BMAL1 sex-specific effects in the neonatal mouse airway exposed to moderate hyperoxia.

Supplemental O2 (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway hyperreactivity (AHR) and asthma. Clinical practice shifted toward the use of moderate hyperoxia (<60% O2), but risk for subsequent airway disease remains. In mouse models of moderate hyperoxia, neonatal mice have increased AHR with effects on airway smooth muscle (ASM), a cell type involved in airway tone, bronchodilation, and remodeling. Understanding mechanisms by which moderate O2 during the perinatal period initiates sustained airway changes is critical to drive therapeutic advancements toward treating airway diseases. We propose that cellular clock factor BMAL1 is functionally important in developing mouse airways. In adult mice, cellular clocks target pathways highly relevant to asthma pathophysiology and Bmal1 deletion increases inflammatory response, worsens lung function, and impacts survival outcomes. Our understanding of BMAL1 in the developing lung is limited, but our previous findings show functional relevance of clocks in human fetal ASM exposed to O2. Here, we characterize Bmal1 in our established mouse neonatal hyperoxia model. Our data show that Bmal1 KO deleteriously impacts the developing lung in the context of O2 and these data highlight the importance of neonatal sex in understanding airway disease.

Predictive performance of the STarT Back tool for poor outcomes in patients with low back pain: protocol for a systematic review and meta-analysis.

INTRODUCTION: Subgroups for Targeted Treatment Back Tool (SBT) is a brief multiple-construct risk prediction tool for patients with low back pain (LBP). Thus far, the predictive ability of this tool has been inconsistent. Therefore, we aim to conduct a literature review on the predictive ability of the SBT to determine the outcomes of patients with LBP. The results of this review should improve the ability of the SBT to predict poor outcomes in patients with LBP. METHODS AND ANALYSIS: Databases including PubMed, EMBASE, Cochrane Central, Web of Science, Chinese National Knowledge Infrastructure Databases, Chinese Science and Technology Journal Database, and Wanfang will be searched for studies on SBT and LBP from their inception until 31 March 2023. Longitudinal studies investigating the association between SBT subgroups and LBP outcomes, including pain, disability and quality of life, will be included. The identified studies will be independently screened for eligibility by two reviewers. A standardised sheet will be used to extract data. The Newcastle-Ottawa Scale will be used to assess the methodological quality of the included studies. Heterogeneity will be evaluated by the χ2 test with Cochran's Q statistic and quantified by the I2 statistic. The results will be synthesised qualitatively and presented as pooled risk ratios or beta coefficients quantitatively. The results will also be presented using their 95% confidence limits. Publication bias will be assessed using the method proposed by Egger and by visual inspection of funnel plots. ETHICS AND DISSEMINATION: This study is a secondary analysis of original studies that received ethics approval. Therefore, prior ethical approval is not required for this study. The findings will be submitted to relevant peer-reviewed journals for publication and presented at profession-specific conferences. TRIAL REGISTRATION NUMBER: PROSPERO registration numberCRD42022309189.

Cortical Hemodynamic Response Associated with Spatial Coding: A Near-Infrared Spectroscopy Study.

Allocentric and egocentric are two types of spatial coding. Previous studies reported the dorsal attention network's involvement in both types. To eliminate possible paradigm-specific confounds in the results, this study employed fine-grained cue-to-target paradigm to dissociate allocentric (aSC) and egocentric (eSC) spatial coding. Twenty-two participants completed a custom visuospatial task, and changes in the concentration of oxygenated hemoglobin (O2-Hb) were recorded using functional near-infrared spectroscopy (fNIRS). The least absolute shrinkage and selection operator-regularized principal component (LASSO-RPC) algorithm was used to identify cortical sites that predicted the aSC and eSC conditions' reaction times. Significant changes in O2-Hb concentration in the right inferior parietal lobule (IPL) and post-central gyrus regions were common in both aSC and eSC. Results of inter-channel correlations further substantiate cortical activities in both conditions were predominantly over the right parieto-frontal areas. Together with right superior frontal gyrus areas be the reaction time neural correlates, the results suggest top-down attention and response-mapping processes are common to both spatial coding types. Changes unique to aSC were in clusters over the right intraparietal sulcus, right temporo-parietal junction, and left IPL. With the left pre-central gyrus region, be the reaction time neural correlate, aSC is likely to involve more orienting attention, updating of spatial information, and object-based response selection and inhibition than eSC. Future studies will use other visuospatial task designs for testing the robustness of the findings on spatial coding processes.

A Novel Synthetic Strategy for Preparing Polyamide 6 (PA6)-Based Polymer with Transesterification.

In the polymerization of caprolactam, the stoichiometry of carboxyl groups and amine groups in the process of melt polycondensation needs to be balanced, which greatly limits the copolymerization modification of polyamide 6. In this paper, by combining the characteristics of the polyester polymerization process, a simple and flexible synthetic route is proposed. A polyamide 6-based polymer can be prepared by combining caprolactam hydrolysis polymerization with transesterification. First, a carboxyl-terminated polyamide 6-based prepolymer is obtained by a caprolactam hydrolysis polymerization process using a dibasic acid as a blocking agent. Subsequently, ethylene glycol is added for esterification to form a glycol-terminated polyamide 6-based prepolymer. Finally, a transesterification reaction is carried out to prepare a polyamide 6-based polymer. In this paper, a series of polyamide 6-based polymers with different molecular weight blocks were prepared by adjusting the amount and type of dibasic acid added, and the effects of different control methods on the structural properties of the final product are analyzed. The results showed that compared with the traditional polymerization method of polyamide 6, the novel synthetic strategy developed in this paper can flexibly design prepolymers with different molecular weights and end groups to meet different application requirements. In addition, the polyamide 6-based polymer maintains excellent mechanical and hygroscopic properties. Furthermore, the molecular weight increase in the polyamide 6 polymer is no longer dependent on the metering balance of the end groups, providing a new synthetic route for the copolymerization of polyamide 6 copolymer.

Caveolin-1 scaffolding domain peptide prevents hyperoxia-induced airway remodeling in a neonatal mouse model.

Reactive airway diseases are significant sources of pulmonary morbidity in neonatal and pediatric patients. Supplemental oxygen exposure in premature infants contributes to airway diseases such as asthma and promotes development of airway remodeling, characterized by increased airway smooth muscle (ASM) mass and extracellular matrix (ECM) deposition. Decreased plasma membrane caveolin-1 (CAV1) expression has been implicated in airway disease and may contribute to airway remodeling and hyperreactivity. Here, we investigated the impact of clinically relevant moderate hyperoxia (50% O2) on airway remodeling and caveolar protein expression in a neonatal mouse model. Within 12 h of birth, litters of B6129SF2J mice were randomized to room air (RA) or 50% hyperoxia exposure for 7 days with or without caveolin-1 scaffolding domain peptide (CSD; caveolin-1 mimic; 10 µl, 0.25 mM daily via intraperitoneal injection) followed by 14 days of recovery in normoxia. Moderate hyperoxia significantly increased airway reactivity and decreased pulmonary compliance at 3 wk. Histologic assessment demonstrated airway wall thickening and increased ASM mass following hyperoxia. RNA from isolated ASM demonstrated significant decreases in CAV1 and cavin-1 in hyperoxia-exposed animals while cavin-3 was increased. Supplementation with intraperitoneal CSD mitigated both the physiologic and histologic changes observed with hyperoxia. Overall, these data show that moderate hyperoxia is detrimental to developing airway and may predispose to airway reactivity and remodeling. Loss of CAV1 is one mechanism through which hyperoxia produces these deleterious effects. Supplementation of CAV1 using CSD or similar analogs may represent a new therapeutic avenue for blunting hyperoxia-induced pulmonary damage in neonates.

Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma.

Recent studies have demonstrated an effect of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), on airway contractility [ via increased airway smooth muscle (ASM) intracellular calcium [Ca2+]i] and remodeling (ASM proliferation and extracellular matrix formation) in the context of airway disease. In the present study, we examined the role of BDNF in allergen-induced airway inflammation using 2 transgenic models: 1) tropomyosin-related kinase B (TrkB) conditional knockin (TrkBKI) mice allowing for inducible, reversible disruption of BDNF receptor kinase activity by administration of 1NMPP1, a PP1 derivative, and 2) smooth muscle-specific BDNF knockout (BDNFfl/fl/SMMHC11Cre/0) mice. Adult mice were intranasally challenged with PBS or mixed allergen ( Alternaria alternata, Aspergillus fumigatus, house dust mite, and ovalbumin) for 4 wk. Our data show that administration of 1NMPP1 in TrkBKI mice during the 4-wk allergen challenge blunted airway hyperresponsiveness (AHR) and reduced fibronectin mRNA expression in ASM layers but did not reduce inflammation per se. Smooth muscle-specific deletion of BDNF reduced AHR and blunted airway fibrosis but did not significantly alter airway inflammation. Together, our novel data indicate that TrkB signaling is a key modulator of AHR and that smooth muscle-derived BDNF mediates these effects during allergic airway inflammation.-Britt, R. D., Jr., Thompson, M. A., Wicher, S. A., Manlove, L. J., Roesler, A., Fang, Y.-H., Roos, C., Smith, L., Miller, J. D., Pabelick, C. M., Prakash, Y. S. Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma.

Patient and Family Member Factors Influencing Outcomes of Poststroke Inpatient Rehabilitation.

OBJECTIVE: To investigate how family members' attitudes toward functional regain, and patients' knowledge and intention of independence influence poststroke rehabilitation. DESIGN: Cross-sectional study. SETTING: Three rehabilitation inpatient settings. PARTICIPANTS: Younger (n=79) and older (n=84) poststroke patients, along with their family members (spouses, n=104; children, n=59). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Custom-designed questionnaires were used to tap into the patients' knowledge about rehabilitation (Patient's Rehabilitation Questionnaire-Knowledge About Rehabilitation) and intention of independence (Patient's Rehabilitation Questionnaire-Intention of Independence), and family members' attitudes toward patients in performing basic activities of daily living (BADL) (Family Member Attitudes Questionnaire-BADL) and instrumental activities of daily living (Family Member Attitudes Questionnaire-instrumental activities of daily living). The rehabilitation outcomes included gains in motor, cognitive, and emotional functions, and self-care independence, measured with common clinical instruments. RESULTS: The Family Member Attitudes Questionnaire-BADL predicted cognitive outcome and the Patient's Rehabilitation Questionnaire-Intention of Independence predicted motor outcome for both groups. Differential age-related effects were revealed for the Patient's Rehabilitation Questionnaire-Intention of Independence in predicting emotional outcome only for the younger group, and self-care independence only for the older group. CONCLUSIONS: Patients' intention of independence positively affected motor recovery, while family members' positive attitudes promoted cognitive regain. The findings suggested plausible age-related differences in how patients' intentions affect emotion versus self-care independence outcomes. Future studies should explore strategies for promoting positive attitudes toward independence among patients and family members during poststroke rehabilitation.

Rater experience influences reliability and validity of the Brief International Classification of Functioning, Disability, and Health Core Set for Stroke.

OBJECTIVE: To investigate how clinical experience and access to patient information regarding functional capability influence inter-rater reliability and validity of the Brief International Classification of Functioning, Disability, and Health Core Set for Stroke (ICF) assessment. METHODS: Study 1 involved expert (clinical experience > 5 years) and novice (clinical experience < 2 years) rater-pairs, each evaluating the same post-stroke patients using the ICF assessment (n = 149). Study 2 involved novice raters separately evaluating a different cohort of post-stroke patients with the ICF assessment (n = 78). The novice raters had prior knowledge of patient functioning through conducting 6 clinical tests. RESULTS: For Study 1, the expert rater-pairs (kappa=0.50-0.85 for categories; intra-class correlation (ICC)=0.76-0.96 for components) had higher reliability coefficients than novice rater-pairs (kappa=0.18-0.69 for categories; ICC=0.63-0.88 for components). For Study 2, the novice raters with prior knowledge of patient's functioning yielded significantly higher ICF component scores than those without prior knowledge. The former raters' component scores were comparable to those of the expert rater-pairs. CONCLUSION: Clinical experience in post-stroke rehabilitation enhances inter-rater reliability of ICF assessment. Know-ledge of patient's functional capability, such as conducting common clinical tests in post-stroke rehabilitation, is useful for improving assessment validity.

The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. METHODS/DESIGN: A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). DISCUSSION: This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

Evaluation of Tai Chi Yunshou exercises on community-based stroke patients with balance dysfunction: a study protocol of a cluster randomized controlled trial.

BACKGROUND: Balance dysfunction after stroke limits patients' general function and participation in daily life. Previous researches have suggested that Tai Chi exercise could offer a positive improvement in older individuals' balance function and reduce the risk of falls. But convincing evidence for the effectiveness of enhancing balance function after stroke with Tai Chi exercise is still inadequate. Considering the difficulties for stroke patients to complete the whole exercise, the current trial evaluates the benefit of Tai Chi Yunshou exercise for patients with balance dysfunction after stroke through a cluster randomization, parallel-controlled design. METHODS/DESIGN: A single-blind, cluster-randomized, parallel-controlled trial will be conducted. A total of 10 community health centers (5 per arm) will be selected and randomly allocated into Tai Chi Yunshou exercise group or balance rehabilitation training group. Each community health centers will be asked to enroll 25 eligible patients into the trial. 60 minutes per each session, 1 session per day, 5 times per week and the total training round is 12 weeks. Primary and secondary outcomes will be measured at baseline and 4-weeks, 8-weeks, 12-weeks, 6-week follow-up, 12-week follow-up after randomization. Safety and economic evaluation will also be assessed. DISCUSSION: This protocol aims to evaluate the effectiveness of Tai Chi Yunshou exercise for the balance function of patients after stroke. If the outcome is positive, this project will provide an appropriate and economic balance rehabilitation technology for community-based stroke patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-13003641. Registration date: 22 August, 2013 http://www.chictr.org/usercenter/project/listbycreater.aspx .

Community-applied research of a traditional Chinese medicine rehabilitation scheme on Broca's aphasia after stroke: study protocol for a randomized controlled trial.

BACKGROUND: Aphasia is a common and severely disabling complication in stroke patients. It usually brings about lower rates of functional recovery, longer rehabilitation length of stay (LOS), and significantly poorer LOS efficiency (LOS-Eff), resulting in higher rehabilitation costs compared to patients without aphasia. It also decreases the quality of life and increases the mortality of stroke patients. The evidence currently available suggests that the effect of acupuncture combined with language training for apoplectic aphasia is statistically better than speech and language therapy (SLT) alone, but there remains a lack of high-quality randomized controlled trials. Acupuncture combined with language training is relatively low-cost and especially suitable for community-based rehabilitation for aphasia patients after stroke, taking its medical and health facilities which are always deficient in manpower and material resources into account. The aim of the present study is to develop an effective standard therapeutic program for apoplectic aphasia in communities. METHODS/DESIGN: In a randomized controlled clinical trial with blinded assessment, 290 eligible patients with aphasia due to stroke will be randomly allocated into a control group or an experimental group. The course of this trial will comprise a 4-week intervention and a 12-week follow-up period. Five assessment points, including baseline, 2 and 4 weeks after treatment, 6 and 12 weeks after follow-up, are set to dynamically observe the changes of curative effects. Primary outcome measures are the differences in the score on both the China rehabilitation research center aphasia examination (CRRCAE) and Boston diagnostic aphasia examination - Chinese version (BDAE-C) after intervention and follow-up. The Modified Barthel Index (MBI), 36-Item Short Form Health Survey (SF-36), and results of blood oxygen level dependent-functional magnetic resonance imaging (BOLD-fMRI) examination are considered as the secondary outcome measures. Other outcomes will include rate of adverse events and economic effects. DISCUSSION: If the outcome is positive, this project will offer a low-cost appropriate technology for community health centers (CHCs) in the rehabilitation of aphasia patients after stroke, and could be implemented on a large scale, both in China and worldwide. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-13003703. Registration date: 18 October 2013.

Structure-activity relationships in rodent diaphragm muscle fibers vs. neuromuscular junctions.

The diaphragm muscle (DIAm) is a highly active muscle of mixed fiber type composition. We hypothesized that consistent with greater activation history and proportion of fatigue-resistant fibers, neuromuscular transmission failure is lower in the mouse compared to the rat DIAm, and that neuromuscular junction (NMJ) morphology will match their different functional demands. Minute ventilation and duty cycle were higher in the mouse than in the rat. The proportion of fatigue-resistant fibers was similar in the rat and mouse; however the contribution of fatigue-resistant fibers to total DIAm mass was higher in the mouse. Neuromuscular transmission failure was less in mice than in rats. Motor end-plate area differed across fibers in rat but not in mouse DIAm, where NMJs displayed greater complexity overall. Thus, differences across species in activation history and susceptibility to neuromuscular transmission failure are reflected in the relative contribution of fatigue resistant muscle fibers to total DIAm mass, but not in type-dependent morphological differences at the NMJ.

Changes in actomyosin ATP consumption rate in rat diaphragm muscle fibers during postnatal development.

Early postnatal development of rat diaphragm muscle (Dia(m)) is marked by dramatic transitions in myosin heavy chain (MHC) isoform expression. We hypothesized that the transition from the neonatal isoform of MHC (MHC(Neo)) to adult fast MHC isoform expression in Dia(m) fibers is accompanied by an increase in both the maximum velocity of the actomyosin ATPase reaction (V(max) ATPase) and the ATP consumption rate during maximum isometric activation (ATP(iso)). Rat Dia(m) fibers were evaluated at postnatal days 0, 14, and 28 and in adults (day 84). Across all ages, V(max) ATPase of fibers was significantly higher than ATP(iso). The reserve capacity for ATP consumption [1 - (ratio of ATP(iso) to V(max) ATP(ase))] was remarkably constant ( approximately 55-60%) across age groups, although at day 28 and in adults the reserve capacity for ATP consumption was slightly higher for fibers expressing MHC(Slow) compared with fast MHC isoforms. At day 28 and in adults, both V(max) ATPase and ATP(iso) were lower in fibers expressing MHC(Slow) followed in rank order by fibers expressing MHC(2A), MHC(2X), and MHC(2B). For fibers expressing MHC(Neo), V(max) ATPase, and ATP(iso) were comparable to values for adult fibers expressing MHC(Slow) but significantly lower than values for fibers expressing fast MHC isoforms. We conclude that postnatal transitions from MHC(Neo) to adult fast MHC isoform expression in Dia(m) fibers are associated with corresponding but disproportionate changes in V(max) ATPase and ATP(iso).