors of non-alcoholic steatohepatitis (NASH), and they often occur together in some populations. The present study investigated the mechanisms of high-fat diet (HFD) and CS, individually and in combination, on the pathogenesis of NASH in mice. C57BL/6 male mice were subjected to either a low-fat chow (CH) or HFD with or without mainstream CS-exposure (4 cigarettes/day, 5 days/ week for 14 weeks). HFD alone caused hepatosteatosis (2.5-fold increase in TG content) and a significant increase in 3-nitrotyrisine (by ∼40-fold) but without an indication of liver injury, inflammation or fibrosis. CS alone in CH-fed mice increased in Tnfα expression and macrophage infiltration by 2-fold and relatively less increase in 3-nitrotyrosine (18-fold). Combination of HFD and CS precipitated hepatosteatosis to NASH reflected by exacerbated makers of liver inflammation and fibrosis which were associated with much severe liver oxidative stress (90-fold increase in 3-nitrotyrisine along with 6-fold increase in carbonylated proteins and 56% increase in lipid oxidations). Further studies were performed to administer the antioxidant tempol to CS exposed HFD mice and the results showed that the inhibition of liver oxidative stress prevented inflammatory and fibrotic changes in liver despite persisting hepatosteatosis. Our findings suggest that oxidative stress is a key mechanism underlying CS-promoted progression of simple hepatosteatosis to NASH. Targeting hepatic oxidative stress may be a viable strategy in halting the progression of metabolic associated fatty liver disease.

Apocynin prevents cigarette smoking-induced loss of skeletal muscle mass and function in mice by preserving proteostatic signalling.

BACKGROUND AND PURPOSE: Skeletal muscle dysfunction is a major comorbidity of chronic obstructive pulmonary disease (COPD). This type of muscle dysfunction may be a direct consequence of oxidative insults evoked by cigarette smoke (CS) exposure. The present study examined the effects of a potent Nox inhibitor and reactive oxygen species (ROS) scavenger, apocynin, on CS-induced muscle dysfunction. EXPERIMENTAL APPROACH: Male BALB/c mice were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days a week for 8 weeks, with or without the coadministration of apocynin (5 mg·kg-1 , i.p.). C2C12 myotubes exposed to either hydrogen peroxide (H2 O2 ) or water-soluble cigarette smoke extract (CSE) with or without apocynin (500 nM) were used as an experimental model in vitro. KEY RESULTS: Eight weeks of CS exposure caused muscle dysfunction in mice, reflected by 10% loss of muscle mass and 54% loss of strength of tibialis anterior which were prevented by apocynin administration. In C2C12 myotubes, direct exposure to H2 O2 or CSE caused myofibre wasting, accompanied by ~50% loss of muscle-derived insulin-like growth factor (IGF)-1 and two-fold induction of Cybb, independent of cellular inflammation. Expression of myostatin and MAFbx, negative regulators of muscle mass, were up-regulated under H2 O2 but not CSE conditions. Apocynin treatment abolished CSE-induced Cybb expression, preserving muscle-derived IGF-1 expression and signalling pathway downstream of mammalian target of rapamycin (mTOR), thereby preventing myofibre wasting. CONCLUSION AND IMPLICATIONS: Targeted pharmacological inhibition of Nox-derived ROS may alleviate the lung and systemic manifestations in smokers with COPD.

Ebselen reduces cigarette smoke-induced endothelial dysfunction in mice.

BACKGROUND AND PURPOSE: It is well established that both smokers and patients with COPD are at a significantly heightened risk of cardiovascular disease (CVD), although the mechanisms underpinning the onset and progression of co-morbid CVD are largely unknown. Here, we explored whether cigarette smoke (CS) exposure impairs vascular function in mice and given the well-known pathological role for oxidative stress in COPD, whether the antioxidant compound ebselen prevents CS-induced vascular dysfunction in mice. EXPERIMENTAL APPROACH: Male BALB/c mice were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days a week for 8 weeks. Mice were treated with ebselen (10 mg·kg-1 , oral gavage once daily) or vehicle (5% w/v CM cellulose in water) 1 h prior to the first CS exposure of the day. Upon killing, bronchoalveolar lavage fluid (BALF) was collected to assess pulmonary inflammation, and the thoracic aorta was excised to investigate vascular endothelial and smooth muscle dilator responses ex vivo. KEY RESULTS: CS exposure caused a significant increase in lung inflammation which was reduced by ebselen. CS also caused significant endothelial dysfunction in the thoracic aorta which was attributed to a down-regulation of eNOS expression and increased vascular oxidative stress. Ebselen abolished the aortic endothelial dysfunction seen in CS-exposed mice by reducing the oxidative burden and preserving eNOS expression. CONCLUSION AND IMPLICATIONS: Targeting CS-induced oxidative stress with ebselen may provide a novel means for treating the life-threatening pulmonary and cardiovascular manifestations associated with cigarette smoking and COPD.

Brief Report: Mindfulness Training for Chinese Adolescents with Autism Spectrum Disorder and Their Parents in Hong Kong.

This study investigated the feasibility and preliminary effectiveness of a concurrent mindfulness program (MYmind) on Chinese adolescents with autism spectrum disorder and their parents in Hong Kong, China using a randomized controlled trial with a waitlist control group. Results showed the study had 80% compliance rate, 0% dropout rate, and 89% response rate. Between-group comparisons showed mindfulness had trend effects on parent's rumination (g = 1.16), mindful parenting (d = 0.6), parenting style (d = 0.59), and parenting stress (d = 0.5). The study demonstrated the feasibility of the MYmind program in the Chinese context. A larger trial with longer follow-up period is suggested to better examine the effect of mindfulness on adolescents with ASD and their parents.