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Background There is limited data on the clinical outcome, long‐term survival and tolerability of sequential therapy of first‐line crizotinib followed by alectinib in a real‐world setting for Chinese patients with advanced ALK+ NSCLC. Methods The medical records of patients who received sequential therapy with first‐line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK‐TKIs) were collected from six centers in China. Combined time treatment to failure (C‐TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause. Results A total of 61 patients were included in our study. Fifty‐two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK‐TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow‐up of 34.3 months, C‐TTF was 39.2 months and estimated 5‐year OS was 68.6% in the overall population. Conclusion Sequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely., Sequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits in a Chinese population. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.

BACKGROUND In mainland China, HPV vaccines have been available to the public. However, only a few related studies among health care providers, as the key information providers, were reported although public concerns on HPV vaccines still exist. In this study, we aim to assess the knowledge of HPV, its vaccines, and attitudes toward HPV vaccines among the three most important groups of health care providers in Western China. METHOD This was a cross-sectional questionnaire-based study. Health care providers including obstetrician-gynecologists (OB-GYNs), pediatricians, and immunization service providers in Western China were investigated regarding their knowledge of HPV and its vaccines and their attitudes toward HPV vaccines. RESULTS Of 1079 health care providers completing the survey, 1015 (94.1%) knew HPV infection is the primary cause of cervical cancer. However, lower knowledge levels of other HPV-related diseases were also found (43.2%). About three-quarters (74.1%) of practitioners interviewed would be willing to recommend HPV vaccination, which was found to be lower among the OB-GYNs (69.6%) and the pediatricians (73.2%). "Lack of relevant knowledge," "concerns on safety and efficacy" and price were the three most important concerns surrounding HPV vaccination. CONCLUSION The interviewed practitioners did not have adequate knowledge of HPV and its vaccines in depth. Education interventions are highly recommended to the health care providers, especially for OB-GYNs and pediatricians, to increase the coverage of HPV vaccination among the population. For the currently high price of vaccines, a future co-sharing mechanism between the government, the providers, and the individuals might be a solution.

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Background Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune‐inflammation index (SII), neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. Methods We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan–Meier method. Results Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19–0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend Conclusions A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.

Fuzhong Li,1 Peter Harmer,2 Jan Voit,3 Li-Shan Chou4 1Oregon Research Institute, Eugene, OR, USA; 2Willamette University, Department of Exercise and Health Science, Salem, OR, USA; 3Voit Better Balance, Seattle, WA, USA; 4Iowa State University, Department of Kinesiology, Ames, IA, USACorrespondence: Fuzhong LiOregon Research Institute 1776 Millrace Dr., Eugene, OR 97403, USAEmail fuzhongl@ori.orgPurpose: This study evaluates the feasibility of delivering a virtual (online) falls prevention intervention for older adults with mild cognitive impairment (MCI).Methods: Community-dwelling older adults with MCI (mean age = 76.2 years, 72% women) were randomized to either a Tai Ji Quan (n = 15) or stretching group (n = 15) and participated in 60-minute virtual exercise sessions, via Zoom, twice weekly for 24 weeks. The primary outcome was the incidence of falls. Secondary outcomes were the number of fallers and changes from baseline in the 4-Stage Balance Test, 30-second chair stands, and Timed Up and Go Test under both single- and dual-task conditions.Results: The intervention was implemented with good fidelity, an overall attendance rate of 79%, and 13% attrition. Compared with stretching, Tai Ji Quan did not reduce falls (incidence rate ratio = 0.58; 95% confidence interval [CI], 0.32 to 1.03) or the number of fallers (relative risk ratio = 0.75; 95% CI, 0.46 to 1.22) at week 24. The Tai Ji Quan group, however, performed consistently better than the stretching group in balance (between-group difference in change from baseline, 0.68 points; 95% CI, 0.12 to 1.24), 30-second chair stands (1.87 stands; 95% CI, 1.15 to 2.58), and Timed Up and Go under single-task (− 1.15 seconds; 95% CI, − 1.85 to − 0.44) and dual-task (− 2.35; 95% CI, − 3.06 to − 1.64) conditions. No serious intervention-related adverse events were observed.Conclusion: Findings from this study suggest the feasibility, with respect to intervention fidelity, compliance, and potential efficacy, of implementing an at-home, virtual, interactive Tai Ji Quan program, delivered in real-time, as a potential balance training and falls prevention intervention for older adults with MCI. The study provides preliminary data to inform future trials.Keywords: cognitive function, dual-task, incidental falls, elderly, exercise, e-health

This study aimed to investigate the mechanism of miR-142-5p and Yin Yang 1 (YY1) on regulating epithelial-mesenchymal transition (EMT) in lung cancer cell metastasis. The expressions of YY1 and miR-142-5p in different lung cancer cell lines were negatively correlated. The results of the dual-luciferase reporter assay further validated that miR-142-5p directly targeted YY1. Subsequently, transwell assays, wound-healing assay, and transplantation tumor model in nude mice proved that YY1 could promote the metastasis of lung cancer cells, whereas miR-142-5p impaired the stimulating effect of YY1 on the metastasis ability of lung cancer cells in vitro and in vivo. Western blot and quantitative real-time polymerase chain reaction analysis of the EMT-related proteins indicated that YY1 could enhance the metastasis ability of lung cancer cells by promoting EMT. On the contrary, miR-142-5p constrained the expression of mesenchymal markers by targeting YY1, reversed the differentiation of cells into mesenchymal cells, and weakened the metastasis ability of tumor cells in vitro and in vivo. In summary, miR-142-5p may regulate the expressions of EMT-related proteins by targeting YY1, thereby inhibiting lung cancer metastasis, which provides a promising therapeutic target for lung cancer.

Methyl mercury (MeHg) is neurotoxic and all fish contain at least trace amounts. Consequently, prenatal or fetal exposure occurs when pregnant women consume fish and children are exposed postnatally when they breastfeed or consume fish. However, the level of exposure at which toxicity occurs is presently unknown. Since behavioural endpoints can be sensitive indicators of toxic exposure, we administered the Child Behaviour Checklist (CBCL) to measure behaviour as part of a prospective, longitudinal, double blind study (n = 779) of prenatal MeHg exposure, the Seychelles Child Development Study (SCDS). The CBCL Total T score was a primary endpoint at 66 and 107 month evaluations of the cohort and showed no association with prenatal or postnatal MeHg exposure. This paper reports the results of a secondary analysis of the CBCL subscales to see if specific aspects of behaviour might show associations. The SCDS main cohort was enrolled in 1989-90 and evaluated on five occasions through 107 months of age. The child's primary caregiver completed the CBCL at the 107 month evaluation. Prenatal exposure was determined by measuring total mercury (THg) in maternal hair growing during pregnancy and recent postnatal exposure by analysing the child's hair taken at the 107 month evaluation. Analysis included linear and nonlinear multiple regression models. For prenatal MeHg exposure, the Social Problems subscale was significantly associated and the Somatic Complaints subscale was marginally associated. Both were beneficial associations. For postnatal exposure the Thought Problems subscale was associated in an adverse direction. This secondary analysis identified a small number of subtle beneficial and adverse associations with prenatal and postnatal MeHg exposure for specific CBCL subscales. These analyses provide no evidence for an adverse effect of prenatal exposure. The adverse postnatal association is difficult to interpret because we measured only recent (about one month) exposure and no adjustment was made for the multiplicity of endpoints.

Background: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)–lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension. Methods: Patients with an office BP of Results: At baseline, office and daytime BP of the 251 participants (mean age, 50.4 years; 53.4% men; mean body mass index 24.5 kg/m 2 ; and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes, and smoking, respectively) averaged 129/82 and 135/89 mm Hg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44/3.39 and 2.91/1.60 mm Hg in the gastrodia-uncaria granules and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mm Hg; P ≤0.025) and 24-hour BP (2.33/1.49 mm Hg; P ≤0.012), but not for the clinic and nighttime BPs ( P ≥0.162). The per-protocol analysis in 229 patients produced similar results. Only 1 adverse event (sleepiness during the day) was reported, and no serious adverse event occurred. Conclusions: BP-lowering treatment with Chinese traditional medicine gastrodia-uncaria granules is efficacious for patients with masked hypertension. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02156024.

BACKGROUND: Healthcare workers (HCWs) play a key role in the recommendation of HPV vaccination. Our study aimed to understand to what extent a structured health intervention could change the knowledge and attitudes toward HPV and its vaccines among HCWs in Western China. METHODS: This was a multi-center, questionnaire-based interventional study conducted across 12 cities of seven provinces in Western China, from November 2018 to July 2019. Participants were recruited from local health systems by e-invitation. Questionnaires were administered to participants before and after the intervention. RESULTS: A total of 1448 HCWs attended the educational lectures and 1354 participants completed both pre- and post-study questionnaires. In general, HCWs had satisfactory baseline knowledge regarding HPV and its vaccines compared with other populations, and a significantly higher knowledge level was observed after the intervention. However, some more specific knowledge on the vaccination procedures, other HPV-related diseases and whether HPV testing was required before vaccination was relatively poor. Following the educational intervention, the correct responses to the above questions increased (P

As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p

Background. Due to difficulties involved in its early diagnosis and adequate prognostication, uterine corpus endometrial carcinoma (UCEC) is one of the most serious threats to human health, with the five-year survival rate being as low as roughly 60%. The discovery of specific biomarkers that serve as prognosticators of UCEC is of great significance. The role of N6-methyladenosine- (m6A-) related long noncoding RNAs (lncRNAs) in the pathogenesis of UCEC remains undefined. In this study, we explored the expression profiles of m6A-related lncRNAs of patients with UCEC and identified novel prognostic markers for UCEC. Methods. Gene expression and clinical data were extracted from The Cancer Genome Atlas. Coexpression analysis was performed to identify m6A-related lncRNAs, which were entered into univariate Cox regression models for evaluating the prognosis of UCEC. Clusters of UCEC patients and enrichment pathways were identified using consistent data clustering and gene set enrichment analysis (GSEA). A risk score model was established, and Kaplan–Meier analysis was conducted for investigating overall survival (OS) across two patient groups (high risk and low risk). Lastly, the relationship between the risk score and the cell content of 22 types of immune cells, clusters, age, programmed cell death 1 ligand-1 (PD-L1) expression level, immune score, and pathological grade was analyzed. Results. We identified a total of 2084 lncRNAs associated with m6A, of which 32 lncRNAs were prognostically relevant. Two clusters (clusters 1 and 2) of patients with UCEC were defined; patients in cluster 1 were found to have significantly higher pathological grades and shorter overall survival time compared to those in cluster 2. GSEA showed that “MITOTIC SPINDLE and other pathways” were more enriched in cluster 1. Five major lncRNAs associated with m6A were screened out, and risk score modeling was used for UCEC prognosis prediction. High risk scores were associated with a shorter OS. The risk score was also verified as an independent prognostic indicator for UCEC and was related to immune cell infiltration levels. Finally, we observed a higher pathological grade and greater levels of PD-L1 in the high-risk group than in the low-risk group of patients. Conclusions. m6A-related lncRNAs play an important role in UCEC progression. The risk-based model constructed from the five key m6A-related lncRNAs was implicated in immune cell infiltration and can potentially be an accurate prognosticator for UCEC.

Globally, pre‑eclampsia (PE) is a gestational disorder that causes increased morbidity of the fetus and mortality induced by pregnancy. Despite various studies, the understanding of the causes or mechanism of the development of PE remains elusive. Thus, the present study aimed to investigate the role of circular (circ)RNA hsa_circ_0026552 (hsa_circ_0026552) in the development of PE and its mechanism of regulation. hsa_circ_0026552 differential expression in PE tissue data and clinical samples were analyzed and it was observed that hsa_circ_0026552 is highly upregulated in PE samples. Furthermore, miR‑331‑3p was detected as an hsa_circ_0026552 target miRNA and TGF‑βR1 gene as a target of miR‑331‑3p. These results were confirmed using various assays, including dual‑luciferase reporter, reverse transcription‑quantitative PCR and RNA pull‑down assay. It was observed that miR‑331‑3p expression was negatively correlated to hsa_circ_0026552 relative expression, while TGF‑βR1 expression was positively correlated to hsa_circ_0026552 expression evaluated by Pearson's correlation test. The functional experiments, including Cell Counting Kit‑8, colony formation and Transwell assay, showed that silencing hsa_circ_0026552 could significantly strengthen the proliferation, migration and invasion of the trophoblastic HTR‑8/SVneo cells, but the subsequent overexpression of hsa_circ_0026552 reversed this. Mechanistically, it was concluded that hsa_circ_0026552 acts as a miR‑331‑3p sponge to upregulate TGF‑βR1 expression in trophoblasts and is involved significantly in PE development and progression in pregnant women. The circRNA hsa_circ_0026552 could be a novel therapeutic target and prognostic biomarker for PE.

A repetitive sit-to-stand (STS) task is often used as a fatiguing protocol. Although post-fatigue reductions in muscle strength have been frequently used to indicate fatigue, little is known about changes in body movement during the fatiguing process. This study examined changes in variability of hip-knee and knee-ankle coordination during the STS fatiguing course in 15 young (age: 26.7 ± 5.8 years; 9 females, 6 males) and 15 older adults (age: 69.3 ± 5.7 years; 9 females, 6 males). Participants were asked to perform repetitive STS movements until exhaustion or for 30 min at a self-selected pace. Motion data from 3 consecutive STS cycles were extracted from every minute during the entire fatiguing course and time normalized to STS duration and dummy coded as five stages: 0-20, 20-40, 40-60, 60-80, and 80-100% of the course. Outcome variables were hip-knee and knee-ankle inter-joint coordination variabilities. A 2*5 mixed-effect ANOVA was used to examine changes in variability during different stages of the course in young and older adults. No Age × Time interactions were found in either hip-knee or knee-ankle coordination variability. The hip-knee coordinative variability significantly increased along the STS fatiguing course regardless of age, and the knee-ankle variability from standing to sitting was also higher at the ending, when compared to the beginning, of the fatiguing protocol. The impact of fatigue during repetitive STS protocol is not only limited to a force production decline but also manifested as increased coordinative variability, which could be considered as a fatigue indicator.

Cockroaches are an important source of indoor allergens. Environmental exposure to cockroach allergens is closely associated with the development of immunoglobulin E (IgE)-mediated allergic diseases. However, the allergenic components in the American cockroaches are not fully studied yet. In order to develop novel diagnostic and therapeutic strategies for cockroach allergy, it is necessary to comprehensively investigate this undescribed allergen in the American cockroach.The full-length cDNA of the potential allergen was isolated from the cDNA library of the American cockroach by PCR cloning. Both the recombinant and natural protein molecules were purified and characterized. The allergenicity was further analyzed by enzyme linked immunosorbent assay, immunoblot, and basophil activation test using sera from cockroach allergic patients.A novel allergen belonging to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was firstly identified in the American cockroach and named as Per a 13. The cDNA of this allergen is 1255 base pairs in length and contains an open reading frame of 999 base pairs, encoding 332 amino acids. The purified Per a 13 was fully characterized and assessed to react with IgEs from 49.3 % of cockroach allergic patients, and patients with allergic rhinitis were more sensitized to it. Moreover, the allergenicity was further confirmed by immunoblot and basophil activation test.We firstly identified GAPDH (Per a 13) in the American cockroach, which is a novel type of inhalant allergen derived from animal species. These findings could be useful in developing novel diagnostic and therapeutic strategies for cockroach allergy.

Declines in muscular function may hinder our ability to properly respond balance perturbations during walking. Examining age-related differences in muscle activation during balance-perturbed walking could be an important summary of literature to guide future clinical or scientific research.Are there differences in lower limb muscle activation between young and older adults when responding to balance perturbations during walking?A literature search was conducted in October 2020 to identify relevant articles using Pubmed, Scopus, Web of Science, Ovid EMBASE, and CINAHL. Inclusion criteria were defined to identify studies investigating lower limb muscle activation in healthy older adults during balance-perturbed walking. Data extraction was independently performed by both authors. Outcome measures included key findings of lower limb muscle activations during walking and balance-related tasks (e.g. multidirectional perturbations, different speeds, cognitive tasks, slippery/slopes, and obstacles).This article reviewed fourteen studies including 230 older adults (age: 70 ± 4.5, females: 124 [53.9%]) and 230 young adults (age: 23 ± 2.0, females: 113 [49.1%]). The overall quality of included studies was fair, with a mean score of 76%. Twelve lower limb muscles were assessed during balance-perturbed walking. All studies reported electromyographic measurements, including magnitude, timing, co-contraction indices, and variability of activation.Compared to young adults, older adults demonstrated different adaptations in lower limb muscle activation during balance-perturbed walking. Co-contraction of ankle and knee joint muscles had more conclusive results, with the majority reporting an increased co-contraction in older adults, especially when balance is perturbed by a physical task. These data suggest that coordination between agonist and antagonist muscles is important to provide necessary stabilization during balance-perturbed walking.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common cause of disability in systemic lupus erythematosus (SLE). This study aims to investigate the metabolic changes in the hypothalamus and frontal cortex in lupus-prone MRL/lpr mice. Metabolic changes were analyzed using gas chromatography-mass spectrometry (GC–MS). According to the principal component analysis (PCA), the metabolic profiles were different between the frontal cortex and hypothalamus, but they were comparable between MRL/lpr and MRL/MpJ mice (16 weeks of age). By OPLS-DA, eight cortical and six hypothalamic differential metabolites were identified in MRL/lpr as compared to MRL/MpJ mice. Among these differential metabolites, we found a decrease of N-acetyl-l-aspartate (NAA, a potential marker of neuronal integrity), an increase of pyruvate and a decrease of glutamate in the frontal cortex but not in the hypothalamus. Prednisone treatment (3 mg/kg from 8 weeks of age) relieved the decrease of NAA but further increased the accumulation of pyruvate in the frontal cortex, additionally affected eight enriched pathways in the hypothalamus, and led to significant imbalances between the excitation and inhibition in both the frontal cortex and hypothalamus. These results suggest that the frontal cortex may be more preferentially affected than the hypothalamus in SLE. Prednisone disrupted rather than relieved metabolic abnormalities in the brain, especially in the hypothalamus, indicating that the risk–benefit balance of prednisone for SLE or NPSLE remains to be further evaluated.

PURPOSE Emerging evidence indicates exercise training improves mobility and cognition and reduces falls in older adults, but underlying mechanisms are not well understood. This study tested the hypothesis that change in dual-task walking capacity mediates the positive effect of Tai Ji Quan and multimodal exercise on physical performance, activity confidence, global cognition, and falls among community-dwelling older adults at high risk of falling. METHODS We conducted a secondary analysis of a 6-month randomized clinical trial comparing Tai Ji Quan: Moving for Better Balance (TJQMBB) and multimodal exercise to stretching exercise in a sample of 670 adults older than 70 yr who had a history of falls or impaired mobility. Distal outcome measures, ascertained at a 12-month follow-up, were the Short Physical Performance Battery, Activities-Specific Balance Confidence, Montreal Cognitive Assessment, and falls. The mediator hypothesized to account for the intervention effects was dual-task cost estimated by calculating changes in gait speed from single-task to dual-task walking from baseline to the end of intervention. RESULTS At 12 months, compared with stretching exercise, multimodal exercise significantly improved Short Physical Performance Battery and Activities-Specific Balance Confidence outcomes and reduced the number of falls (P < 0.05). However, it did not lower dual-task cost or mediate the intervention effects on distal outcomes. In contrast, TJQMBB significantly reduced dual-task cost relative to multimodal and stretching exercises (P < 0.05) which in turn resulted in improvements in lower-extremity physical performance, activity confidence, global cognitive function, and reductions in falls (P < 0.05) during follow-up. CONCLUSIONS Enhanced dual-task walking capacity as a result of Tai Ji Quan training mediated improvements in physical and cognitive outcomes in older adults at high risk of falling.

Background Gait balance control assessment using whole body center of mass (COM) kinematic measures in concussed individuals reveals persistent balance deficits up to two months post-injury. A reliable and clinically practical gait balance control assessment leveraging similar kinematic measures is necessary to improve concussion assessment and management. Research question Can peak accelerations collected during a dual-task (DT) gait assessment from a single low back placed accelerometer be measured reliably on different days, by different raters, in different environments, and be practically applied in a Division One (D1) athletics program? Methods A single accelerometer placed on the low back over the L5 vertebra was utilized with a DT gait analysis protocol. Twenty (10 F) healthy participants performed the assessment in a laboratory and non-laboratory environment, on two separate days, and with two different raters. Eight gait event specific peak accelerations along three orthogonal axes were collected. In addition, data were collected from a cohort of 14 D1 female soccer players during a single assessment to explore the practical clinical application. Results Cronbach’s α values for the eight metrics ranged from 0.881 to 0.980 and ICC values from 0.868 to 0.987. Average assessment time for the 14 D1 female athletes was 8.50 ± 0.58 min, and significant differences between walking conditions were identified for Vert Accel 1 (p Significance High Cronbach’s α and ICC values coupled with a short assessment time and sensitivity to differences in gait balance control indicate our testing apparatus and protocol are both reliable and clinically practical. Additionally, gait event specific peak accelerations from a single accelerometer can detect subtle changes in gait balance control and may facilitate improvements in sport-related concussion diagnosis and return to activity decision making.

Background Differences in coordinative variability have been previously reported between healthy and injured runners. Many running-related injuries have a sex bias, particularly patellofemoral pain (PFP), as female runners are approximately twice as likely to develop PFP compared to males. However, very little is currently known regarding sex differences in coordinative variability during running. Research Question Are there sex differences in continuous relative phase (CRP) variability for pelvis-thigh and thigh-shank couplings during the stance phase of running? Methods Pelvis, thigh, and shank segment kinematics were collected on 15 female and 15 male subjects during overground running at a self-selected easy pace (2.39–3.56 m/s) using a 10-camera 3D motion capture system. Continuous relative phase (CRP) variability was calculated between the pelvis-thigh and thigh-shank, and averaged during four distinct stance sub-phases. A mixed effects linear model compared CRP variability between sexes at each stance sub-phase. Results Compared to males, females displayed significantly lower pelvis-thigh CRP variability in the transverse plane during the loading response phase, and significantly lower thigh-shank CRP variability in the sagittal plane during the loading response and pre-swing phases. Significance Lower coordinative variability in females during the loading response for two couplings may provide additional insight into the sex bias for developing certain running-related injuries. However, any injury implications from these results are speculative and should be interpreted with caution.

The efficacy of crizotinib for anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) patients with brain metastasis is controversial. Real-world research data are needed as further evidence. We conducted a multicenter, retrospective study to explore how crizotinib affects the control of brain metastasis and the survival outcomes among Chinese patients. We reviewed the medical records of unselected ALK-rearranged NSCLC patients treated with crizotinib at five hospitals in China from January 1, 2013 to November 30, 2017. Patients developing brain metastasis either before or during crizotinib treatment were included. Survival outcomes were analyzed by the Kaplan–Meier method, and prognostic factors were analyzed by multivariate Cox regression. A total of 174 patients were included in the analysis; 95 of these patients had baseline brain metastasis, while 79 patients developed brain metastasis during crizotinib treatment. Among patients with baseline brain metastasis, the median intracranial time to progression was 19.3 months (95% confidence interval [CI] 12.5–26.2) and the median overall survival (OS) was 53.4 months (95% CI not reached). A total of 135 patients experienced intracranial progression, and 94 of these patients continued crizotinib beyond progressive disease (CBPD). There was no significant difference in the median OS between patients with CBPD and without CBPD (48.3 months vs 53.4 months; p = 0.296). ALK-rearranged advanced NSCLC patients with baseline brain metastasis can still achieve OS benefits from crizotinib treatment. However, patients with intracranial progression may not obtain a long-term survival benefit from continuation of CBPD.

Background Crizotinib is associated with a favorable survival benefit in patients with ALK‐positive non‐small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response. Methods We collected the clinical features and survival outcomes of 28 primary‐resistant responders (PRR) with progression‐free survival (PFS) of < 3 months on crizotinib and compared these with 78 long‐term responders (LTR) that achieved > 24 months PFS (control). Results Primary resistance was observed in 6.5% of the patients. The median PFS of the PRR and LTR groups was 1.2 months (95% confidence interval [CI] 0.70–1.73) and 47.0 months (95% CI 34.39–59.64), respectively. A better Eastern Cooperative Oncology Group performance status score was significantly associated with longer PFS (odds ratio 0.06, 95% CI 0.01–0.33; P = 0.001). The median overall survival (OS) of the PRR group was 8.4 months (95% CI 3.47–13.42) and crizotinib as first‐line treatment was an independent predictive factor for survival outcome (P = 0.005). Patients administered ALK‐tyrosine kinase inhibitors after crizotinib progression had significantly longer survival than the PRR group treated with best supportive care (P = 0.007), but no significant difference was found between ALK‐tyrosine kinase inhibitor treatment and single chemotherapy (P = 0.944). Conclusion Patients with primary resistance to crizotinib displayed unfavorable survival outcomes and the underlying mechanism cannot be identified in clinical features. Nevertheless, next‐generation ALK inhibitors and chemotherapy after crizotinib progression could confer a therapeutic and survival benefit in this population.

Background Health technology assessment (HTA) has become essential in many countries over the past few years, and the demand for HTA professionals has increased in academia, governments, and industries. This study aimed to examine which courses are most important and which training activities are most helpful for the development of HTA proficiency as perceived by HTA experts. Methods The survey questionnaire was developed by literature review and expert opinion. Convenience sampling was used to survey HTA experts from the industrial sector, academic/research units, and government/independent assessment organizations using an online survey tool, SurveyCake. We collected respondents’ demographic information and asked them to assess the importance of each course included in an HTA program on a 5-point Likert Scale (1 = least important; 5 = highly important). In addition, respondents were asked to assess the extent to which various activities are helpful for HTA proficiency development. Results A total of 158 domestic and overseas experts in HTA-related fields were invited to participate in the survey and 68 completed the questionnaire. Among the respondents, the majority were female (57.4%) and working in academia (44.1%). The mean ± standard deviation of respondents’ age and number of years spent in HTA-related fields were 43.2 ± 11.0 years and 11.3 ± 9.9 years, respectively. The course that was rated the most important was “Pharmacoeconomics/Cost-effectiveness analysis” with a score of 4.8 ± 0.4 points, followed by “Health economics” at 4.7 ± 0.7 points. Moreover, internships at HTA-related institutions were perceived to be the most helpful training activity for HTA proficiency development. Conclusions Our study findings provide a better understanding of the requirements for developing HTA proficiency and can serve as a reference for the modification of current HTA education and training programs.

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is calledquot;an effective medicine of promoting blood circulationquot;. It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.

This qualitative study evaluated an attachment-based group parenting program that utilises mentalisation-based approach. The Building Early Attachment and Resilience (BEAR) program was designed to promote parent-child attachment across the perinatal period and has pre- and post-natal arms. The post-natal component targets mothers and infants at risk for early disturbances of attachment to, and emotional interaction. This evaluation study aimed to explore mothers’ subjective experiences of the post-natal BEAR program in encouraging mothers’ reflection on their role as a parent. Thirteen mothers were interviewed. Transcripts were analysed using thematic analysis, with five themes emerging. Overall, mothers reported that the intervention promoted reflection about the parenting role, contributed to perceptions of improved mother-infant interactions and increased understanding of their infant’s internal experiences. The results suggest the BEAR program is acceptable and facilitates the development of secure parent-infant attachment.

The Seychelles Child Development Study is a longitudinal cohort study following a group of 779 children exposed prenatally to methyl mercury (MeHg) through a maternal diet high in fish. The cohort has been examined six times beginning in infancy with no consistent evidence of adverse effects. In fact, their performance resembles what would be expected from normal children of comparable ages growing up in western cultures. During a neurodevelopment assessment at 66 months, the children were tested for scholastic achievement using the Woodcock Johnson Tests of Achievement. Their reading scores were depressed relative to US norms while arithmetic scores were within normal limits. This disparity was not evident at 107 months; in fact, reading achievement scores far exceeded expected performance relative to US norms, with over 75% of the cohort obtaining scores at or above the 90th percentile. This study reports a secondary analysis of the scholastic achievement data to test the hypothesis that the results obtained in the primary analysis were probably due to the onset of the primary school curriculum between the first and second testing, and not to inherent cognitive deficits among the children at 66 months. The results suggest that a combination of reading instruction and characteristically consistent letter-sound relationships in Creole, the language spoken at home by the majority of Seychellois families, probably accounted for the high achievement scores at 107 months.

Natural killer (NK) cells are the main immune cells at the maternal-fetal interface and accumulate in the uterine decidua in early pregnancy. Many studies have shown that NK cells at the maternal-fetal interface have unique phenotypes and play critical roles in various processes, including immune tolerance during pregnancy, decidualization, invasion of trophoblasts, remodeling of the uterine spiral artery, formation of the placenta and growth of embryo. However, specific functions of NK cells and their mechanism remain to be fully elucidated. This review summarizes the research progress of NK cells at the maternal-fetal interface and their roles in the pregnancy-related disorders in recent years. The aims of this review are to gain deep insight of the function of NK cells at the maternal-fetal interface and provide new ideas for intervention of pregnancy-related diseases.

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Objective Exercise prevents falls in the general older population, but evidence is inconclusive for older adults living with cognitive impairment. We performed an updated systematic review and meta-analysis to assess the potential effectiveness of interventions for reducing falls in older persons with cognitive impairment. Methods PubMed, EMBASE, CINAHL, Scopus, CENTRAL and PEDro were searched from inception to 10 November 2020. We included randomised controlled trials (RCTs) that evaluated the effects of physical training compared to a control condition (usual care, waitlist, education, placebo control) on reducing falls among community-dwelling older adults with cognitive impairment (i.e. any stage of Alzheimer’s disease and related dementias, mild cognitive impairment). Results We identified and meta-analysed nine studies, published between 2013 and 2020, that included 12 comparisons (N = 1,411; mean age = 78 years; 56% women). Overall, in comparison to control, interventions produced a statistically significant reduction of approximately 30% in the rate of falls (incidence rate ratio = 0.70; 95% CI, 0.52-0.95). There was significant between-trial heterogeneity (I2 = 74%), with most trials (n = 6 studies [eight comparisons]) showing no reductions on fall rates. Subgroup analyses showed no differences in the fall rates by trial-level characteristics. Exercise-based interventions had no impact on reducing the number of fallers (relative risk = 1.01; 95% CI, 0.90–1.14). Concerns about risk of bias in these RCTs were noted, and the quality of evidence was rated as low. Conclusions The positive statistical findings on reducing fall rate in this meta-analysis were driven by a few studies. Therefore, current evidence is insufficient to inform evidence-based recommendations or treatment decisions for clinical practice. PROSPERO Registration number: CRD42020202094.

Forceps-assisted deliveries are an established risk factor for pelvic organ prolapse and pelvic floor injury. However, specific comparison of incontinence outcomes between vacuum-assisted and forceps-assisted deliveries are scarce in the literature. We aimed to compare the initial impact of vacuum and forceps deliveries on new-onset urinary and faecal incontinence as well as pelvic floor muscle strength, with the hypothesis that incontinence outcomes were poorer after forceps- than after vacuum-assisted delivery. This is a retrospective cohort study of incontinence outcomes in patients who had primary vacuum- or forceps-assisted delivery. The study population included 108 postpartum patients who had undergone operative vaginal delivery (63 vacuum-assisted, 45 forceps-assisted), met the inclusion criteria and attended the postpartum assessment service. Outcomes studied were the presence and severity of symptoms manifesting beyond 1 month postpartum — faecal incontinence and stress, urgency and mixed urinary incontinence — as well as pelvic floor muscle strength scores based on the modified Oxford scale. Prevalence of new-onset urinary and faecal incontinence was 35.6% in the forceps group and 30.2% in the vacuum group. The data suggest that there is no significant difference in the prevalence of new-onset incontinence symptoms (p = 0.70, difference in prevalence [forceps − vacuum]: 5.4%, 95% CI −0.25, +0.15), frequency (p = 0.40) and amount (p = 0.48) of urine leakage or mean muscle strength scores (p = 0.89). In our maternity unit, we observed that type of operative vaginal delivery was not associated with significant differences in urinary incontinence and pelvic floor muscle strength outcomes.

Background This quantitative meta-analysis was conducted to evaluate the efficacy and safety of drug-eluting balloon (DEB) vs. uncoated balloon (UCB) in patients with femoropopliteal arterial occlusive disease. Methods Electronic databases were searched to identify randomized controlled trials (RCTs) that compared DEB and UCB till November 2018. The random-effects model was used for conducting pooled analyses. Results Seventeen RCTs with 2706 patients were included in the final meta-analysis. Patients who received DEB had higher levels of minimal luminal diameter (MLD) at 6 (WMD: 0.77; 95%CI: 0.53 to 1.02; P P P = 0.029) and 12 months (WMD: -0.95; 95%CI: − 1.28 to − 0.62; P P = 0.149), whereas DEB increased the primary patency after 12 (RR: 1.51; 95%CI: 1.25–1.83; P P P P = 0.008). DEB reduced the risk of major adverse events after 6 (RR: 0.30; 95%CI: 0.14–0.61; P = 0.001), 12 (RR: 0.49; 95%CI: 0.32–0.76; P = 0.001) and 24 months (RR: 0.62; 95%CI: 0.41–0.92; P = 0.018). Conclusions DEB yielded additional benefits on MLD, LLL, primary patency, restenosis, TLR, and major adverse events than UCB in patients with femoropopliteal arterial occlusive disease.

To investigate the prevalence of refractive error in adults 40 years of age and older in Kailu, Inner Mongolia.A population-based, cross-sectional study was conducted in Chinese adults. Spherical equivalent (S.E.) refractive error was determined from the right eye. Myopia and hyperopia were defined as a spherical equivalent (S.E.) -0.5 dioptres (D) and0.5 D, respectively. Since the prevalence of high myopia will vary with the precise criterion chosen, the prevalence of this condition was calculated for thresholds of both-5.0 D and6.0 D. Astigmatism was defined as cylinder power0.5 D. Anisometropia was defined as a difference in S.E. between the two eyes1.0 D.The prevalence of myopia, high myopia (-5.0 D/-6.0 D) and hyperopia in Kailu adults was 60.3% (95%CI: 58.95-61.71), 5.5% (95%CI: 4.82-6.10) /4.0% (95%CI: 3.47-4.57) and 12.2% (95%CI: 11.26-13.11), respectively. The age- and gender-standardised prevalence of myopia, high myopia (-5.0 D/-6.0 D) and hyperopia were 62.5% (95%CI: 61.05-63.99), 5.0% (95%CI: 4.34-5.61) /3.5% (95%CI: 2.99-4.04) and 10.6% (95%CI: 9.71-11.49), respectively. 52.9% had refractive astigmatism0.5 D and 18.8% of subjects had clinically significant anisometropia. Age was significantly associated with hyperopia, high myopia, astigmatism and anisometropia. Myopia was more prevalent in females. Individuals with a higher educational level had a greater and lesser likelihood of myopia and astigmatism, respectively.Myopia affects around two-thirds of the rural Chinese population over 40 years of age in Kailu. This high prevalence highlights that rural populations should be included in epidemiological studies of refractive error. Further investigations are needed to clarify the role of environmental factors in myopia development.

Background. We provide an updated meta-analysis with detailed information on a combination of TCM and routine treatment. Methods. Retrieve appropriate articles with no language restrictions on keywords until 8 July 2019 in an electronic database. All trajectories are screened according to certain criteria. The quality of certified research was also evaluated. We made a detailed record of the results of the measurement. Meta-analysis was carried out by using the Revman 5.3 software. Results. Sixty-seven RCTs were included, and 6594 subjects were analyzed. Compared with routine treatment, the total effective rate (TER) of TCM combined with routine treatment was improved, and the recovery of stroke was also significantly accelerated. Regulation of blood lipids by notably shrinking the contents of TC, TG, and LDL and enhancing the levels of HDL. The levels of serum hs-CRP, WHV, and WLV decreased significantly, indicating that the expression of thrombomodulin was decreased after the comprehensive treatment of traditional Chinese medicines (TCMs). The combination of TCM treatment could enhance the protection of neural function by decreasing the NIHSS scoring while increasing the BI scoring. Paeoniae Radix Rubra, Angeticae Sinensis Radix, etc., can effectively improve the clinical symptoms of stroke convalescent patients and promote the recovery of neurological function. ACU of Baihui, Renzhong, etc., can improve the clinical rehabilitation effect of patients. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results. Conclusion. A combination of TCM and routine treatment in the treatment of stroke could improve TER, and it is beneficial to the rehabilitation of patients in the recovery period of apoplexy. These effects can be mediated by a combination of several mechanisms. Nevertheless, due to the limitations of this study, these results should be handled with caution.

Objective To examine the acute (within 72h of injury) and long-term (2mo postinjury) independent associations between objective dual-task gait balance and neurocognitive measurements among adolescents and young adults with a concussion and matched controls. Design Longitudinal case-control. Setting Motion analysis laboratory. Participants A total of 95 participants completed the study: 51 who sustained a concussion (mean age, 17.5±3.3y; 71% men) and 44 controls (mean age, 17.7±2.9y; 72% men). Participants who sustained a concussion underwent a dual-task gait analysis and computerized neurocognitive testing within 72 hours of injury and again 2 months later. Uninjured controls also completed the same test protocol in similar time increments. Interventions Not applicable. Main Outcome Measures We compared dual-task gait balance control and computerized neurocognitive test performance between groups using independent samples t tests. Multivariable binary logistic regression models were then constructed for each testing time to determine the association between group membership (concussion vs control), dual-task gait balance control, and neurocognitive function. Results Medial-lateral center-of-mass displacement during dual-task gait was independently associated with group membership at the initial test (adjusted odds ratio [aOR], 2.432; 95% confidence interval [CI], 1.269–4.661) and 2-month follow-up test (aOR, 1.817; 95% CI, 1.014–3.256) tests. Visual memory composite scores were significantly associated with group membership at the initial hour postinjury time point (aOR, .953; 95% CI, .833–.998). However, the combination of computerized neurocognitive test variables did not predict dual-task gait balance control for participants with concussion, and no single neurocognitive variable was associated with dual-task gait balance control at either testing time. Conclusions Dual-task assessments concurrently evaluating gait and cognitive performance may allow for the detection of persistent deficits beyond those detected by computerized neurocognitive deficits alone.

Texting during walking has become a very common daily activity and could alter gait performance, especially during locomotion when additional visual attention is demanded, such as obstacle crossing. The purpose of this study was to examine biomechanical changes in obstructed gait characteristics while engaging in a phone texting activity. Gait analyses were performed on ten young healthy adults under the following two tasks: 1) walking and crossing an obstacle set at a 10% of the subject’s height and 2) walking and crossing an obstacle while responding to a text message. Whole body motion data were collected with a 10-camera motion capture system. Our data demonstrated that a conservative gait pattern was adopted while performing texting when approaching and crossing over the obstacle, which was indicated by slower walking speeds and greater toe-obstacle clearances. This gait pattern was, however, accompanied by a greater body sway in the frontal plane during crossing, which could be an indication of perturbed gait balance control. Increased visual-attentional demand from a concurrent phone texting could negatively impact young pedestrians’ safety during obstacle crossing.

Objective To examine the association of muscle strength and balance control with the amount of time taken to perform sit-to-walk (STW) or turning components of the Timed Up and Go (TUG) test in older adults. Design Correlations; multiple regression models. Setting General community. Participants Older adults (N=60) age >70 years recruited from the community. Interventions Not applicable. Main Outcome Measures Muscle strength, balance control, and TUG test performance time. Muscle strength was quantified by peak joint moments during the isometric maximal voluntary contraction test for bilateral hip abductors, knee extensors, and ankle plantar flexors. Balance control was assessed with the Berg Balance Scale, Fullerton Advanced Balance Scale, and center of mass and ankle inclination angle derived during the TUG test performance. Results We found that balance control measures were significantly associated with both STW and turning durations even after controlling for muscle strength and other confounders (STW duration: P P =.001). Adding strength to the regression model was found to significantly improve its prediction of STW duration (F change=5.945, P =.018), but not turning duration (F change=1.03, P =.14). Conclusions Our findings suggest that poor balance control is an important factor that contributes to longer STW and turning durations on the TUG test. Furthermore, strength has a higher association with STW than turning duration.

Background: There is disagreement in the literature regarding whether the excessive excursion or velocity of rearfoot eversion is related to the development of 2 common running injuries: Achilles tendinopathy (AT) and medial tibial stress syndrome (MTSS). An alternative hypothesis suggests that the duration of rearfoot eversion may be an important factor. However, the duration of eversion has received relatively little attention in the biomechanics literature. Hypothesis: Runners with AT or MTSS will demonstrate a longer duration of eversion but not greater excursion or velocity of eversion compared with healthy controls. Study Design: Controlled laboratory study. Methods: Forty-two runners participated in this study (13 with AT, 8 with MTSS, and 21 matched controls). Participants were evaluated for lower extremity alignment and flexibility, after which a 3-dimensional kinematic and kinetic running gait analysis was performed. Differences between the 2 injuries and between injured and control participants were evaluated for flexibility and alignment, rearfoot kinematics, and 3 ground-reaction force metrics. Binary logistic regression was used to evaluate which variables best predicted membership in the injured group. Results: Injured participants, compared with controls, demonstrated higher standing tibia varus angles (8.67° ± 1.79° vs 6.76° ± 1.75°, respectively; P = .002), reduced static dorsiflexion range of motion (6.14° ± 5.04° vs 11.19° ± 5.10°, respectively; P = .002), more rearfoot eversion at heel-off (–6.47° ± 5.58° vs 1.07° ± 2.26°, respectively; P < .001), and a longer duration of eversion (86.02% ± 15.65% stance vs 59.12% ± 16.50% stance, respectively; P < .001). There were no differences in the excursion or velocity of eversion. The logistic regression (χ2 = 20.84, P < .001) revealed that every 1% increase in the duration of eversion during the stance phase increased the odds of being in the injured group by 1.08 (95% CI, 1.023-1.141; P = .006). Conclusion: Compared with healthy controls, runners currently symptomatic with AT or MTSS have a longer duration of eversion but not greater excursion or velocity of eversion. Clinical Relevance: Static measures of the tibia varus angle and dorsiflexion range of motion, along with dynamic measures of the duration of eversion, may be useful for identifying runners at risk of sustaining AT or MTSS.

Rheumatoid arthritis (RA) is characterized by synovial lining hyperplasia, which involves abnormal growth of fibroblast-like synoviocytes (FLSs). This study aimed to investigate the function and molecular mechanism of peptidylarginine deiminase type 4 (PADI4) in FLSs isolated from RA patients (RA-FLSs). FLSs were isolated from RA patients and transfected with small interfering RNAs (siRNAs) or PADI4 overexpression plasmid. FLSs were treated by Adriamycin (ADR) to induce apoptosis, and apoptotic cells were detected by flow cytometry. The expression of PADI4, p53 and p21 was detected by qRT-PCR and Western blot analysis. The recruitment of PADI4 and histone H3 arginine modifications to p21 promoter was measured by chromatin immunoprecipitation. The results showed that knockdown of PADI4 promoted the apoptosis of RA-FLSs and the expression of p53 and p21. Ectopic expression of PADI4 inhibited ADR-induced apoptosis of RA-FLSs, and down-regulated the expression of p53 and p21. In RA-FLSs, global H3 citrullination (CitH3) and H3 arginine 17 methylation levels were dynamically changed by PADI4 and ADR treatment. PADI4 and H3 could bind p21 promoter region to regulate p21 expression. In conclusion, PADI4 contributes to the pathogenesis of RA by protecting FLSs from apoptosis. PADI4 suppresses p21 transcription through altering histone H3 arginine modifications on p21 promoter region. Our study provides new insight into the anti-apoptotic role of PADI4 in RA development.

Background Numerous investigations suggest mild traumatic brain injury (mTBI) may result in persistent gait balance control deficits. Furthermore, military Veterans with symptoms of chronic mTBI often present with physical symptoms that may be associated with impaired gait balance control which may lead to prolonged recovery, difficulty performing activities of daily living, and increased disability. It is therefore important to objectively quantify gait balance deficits in Veterans with chronic mTBI. Research Question Is gait balance control impaired in a group of Veterans with chronic symptoms of mTBI when compared to healthy matched Veterans? Methods Eight Veterans with symptoms of chronic mTBI (1 F/7 M) and eight healthy matched Veterans (1 F/7 M) completed a gait balance assessment under single- (ST) and dual-task (DT) conditions. Gait balance control was quantified with whole body center of mass (COM) total medial-lateral (ML) displacement and peak ML velocity, which were calculated from camera-based motion capture. Results Veterans with chronic mTBI walked with greater ML COM displacement (approximately 25 % increase) in both ST and DT walking (main effect of group, p = 0.018) when compared to healthy Veterans. The peak ML COM velocity was affected for both groups by performing a concurrent cognitive task (interaction effect, p = .012). Slower ML COM velocities in healthy Veterans suggest the adoption of a conservative balance control strategy, while faster ML COM velocities for Veterans with chronic mTBI may indicate a diminished ability to control ML momentum. Significance Increased frontal plane COM motion under both ST and DT walking was observed in Veterans with chronic mTBI symptoms many years after injury. This suggests gait balance control may be adversely affected during divided attention gait and highlights the need for comprehensive gait analysis in the management of these individuals.

This follow-up analysis of a randomized clinical trial compares the effectiveness of tai ji quan, multimodal exercises, and stretching exercise interventions for older adults at high risk of falling., Key Points Question Is a therapeutically tailored tai ji quan intervention more effective than stretching exercise or a proven multimodal exercise intervention in decreasing injurious falls among community-dwelling older adults at high risk of falling? Findings In this follow-up analysis of a randomized clinical trial that included 670 older adults with a history of falls or impaired mobility, a therapeutic tai ji quan intervention, Tai Ji Quan: Moving for Better Balance, was significantly more effective for lowering the incidence of both moderate injurious falls compared with stretching exercise and serious injurious falls compared with stretching exercise and multimodal exercise. Meaning The therapeutically tailored tai ji quan training intervention proved to be more safe and effective than stretching or multimodal exercises in reducing the incidence of injurious falls in older adults at high risk of falling., Importance Exercise has been shown to reduce injurious falls in older adults. Evidence, however, is lacking regarding the types of intervention that are most effective in preventing injurious falls among older adults at high risk of falling. Objective To determine the longer-term effectiveness of therapeutic tai ji quan intervention vs multimodal exercise and stretching exercise in decreasing injurious falls among older adults at high risk of falling. Design, Setting, and Participants This trial involves a prespecified analysis with the data analyzed by intent-to-treat. Follow-up analysis of a single-blind randomized trial conducted in community settings of 7 urban and suburban cities in Oregon from February 20, 2015, to September 15, 2018, compared a therapeutic tai ji quan intervention with multimodal exercise and stretching exercise. Eligible participants were community-dwelling adults aged at least 70 years who were considered by a clinician to be at high risk of falling because they had fallen during the preceding year or who had impaired mobility with scores higher than 13.5 seconds on the Timed Up & Go test. Participants were randomized to 1 of the 3 interventions and were assessed monthly after randomization for 12 months, encompassing a 6-month active intervention phase and a 6-month after intervention follow-up phase. Interventions The 3 group-based interventions were therapeutic tai ji quan (Tai Ji Quan: Moving for Better Balance [TJQMBB]), multimodal exercise, and stretching exercise, each implemented twice weekly in 60-minute sessions for 24 weeks. Main Outcomes and Measures Primary outcomes were the incidence of moderate and serious injurious falls at 12 months, measured as incidence rate ratios (IRRs). Results Of the 1147 persons screened, 670 (mean [SD] age, 77.7 [5.6] years; 436 women [65.1%]) were randomly assigned to 1 of 3 intervention groups: 224 persons in TJQMBB, 223 in multimodal exercise, and 223 in stretching exercise. At 12 months, the unadjusted IRR for moderate injurious falls was lower in the TJQMBB (IRR, 0.51; 95% CI, 0.35-0.74; P

To investigate whether glucocorticoids, the hallmark medication for systemic lupus erythematosus (SLE), could prevent the development of neuropsychiatric SLE (NPSLE). The protective effects of prednisone on NPSLE were tested using the open field, object recognition/placement, forced swim, tail suspension, and sucrose preference tests in MRL/lpr mice. Auto-antibody titres and the weight of lymph nodes were also measured. MRL/lpr mice exhibited mild depression at the age of 8 weeks before progressing with spatial cognitive impairment and severe depression-like behaviour at the age of 16 weeks. Treating MRL/lpr mice with prednisone (5 mg/kg) from the age of 8 weeks decreased anti-cardiolipin and anti-N-methyl-d-aspartate (NMDA) receptor antibody titres in the brain, reduced the weight of lymph nodes, and prolonged the floating latency in the forced swim test. However, prednisone (3 or 5 mg/kg) had no preventive effect on the development of spatial cognitive impairment and other depression-like behaviours in MRL/lpr mice. The dose of prednisone had a positive correlation with the floating latency in the forced swim test, while it offered no effects on all other behavioural tests. Our results provide evidence that early treatment with prednisone had a limited effect on the development of neuropsychiatric symptoms in MRL/lpr mice. Further work is needed in other models beyond NPSLE in MRL/lpr mice before any definitive conclusions are made on the efficacy of prednisone in human NPSLE.

Background Concussion may result in acutely impaired dynamic balance control that can persist up to two months post injury. Such impairment has been detected using sophisticated whole body center of mass kinematic metrics derived from camera-based motion analysis under a dual-task paradigm. However, wearable sensor kinematics for describing gait imbalance is lacking. Methods This study employed a longitudinal design. Gait balance control of acutely concussed and healthy matched control participants was assessed at five post-injury time points (within 72 h of injury, at one week, two weeks, one month, and two months). Tri-axial accelerations and angular velocities were collected with a dual-task gait protocol using an inertial measurement unit placed over the fifth lumbar vertebra. Findings Eight consistent gait event specific peak accelerations and six peak angular velocities measured by the inertial measurement unit were examined. Peak yaw and roll angular velocities at heel strike and peak roll angular velocities during early single-support, distinguished healthy from concussed participants across the two month post-injury period, while peak vertical acceleration at the end of terminal stance peak medial-lateral acceleration to the right during loading response showed promise. Interpretation Utilization of peak accelerations and angular velocities collected from a single inertial measurement unit placed over the fifth lumbar vertebra in a divided attention paradigm may offer a clinically feasible method for detecting subtle changes in gait balance control in concussed individuals.

Background: Studies have indicated that family members or health professionals may not know or predict their older relatives’ or patients’ health preferences. Although advance care planning is encouraged for older people to prepare end-of-life care, it is still challenging. Aim: To understand the experiences and perspectives of older people regarding advance care planning. Design: A systematic review of qualitative studies and meta-synthesis was conducted. Data sources: CINAHL, MEDLINE, EMBASE, and PsycINFO databases were searched. Results: A total of 50 articles were critically appraised and a thematic synthesis was undertaken. Four themes were identified: life versus death, internal versus external, benefits versus burdens, and controlling versus being controlled. The view of life and death influenced older people’s willingness to discuss their future. The characteristics, experiences, health status, family relationship, and available resources also affected their plans of advance care planning. Older people needed to balance the benefits and burdens of advance care planning, and then judge their own ability to make decisions about end-of-life care. Conclusion: Older people’s perspectives and experiences of advance care planning were varied and often conflicted; cultural differences amplified variances among older people. Truthful information, available resources, and family support are needed to enable older people to maintain dignity at the end of life. The views of life and death for older people from different cultures should be compared to assist health professionals to understand older people’s attitudes toward advance care planning, and thus to develop appropriate strategies to promote advance care planning in different cultures.

Objective The purpose of this study was to examine sagittal plane momentum control during walking with the use of center of mass (COM) velocity and acceleration. Methods COM control in the antero-posterior direction during walking of healthy young and elderly adults, and elderly fallers (n = 15/group) was examined. Using a single-link-plus-foot inverted pendulum model, boundaries for the region of stability were determined based on the COM position at toe-off and its instantaneous velocity or the peak acceleration prior to toe-off (ROSv or ROSa, respectively). Results Although no significant difference in forward COM velocity was detected between healthy young and elderly subjects, the peak forward COM acceleration differed significantly, suggesting age-related differences in momentum control during walking. Elderly fallers demonstrated significantly slower forward COM velocities and accelerations and placed their COM significantly more anterior than healthy young and elderly subjects at toe-off, which resulted in their COM position-velocity combination located within the ROSv. Similar results were obtained in the ROSa, where elderly fallers demonstrated a larger stability margin than healthy young and elderly subjects. Interpretations Significantly slower peak COM accelerations could be indicative of a poor momentum control ability, which was more pronounced in elderly fallers. Examining COM acceleration, in addition to its velocity, would provide a greater understanding of person's momentum control, which would allow us to better reveal underlying mechanisms of gait imbalance or falls.

Objectives: Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR. Methods: At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. Results: We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines. Conclusion: Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally.

Background: Cervical cancer (CC) is the second most common type of malignant tumor survival rate is low in advanced stage, metastatic, and recurrent CC patients. This study aimed at identifying potential genes and drugs for CC diagnosis and targeting therapies. Methods: Three GEO mRNA microarray datasets of CC tissues and non-cancerous tissues were analyzed for differentially expressed genes (DEGs) by limma package. GO (Gene Ontologies) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to explore the relationships between the DEGs. Protein-protein interaction (PPI) of these genes was established by the STRING database. MCODE was used for screening significant modules in the PPI networks to select hub genes. Biochemical mechanisms of the hub genes were investigated with Metascape. GEPIA database was used for validating the core genes. According to these DEGs, molecular candidates for CC were recognized from the CMAP database. Results: We identified 309 overlapping DEGs in the 2 tissue-types. Pathway analysis revealed that the DEGs were involved in cell cycle, DNA replication, and p53 signaling. PPI networks between overlapping DEGs showed 68 high-connectivity DEGs that were chosen as hub genes. The GEPIA database showed that the expression levels of RRM2, CDC45, GINS2, HELLS, KNTC1, MCM2, MYBL2, PCNA, RAD54 L, RFC4, RFC5, TK1, TOP2A, and TYMS in CC tissues were significantly different from those in the healthy tissues and were significantly relevant to the OS of CC. We found 10 small molecules from the CMAP database that could change the trend of gene expression in CC tissues, including piperlongumine and chrysin. Conclusions: The 14 DEGs identified in this study could serve as novel prognosis biomarkers for the detection and forecasting of CC. Small molecule drugs like piperlongumine and chrysin could be potential therapeutic drugs for CC treatment.

Self-regulation strategies are helpful for increasing goal commitment and maintaining behavior change. Evidence suggests that the self-regulation strategy of mental contrasting with implementation intentions (MCII) shows promise in helping people increase their physical activity. The purpose of this research was to investigate whether these self-regulation strategies would increase physical activity, which would, in turn, improve well-being and mental health. In a quasi-experimental study, participants were randomized by school to an experimental group (n = 40) and control group (n = 45). The experimental group received self-regulation strategies, whereas the control group did not. Both groups were given a Fitbit and the goal of 10,000 steps per day. Participants' well-being and depressive, anxiety, and stress symptoms were measured at baseline and after the 3-week intervention. The experimental group's physical activity increased from 7,938 to 9,288 steps per day (p = 0.001), whereas that of the control group did not increase. In the experimental group, the findings suggested a significant increase for men, and a nonsignificant increasing trend for women. The study demonstrated the benefits of self-regulation strategies such as MCII on achieving physical activity goals. Findings also suggested that self-regulation strategies provided improvement beyond physical activity by decreasing the depressive symptoms of female participants in the experimental group. Given the small sample size, effects by gender have to be interpreted with caution. Limitations and suggestions for future research are discussed.

Objective: This article analyzed the clinical efficacy and tolerability of rivaroxaban and enoxaparin in patients undergoing total knee arthroplasty (TKA) surgery. Methods: Five randomized, controlled clinical trials on rivaroxaban versus enoxaparin in patients who underwent TKA were identified and included in this meta-analysis. Results: The meta-analysis indicated that rivaroxaban prophylaxis was associated with lower rates of symptomatic venous thromboembolism (VTE) (relative risk[RR]:0.55; 95% confidence interval [CI]: 0.35–0.86; P = .009), symptomatic deep vein thrombosis (DVT) (RR 0.44, 95% CI 0.25–0.80, P = .007), asymptomatic DVT (RR: 0.57; 95% CI: 0.37–0.89; P = .01), distal DVT (RR: 0.62; 95% CI: 0.45–0.85; P = .003) and proximal DVT (RR: 0.42; 95% CI: 0.24–0.75; P = .004). Compared with the enoxaparin group, the incidence of symptomatic pulmonary embolism (PE) (RR: 0.48; 95% CI: 0.19–1.24; P = .13) in the rivaroxaban group was not significantly different. A nonsignificant trend towards all-cause death (RR: 0.38; 95% CI: 0.03–4.92; P = .46) or major bleeding (RR: 1.59; 95% CI: 0.77–3.27; P = .21) risk between rivaroxaban and enoxaparin prophylaxis was found. Conclusion: Compared with the enoxaparin group, the group using rivaroxaban after TKA had a significantly lower rate of symptomatic VTE, symptomatic DVT, asymptomatic DVT, distal DVT, and proximal DVT. Our study shows that rivaroxaban after TKA is more effective than enoxaparin and did not increase major bleeding or all-cause mortality. Level of evidence II

Attention involves three distinct networks for alerting, orienting, and executive control. Interventions targeting the specific attentional networks remain lacking. Transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability, which potentially serves as an interventional tool to treat individuals with attention impairment. The purpose of this study was to examine the effects of applying tDCS over the right posterior parietal cortex (PPC) on the performance of the three attentional networks. Twenty-six healthy young adults performed the Attention Network Test before and after anodal or sham tDCS stimulation over the right PPC. The alerting, orienting, and executive effects were assessed before and after the stimulation. The results demonstrated that the orienting effect was significantly improved after real tDCS relative to sham, whereas the alerting and executive control effects remained unaffected. Consistent with previous clinical and functional imaging studies, this suggests that the right PPC is actively engaged with the spatial orienting of attention.