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Parkinson’s Disease (PD) is the second most common neurodegenerative disease world-wide. Mutations in the multidomain protein Leucine Rich Repeat Kinase 2 (LRRK2) are the most frequent cause of hereditary PD. Furthermore, recent data suggest that independent of mutations, increased kinase activity of LRRK2 plays an essential role in PD pathogenesis. Isolated mitochondria of tissue samples from PD patients carrying LRRK2 mutations display a significant impairment of mitochondrial function. However, due to the complexity of the mitochondrial signaling network, the role of LRRK2 in mitochondrial metabolism is still not well understood. Previously we have shown that D. discoideum Roco4 is a suitable model to study the activation mechanism of LRRK2 in vivo. To get more insight in the LRRK2 pathways regulating mitochondrial activity we used this Roco4 model system in combination with murine RAW macrophages. Here we show that both Dictyostelium roco4 knockout and cells expressing PD-mutants show behavioral and developmental phenotypes that are characteristic for mitochondrial impairment. Mitochondrial activity measured by Seahorse technology revealed that the basal respiration of D. discoideum roco4- cells is significantly increased compared to the WT strain, while the basal and maximal respiration values of cells overexpressing Roco4 are reduced compared to the WT strain. Consistently, LRRK2 KO RAW 264.7 cells exhibit higher maximal mitochondrial respiration activity compared to the LRRK2 parental RAW264.7 cells. Measurement on isolated mitochondria from LRRK2 KO and parental RAW 264.7 cells revealed no difference in activity compared to the parental cells. Furthermore, neither D. discoideum roco4- nor LRRK2 KO RAW 264.7 showed a difference in either the number or the morphology of mitochondria compared to their respective parental strains. This suggests that the observed effects on the mitochondrial respiratory in cells are indirect and that LRRK2/Roco proteins most likely require other cytosolic cofactors to elicit mitochondrial effects.

Yuluo Rong,* Jiaxing Wang,* Tao Sui, Wei Liu, Yongjun Luo, Weihua CaiDepartment of Orthopaedics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of China*These authors contributed equally to this workObjective: To report a rare case of cervical intradural disc herniation (IDH) with Brown-Séquard syndrome and to review the related literature.Methods: Pathogenesis, preoperative diagnosis, and the surgical technique are discussed, and previous literature reports are reviewed.Results: A 44-year-old woman complained of weakness of the left upper and lower extremities and paresthesias in the right limbs after a bicycle ride 3 days earlier. She had a history of neck pain for 2 years prior. CT showed obvious ossification of the posterior longitudinal ligament (OPLL), and MRI revealed C3-7 disc herniations, with a positive “halo sign” around the herniated C4/5. We performed emergency decompression through anterior cervical corpectomy, and vertebrotomy decompression and fusion. At review 3 months after surgery, the patient’s neck pain was markedly relieved, and motor strength in the limbs had improved. At 1 year after surgery, she had recovered completely.Conclusion: Cervical IDH is a rare condition that may be related to the traumatic inflammatory response and OPLL. Relatively rare imaging features such as the hawk-beak sign, halo sign, Y sign, and epidural gas sign could help in preoperative diagnosis. Prompt anterior cervical decompression is the preferred treatment for this condition.Keywords: cervical intradural disc herniation, Brown-Séquard syndrome, ossification of posterior longitudinal ligament, cerebrospinal fluid leakage, surgical treatment

In combination with studies of post-mortem Parkinson's disease (PD) brains, pharmacological and genetic models of PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis and mitochondrial respiration. We have re-examined the role of mitochondrial dysfunction in lymphoblasts isolated from individuals with idiopathic PD and an age-matched control group. As previously reported for various PD cell types, the production of reactive oxygen species (ROS) by PD lymphoblasts was significantly elevated. However, this was not due to an impairment of mitochondrial respiration, as is often assumed. Instead, basal mitochondrial respiration and ATP synthesis are dramatically elevated in PD lymphoblasts. The mitochondrial mass, genome copy number and membrane potential were unaltered, but the expression of indicative respiratory complex proteins was also elevated. This explains the increased oxygen consumption rates by each of the respiratory complexes in experimentally uncoupled mitochondria of iPD cells. However, it was not attributable to increased activity of the stress- and energy-sensing protein kinase AMPK, a regulator of mitochondrial biogenesis and activity. The respiratory differences between iPD and control cells were sufficiently dramatic as to provide a potentially sensitive and reliable biomarker of the disease state, unaffected by disease duration (time since diagnosis) or clinical severity. Lymphoblasts from control and PD individuals thus occupy two distinct, quasi-stable steady states; a ‘normal’ and a ‘hyperactive’ state characterized by two different metabolic rates. The apparent stability of the ‘hyperactive’ state in patient-derived lymphoblasts in the face of patient ageing, ongoing disease and mounting disease severity suggests an early, permanent switch to an alternative metabolic steady state. With its associated, elevated ROS production, the ‘hyperactive’ state might not cause pathology to cells that are rapidly turned over, but brain cells might accumulate long-term damage leading ultimately to neurodegeneration and the loss of mitochondrial function observed post-mortem. Whether the ‘hyperactive’ state in lymphoblasts is a biomarker specifically of PD or more generally of neurodegenerative disease remains to be determined.

The fragile X premutation (PM) allele contains a CGG expansion of 55–200 repeats in the FMR1 gene’s promoter. Male PM carriers have an elevated risk of developing neurological and psychiatric changes, including an approximately 50% risk of the fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to assess the relationships of regional white matter hyperintensities (wmhs) semi-quantitative scores, clinical status, motor (UPDRS, ICARS, Tremor) scales, and cognitive impairments, with FMR1-specific genetic changes, in a sample of 32 unselected male PM carriers aged 39–81 years. Half of these individuals were affected with FXTAS, while the non-FXTAS group comprised subcategories of non-affected individuals and individuals affected with non-syndromic changes. The dynamics of pathological processes at the cellular level relevant to the clinical status of PM carriers was investigated using the enzyme AMP-activated protein kinase (AMPK), which is a highly sensitive cellular stress-sensing alarm protein. This enzyme, as well as genetic markers – CGG repeat number and the levels of the FMR1 mRNA – were assessed in blood lymphoblasts. The results showed that the repeat distribution for FXTAS individuals peaked at 85–90 CGGs; non-FXTAS carriers were distributed within the lowest end of the PM repeat range, and non-syndromic carriers assumed an intermediate position. The size of the CGG expansion was significantly correlated, across all three categories, with infratentorial and total wmhs and with all motor scores, and the FMR1 mRNA levels with all the wmh scores, whilst AMPK activity showed considerable elevation in the non-FXTAS combined group, decreasing in the FXTAS group, proportionally to increasing severity of the wmhs and tremor/ataxia. We conclude that the size of the CGG expansion relates to the risk for FXTAS, to severity of infratentorial wmhs lesions, and to all three motor scale scores. FMR1 mRNA shows a strong association with the extent of wmhs, which is the most sensitive marker of the pathological process. However, the AMPK activity findings – suggestive of a role of this enzyme in the risk of FXTAS – need to be verified and expanded in future studies using larger samples and longitudinal assessment.

Abstract Two major earthquakes of Mw7.8 and Mw7.5 ruptured the Southern East Anatolian Fault (SEAF) and the Savrun‐Çardak‐Sürgü fault (SCSF), devastating southeast Türkiye and northwest Syria on 6 February 2023. We adopt innovative nonlinear and linear approaches to analyze the coseismic ground displacements and estimate the complex slip geometry. Unlike conventional analytical solutions that simplify crust heterogeneity, finite‐element fault models invert the displacement data and simulate the dual‐fault geometry with non‐uniformly distributed shallow crustal materials. Our results suggest the west‐dipping SEAF and north‐dipping SCSF accommodate earthquake slips of >10 m. Their respective slip distributions and proximal aftershocks correlate spatially with local seismic velocity anomalies (i.e., ΔVp and ΔVs), which implies differences in structural control along these two faults and provides insights into assessing the seismic hazard of mixed incipient‐mature fault systems.

Ying Wei,1 Yan-Zhi Wang,2 Ying Li,1 Ling Liu,1 Ting-Ting Sui,2 Yuan Li1 1Department II of Anorectal Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 2Department I of Anorectal Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of ChinaCorrespondence: Ying Wei, Department II of Anorectal Department, China-Japan Friendship Hospital, No. 2, Sakura East Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-01053236548, Email Yingwei_2023@163.comObjective: To explore the effect of comprehensive nursing on pain relief, comfort and burden of family care of infantile anal fistula.Methods: This was a randomized, double-blind, controlled clinical trial. A total of 106 cases of children with anal fistula from January 2021 to December 2021 were selected and divided into observation group and control group, there were 53 cases in each group. The control group were underwent with routine nursing intervention. The observation group were underwent with video health education, peer support, music relaxation training, physiotherapy and auricular point pressing on the basis of routine nursing therapy and other measures (comprehensive nursing). The wound healing time, comfort score, complication rate and family care burden of two groups were compared.Results: After intervention, the scores of pain degree in the observation group were significantly lower than those in the control group (4.02 ± 0.85 vs 5.89 ± 2.36, p < 0.05), and the scores of comfort degree in the observation group were higher than those in the control group (70.23 ± 5.98 vs 46.88 ± 5.23, p < 0.05). After intervention, the wound healing time of the observation group was shorter than that of the control group (3.98 ± 0.63 vs 5.77 ± 1.02, p < 0.05), and the crying times of the observation group were less than that of the control group (1.22 ± 0.26 vs 4.02 ± 0.48, p < 0.05). After intervention, the total scores of family members’ care load in the observation group were significantly lower than those in the control group (37.26 ± 4.78 vs 55.99 ± 5.02, p < 0.05).Conclusion: Comprehensive nursing can effectively promote wound healing in infantile anal fistula, reduce pain, prompt children’s comfort, reduce the number of children crying, and reduce the burden of care for children’s families.Keywords: comprehensive nursing, infantile anal fistula, comfort, complications, family care burden

Monitoring and predicting the dynamic responses of railway bridges under moving trains, including displacement and acceleration, are vital for evaluating the safety and serviceability of the train–bridge system. Traditionally, finite element analysis methods with high computational burden are used to predict the train-induced responses according to the given train loads and, hence, cannot easily be integrated as an available structural-health-monitoring strategy. Therefore, this study develops a novel framework, combining the train–bridge coupling mechanism and deep learning algorithms to efficiently predict the train-induced bridge responses while considering train load duration. Initially, the feasibility of using neural networks to calculate the train–bridge coupling vibration is demonstrated by leveraging the nonlinear relationship between train load and bridge responses. Subsequently, the instantaneous multiple moving axial loads of the moving train are regarded as the equivalent node loads that excite adjacent predefined nodes on the bridge. Afterwards, a deep long short-term memory (LSTM) network is established as a surrogate model to predict the train-induced bridge responses. Finally, the prediction accuracy is validated using a numerical case study of a simply supported railway bridge. The factors that may affect the prediction accuracy, such as network structure, training samples, the number of structural units, and noise level, are discussed. Results show that the developed framework can efficiently predict the train-induced bridge responses. The prediction accuracy of the bridge displacement is higher than that of the acceleration. In addition, the robustness of the displacement prediction is proven to be better than that of the acceleration with the variation of carriage number, riding speed, and measurement noise.

An improved method for the separation and purification of rubropunctatin from red yeast glutinous rice was developed. In this method, silica gel column chromatography and thin layer chromatography were used to separate the Monascus pigments. Pure methanol and a mixture of ethyl acetate and methanol (13:7, v/v) were selected as the eluent and running solvent, respectively. When compared with previously reported methods, the developed method required fewer types of solvents, and could be suitable for large-scale laboratory production. The extracted pigment was analysed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) (1H NMR, 13C NMR). Structural analysis revealed a molecular mass of 353.2 m/z [M-H]-, and a structure including an azaphilone body with two side chains. This structure was consistent with that reported for rubropunctatin. Therefore, the improved purification method reported herein could efficiently be used for the extraction of rubropunctatin from red yeast glutinous rice. [ABSTRACT FROM AUTHOR]

This paper focuses on the application of pile foundation underpinning technology in a deep foundation pit of a subway Viaduct Project in Beijing. The study aims to address the engineering characteristics of the project, including a large number of new piles, a wide span of underpinning abutment, a long length of deep foundation pit, and a wide range of influences. This research utilizes field monitoring and numerical simulation methods to investigate the pile foundation underpinnings. The impact and management of road-deep foundation pit construction are considered, as well as their combined effect on subway viaducts and track structures. The primary accomplishments are as follows: (1) By analyzing the data from on-site deformation monitoring, it is evident that the pier exhibits maximum vertical deformation and maximum transverse deformation at the same location. The measuring locations are specifically situated on Pier 7# at the pile foundation underpinning. The maximum vertical and transverse deformations of the track are directly proportional to the maximum deformation of the pier. (2) By comparing the numerical simulation results with the field monitoring data, it is observed that although there is some discrepancy between the two, the deformation trend is largely consistent. This suggests that the numerical simulation analysis method is effective in reflecting the deformation of the bridge and track. (3) Through the numerical model and changing the values of the retaining structure parameters, the sensitivity of the pier deformation near the road foundation pit to the retaining structure parameters is systematically analyzed. The sensitivity of the pier deformation to the foundation pit parameters is as follows: the embedded depth insertion ratio of the retaining pile > the diameter of the retaining pile > the pile spacing.

Abstract The Coronavirus Disease 2019 (COVID-19) has had a profound impact on global health and economy, making it crucial to build accurate and interpretable data-driven predictive models for COVID-19 cases to improve public policy making. The extremely large scale of the pandemic and the intrinsically changing transmission characteristics pose a great challenge for effectively predicting COVID-19 cases. To address this challenge, we propose a novel hybrid model in which the interpretability of the Autoregressive model (AR) and the predictive power of the long short-term memory neural networks (LSTM) join forces. The proposed hybrid model is formalized as a neural network with an architecture that connects two composing model blocks, of which the relative contribution is decided data-adaptively in the training procedure. We demonstrate the favorable performance of the hybrid model over its two single composing models as well as other popular predictive models through comprehensive numerical studies on two data sources under multiple evaluation metrics. Specifically, in county-level data of 8 California counties, our hybrid model achieves 4.173% MAPE, outperforming the composing AR (5.629%) and LSTM (4.934%) alone on average. In country-level datasets, our hybrid model outperforms the widely-used predictive models such as AR, LSTM, Support Vector Machines, Gradient Boosting, and Random Forest, in predicting the COVID-19 cases in Japan, Canada, Brazil, Argentina, Singapore, Italy, and the United Kingdom. In addition to the predictive performance, we illustrate the interpretability of our proposed hybrid model using the estimated AR component, which is a key feature that is not shared by most black-box predictive models for COVID-19 cases. Our study provides a new and promising direction for building effective and interpretable data-driven models for COVID-19 cases, which could have significant implications for public health policy making and control of the current COVID-19 and potential future pandemics.

Hong Kong women activists’ understanding of love and justice has shaped, and been shaped, by their political engagement under changing circumstances through two phases of mass protest: in 2014 and 2019. This article is focused on the sentiments of love and justice and how they evolved over time, from the peaceful protest of the Umbrella Movement in 2014 to the violent confrontations of 2019 in the context of the rise of ethno-nationalism. This shift reflects a changed understanding of justice – revenge against China – and a specific version of passionate love for Hong Kong and protective love for their comrades. Women activists’ experiences offer insights into how a social movement has engaged women’s emotional energies in particular gendered ways, while persistently marginalising gender issues. In the aftermath of the movement, when protest was effectively banned by both COVID-19 restrictions and the 2020 National Security Law, these women’s emotions have found a new object of their fierce love for Hong Kong: the boy band Mirror, which has come to symbolise Hongkonger pride, belonging and resistance.

The fragile X premutation (PM) allele contains a CGG expansion of 55–200 repeats in the FMR1 gene's promoter. Male PM carriers have an elevated risk of developing neurological and psychiatric changes, including an approximately 50% risk of the fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to assess the relationships of regional white matter hyperintensities (wmhs) semi-quantitative scores, clinical status, motor (UPDRS, ICARS, Tremor) scales, and cognitive impairments, with FMR1 -specific genetic changes, in a sample of 32 unselected male PM carriers aged 39–81 years. Half of these individuals were affected with FXTAS, while the non-FXTAS group comprised subcategories of non-affected individuals and individuals affected with non-syndromic changes. The dynamics of pathological processes at the cellular level relevant to the clinical status of PM carriers was investigated using the enzyme AMP-activated protein kinase (AMPK), which is a highly sensitive cellular stress-sensing alarm protein. This enzyme, as well as genetic markers – CGG repeat number and the levels of the FMR1 mRNA – were assessed in blood lymphoblasts. The results showed that the repeat distribution for FXTAS individuals peaked at 85–90 CGGs; non-FXTAS carriers were distributed within the lowest end of the PM repeat range, and non-syndromic carriers assumed an intermediate position. The size of the CGG expansion was significantly correlated, across all three categories, with infratentorial and total wmhs and with all motor scores, and the FMR1 mRNA levels with all the wmh scores, whilst AMPK activity showed considerable elevation in the non-FXTAS combined group, decreasing in the FXTAS group, proportionally to increasing severity of the wmhs and tremor/ataxia. We conclude that the size of the CGG expansion relates to the risk for FXTAS, to severity of infratentorial wmhs lesions, and to all three motor scale scores. FMR1 mRNA shows a strong association with the extent of wmhs , which is the most sensitive marker of the pathological process. However, the AMPK activity findings – suggestive of a role of this enzyme in the risk of FXTAS – need to be verified and expanded in future studies using larger samples and longitudinal assessment. [ABSTRACT FROM AUTHOR]

The human protein arginine methyltransferase NDUFAF7 controls the assembly of the ∼1-MDa mitochondrial complex I (CI; the NADH ubiquinone oxidoreductase) by methylating its subunit NDUFS2. We determined crystal structures of MidA, the Dictyostelium ortholog of NDUFAF7. The MidA catalytic core domain resembles other eukaryotic methyltransferases. However, three large core loops assemble into a regulatory domain that is likely to control ligand selection. Binding of MidA to NDUFS2 is weakened by methylation, suggesting a mechanism for methylation-controlled substrate release. Structural and bioinformatic analyses support that MidA and NDUFAF7 and their role in CI assembly are conserved from bacteria to humans, implying that protein methylation already existed in proteobacteria. In vivo studies confirmed the critical role of the MidA methyltransferase activity for CI assembly, growth, and phototaxis of Dictyostelium. Collectively, our data elucidate the origin of protein arginine methylation and its use by MidA/NDUFAF7 to regulate CI assembly. • We determined the 3D structure of a mitochondrial methyltransferase • Structural similarity suggests that protein methylation exists in proteobacteria • Binding studies suggest a methylation-controlled substrate release mechanism • Methylation by MidA controls Dictyostelium complex I assembly, growth, and phototaxis The biological role of protein arginine methyltransferases (PRMTs) outside of the nucleus is poorly understood. Hameed et al. provide structural evidence for a proteobacterial origin of PRMTs. Their work suggests a methylation-controlled substrate release mechanism and reveals that arginine methylation controls complex I assembly, growth, and phototaxis in Dictyostelium. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of our study was to make a comparison between the fixation strength of optimum placed pedicle screw (OS) and re-directionally accurate placed pedicle screw (RS) after lateral pedicle breach. PATIENTS AND METHODS: A total of 30 fresh lumbar vertebrae (L1-5) were gained from 6 male or female pigs weighing about 100 kg, which were divided into 2 groups according to different ways of pedicle screws placement: OS group (n=30) and RS group (n=30). MTS machine was employed to detect the screw loosening and axial pullout. We examined seating torque, screw-loosening force, the maximal torque and post-loosening axial pullout in each pedicle screw. RESULTS: Maximal insertion torque of OS was (111.6±8.4) N•cm and RS was (79.0±6.3) N•cm, which indicated a significant difference (Z=3.012, p=0.003). Seating torque of OS and RS were (85.9±5.6) N•cm and (60.3±4.8) N•cm separately, and the difference was statistically significant (Z=2.799, p=0.006). Screw loosening force of OS and RS were (75.9±7.0) N and (52.4±6.3) N respectively, and the difference was statistically significant (Z=2.652, p=0.003). Post-loosening axial pullout force of OS and RS were (328.5±11.3) N and (269.1±9.6) N separately, demonstrating that the difference was statistically significant (Z=2.865, p=0.004). CONCLUSIONS: RS placement is an alternative for remediation following a lateral wall breach evidenced by significantly decreased seating torque, screw loosening force, the maximal torque and post-loosening axial pullout compared with OS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Free-hand technique is widely used in pedicle screw placement for lumbar spine and generally safe; however, screw malposition still occurs. To develop a novel multi-level drill guide template for pedicle screw placement in lumbar spine and evaluate its accuracy. MATERIALS AND METHODS: Twelve lumbar cadaveric specimens were randomly allocated into guide template group (n=6) and free-hand group (n=6). Computed tomography (CT) scans were obtained for reconstruction of three-dimensional (3D) model of each lumbar vertebra, and further an individual guide template was designed. Then the templates and their corresponding vertebra were developed by rapid prototyping (RP) technology. With the guide of the templates, screws were inserted via mini-open Wiltse approach. The positions of the screws were assessed based on postoperative CT images. RESULTS: In total, 120 pedicle screws inserted (guide template group: n=60 vs. free-hand group: n=60). For all 30 vertebras in the guide template group, all pre-designed personalized drill guide templates can be fitted into the facet joints of each vertebra well. Furthermore, our results revealed a significant improvement for the guide template group in the accuracy rate (p=0.026). CONCLUSIONS: Armed with advantages of minimal invasion, enhanced accuracy and safety, the novel technique of multi-level drill guide template can be properly applied in pedicle screw placement for lumbar spine and promises to be a potential option in clinical application. [ABSTRACT FROM AUTHOR]

Improved accessibility by transit service constitutes a critical component in removing spatial barriers in daily mobility for disadvantaged groups. However, the effects of transit accessibility on the daily mobility and activity participation of different social strata remain inconclusive. This study investigates the role of transit accessibility on the activity space of three income groups in Hong Kong. The results show that the availability of transit stations and network accessibility by mass transit rail (MTR) are significantly linked to the spatial extensiveness of activity space of the higher- and medium-income commuters, while bus plays a more important role for the daily mobility of the low-income group. Concerning non-work activity participation, the low-income non-commuters appear less affected by the availability of MTR stations than the other two groups, suggesting a potentially lower ability of using MTR to carry out different daily activities. Our findings offer some in-depth insights into the possible social inequality of using transit service, thereby contributing to a more nuanced understanding of the relationship between transit accessibility and mobility in relation to economic status. Policy recommendations to alleviate transport disadvantage and improve social equity are proposed.

OBJECTIVE: The long non-coding RNA (lncRNA) H19, a maternally expressed imprinted gene, has involvement in cancer susceptibility and disease progression. However, the association between H19 polymorphisms and osteosarcoma susceptibility has remained elusive. We designed this case-control study to explore the association between H19 polymorphism and osteosarcoma risk. PATIENTS AND METHODS: In this study, we genotyped 4 tagger SNPs of the H19 gene in a case-control study including 193 osteosarcoma cases and 393 cancer-free controls. RESULTS: For the main effect analysis, rs217727 (G>A) was associated with osteosarcoma risk (GA/GG: adjusted OR = 1.51, 95% CI: 1.06-2.17, p = 0.024; AA/GG: adjusted OR = 1.89, 95% CI: 1.23-2.91, p = 0.004; additive model: adjusted OR = 1.35, 95% CI: 1.01-1.80, p = 0.043). CONCLUSIONS: This finding indicates that rs217727 polymorphism may play a role in genetic susceptibility to the risk of osteosarcoma, which may improve our understanding of the potential contribution of H19 SNPs to cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract Background Bronchial asthma is one of the most common inflammatory airway disorders. As one of the main non-drug therapies, the Sanfu herbal patch (SHP) has been widely used to treat bronchial asthma, although the evidence for its efficacy and associated mechanism are inconclusive. The objective of this trial is to clarify the clinical efficacy and safety of the SHP in the treatment of bronchial asthma in the chronic persistent or clinical remission stage and to provide high-quality data for further research. Methods We propose a multicentre, double-blinded, parallel, randomized, placebo-controlled clinical trial involving 4 study hospitals in China. A total of 72 eligible participants will be randomized into an SHP group and a placebo group. They will receive an SHP for 3 treatment sessions. The primary outcome will be changes in forced expiratory volume in 1 s after 3 treatment sessions. Secondary outcomes will include the following: (1) the Asthma Quality of Life Questionnaire, Asthma Control Test, and Asthma Long-term Follow-up Scale; (2) levels of Metallothionein-2 and Transgelin-2 in blood and urine; and (3) levels of IL-5, IL-13, IL-23, IL-25, and thymic stromal lymphopoietin in blood. Analysis of the data will be performed at baseline, at the end of the 2nd and 3rd treatment sessions, and at the 24-week follow-up. The safety of the SHP will be evaluated at each treatment session. Discussion The aims of this trial are to determine whether the SHP is more effective than placebo in the treatment of patients with bronchial asthma, as well as whether the SHP works by reducing airway inflammation and reversing bronchoconstriction. Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR1900024616. Registered on 19 July 2019.

Physical activity and social support are associated with better outcomes after surviving acute myocardial infarction (AMI), and greater walkability has been associated with activity and support. We used data from the SILVER-AMI study (November 2014–June 2017), a longitudinal cohort of community-living adults ≥ 75 years hospitalized for AMI to assess associations of neighborhood walkability with health outcomes, and to assess whether physical activity and social support mediate this relationship, if it exists. We included data from 1345 participants who were not bedbound, were discharged home, and for whom we successfully linked walkability scores (from Walk Score®) for their home census block. Our primary outcome was hospital-free survival time (HFST) at six months after discharge; secondary outcomes included physical and mental health at six months, assessed using SF-12. Physical activity and social support were measured at baseline. Covariates included cognition, functioning, comorbidities, participation in rehabilitation or physical therapy, and demographics. We employed survival analysis to examine associations between walkability and HFST, before and after adjustment for covariates; we repeated analyses using linear regression with physical and mental health as outcomes. In adjusted models, walkability was not associated with physical health (ß = 0.010; 95% CI: −0.027, 0.047), mental health (ß = −0.08; 95% CI: −0.175, −0.013), or HFST (ß = 0.008; 95% CI: −0.023, 0.009). Social support was associated with mental health in adjusted models. Neighborhood walkability was not predictive of outcomes among older adults with existing coronary disease, suggesting that among older adults, mobility limitations may supercede neighborhood walkability.

Background: The need for accessible cellular biomarkers of neurodegeneration in carriers of the fragile X mental retardation 1 (FMR1) premutation (PM) alleles. Objective: To assess the mitochondrial status and respiration in blood lymphoblasts from PM carriers manifesting the fragile X-associated tremor/ataxia syndrome (FXTAS) and non-FXTAS carriers, and their relationship with the brain white matter lesions. Methods: Oxygen consumption rates (OCR) and ATP synthesis using a Seahorse XFe24 Extracellular Flux Analyser, and steady-state parameters of mitochondrial function were assessed in cultured lymphoblasts from 16 PM males (including 11 FXTAS patients) and 9 matched controls. The regional white matter hyperintensity (WMH) scores were obtained from MRI. Results: Mitochondrial respiratory activity was significantly elevated in lymphoblasts from PM carriers compared with controls, with a 2- to 3-fold increase in basal and maximum OCR attributable to complex I activity, and ATP synthesis, accompanied by unaltered mitochondrial mass and membrane potential. The changes, which were more advanced in FXTAS patients, were significantly associated with the WMH scores in the supratentorial regions. Conclusion: The dramatic increase in mitochondrial activity in lymphoblasts from PM carriers may represent either the early stages of disease (specific alterations in short-lived blood cells) or an activation of the lymphocytes under pathological situations. These changes may provide early, convenient blood biomarkers of clinical involvements. [ABSTRACT FROM AUTHOR]

Otolith δ18O profiles for four slickhead species (Alepocephalidae) suggested that Alepocephalus umbriceps, Talismania okinawensis and Rouleina watasei migrated hundreds of metres to shallower depths during the juvenile to young stages before returning to their original depth or even deeper waters. Xenodermichthys nodulosus gradually shifted residence depth from shallow to deeper water during their life. These migratory patterns indicated that the slickheads examined had allopatric residence depths at different life stages, which might enhance the pelagic survival and growth rates of the juvenile and young fishes. [ABSTRACT FROM AUTHOR]

Numerous diseases are known to cause microstructural alteration of dental tissues structure. One type in particular is associated with neonatal jaundice and circulation of bilirubin in blood at high concentration due to increased hemolysis in conditions such as erythroblastosis fetalis, septicemia, biliary atresia, and other causes of hyperbilirubinemia. In those conditions, the products of the catabolism of hemoglobin end up deposited in various tissues, including teeth, where they can present clinically as visibly stained brown/ green teeth. There is almost no information on the nature or extent of the structural changes taking place in these conditions. Here, advanced nondestructive wide-angle synchrotron X-ray scattering techniques combined with scanning microscopy methods were used to investigate for the first time the ultrastructure of the dental hard tissues in an archival case of intrinsically pigmented green teeth. Despite no obvious elemental variation across the pigmented tissue region, the high-resolution crystallographic properties probed by wide-angle synchrotron X-ray scattering revealed an ultrastructural variation (orientation, particle size, and lattice parameter of hydroxyapatite crystallites) associated with a pigmentation line in dentine and with a distinct neonatal line in enamel. [ABSTRACT FROM AUTHOR]

Objective To develop a 180-day readmission risk model for older adults with acute myocardial infarction (AMI) that considered a broad range of clinical, demographic and age-related functional domains.Methods We used data from ComprehenSIVe Evaluation of Risk in Older Adults with AMI (SILVER-AMI), a prospective cohort study that enrolled participants aged ≥75 years with AMI from 94 US hospitals. Participants underwent an in-hospital assessment of functional impairments, including cognition, vision, hearing and mobility. Clinical variables previously shown to be associated with readmission risk were also evaluated. The outcome was 180-day readmission. From an initial list of 72 variables, we used backward selection and Bayesian model averaging to derive a risk model (N=2004) that was subsequently internally validated (N=1002).Results Of the 3006 SILVER-AMI participants discharged alive, mean age was 81.5 years, 44.4% were women and 10.5% were non-white. Within 180 days, 1222 participants (40.7%) were readmitted. The final risk model included 10 variables: history of chronic obstructive pulmonary disease, history of heart failure, initial heart rate, first diastolic blood pressure, ischaemic ECG changes, initial haemoglobin, ejection fraction, length of stay, self-reported health status and functional mobility. Model discrimination was moderate (0.68 derivation cohort, 0.65 validation cohort), with good calibration. The predicted readmission rate (derivation cohort) was 23.0% in the lowest quintile and 65.4% in the highest quintile.Conclusions Over 40% of participants in our sample experienced hospital readmission within 180 days of AMI. Our final readmission risk model included a broad range of characteristics, including functional mobility and self-reported health status, neither of which have been previously considered in 180-day risk models.

Background Functional decline (ie, a decrement in ability to perform everyday activities necessary to live independently) is common after acute myocardial infarction (AMI) and associated with poor long‐term outcomes; yet, we do not have a tool to identify older AMI survivors at risk for this important patient‐centered outcome. Methods and Results We used data from the prospective SILVER‐AMI (Comprehensive Evaluation of Risk Factors in Older Patients With Acute Myocardial Infarction) study of 3041 patients with AMI, aged ≥75 years, recruited from 94 US hospitals. Participants were assessed during hospitalization and at 6 months to collect data on demographics, geriatric impairments, psychosocial factors, and activities of daily living. Clinical variables were abstracted from the medical record. Functional decline was defined as a decrement in ability to independently perform essential activities of daily living (ie, bathing, dressing, transferring, and ambulation) from baseline to 6 months postdischarge. The mean age of the sample was 82±5 years; 57% were men, 90% were White, and 13% reported activity of daily living decline at 6 months postdischarge. The model identified older age, longer hospital stay, mobility impairment during hospitalization, preadmission physical activity, and depression as risk factors for decline. Revascularization during AMI hospitalization and ability to walk a quarter mile before AMI were associated with decreased risk. Model discrimination (c=0.78) and calibration were good. Conclusions We identified a parsimonious model that predicts risk of activity of daily living decline among older patients with AMI. This tool may aid in identifying older patients with AMI who may benefit from restorative therapies to optimize function after AMI.

Older patients presenting with acute myocardial infarction (AMI) often have comorbidities. Our objective was to examine how outcomes differ by cognitive and vision status in older AMI patients. We use data from a prospective cohort study conducted at 94 hospitals in the United States between January 2013 and October 2016 that enrolled men and women aged ≥75 years with AMI. Cognitive impairment (CI) was defined as telephone interview for cognitive status (TICS) score

In order to improve stability and capability of rejecting disturbance of the platform, the feedforward controller and disturbance observer (DOB) are used in angular loop of the 3-axis stabilized platform. This method can effectively avoid the conflict between stability and rapidity of system. Using the error signal as the evaluation index, the DOB can accurately track external disturbances, such as constant, periodic and random disturbance signal, eliminate model mismatches and improve the stability and robustness of the inner loop. Finally, the simulation result shows that the composite control method has better dynamic performance and smaller steady-state error than cascade lead-lag compensation.

Abstract Background Amidst the high disease burden, non-adherence to medications among patients with type 2 diabetes mellitus (T2DM) has been reported to be common and devastating. Sarawak Pharmaceutical Services Division has formulated a pharmacist-led, multiple-theoretical-grounding, culturally sensitive and structured group-based program, namely “Know Your Medicine – Take if for Health” (MEDIHEALTH), to improve medication adherence among Malay patients with T2DM. However, to date, little is known about the effectiveness and sustainability of the Program. Methods/design This is a prospective, parallel-design, two-treatment-group randomized controlled trial to evaluate the effectiveness and sustainability of MEDIHEALTH in improving medication adherence. Malay patients who have underlying T2DM, who obtain medication therapy at Petra Jaya Health Clinic and Kota Samarahan Health Clinic, and who have a moderate to low adherence level (8-item Morisky Medication Adherence Scale, Malaysian specific, score

The objective of this study was to investigate the composite behavior of rectangular concrete-filled cold-formed steel (CFS) tubular stub columns under axial compression. A fine finite 3D solid element model of rectangular concrete-filled cold-formed steel tubular stub column was established by ABAQUS, which utilized a constitutive model of cold-formed steel considering the cold-forming effect and a triaxial plastic-damage constitutive model of the infilled concrete. Good agreement was achieved and the average discrepancy between the experimental and FE results was less than 5%. Based on the verified models, a further parametric analysis was carried out to reveal the influence of various factors on the strength and behavior of the concrete-filled rectangular cold-formed steel tubular stub columns. The factors included constitutive models adopted for cold-formed steel, length over width ratio of the rectangular section, wall-thickness and width, and concrete strength and yield strength of the cold-formed steel. A total of 144 FE models were analyzed. The stress nephogram was reasonably simplified in accordance with the limit state and a theoretical formula considering confinement coefficient was proposed to estimate the ultimate bearing capacity of concrete-filled rectangular cold-formed steel tubular stub columns using the superposition method. The calculated results showed satisfactory agreement with both the experimental and FE results, which proved the validity and accuracy of the formula proposed in this paper. In the proposed formula, the confinement coefficient of square concrete-filled cold-formed steel tubular stub columns is larger than that of hot-rolled steel counterparts but smaller than that of the stainless steel counterparts.

Numerous studies have been carried out on the axially loaded circular concrete-filled steel tube (CCFST) stub columns. However, to date, no clear evaluation criterion for the compatibility of its design parameters has been established. In the present study, the compatibility of the design parameters (concrete compressive strength fc, steel yield strength fy, diameter D and thickness of steel tube t) of axially loaded CCFST stub columns was quantitatively investigated in terms of the contribution of the composite actions to the axial bearing capacity of the columns. The composite ratio λ was proposed as an indicator to represent the effectiveness of the composite actions. A numerical framework of the determination of λ was established, making use of a series of existing widely recognized constitutive models of structural steel and concrete. Some modifications were carried out on these models to ensure the numerical stability of the presented analysis. Moreover, the rationality of the combined use of these models was verified. The analytical results show that excessive or very small D/t ratio should be avoided in design. Meanwhile, the combined use of low-strength steel and high-strength concrete should be avoided. A table of optimal D/t ratios corresponding to different material strength matches was provided for designers. Finally, an optimization of the design parameters using the proposed method and the existing design specification was performed.

Understanding public transport passengers' loyalty has received growing research attention, given its potential to inform the long-term market management of a public transport service. However, the nature of public transport passengers' loyalty is arguably yet to be fully understood concerning its relationship to passengers' captivity and attitudes towards private car use, and their intentions to change their modal use. Hence questions remain largely unexplored that: Is public transport passengers' loyalty a result of a preferred or constrained choice? And does their loyalty have the potential to encourage more sustainable transport modal use patterns? Drawing on the busway network in Brisbane, Australia, as the case study, this paper aims to broaden the research on public transport passengers' loyalty by addressing these questions. Through developing a series of linear regression models, our findings highlight: (1) busway passengers were influenced by preferential (the experience of riding the busway service), moral (pro-environmental concerns) and constraint (cost of busway and car use) considerations; and (2) the potential of loyalty to alleviate busway passengers' intentions to shift to private car use for their trip-making. Through these findings, a series of implications are developed with the potential for the improvement of busway service and travel demand management to encourage more sustainable transport especially within a highly motorised context. Future research is encouraged to provide more evidence concerning passenger loyalty and their public transport use.

Weather influences our daily travel decisions in a number of important ways. At the individual scale, weather has been shown to influence trip-making behaviours where inclement conditions can induce re-scheduling, re-routing and cancellation of a planned journey. Furthermore at the transit system-level, poor weather can increase traffic congestion and reduce operational efficiencies. While some research has examined the weather–transit relationship, focus on the spatial dimension remain in their infancy. In this paper we adopt a visual analytic approach to spatially explore the complex weather–transit relationship at a micro geographical scale. We demonstrate that through spatially integrating a large disaggregate smart card database of bus ridership with hourly local weather measurements we can reveal how ‘heat stress’ changes the way in which passengers use the public transit system in sub-tropical Brisbane, Australia. Our approach has the potential for broader application across other public and private transport and climatic contexts to unveil the way in which weather influences our daily travel behaviour.