Correction: He et al. Impacts of Cigarette Smoke (CS) on Muscle Derangement in Rodents-A Systematic Review. Toxics 2022, 10, 262.

In the original publication [...].

Within-subjects vs between-subjects co-variation of prepulse-elicited reaction and the diminution of startle to the succeeding pulse stimulus in the prepulse inhibition paradigm.

Prepulse inhibition (PPI) refers to the diminution of the startle reflex to a sudden and intense acoustic stimulus (pulse) when this startle-eliciting pulse is preceded shortly by a weaker prepulse stimulus. PPI is widely used in evaluating the effects of psychomimetic and antipsychotic drugs on sensorimotor gating, but individual differences in PPI expression have received scant attention. We have previously shown that mice and rats exhibiting stronger motor response to the prepulse also exhibit more PPI. It remains unexplored, however, if this between-subjects correlation may be similarly observed across trials from a within-subjects perspective. Here, we mapped the prepulse-elicited response to the diminution of the startle response to the succeeding pulse stimulus, trial-by-trial, across nine prepulse-pulse definitions with varying prepulse and pulse intensities. The resulting within-subjects correlation independently obtained in 113 adult C57BL6 mice revealed that trials registering a stronger prepulse reaction also recorded a larger startle response to the pulse stimulus, indicative of weaker PPI, especially when higher-intensity prepulses were paired with low-intensity pulses. The within- and between-subjects analyses have apparently yielded two contrasting relationships between the direct motor response to the prepulse and the inhibition of subsequent startle reaction induced by the same prepulse. One interpretation is that the within-subjects correlation reflects state-dependent variation, whereas the between-subjects correlation stems from trait-dependent individual variation. Finally, whether our present findings may depend on the nature of the prepulse reaction is further discussed.

Impacts of Cigarette Smoke (CS) on Muscle Derangement in Rodents-A Systematic Review.

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD) and can induce systemic manifestations, such as skeletal muscle derangement. However, inconsistent findings of muscle derangement were reported in previous studies. The aim of the present study was to consolidate the available evidence and assess the impact of CS on muscle derangement in rodents. A comprehensive literature search of five electronic databases identified ten articles for final analysis. Results showed that the diaphragm, rectus femoris, soleus, and gastrocnemius exhibited significant oxidative to glycolytic fiber conversions upon CS exposure. In contrast, the extensor digitorum longus (EDL), plantaris, and tibialis did not exhibit a similar fiber-type conversion after CS exposure. Hindlimb muscles, including the quadriceps, soleus, gastrocnemius, and EDL, showed significant reductions in the CSA of the muscle fibers in the CS group when compared to the control group. Changes in inflammatory cytokines, exercise capacity, and functional outcomes induced by CS have also been evaluated. CS could induce a shift from oxidative fibers to glycolytic fibers in high-oxidative muscles such as the diaphragm, rectus femoris, and soleus, and cause muscle atrophy, as reflected by a reduction in the CSA of hindlimb muscles such as the quadriceps, soleus, gastrocnemius, and EDL.

Biomarkers for prognostic functional recovery poststroke: A narrative review.

Background and objective: Prediction of poststroke recovery can be expressed by prognostic biomarkers that are related to the pathophysiology of stroke at the cellular and molecular level as well as to the brain structural and functional reserve after stroke at the systems neuroscience level. This study aimed to review potential biomarkers that can predict poststroke functional recovery. Methods: A narrative review was conducted to qualitatively summarize the current evidence on biomarkers used to predict poststroke functional recovery. Results: Neurophysiological measurements and neuroimaging of the brain and a wide diversity of molecules had been used as prognostic biomarkers to predict stroke recovery. Neurophysiological studies using resting-state electroencephalography (EEG) revealed an interhemispheric asymmetry, driven by an increase in low-frequency oscillation and a decrease in high-frequency oscillation in the ipsilesional hemisphere relative to the contralesional side, which was indicative of individual recovery potential. The magnitude of somatosensory evoked potentials and event-related desynchronization elicited by movement in task-related EEG was positively associated with the quantity of recovery. Besides, transcranial magnetic stimulation (TMS) studies revealed the potential values of using motor-evoked potentials (MEP) and TMS-evoked EEG potentials from the ipsilesional motor cortex as prognostic biomarkers. Brain structures measured using magnetic resonance imaging (MRI) have been implicated in stroke outcome prediction. Specifically, the damage to the corticospinal tract (CST) and anatomical motor connections disrupted by stroke lesion predicted motor recovery. In addition, a wide variety of molecular, genetic, and epigenetic biomarkers, including hemostasis, inflammation, tissue remodeling, apoptosis, oxidative stress, infection, metabolism, brain-derived, neuroendocrine, and cardiac biomarkers, etc., were associated with poor functional outcomes after stroke. However, challenges such as mixed evidence and analytical concerns such as specificity and sensitivity have to be addressed before including molecular biomarkers in routine clinical practice. Conclusion: Potential biomarkers with prognostic values for the prediction of functional recovery after stroke have been identified; however, a multimodal approach of biomarkers for prognostic prediction has rarely been studied in the literature. Future studies may incorporate a combination of multiple biomarkers from big data and develop algorithms using data mining methods to predict the recovery potential of patients after stroke in a more precise way.

Therapeutic Effect and Mechanisms of Essential Oils in Mood Disorders: Interaction between the Nervous and Respiratory Systems.

Essential oils (EOs) are extracted from plants and contain active components with therapeutic effects. Evidence shows that various types of EOs have a wide range of health benefits. In our previous studies, the potential of lavender EO for prevention and even treatment of depression and anxiety symptoms was demonstrated. The favourable outcomes may be due to multiple mechanisms, including the regulation of monoamine level, the induction of neurotrophic factor expression, the regulation of the endocrine system and the promotion of neurogenesis. The molecules of EOs may reach the brain and exert an effect through two distinctive pathways, namely, the olfactory system and the respiratory system. After inhalation, the molecules of the EOs would either act directly on the olfactory mucosa or pass into the respiratory tract. These two delivery pathways suggest different underlying mechanisms of action. Different sets of responses would be triggered, such as increased neurogenesis, regulation of hormonal levels, activation of different brain regions, and alteration in blood biochemistry, which would ultimately affect both mood and emotion. In this review, we will discuss the clinical effects of EOs on mood regulation and emotional disturbances as well as the cellular and molecular mechanisms of action. Emphasis will be put on the interaction between the respiratory and central nervous system and the involved potential mechanisms. Further evidence is needed to support the use of EOs in the clinical treatment of mood disturbances. Exploration of the underlying mechanisms may provide insight into the future therapeutic use of EO components treatment of psychiatric and physical symptoms.

COVID-19 Rehabilitation With Herbal Medicine and Cardiorespiratory Exercise: Protocol for a Clinical Study.

BACKGROUND: Recent studies have revealed that many discharged patients with COVID-19 experience ongoing symptoms months later. Rehabilitation interventions can help address the consequences of COVID-19, including medical, physical, cognitive, and psychological problems. To our knowledge, no studies have investigated the effects of rehabilitation following discharge from hospital for patients with COVID-19. OBJECTIVE: The specific aims of this project are to investigate the effects of a 12-week exercise program on pulmonary fibrosis in patients recovering from COVID-19. A further aim will be to examine how Chinese herbal medicines as well as the gut microbiome and its metabolites regulate immune function and possibly autoimmune deficiency in the rehabilitation process. METHODS: In this triple-blinded, randomized, parallel-group, controlled clinical trial, we will recruit adult patients with COVID-19 who have been discharged from hospital in Hong Kong and are experiencing impaired lung function and pulmonary function. A total of 172 eligible patients will be randomized into four equal groups: (1) cardiorespiratory exercise plus Chinese herbal medicines group, (2) cardiorespiratory exercise only group, (3) Chinese herbal medicines only group, and (4) waiting list group (in which participants will receive Chinese herbal medicines after 24 weeks). These treatments will be administered for 12 weeks, with a 12-week follow-up period. Primary outcomes include dyspnea, fatigue, lung function, pulmonary function, blood oxygen levels, immune function, blood coagulation, and related blood biochemistry. Measurements will be recorded prior to initiating the above treatments and repeated at the 13th and 25th weeks of the study. The primary analysis is aimed at comparing the outcomes between groups throughout the study period with an α level of .05 (two-tailed). RESULTS: The trial has been approved by the university ethics committee following the Declaration of Helsinki (approval number: REC/19-20/0504) in 2020. The trial has been recruiting patients. The data collection will be completed in 24 months, from January 1, 2021, to December 31, 2022. CONCLUSIONS: Given that COVID-19 and its sequelae would persist in human populations, important findings from this study would provide valuable insights into the mechanisms and processes of COVID-19 rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04572360; https://clinicaltrials.gov/ct2/show/NCT04572360. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/25556.

Integrative psycho-biophysiological markers in predicting psychological resilience.

The hypothalamic-pituitary-adrenal (HPA) and parasympathetic nervous systems have been reported to play important roles in emotion regulation and stress coping. Yet, their direct relationship with psychological resilience remains unclear. These biophysiological features should be considered together with the traditional psychometric properties in studying resilience more comprehensively. The current study aimed to examine the role of these systems during a laboratory stress task and to determine the prediction power of resilience by combining psychological and biophysiological features. One hundred and seven (52 females) university students without psychiatric disorders underwent the Trier Social Stress Task (TSST). Psychometric properties of resilience were measured at rest; vagal heart rate variability (HRV), salivary cortisol, and dehydroepiandrosterone (DHEA) levels were captured at baseline, during, and after TSST. Multivariate linear regression as well as support vector regression machine-learning analyses were performed to investigate significant predictors and the prediction power of resilience. Results showed that positive and negative affects, HRV during the anticipatory phase of stress, and the ratio of cortisol/DHEA at the first recovery time point were significant predictors of resilience. The addition of biophysiological features increased the prediction power of resilience by 1.2-fold compared to psychological features alone. Results from machine learning analyses further demonstrated that the increased prediction power of resilience by adding the ratio of cortisol/DHEA was significant in "cortisol responders"; whereas a trend level was observed in "cortisol non-responders". Our findings extend the knowledge from the literature that high vagal activity during the anticipating phase of stress and the ability to restore the balance between cortisol and DHEA after a stress event could be an important feature in predicting resilience. Our findings also further support the need of combining psychological and biophysiological features in studying/predicting resilience.

The acute effects of cigarette smoke exposure on muscle fiber type dynamics in rats.

Reduced exercise capacity is common in people with chronic obstructive pulmonary diseases (COPD) and chronic smokers and is suggested to be related to skeletal muscle dysfunction. Previous studies using human muscle biopsies have shown fiber-type shifting in chronic smokers particularly those with COPD. These results, however, are confounded with aging effects because people with COPD tend to be older. In the present study, we implemented an acute 7-day cigarette smoke-exposed model using Sprague-Dawley rats to evaluate early effects of cigarette smoking on soleus muscles. Rats (n = 5 per group) were randomly assigned to either a sham air (SA) or cigarette smoking (CS) groups of three different concentrations of total particulate matters (TPM) (CSTPM2.5, CSTPM5, CSTPM10). Significantly lower percentages of type I and higher type IIa fiber were detected in the soleus muscle in CS groups when compared with SA group. Of these, only CSTMP10 group exhibited significantly lower citrate synthase activity and higher muscle tumor necrosis factor-α level than that of SA group. Tumor necrosis factor-α level was correlated with the percentage of type I and IIa fibers. However, no significant between-group differences were found in fiber cross-sectional area, physical activities, or lung function assessments. In conclusion, acute smoking may directly trigger the onset of glycolytic fiber type shift in skeletal muscle independent of aging.

Resting-state abnormalities in Autism Spectrum Disorders: A meta-analysis.

The gold standard for clinical assessment of Autism Spectrum Disorders (ASD) relies on assessing behavior via semi-structured play-based interviews and parent interviews. Although these methods show good sensitivity and specificity in diagnosing ASD cases, behavioral assessments alone may hinder the identification of asymptomatic at-risk group. Resting-state functional magnetic resonance imaging (rs-fMRI) could be an appropriate approach to produce objective neural markers to supplement behavioral assessments due to its non-invasive and task-free nature. Previous neuroimaging studies reported inconsistent resting-state abnormalities in ASD, which may be explained by small sample sizes and phenotypic heterogeneity in ASD subjects, and/or the use of different analytical methods across studies. The current study aims to investigate the local resting-state abnormalities of ASD regardless of subject age, IQ, gender, disease severity and methodological differences, using activation likelihood estimation (ALE). MEDLINE/PubMed databases were searched for whole-brain rs-fMRI studies on ASD published until Feb 2018. Eight experiments involving 424 subjects were included in the ALE meta-analysis. We demonstrate two ASD-related resting-state findings: local underconnectivity in the dorsal posterior cingulate cortex (PCC) and in the right medial paracentral lobule. This study contributes to uncovering a consistent pattern of resting-state local abnormalities that may serve as potential neurobiological markers for ASD.

Vocational evaluation and vocational guidance for young people with a history of drug abuse.

BACKGROUND: Young people recovering from drug addiction often face challenges in returning to the job market and in maintaining their jobs. Many of them feel they have no choice but to do entry-level work, and they are often unsure about their work ability and vocational choice. OBJECTIVE: In collaboration with a youth outreach service, this study aims to provide a package of vocational assessment, guidance, and support for these clients. METHODS: Using a strength-based case management framework, we conducted a comprehensive vocational evaluation for each participant (N = 17), which covered self-perception of abilities, work and occupational interests, work readiness, work-related self-efficacy, and work aptitudes. We presented assessment results to each client and provided guidance on their education, training, or vocational choice. RESULTS: The results of aptitude tests indicate that most participants can cope with an entry-level job. Many participants are strong in jobs that require quick decision-making, sorting, assembly, and clerical tasks, but many are weak in fine manual dexterity and eye-hand-foot coordination. Many participants preferred jobs that are creative, indefinite, and autonomous in nature. CONCLUSION: Longer-term vocational counseling and coaching is needed to help clients make vocational choices and extend their job tenure. Many clients will also need training in job seeking and job maintenance skills.

Eosinophilia and clinical outcome of chronic obstructive pulmonary disease: a meta-analysis.

Numerous studies have investigated the association between eosinophilia and clinical outcome of patients with chronic obstructive pulmonary disease (COPD) but the evidence is conflicting. We conducted a pooled analysis of outcome measures comparing eosinophilic and non-eosinophilic COPD patients. We searched articles indexed in four databases using Medical Subject Heading or Title and Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from inception to December 2016. Observational studies and randomized controlled trials with parallel groups comparing COPD patients with and without eosinophilia were included. Comparing to the non-eosinophilic group, those with eosinophilic COPD had a similar risk for exacerbation in 12 months [Odds ratio = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55] and in-hospital mortality [OR = 0.52, 95% CI 0.25-1.07]. Eosinophilia was associated with reduced length of hospital stay (P = 0.04). Subsequent to therapeutic interventions, eosinophilic outpatients performed better in pulmonary function tests [Mean Difference = 1.64, 95% CI 0.05-3.23, P < 0.001]. Inclusion of hospitalized patients nullified the effect. Improvement of quality of life was observed in eosinophilic subjects [Standardized Mean Difference = 1.83, 95% CI 0.02-3.64, P = 0.05], independent of hospitalization status. In conclusion, blood eosinophilia may be predictive of favorable response to steroidal and bronchodilator therapies in patients with stable COPD.

Interaction Effect of Social Isolation and High Dose Corticosteroid on Neurogenesis and Emotional Behavior.

Hypercortisolemia is one of the clinical features found in depressed patients. This clinical feature has been mimicked in animal studies via application of exogenous corticosterone (CORT). Previous studies suggested that CORT can induce behavioral disturbance in anxious-depressive like behavior, which is associated with suppressed neurogenesis. Hippocampal neurogenesis plays an important role in adult cognitive and behavioral regulation. Its suppression may thus lead to neuropsychiatric disorders. Similar to the effects of CORT on the animals' depression-like behaviors and neurogenesis, social deprivation has been regarded as one factor that predicts poor prognosis in depression. Furthermore, social isolation is regarded as a stressor to social animals including experimental rodents. Hence, this study aims to examine if social isolation would induce further emotional or anxiety-like behavior disturbance and suppress neurogenesis in an experimental model that was repeatedly treated with CORT. Sprague-Dawley rats were used in this study to determine the effects of different housing conditions, either social isolated or group housing, in vehicle-treated control and CORT-treated animals. Forced swimming test (FST), open field test (OFT) and social interaction test (SIT) were used to assess depression-like, anxiety-like and social behaviors respectively. Immunohistochemistry was performed to quantify the number of proliferative cells and immature neurons in the hippocampus, while dendritic maturation of immature neurons was analyzed by Sholl analysis. Social isolation reduced latency to immobility in FST. Furthermore, social isolation could significantly reduce the ratio of doublecortin and bromodeoxyuridine (BrdU) positive cells of the neurogenesis assay under CORT-treated condition. The current findings suggested that the behavioral and neurological effect of social isolation is dependent on the condition of hypercortisolemia. Furthermore, social isolation may possibly augment the signs and symptoms of depressed patients with potential alteration in neurogenesis.

PM2.5 Exposure Suppresses Dendritic Maturation in Subgranular Zone in Aged Rats.

Detrimental effects of long-term inhalation of fine particulate matter (PM2.5) on the pulmonary and cardiovascular systems have been widely reported. Recent studies have shown that exposure to PM2.5 also causes adverse neurocognitive effects. This study investigates the effects of inhaled ammonium sulfate, which is a major compound of inorganic air pollutants in PM2.5, on adult neurogenesis in aged Sprague-Dawley rats. A total of 20 rats were randomly assigned to experimental (n = 10) and control (n = 10) conditions, wherein they were exposed to either ammonium sulfate or sham air for 2 h per day and for 28 consecutive days. It was observed that ammonium sulfate inhibited the maturation process and diminished dendritic complexity of immature neurons in the subgranular zone (SGZ) of the hippocampus significantly, although the number of neural stem cells or the rates of differentiation were comparable between the two groups. Our findings provide clear evidence on the direct relationship between air quality and advantageous neurogenesis. Exposure to PM leads to specific adverse effects on the maturation process during neurogenesis.

Pathological Role and Diagnostic Value of Endogenous Host Defense Peptides in Adult and Neonatal Sepsis: A Systematic Review.

BACKGROUND: Sepsis is a systemic host response to an infection leading to organ failure. This is associated with dynamic expression of endogenous host defense peptides. Dysregulation of these peptides is associated with septic morbidity and mortality. METHODS: We performed a systematic search of articles indexed in PubMed, ISI Web of Knowledge, EmBase, and Scopus database from inception to October 2016. Both preclinical and clinical studies investigating the role of host defense peptides in pathogenesis and as biomarkers for sepsis were included. RESULTS: Of the available literature, cathelicidin, defensin, and hepcidin are among the best-characterized peptides. These regulate immune response, and crosstalk with pyroptosis and coagulation cascades. The applicability of these peptides as septic biomarkers has been investigated in vitro and in vivo studies. However, numerous studies were based on endotoxemia without an infection, jeopardizing interpretation of the outcomes. Cathelicidin and defensin were frequently reported in adult sepsis while hepcidin in neonatal sepsis. The expression level of these peptides is significantly associated with septic condition. Most of the studies employed a cross-sectional design, precluding the establishment of a temporal relationship between candidate peptide biomarkers and sepsis. CONCLUSIONS: Innate defense peptides have been insufficiently evaluated as either diagnostic or prognostic biomarkers. In the future, evaluation of host defense peptides as septic biomarkers may employ a longitudinal design and consider a panel of multiple peptides.

A randomized controlled trial of qigong exercise on fatigue symptoms, functioning, and telomerase activity in persons with chronic fatigue or chronic fatigue syndrome.

BACKGROUND: Chronic fatigue is common in the general population. Complementary therapies are often used by patients with chronic fatigue or chronic fatigue syndrome to manage their symptoms. PURPOSE: This study aimed to assess the effect of a 4-month qigong intervention program among patients with chronic fatigue or chronic fatigue syndrome. METHODS: Sixty-four participants were randomly assigned to either an intervention group or a wait list control group. Outcome measures included fatigue symptoms, physical functioning, mental functioning, and telomerase activity. RESULTS: Fatigue symptoms and mental functioning were significantly improved in the qigong group compared to controls. Telomerase activity increased in the qigong group from 0.102 to 0.178 arbitrary units (p < 0.05). The change was statistically significant when compared to the control group (p < 0.05). CONCLUSION: Qigong exercise may be used as an alternative and complementary therapy or rehabilitative program for chronic fatigue and chronic fatigue syndrome.

Roles of paroxetine and corticosterone on adult mammalian ciliary body cell proliferation.

BACKGROUND: The neurogenesis in retina of adult mammals is generally abolished, and this renders the retina lack of regenerative capacity. Despite this, there is a small population of nestin-positive cells in the ciliary epithelium which retains neurogenic potential. The present study aimed at investigating the effect of two drugs, corticosterone and paroxetine, on the cell proliferation of the ciliary body. METHODS: Adult Sprague-Dawley rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine treatment for 14 days. Cell proliferation in the ciliary body was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry. Co-labelling of BrdU and stem cell marker was used to phenotype the BrdU immunoreactive cells. RESULTS: Corticosterone treatment suppressed while paroxetine treatment increased the cell proliferation of the ciliary body. Co-labelling with cell markers revealed that the BrdU positive cells also showed nestin expression but not glial fibrillary acidic protein (GFAP). CONCLUSIONS: The results illustrate that proliferation of retinal progenitor cells situated in ciliary body are subjected to regulation by selective serotonin reuptake inhibitors (SSRI) and corticosteroid, which is similar to our previous findings in neurogenic regions in central nervous system (CNS). Paroxetine treatment could reverse the suppressive effect of corticosterone on ciliary body cell proliferation. This provides information for future investigation of retinal stem cell biology and potential treatment of retinal degenerative diseases.

Intracerebroventricular infusion of cytosine-arabinoside causes prepulse inhibition disruption.

Adult neurogenesis in hippocampus is associated with behaviors such as learning. Hippocampus is involved in the regulation of prepulse inhibition (PPI), but the relationship between neurogenesis and PPI is unexplored. We conducted four experiments to determine the role of neural progenitor cell proliferation in PPI. Intracerebroventricular infusion of cytostatic cytosine arabinoside caused PPI disruption but repeated exposure to PPI sessions prevented the PPI disruption. Corticosterone treatment, which decreases hippocampal cell proliferation, caused PPI disruption, whereas antidepressant and exercise, which increased cell proliferation, did not affect PPI. These results suggest that cell proliferation is involved in the first encounter with PPI test while its importance may decrease upon repeated exposures to the tests.

Expression of telomerase reverse transcriptase in adult goldfish retina.

Telomerase, a specialized reverse transcriptase that maintains telomere during cell division, is commonly associated with cell proliferation. Increasing evidence suggests that telomerase may bear functions other than telomere elongation. We investigated whether telomerase is expressed in the continuously growing goldfish retina. Telomeric repeat amplification protocol (TRAP) assay reveals telomerase activity in goldfish retina. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot show that telomerase catalytic subunit (TERT) is expressed at both mRNA and protein levels. Localization of TERT by immunohistochemistry indicates prominent expression of TERT in the outer nuclear layer, the inner nuclear layer, and, in a small population of cells, in the ganglion cell layer. Coexpression of TERT with proliferative cell nuclear antigen (PCNA) immunoreactivity is found in rod progenitor cells. These results suggest the role of telomerase in vertebrate central nervous system (CNS) other than telomere maintenance, such as regulation of cell cycle progression and maintenance of retinal cell phenotypes.