ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Cognitive behavioural therapy (CBT) for patients with chronic lung disease and psychological comorbidities undergoing pulmonary rehabilitation.

BACKGROUND: The study aimed to determine the effects of adding cognitive behavioural therapy (CBT) to pulmonary rehabilitation to treat patients with chronic lung disease and comorbid anxiety and/or depression symptoms. METHODS: An open, parallel group, randomised controlled trial (RCT) was conducted, with longitudinal follow-up of 12 months. CBT was delivered in 2 face-to-face sessions and 4 phone sessions to patients with depression or anxiety undergoing pulmonary rehabilitation. The main outcome measures were change in Geriatric Depression Scale (GDS) and Geriatric Anxiety Inventory (GAI); secondary outcomes were St. Georges Respiratory Questionnaire (SGRQ), 6-minute walk test (6MWT) and pulmonary rehabilitation attendance. RESULTS: A total of 65 patients were randomized to Intervention (n=24) and Control (n=41) groups. Of the 24 patients in the Intervention group, 6 patients (25%) withdrew and 4 patients (12.5%) failed to attend more than 2 CBT sessions, which was significantly more than the Control group. The majority of patients (75.4%) had chronic obstructive pulmonary disease. Fourteen (21.5%) had symptoms of depression only, 12 (18.4%) had symptoms of anxiety only, and 39 (60.0%) had symptoms of both anxiety and depression. In the Intervention group, GDS significantly improved at the end of pulmonary rehabilitation (mean difference -3.1, 95% CI: -4.39 to -1.70; P=0.0001), 3 months follow-up (mean difference -1.5, 95% CI: -4.17 to -0.75; P=0.008), and at 12 months follow-up (mean difference -1.6, 95% CI: -3.29 to -0.03, P=0.04), compared to baseline. The Control group demonstrated improvement in GDS by the end of pulmonary rehabilitation (mean difference -1.3, 95% CI: -2.4 to -0.27; P=0.01) which was not maintained at 3 months (P=0.14) and 12 months (P=0.25). GAI significantly improved by the end of rehabilitation in both the Intervention (mean difference -2.6, 95% -4.69 to -0.57; P=0.01) and Control groups (mean difference -2.6, 95% -4.16 to -1.14; P=0.001) and there was no significant improvement at 3 and 12 months. No statistically significant differences in changes in GDS or GAI were observed between the Intervention and Control groups at any time point. There was no significant improvement in SGRQ or 6MWT. There was a significant increase in attended pulmonary rehabilitation sessions in the Intervention group, compared to the Control group (mean difference 1.59; 95% CI: 0.11 to 3.07; P=0.03). CONCLUSIONS: In this RCT of patients with chronic lung diseases attending pulmonary rehabilitation, there was no evidence found for improved symptoms of anxiety or depression or health-related quality of life with the addition of CBT given in a mixed face-to-face and telephone format, compared to usual care. Slower than anticipated recruitment, leading to a smaller than planned sample size, and a high dropout rate in the group allocated to CBT may have limited the effectiveness of the behavioural intervention approach in this study.

Peripheral compartment innate immune response to Haemophilus influenzae and Streptococcus pneumoniae in chronic obstructive pulmonary disease patients.

Alterations in innate immunity that predispose to chronic obstructive pulmonary disease (COPD) exacerbations are poorly understood. We examined innate immunity gene expression in peripheral blood polymorphonuclear leukocytes (PMN) and monocytes stimulated by Haemophilus influenzae and Streptococcus pneumoniae. Thirty COPD patients (15 rapid and 15 non-rapid lung function decliners) and 15 smokers without COPD were studied. Protein expression of IL-8, IL-6, TNF-α and IFN-γ (especially monocytes) increased with bacterial challenge. In monocytes stimulated with S. pneumoniae, TNF-α protein expression was higher in COPD (non-rapid decliners) than in smokers. In co-cultures of monocytes and PMN, mRNA expression of TGF-ß1 and MYD88 was up-regulated, and CD14, TLR2 and IFN-γ down-regulated with H. influenzae challenge. TNF-α mRNA expression was increased with H. influenzae challenge in COPD. Cytokine responses were similar between rapid and non-rapid decliners. TNF-α expression was up-regulated in non-rapid decliners in response to H. influenzae (monocytes) and S. pneumoniae (co-culture of monocytes and PMN). Exposure to bacterial pathogens causes characteristic innate immune responses in peripheral blood monocytes and PMN in COPD. Bacterial exposure significantly alters the expression of TNF-α in COPD patients, although not consistently. There did not appear to be major differences in innate immune responses between rapid and non-rapid decliners.

Effectiveness of hospital-based smoking cessation.

STUDY OBJECTIVES: Smoking cessation for current smokers is a health-care imperative. It is not clear which approaches to smoking cessation are the most effective in the hospital setting and which factors predict long-term abstinence. We hypothesized that a hospital-based smoking cessation program involving behavioral modification and support would provide an effective intervention for smoking cessation. DESIGN: Prospective cohort study. SETTING: Smoking cessation clinics in a tertiary referral, cardiothoracic hospital. PATIENTS OR PARTICIPANTS: Two hundred forty-three smokers and 187 never-smoker control subjects. INTERVENTIONS: Smokers underwent specific sessions of individual counseling on behavioral modification, including written information, advice about quit aids, and support during the quit attempt. Abstinence was confirmed by exhaled carbon monoxide measurements. MEASUREMENTS AND RESULTS: Compared to never-smoker control subjects, smokers were more likely to have grown up with a smoking father or siblings, and to currently live or socialize with other smokers. Two hundred sixteen smokers attended at least two sessions of the smoking cessation program. Of these, 25% were unavailable for follow-up at 12 months and were assumed to be smoking. The point prevalence abstinence rate at 12 months was 32%. Independent factors associated with abstinence at 12 months were self-belief in quitting ability, having a heart condition, growing up without siblings who smoked, and increasing number of pack-years. CONCLUSIONS: This prospective study has demonstrated that this hospital-based smoking cessation program was as effective as programs in other settings. Social and psychological factors were associated with a greater chance of abstinence.