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To investigate the effect of open wedge tibial high osteotomy on patella position, anterior knee pain and joint function.From June 2016 to June 2021, 109 patients (111 knees) with medial knee osteoarthropathy treated by open wedge tibial high osteotomy were included according to the inclusion and exclusion criteria, including 41 males and 68 females;the age ranged from 38 to 78 years old with an average of(57.98±7.07) years;the course of disease ranged from 1 to 36 months with an average of (8.58±6.91) months. The femoral tibial angle(FTA), medial proximal tibial angle(MPTA), weight bearing line(WBL) percentage, Caton Deschamps index (CD index), lateral patella tilt angle (LPTA) and lateral patella shift (LPS) were observed and compared before and after operation. Lysholm score was used to evaluate the knee function, visual analogue scale(VAS) was used to evaluate the degree of anterior knee pain, and Kellgren Lawrence(K-L) grading system was used to evaluate the progress of patellofemoral osteoarthritis.All patients were followed up for 6 to 38 months with an average of (12.41±2.40) months. The preoperative FTA, MPTA, WBL percentage, CD index, and LPTA were significantly different from those at the last follow-up(After open wedge tibial high osteotomy, the position of patella is lowered and the patella is tilted outward, but the knee function and anterior knee pain are significantly improved. Adverse changes in patella position caused by open wedge tibial high osteotomy may not affect clinical outcomes.

Background The patch neointima technique is a modified valve-sparing aortic root repair surgery for acute type A aortic dissection and the short-term outcomes are satisfactory. The midterm outcomes have not been reported. Methods From January 2009 to December 2012, 147 patients underwent valve-sparing aortic root repair with the patch neointima technique for type A aortic dissection in our center. The midterm outcomes of the patients were evaluated by echocardiography and aortic computed tomography angiography. Results Of 147 patients, 32 patients (21.8%) underwent proximal arch repair, and 115 patients (78.2%) underwent proximal arch repair combined with triple-branched stent graft implantation. The perioperative mortality was 5.4%. Preoperative aortic insufficiency (AI) was observed in 94 patients (63.9%); 131 patients (89.1%) left the operating room with 0 AI; the remaining 16 patients (10.9%) had trace or less than 1+ AI. A total of 128 patients (87.1%) completed 7-year follow-up. The mean follow-up time was 5.7 ± 1.2 years. As many as 82% of patients (105) were 0 AI and 15.6% of patients (20) were 0.5+ trace or less than 1+ AI. No reoperation was performed for the aortic root. The diameters of sinotubular junction and sinus were reduced to the normal range (28.3 ± 4.2 mm and 30.5 ± 3.6 mm, respectively) and remained stable (28.9 ± 5.6 mm, P = .300, and 30.8 ± 4.2 mm, P = .540, respectively) during 7 years of follow-up. Conclusions Valve-sparing aortic root repair with patch neointima technique was associated with stable function of the aortic valves and no expansion of the aortic root in the midterm.

Background The interference screw is the most popular device that fixes the graft for anterior cruciate ligament reconstruction, reducing the incidence of windshield effect and bungee effect. For the screw, either metallic, “bioresorbable,” or polyetheretherketone (PEEK) material is available. PEEK is popular and extensively used due to its stability, biocompatibility, radiolucency, and elastic modulus. Rare relevant complications were reported, but here, we report two cases of extra-articular migrations of PEEK interference screw from the tibial tunnel after anterior cruciate reconstruction. Case report An 18-year-old boy and a 56-year-old woman underwent anterior cruciate ligament reconstruction using a PEEK interference screw to fix the graft in the tibial tunnel. They suffered from screw extrusion from the tibial tunnel after 40 days and six months, respectively, with an incision rupture or palpable subcutaneous mass. They underwent a second operation and recovered well. Conclusions The exact incidence of extra-articular migrations of PEEK interference screws is unknown, but it seems to be quite low; despite this and its uncertain cause, the negative effects caused by the PEEK material need to be considered.

We previously reported that intraspinal transplantation of human amniotic mesenchymal stem cells (hAMSCs) promotes functional recovery in a rat model of acute traumatic spinal cord injury (SCI). However, whether intravenous transplantation of hAMSCs also has therapeutic benefit remains uncertain. In this study, we assessed whether intravenous transplantation of hAMSCs improves outcomes in rats with acute traumatic SCI. In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Adult female Sprague-Dawley rats were subjected to SCI using a weight drop device, and then hAMSCs or PBS were administered after 2 h via the tail vein. Our results indicated that transplanted hAMSCs could migrate to injured spinal cord lesion. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1 macrophages/microglia and caspase-3 cells, and reduced levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and IL-1β. In addition, hAMSCs transplantation significantly attenuated Evans blue extravasation, promoted angiogenesis and axonal regeneration. hAMSCs transplantation also significantly improved functional recovery. These results suggest that intravenous administration of hAMSCs provides neuroprotective effects in rats after acute SCI, and could be an alternative therapeutic approach for the treatment of acute SCI.

This study evaluated the performance of children with learning problems in Taiwan by using the Taiwan Data Bank of Persons with Disability.We included 3854 children (2343 males, 1511 females; mean [SD] age 9y 11mo [2y 4mo]) with specific learning disorder (SLD), attention-deficit/hyperactivity disorder (ADHD), autism, epilepsy, or intellectual disabilities for analysis. We used the Functioning Scale of the Disability Evaluation System-Child version to investigate performance at follow-up for at least 3 years.These participants demonstrated improvement across all the domains of the International Classification of Functioning, Health, and Disability including for mobility, learning, social participation, and daily living. The children with SLD (p=0.3) and epilepsy (p=0.442) did not demonstrate significant improvement in learning, whereas those with ADHD (p0.001), autism (p0.001), and intellectual disabilities (p0.001) did. The children with epilepsy displayed the most impairment and least improvement.This cross-diagnostic study of learning problems indicated the children with autism or ADHD received more structural education. However, education strategies for those with SLD or epilepsy required improvement. Finally, SLD is possibly underdiagnosed in children, and children with epilepsy are affected in multiple aspects.Specific learning disorder (SLD), ADHD, autism, epilepsy, and intellectual disability can cause learning problems in children. Children with ADHD and autism showed more improvement in academic performance. SLD has been neglected and underdiagnosed, resulting in poor improvement. Children with epilepsy have multiple impairments and exhibited minimal improvement.Movilidad y desempeño educativo y social de niños con problemas de aprendizaje en Taiwán: un estudio de seguimiento de 3 años OBJETIVO: Este estudio evaluó el desempeño de los niños con problemas de aprendizaje en Taiwán utilizando el Banco de Datos de Personas con Discapacidad de Taiwán. MÉTODO: Para el análisis incluimos 3854 niños (2343 varones, 1511 mujeres; edad media [DE] 9 años 11 meses [2 años 4 meses]) con trastorno específico del aprendizaje (SLD), trastorno por déficit de atención/hiperactividad (TDAH), autismo, epilepsia, o trastornos intelectuales. Utilizamos la Escala de Funcionamiento del Sistema de Evaluación de la Discapacidad-versión infantil para investigar el desempeño en el seguimiento durante al menos 3 años. RESULTADOS: Estos participantes demostraron una mejora en todos los dominios de la Clasificación Internacional del Funcionamiento, de la Discapacidad, y de la Salud (CIF) incluida la movilidad, el aprendizaje, la participación social y la vida diaria. Los niños con SLD (p = 0,3) y epilepsia (p = 0,442) no demostraron una mejora significativa en el aprendizaje, mientras que aquellos con TDAH (p 0,001), autismo (p 0,001) y discapacidad intelectual (p 0,001) sí lo hicieron. Los niños con epilepsia mostraron el mayor deterioro y la menor mejora. INTERPRETACIÓN: Este estudio de desempeño en niños con distintos diagnósticos indicó que los niños con autismo o TDAH recibieron una educación más estructural. Sin embargo, las estrategias educativas para las personas con SLD o epilepsia requerían mejoras. Finalmente, la SLD posiblemente esta poco diagnosticada en niños, y los niños con epilepsia se ven afectados en múltiples aspectos del desempeño.Mobilidade e desempenho educacional e social das crianças com dificuldades de aprendizagem em Taiwan: Um estudo de acompanhamento de 3 anos OBJETIVO: Este estudo avaliou o desempenho de crianças com problemas de aprendizagem usando o Banco de Dados de Pessoas com Deficiência em Taiwan. MÉTODO: Foram incluídas 3.854 crianças (2.343 homens, 1.511 mulheres; idade média [SD] de 9 anos e 11 meses [2 anos e 4 meses] com transtorno específico de aprendizagem (TEA), transtorno de déficit de atenção/hiperatividade (TDAH), autismo, epilepsia ou deficiência intelectual para análise. Utilizou-se uma Escala de Funcionamento do Sistema de Avaliação de Incapacidade-Criança para investigar o desempenho no acompanhamento por pelo menos 3 anos. RESULTADOS: Esses participantes demonstraram melhora em todos os domínios do Classificação Internacional de Funcionalidade, Saúde e Incapacidade, incluindo para mobilidade, aprendizagem, participação social e vida diária. As crianças com TEA (p = 0,3) e epilepsia (p = 0,442) não apresentaram melhora significativa no aprendizado, enquanto aquelas com TDAH (p 0,001), autismo (p 0,001) e deficiência intelectual (p 0,001) apresentaram melhora significativa. Crianças com epilepsia apresentaram maior comprometimento e menor melhora. INTERPRETAÇÃO: Este estudo de diagnóstico cruzado de problemas de aprendizagem indicou que as crianças com autismo ou TDAH receberam mais educação estrutural. No entanto, as estratégias de educação para aqueles com TEA ou epilepsia exigia melhora. Finalmente, o TEA é possivelmente subdiagnosticado em crianças, e crianças com epilepsia são afetadas em múltiplos aspectos.

This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.

Background Sexual dysfunction after cardiac surgery can seriously affect patients’ quality of life, but the impact of cardiac surgery on sexual function has long been neglected. Compared with conventional cardiac surgery, minimally invasive cardiac surgery has the advantages of aesthetic appearance and no disruption of the sternal structure, which can greatly improve the patient's quality of life. However, studies focusing on the effects of minimally invasive mitral valve surgery (MIMVS) on sexual function have not been reported. The objective of this research was to investigate the effects of totally endoscopic mitral valve surgery on health-related quality of life and sexual function in male patients and to provide possible recommendations. Methods Patients who underwent median sternotomy or totally endoscopic mitral valve surgery at our institution from January 2019 to December 2020 were selected using an electronic medical record system. Data were collected by questionnaires, including the MOS 36-item short-form health survey and the International Erectile Function Questionnaire. Results There were 156 male patients who participated in our study. Of these, 112 patients completed all questionnaires. Forty-five patients (40.18%) developed postoperative sexual dysfunction, including 15 patients (29.41%) in the MIMVS group and 30 patients (49.18%) in the conventional MVS group, indicating that the incidence of sexual dysfunction could be reduced by MIMVS and that the MIMVS group scored better on the International Erectile Function Questionnaire (P Conclusions In our study, totally endoscopic mitral valve surgery had less adverse effects on sexual function in male patients than conventional mitral valve surgery. In terms of health-related quality of life, totally endoscopic mitral valve surgery was superior to conventional surgery. Patients who opt for totally endoscopic mitral valve surgery may have a more satisfying and healthier sexual life than those who undergo conventional mitral valve surgery.

To evaluate the value of serum Lactate Dehydrogenase (LDH) level in predicting recurrence and the overall survival (OS) of glioma patients.A total number of 216 patients with glioma in our institution were retrospectively recruited to analyze the relationship between preoperative serum LDH level and prognosis.Overall, the median age of patients was 46.0 (31.0-57.0) years old; 53.7% (116 of 216) of the enrolled patients were male. Multivariate analysis revealed that serum LDH level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.96-0.98, P 0.001) and World Health Organization (WHO) grade (grade II: OR = 19.64, 95%CI = 5.56-69.35, P 0.001; grade III: OR =1 9.50, 95%CI = 7.08-53.73, P 0.001; grade IV: OR = 15.23, 95%CI = 4.94-46.97, P 0.001) were significant and independent of 1-year Progression-free survival (PFS) after adjusting for confounders. The predictive performance of serum LDH level was represented with area under curve (AUC) = 0.741, 95%CI = 0.677-0.798. Multivariate Cox analysis revealed that LDH level (hazard ratio [HR] = 2.56, 95%CI = 1.59-4.15, P 0.001) and WHO grade (grade II: HR = 4.58, 95%CI = 0.56-37.23, P = 0.155; grade III: HR = 16.35, 95%CI = 2.16-123.80, P = 0.007; grade IV: HR = 42.13, 95%CI = 5.83-304.47, P 0.001) remained associated with survival at 2-year follow-up. At 3-year follow-up, lymphocyte count (HR = 0.68, 95%CI = 0.51-0.91, P = 0.008), LDH level (HR = 2.21, 95%CI = 1.40-3.49, P = 0.001), and WHO grade (grade II: HR = 1.44, 95%CI = 0.44-4.68, P = 0.543; grade III: HR = 4.99, 95%CI = 1.68-14.87, P = 0.004; grade IV: HR = 16.96, 95%CI = 6.13-46.93, P 0.001) remained associated with survival in multivariate Cox analysis.Our study demonstrated that preoperative serum LDH level could serve as a reliable indicator for predicting prognosis of glioma patients. Further multicenter studies are still required to verify our findings.

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer1,2. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies3. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood. Here we report that V-domain immunoglobulin suppressor of T cell activation (VISTA) engages and suppresses T cells selectively at acidic pH such as that found in tumour microenvironments. Multiple histidine residues along the rim of the VISTA extracellular domain mediate binding to the adhesion and co-inhibitory receptor P-selectin glycoprotein ligand-1 (PSGL-1). Antibodies engineered to selectively bind and block this interaction in acidic environments were sufficient to reverse VISTA-mediated immune suppression in vivo. These findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement. V-domain immunoglobulin suppressor of T cell activation (VISTA) selectively engages P-selectin glycoprotein ligand-1 (PSGL-1) and suppresses T cells at acidic pH similar to those in tumour microenvironments, thereby mediating resistance to anti-tumour immune responses.

Background Little is known about the genetic architecture of economically important traits in Brown Swiss cattle because only few genome-wide association studies (GWAS) have been carried out in this breed. Moreover, most GWAS have been performed for single traits, thus not providing detailed insights into potentially existing pleiotropic effects of trait-associated loci. Results To compile a comprehensive catalogue of large-effect quantitative trait loci (QTL) segregating in Brown Swiss cattle, we carried out association tests between partially imputed genotypes at 598,016 SNPs and daughter-derived phenotypes for more than 50 economically important traits, including milk production, growth and carcass quality, body conformation, reproduction and calving traits in 4578 artificial insemination bulls from two cohorts of Brown Swiss cattle (Austrian-German and Swiss populations). Across-cohort multi-trait meta-analyses of the results from the single-trait GWAS revealed 25 quantitative trait loci (QTL; P, BMC Genomics, 20 (1)

NF-κB is a core transcription factor, the activation of which can lead to hypoxic-ischemic brain damage (HIBD), while RCAN1 plays a protective role in HIBD. However, the relationship between NF-κB and RCAN1 in HIBD remains unclear. This study aimed to explore the mechanism of NF-κB signaling pathway in hippocampal neuron apoptosis and cognitive impairment of neonatal rats with HIBD in relation to RCAN1. Initially, microarray analysis was used to determine the differentially expressed genes related to HIBD. After the establishment of HIBD rat models, gain- or loss-of-function assay was performed to explore the functional role of NF-κB signaling pathway in HIBD. Then, the learning and memory ability of rats was evaluated. Expression of RCAN1, NF-κB signaling pathway-related genes and glial fibrillary acidic protein (GFAP), S-100β and acetylcholine (Ach) level, and acetylcholinesterase (AchE) activity were determined with neuron apoptosis detected to further explore the function of NF-κB signaling pathway. RCAN1 could influence the development of HIBD. In the HIBD model, the expression of RCAN1 and NF-κB-related genes increased, and NF-κB p65 showed a significant nuclear shift. By activation of NF-κB or overexpression of RCAN1, the number of neuronal apoptosis, S-100β protein level, and AchE level increased significantly, Ach activity decreased significantly, and GFAP positive cells increased. In addition, after the activation of NF-κB or overexpression of RCAN1, the learning and memory ability of HIBD rats was inhibited. All the results show that activation of NF-κB signaling pathway promotes RCAN1 expression, thus increasing neuronal apoptosis and aggravating cognitive impairment in HIBD rats.

Little is known about the changes of people with schizophrenia disability in Taiwan who receive routine treatments under the current mental healthcare system. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess and track changes in the degree of disability in people with schizophrenia before and after 4 years of follow-up. Data on 4497 people with schizophrenia were acquired from the Taiwan Data Bank of Persons with Disability. The WHODAS 2.0 was used for disability assessment, and the chi-square test, logistic regression and generalised estimating equations were adopted for statistical analysis. People with schizophrenia exhibited improvement in cognition, mobility and participation among the six domains as well as in the overall score. The degree of disability in all domains remained mild to moderate among people aged 18-64 years; the degree of disability in cognition declined from moderate to severe among patients aged ≥65 years. The degree of disability in all domains remained mild to moderate among people with mild to moderate impairment; among those with severe impairment, the degree of disability in the domains of cognition and life activities declined from moderate to severe and the degree of disability in the domain of mobility declined from mild to moderate. Community-dwelling patients exhibited less degree of disability in all domains than their institutionalised peers. Early detection and treatment and an emphasis on communication and social problem-solving skills in rehabilitation programmes are recommended for people with schizophrenia.

Rotational malalignment between the femoral and tibial components in total knee arthroplasty (TKA) can affect clinical outcomes, but there is no consensus on how to best determine tibia tray orientation. The posterolateral corner-locked (PLCL) technique may be a new method. This study aims to assess the applicability of this technique in a Chinese population. Forty normal Chinese volunteers were recruited and underwent computed tomography (CT) of the lower limbs. Knee model reconstructions and simulated standard tibial osteotomy were conducted digitally. The transepicondylar axis (TEA), the Akagi line, and the line connecting the medial third of the tibial tubercle with the midpoint of the posterior cruciate ligament (PCL) were projected to the tibial cross-section and marked. The PLCL technique was applied using either symmetrical or asymmetrical tibial tray templates, and the anteroposterior (AP) axis of the tibial tray was marked. The angles between the TEA and these lines were calculated, and the statistical differences were analyzed. The angle between the TEA and the Akagi line and between the TEA and the line connecting the medial third of the tibial tubercle with the midpoint of the PCL were 96.90 ± 5.57 and 107.31 ± 5.95 degrees, respectively. The angles between the TEA and the AP axis of the symmetrical and the asymmetrical design tibial trays were 94.01 ± 4.21 and 96.65 ± 4.70 degrees, respectively. Except for the Akagi line and AP axis of the asymmetrical tibial tray, statistical differences were found between all lines (p

To investigate and analyze the learning curve of totally thoracoscopic mitral valve replacement and provide a quantitative reference for cardiac surgeons to carry out the operation step by step.The clinical data were retrospectively analyzed of 100 consecutive patients with totally thoracoscopic mitral valve replacement successively performed by the same surgeon in a single center from May 2019 to June 2020. The learning curve was divided into 2 stages by using cumulative sum analysis, and relevant surgical parameters and perioperative indicators were analyzed.The first stage of the learning curve is the skill acquisition stage, which includes 1 to 40 surgical procedures. The second stage is the proficiency stage, involving 41 to 100 operations. Among the surgical parameters of the patients in the 2 stages, detectable improvements were observed in operative time, cardiopulmonary bypass time, cross-clamp time, and intraoperative injury. After surgery, the amount of drainage, length of hospital stay, blood creatinine levels, and oxygenation index 24 h after surgery were also significantly different between the 2 groups (all P.05). The age and sex distributions of the patients were balanced, and there was no statistically significant difference in terms of conversion to median sternotomy between the 2 stages (P.05).Cumulative sum analysis was used to accurately analyze the learning curve of totally thoracoscopic mitral valve replacement, indicating that 40 cases are needed to master the technique.

Many genomic analyses start by aligning sequencing reads to a linear reference genome. However, linear reference genomes are imperfect, lacking millions of bases of unknown relevance and are unable to reflect the genetic diversity of populations. This makes reference-guided methods susceptible to reference-allele bias. To overcome such limitations, we build a pangenome from six reference-quality assemblies from taurine and indicine cattle as well as yak. The pangenome contains an additional 70,329,827 bases compared to the Bos taurus reference genome. Our multiassembly approach reveals 30 and 10.1 million bases private to yak and indicine cattle, respectively, and between 3.3 and 4.4 million bases unique to each taurine assembly. Utilizing transcriptomes from 56 cattle, we show that these nonreference sequences encode transcripts that hitherto remained undetected from the B. taurus reference genome. We uncover genes, primarily encoding proteins contributing to immune response and pathogen-mediated immunomodulation, differentially expressed between Mycobacterium bovis-infected and noninfected cattle that are also undetectable in the B. taurus reference genome. Using whole-genome sequencing data of cattle from five breeds, we show that reads which were previously misaligned against the Bos taurus reference genome now align accurately to the pangenome sequences. This enables us to discover 83,250 polymorphic sites that segregate within and between breeds of cattle and capture genetic differentiation across breeds. Our work makes a so-far unused source of variation amenable to genetic investigations and provides methods and a framework for establishing and exploiting a more diverse reference genome. ISSN:0027-8424 ISSN:1091-6490

BackgroundCD40 agonist immunotherapy can potentially license antigen-presenting cells to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma. Systemic administration of CD40 agonists has historically been associated with considerable toxicity, providing the rationale for development of tumor-targeted immunomodulators to improve clinical safety and efficacy. This phase I study assessed the safety, tolerability, preliminary antitumor activity, and preliminary biomarkers of ABBV-428, a first-in-class, mesothelin-targeted, bispecific antibody designed for tumor microenvironment-dependent CD40 activation with limited systemic toxicity.MethodsABBV-428 was administered intravenously every 2 weeks to patients with advanced solid tumors. An accelerated titration (starting at a 0.01 mg/kg dose) and a 3+3 dose escalation scheme were used, followed by recommended phase II dose cohort expansions in ovarian cancer and mesothelioma, tumor types associated with high mesothelin expression.ResultsFifty-nine patients were treated at doses between 0.01 and 3.6 mg/kg. The maximum tolerated dose was not reached, and 3.6 mg/kg was selected as the recommended phase II dose. Seven patients (12%) reported infusion-related reactions. Treatment-related grade ≥3 treatment-emergent adverse events were pericardial effusion, colitis, infusion-related reaction, and pleural effusion (n=1 each, 2%), with no cytokine release syndrome reported. The pharmacokinetic profile demonstrated roughly dose-proportional increases in exposure from 0.4 to 3.6 mg/kg. Best response was stable disease in 9/25 patients (36%) treated at the recommended phase II dose. CD40 receptor occupancy >90% was observed on peripheral B-cells starting from 0.8 mg/kg; however, no consistent changes from baseline in intratumoral CD8+ T-cells, programmed death ligand-1 (PD-L1+) cells, or immune-related gene expression were detected post-ABBV-428 treatment (cycle 2, day 1). Mesothelin membrane staining showed greater correlation with progression-free survival in ovarian cancer and mesothelioma than in the broader dose escalation population.ConclusionsABBV-428 monotherapy exhibited dose-proportional pharmacokinetics and an acceptable safety profile, particularly for toxicities characteristic of CD40 agonism, illustrating that utilization of a tumor-targeted, bispecific antibody can improve the safety of CD40 agonism as a therapeutic approach. ABBV-428 monotherapy had minimal clinical activity in dose escalation and in a small expansion cohort of patients with advanced mesothelioma or ovarian cancer.Trial registration numberNCT02955251.

In this study, the potential of specific Circular RNAs (circRNAs) as novel peripheral blood biomarkers for myasthenia gravis (MG) was explored. We analyzed circRNAs in the peripheral blood of three normal controls and three MG patients using RNA microarray. Candidate circRNAs were validated in three independent cohorts by Quantitative Real-time polymerase chain reaction (qPCR). Eleven differentially expressed circRNAs were initially identified and four were confirmed in the first independent cohort. Hsa_circ_0076490 and hsa-circ_5333-4 had the largest areas under the curve (AUCs) of the receiver operating characteristics (ROC) and were validated in the second cohort. In the third cohort, hsa-circRNA5333-4 had a larger AUC: 0.864 (95% confidence interval [CI] = 0.801-0.928, P 0.001), a stronger correlation with the Quantitative Myasthenia Gravis Score (qMG): r = 0.505 (P 0.001) and was correlated with gender and acetylcholine receptor antibody levels (P 0.05). So hsa-circRNA5333-4 represents a novel biomarker for the diagnosis and monitoring of MG.

China General Administration of Sport has published and adopted the National Physical Fitness Measurement (NPFM—preschool children version) since 2000. However, studies on intraday reliability, sensitivity, and minimum detectable change (MDC) are lacking. This study aimed to investigate and compare the reliability, sensitivity, and MDC values of NPFM in preschool children between the ages of 3.5 to 6 years. Six items of NPFM including 10-m shuttle run, standing long jump, balance beam walking, sit-and-reach, tennis throwing, and double-leg timed hop, were tested for 209 Chinese kindergarten children in Beijing in the morning. Intraday relative reliability was tested using intraclass correlation coefficient (ICC3,1) with a 95% confidence interval while absolute reliability was expressed in standard error of measurement (SEM) and percentage of coefficient of variation (CV%). Test sensitivity was assessed by comparing the smallest worthwhile change (SWC) with SEM, while MDC values with 95% confidence interval (MDC95) were established. Measurements in most groups, except 10-m shuttle run test (ICC3,1: 0.56 to 0.74 [moderate]) in the 3.5 to 5.5-year-old groups, balance beam test in 4- and 5-year-old (ICC3,1: 0.33 to 0.35 [poor]) and 5.5-year-old (ICC3,1= 0.68 [moderate]) groups, and double-leg timed hop test (ICC3,1= 0.67 [moderate]) in the 4.5-year-old group, demonstrated good to excellent relative reliability (ICC3,1: 0.77 to 0.97). The balance beam walking test showed poor absolute reliability in all the groups (SEM%: 11.76 to 22.28 and CV%: 15.40 to 24.78). Both standing long jump and sit-and-reach tests demonstrated good sensitivity (SWC > SEM) in all subjects group, boys, and girls. Pairwise comparison revealed systematic bias with significantly better performance in the second trial (p

This study aimed to investigate the predictive factors for uveitis recurrence (UR) risk in Behcet's disease (BD) patients. BD patients (n=164) with a history of uveitis were recruited, and demographic data, clinical features, and laboratory tests were recorded. Uveitis was defined as anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis referring to the "International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease". In total, there were 70 UR patients and 94 non-UR patients. Compared to non-UR patients, UR patients appeared to be older and presented with increased uveitis occurrence rate and times within 3 months, oral ulcers occurrence rate, as well as higher concentrations of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and serum amyloid A (SAA). Multivariate logistic model disclosed that uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA independently predicted higher risk of UR. Furthermore, receiver operating characteristic curve analysis showed that the combination of uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA exhibited a high predictive value for UR risk with an area under the curve of 0.983 (95%CI: 0.969-0.998). In conclusion, uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA might be potential predictive factors for UR risk in BD patients, which can help in prevention and management of the disease.

Background To investigate the role of two-dimensional shear wave elastography (2D-SWE) in the preoperative evaluation of pediatric patients with biliary atresia awaiting liver transplantation. Methods Among a total of 152 pediatric patients enrolled in this single-institution prospective study between March 2018 and August 2019, 143 patients (age range, 4-97 months; median age, 7 months; 84 males, 59 females) who underwent successful routine ultrasound examination, SWE examination, and blood test before liver transplantation were included in the final analysis. The values of liver stiffness measured by SWE were compared with ultrasound and blood test parameters by Spearman's correlation analysis. Results The overall median liver stiffness with 2D-SWE was 29.0 ± 10.9 kPa, with a range of 9.0-53.3 kPa. The success rate of 2D-SWE measurements was 98.0% (149/152). Liver stiffness measurement (LSMs) had no significant correlation with gender, age, weight, and height of the pediatric recipients. LSMs were correlated with ultrasound parameters including portal vein (PV) maximum velocity, PV direction, hepatic artery resistance index (HARI), spleen diameter, ascites, and blood test parameters (albumin level, platelet count level, and international normalized ratio). In the pediatric recipients with hepatofugal PV flow, high HARI (HARI ≧ 0.90), and ascites, or without Kasai operation, LSMs were significantly higher (P Conclusions SWE is feasible and valuable for assessing liver damage in children with biliary atresia awaiting liver transplantation and might be used as selection criteria for children in need of priority access to liver transplantation.

BackgroundArthroscopic surgery procedures vary depending on the types of meniscus tear, including meniscectomy and meniscus repair. Among the several types of meniscus tear, the horizontal tear of the lateral meniscus at the popliteal hiatus region is a common injury, and its surgical treatment is still inconsistent.MethodsBetween January 2018 and October 2018, 20 patients who underwent all-inside repair with suture hook for the horizontal tear of the lateral meniscus at the popliteal hiatus region were recruited. Any operative complication was recorded, and postoperative MRI scans were conducted at the 6 months. The clinical results were graded based on the scale of the Lysholm knee score preoperatively and at follow-up.ResultsNo operative complications were recorded. Postoperative MRIs at the 6 months showed that there was no re-tear for all patients, though signal intensity remained high in T2-weighted MRI in the lateral meniscus for nine cases. The average preoperative Lysholm knee score was 58.6 ± 10.1, which increased significantly to 89.3 ± 7.8 (t = − 11.01,p = 0.001) at the last follow-up. Recurrence or aggravation of symptoms was not noted at the final follow-up.ConclusionAll-inside repair with suture hook may be a good option for the horizontal tear of the lateral meniscus at the popliteal hiatus region which preserves the meniscus; avoids iatrogenic injury on the adjacent popliteal tendon, common peroneal nerve, and inferior lateral geniculate artery.

Background The aim of this study was to explore the value of SMI compared with conventional ultrasonography for assessing hepatic arterial blood flow after pediatric liver transplantation. Methods From March 2018 to November 2018, a total of 105 pediatric recipients with biliary atresia underwent liver transplantation in our hospital. Ultrasound examinations were performed at the bedside in the intensive care unit to check the patency of the blood flow in the hepatic allograft. CDI, PDI, cSMI, and mSMI were performed to assess the display, orientation, and distribution of the graft hepatic artery. Ultrasound examinations were performed by one radiologist, and the images were judged by two observers. Results The median age, weight, and height of the recipients were 6.97 (5.92, 9.58) months, 6.50 (6.00, 7.80) kg, and 64.00 (62.00, 68.00) cm, respectively. The measure of kappa agreement was 0.902, 0.889, 0.882, and 0.882 for CDI, PDI, cSMI, and mSMI, respectively. HAT occurred in 7 pediatric recipients and was confirmed by CTA (computed tomography angiography) and surgery. The diagnostic performance of sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and accuracy were 100%, 92.86%, 50%, 100%, and 93.33% for CDI and 100%, 98.98%, 87.50%, 100%, and 99.05% for SMI. Conclusions As an additional method to CDI, SMI can clearly show the distribution of hepatic arterial blood flow and provide more details, thereby markedly improving the diagnostic performance of postoperative HAT.

Recent studies have demonstrated an effect of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), on airway contractility [via increased airway smooth muscle (ASM) intracellular calcium [Ca(2+)](i)] and remodeling (ASM proliferation and extracellular matrix formation) in the context of airway disease. In the present study, we examined the role of BDNF in allergen-induced airway inflammation using 2 transgenic models: 1) tropomyosin-related kinase B (TrkB) conditional knockin (TrkBKI) mice allowing for inducible, reversible disruption of BDNF receptor kinase activity by administration of 1NMPP1, a PP1 derivative, and 2) smooth muscle–specific BDNF knockout (BDNF(fl/fl)/SMMHC11(Cre/0)) mice. Adult mice were intranasally challenged with PBS or mixed allergen (Alternaria alternata, Aspergillus fumigatus, house dust mite, and ovalbumin) for 4 wk. Our data show that administration of 1NMPP1 in TrkBKI mice during the 4-wk allergen challenge blunted airway hyperresponsiveness (AHR) and reduced fibronectin mRNA expression in ASM layers but did not reduce inflammation per se. Smooth muscle–specific deletion of BDNF reduced AHR and blunted airway fibrosis but did not significantly alter airway inflammation. Together, our novel data indicate that TrkB signaling is a key modulator of AHR and that smooth muscle–derived BDNF mediates these effects during allergic airway inflammation.—Britt, R. D., Jr., Thompson, M. A., Wicher, S. A., Manlove, L. J., Roesler, A., Fang, Y.-H., Roos, C., Smith, L., Miller, J. D., Pabelick, C. M., Prakash, Y. S. Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma.

The purpose of this study is to investigate the efficacy, safety, and tolerability of agomelatine and paroxetine in Chinese Han patients with major depressive disorder (MDD).A 8-week, double-blind, randomized, parallel study was conducted in 14 medical centers in mainland China from December 2011 to September 2012. A total of 264 subjects with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD were randomly assigned to receive agomelatine 25-50 mg/d (n = 132) or paroxetine 20-40 mg/d (n = 132). The primary efficacy was evaluated by the decrease of Hamilton Depression Rating Scale (HAM-D17) scores. The secondary measurements of efficacy included Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, Sheehan Disability Scale, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. The laboratory test abnormity, and observed and self-reported adverse events were all assessed as the measurements of safety and tolerability.Both the agomelatine and paroxetine groups showed significant improvement from baseline to the end point (P0.05) without between-group differences (P0.05). The mean decrease of HAM-D17 of agomelatine group was not inferior to the paroxetine group over the 8-week treatment (agomelatine 15.26 ± 6.44 vs paroxetine 14.87 ± 5.89, δ = 2.0; μA-μB 95% confidence interval, -1.13 to 1.91). The percentage of responders at the last postbaseline assessment was similar in the 2 groups on both HAM-D17 (agomelatine 66.15% vs paroxetine 63.49%) and Clinical Global Impressions-Improvement (agomelatine 79.09% vs paroxetine 80.36%). The anxiety (Hamilton Anxiety Rating Scale) and sleep symptoms (sleep items of HAM-D17) of the patients were improved significantly in the 2 groups at week 8 without between-group differences (P0.05). The incidence of overall adverse events was similar in the 2 groups (agomelatine 49.62% vs paroxetine 56.15%, P0.05). The incidence of adverse events in skin and subcutaneous tissue was higher in the paroxetine group than in the agomelatine group (none in agomelatine and 4.62% in paroxetine, P = 0.0144).Agomelatine showed equivalent antidepressant efficacy to paroxetine in treating MDD patients after 8 weeks of treatment with an acceptable safety.

To explore the perceptions and attitudes among people with disabilities towards the newly implemented International Classification of Functioning, Disability and Health-based disability evaluation system (the new system) in Taiwan.Using a self-administered questionnaire, we conducted a nationwide survey. The questionnaire focused on the domains of quality, satisfaction, and revision of the new system. In total, 1073 persons (age, ≥18 years) with disabilities or their primary caregivers, who experienced both the old and the new system, responded to the questionnaire.Most participants were satisfied with the new system overall (58.7%) and the subscale of quality of structure (91.3%) and quality of outcome (63.6%). However, only 20.5% of the participants were favourable to the quality of process. The probability of being satisfied with the system overall was low for the quality of process subscale (adjusted odds ratio range, 0.3 ∼ 0.4) and its item of long interval (0.2 ∼ 0.6). Contrariwise, the probability was high for the other subscales (3.9 ∼ 13.7) and the item of identifying needs (21.9 ∼ 23.4).Persons with disabilities and their primary caregivers have positive attitudes towards the new system. It is important to simplify the assessment tools and procedures to improve the system's quality of process and facilitate its usability. IMPLICATIONS FOR REHABILITATION Persons with disabilities have positive attitudes towards the newly implemented International Classification of Functioning, Disability, and Health-based disability evaluation system in Taiwan. The system that provides comprehensive information about functioning and disability of persons with disabilities is able to capture the difficulties and needs of those individuals in their daily lives. The system hence helps people to mitigate the effects of disability and guide rehabilitation. The assessment items and processes of the system, however, were perceived to be complicated, time-consuming, and inconvenient. Simplifying the assessment items and processes, such as developing a short form version of the assessment tool and increasing the service time, may facilitate the usability of the system.

Background Perventricular and transcatheter device closures are performed for perimembranous ventricular septal defect (pmVSD) to reduce the surgical trauma of conventional surgical repair via median sternotomy. Few comparative studies have been conducted among these three procedures. Methods From June 2015 to May 2016, 247 patients with isolated pmVSD who had undergone perventricular or transcatheter device closure or conventional surgical repair were reviewed to compare these three procedures. Results The procedure success rate was similar in these three groups. There were a statistically significant difference in operative time, aortic cross-clamping time, duration of cardiopulmonary bypass (CPB), blood transfusion amount, and medical cost in these three groups. Meanwhile, postoperative mechanical ventilation time, duration of intensive care, and length of hospital stay were longer in surgical group than the other two groups. The surgical group required the longest incision. No significant difference was noted in major adverse events. There were different advantages and disadvantages in these three kinds of procedures. Conclusions Device closure may be alternative to conventional surgical repair for patients with isolated pmVSD. Perventricular device closure was the preferred procedure because it showed more maneuverable than transcatheter procedure with the same clinical result.

Background Intramedullary screw (IMS) fixation was wildly used in fifth metatarsal base fractures (FMBFs) and the results were satisfactory. However, in the comminuted osteoporosis or small displaced avulsion FMBFs, anatomical reduction and stable fixation could not be achieved with IMS. The Locking Compression Plate (LCP) distal ulna hook plate fixation was a novel alternative fixation method. The aim of this retrospective cohort study was to determine if LCP distal ulna hook plate fixation resulted in improved outcomes compared to the traditional IMS fixation in displaced avulsion FMBFs. Methods Of 43 patients with displaced avulsion FMBFs, 18 patients were treated with LCP distal ulna hook plate fixation and 25 were treated with IMS fixation. The patients were evaluated clinically and radiographically and followed up to 12 months. The surgery time, time for hospital stay, time for weight-bearing, time for bony union, time for return to daily life, pain relief, functional outcome and complications after treatment with LCP distal ulna hook plate fixation or IMS fixation were compared. The functional outcome was assessed by the AOFAS (American Orthopedic Foot and Ankle Society) mid-foot score at 3, 6, 9, and 12 months after surgery. Meanwhile, pain scores were obtained at 3, 6, 9, and 12 months after surgery. Results The two cohorts had similar baseline characteristics. Surgery time was less in LCP distal ulna hook plate fixation cohort compare to IMS fixation cohort (p

Schizophrenia is a common mental disorder characterized by deficits in multiple domains of functioning. This study is arguably the first of its kind in Taiwan to examine, in a multifaceted and objective manner, the disability of patients with schizophrenia and the factors affecting it. A cross-sectional design was adopted to gather data from 24,299 patients with schizophrenia who were listed in the Taiwan Databank of Persons with Disabilities. The level of disability in these patients was measured using the World Health Organization Disability Assessment Schedule 2.0. Statistical analyses were conducted through the χ 2 statistic and Poisson regression. The highest level of disability was in participation and the lowest was in self-care. An analysis of disability in all six domains of functioning on the basis of sex, age, type of residence, and socioeconomic status (SES) showed significant differences (P

Background In 2010, the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was developed, based on the concept of the International Classification of Functioning, Disability and Health (ICF). The ICF provides a common language and framework for health and health-related status and attempts to integrate the biopsychosocial model as a multidimensional perspective in understanding functioning. Activities and participation (AP) is one salient component of the ICF refers to the execution of a task by an individual, and how such tasks are involved in their daily life. It is essential to examine the gap between the general adult population and adults with disabilities. This gap may be attributed to health status, personal factors, and natural and social environments, which include social and health services and policies. The purposes: (1) To develop a normative activity and participation (AP) value for the adult population and people with disabilities; and (2) to compare the gap in AP normative values between the two groups in Taiwan. Methods We use the WHODAS 2.0 to survey and develop a normative AP value for the general adult population, and used secondary data from National Disability Eligibility Determination System (NDEDS) of Taiwan to describe the AP functioning distribution of adult with disability. There were 1100 participants, selected by stratified proportional sampling from two cities. There were also 144,850 participants who were adults with disability, selected from the secondary database in Taiwan. Results and conclusions The AP curve for the disabled population increased rapidly at the beginning. The summary score was 13.21 in the performance at 90 percentile for the general population and 82.61 score for disabled adults that the similar gap in every domain, its means that there are significant functioning difference and health equality in general adults population and adults with disabilities. This presents a substantial challenge for both the government and the whole population of Taiwan, to begin considering how to reduce the gap in AP functioning and promote equality for people with disabilities, using social welfare policy. It is important to make sure disabled people have the same rights to be included in society as anybody else and better access to things in all areas of life that are according to Convention on the Rights of Persons with Disabilities (CRPD).

Background Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis. Methods Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated. Findings Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema – patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89. Interpretation Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy., Highlights • The oral microbiota of NPC patients are different to that of healthy persons. • The biodiversity of oral microbiota changed significantly as mucositis progressed during radiotherapy. • Oral microbiota represents a potential strategy for predicting the aggravation of severe mucositis during radiotherapy. Oral or oropharyngeal mucositis is the most common side effect of radiation therapy for head and neck cancers. In this prospective cohort study, we found that changes in an oral microbial community correlated with the progression and aggravation of radiotherapy-induced mucositis in the patients with nasopharyngeal carcinoma; and patients who eventually developed severe mucositis transiently harbored a notably higher proportion of Actinobacillus during a mild phase of mucositis, which may potentially play a role in the aggravation of severe mucosal lesions. Moreover, our findings also showed that microbiota-based strategies can be used for the early prediction of the incidence of severe mucositis during radiotherapy.

Background Several questionnaires have been used to assess the health status of patients with Kashin-Beck disease (KBD) in clinical trials, but the evidence regarding the responsiveness of these instruments in KBD patients is limited. Therefore, the aim of this study was to evaluate and compare the responsiveness of the Chinese version of the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in KBD patients undergoing intra-articular injection of hyaluronic acid (HA). Methods A sample of 232 KBD patients treated with intra-articular injection of HA completed the WOMAC, 12-item WHODAS 2.0 and joint dysfunction index (JDI) both pre- and post-treatment. Responsiveness was assessed using correlation and receiver operating characteristic (ROC) curve analyses following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Results Overall, there were significant improvements in the mean scores on the WOMAC and on the 12-item WHODAS 2.0, except for in the cognition domain. Correlation analysis showed that changes in the WOMAC and 12-item WHODAS 2.0 scores had moderate or weak positive associations with the changes in the JDI. However, acceptable areas under the ROC curve (value > 0.7) were found for all domains and for the total score on the WOMAC, but only for the mobility domain and the total score on the 12-item WHODAS 2.0. Conclusions These results demonstrated that the WOMAC was more responsive than the 12-item WHODAS 2.0 in KBD patients treated with intra-articular injection of HA. Our findings support the continued use of the WOMAC as an outcome measure in assessing disability in KBD patients.

Background We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine. Methods This case‐control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High‐performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated. Results Intra‐ and post‐operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine‐lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine‐lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine‐lidocaine complex, elimination half‐life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone. Conclusions Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half‐life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions.

Enhancing children's daily participation is the optimal goal of early childhood intervention. This study aimed to identify child and family predictors of participation for toddlers with global developmental delay.Fifty-nine toddlers with global developmental delay (aged 24-43 months) and their mothers participated in a 6-month longitudinal study. Predictors for participation were child factors [age, gender, delay severity, mastery motivation (perceived persistence and task persistence), and withdrawal behavior], and family factors (socioeconomic status, family income, maternal education, stress, and maternal teaching behavior). Dependent variables were participation diversity and intensity of four activity types measured 6-month later using the Assessment of Preschool Children's Participation (Chinese version). Correlation and hierarchical regression statistical methods were used.Older children with higher persistence had higher overall participation. Different factors predicted different participation dimensions and different activity types. Older age, higher perceived persistence, and being less withdrawn predicted higher diversity and intensity for play participation. For skill development participation, older age, less severity, higher mastery motivation, and better maternal teaching behaviors predicted higher diversity; and age, mastery motivation and maternal teaching predicted intensity.Different factors predict participation attendance differently. Supporting parents to enhance toddlers' mastery motivation may optimize children's participation in daily activities.Implications for rehabilitationBased on the child and their caregiver preferences, applicability and/or engagement for different activity types, interventionists could collaborate further with caregivers to find strategies to increase children's participation attendance in daily life.Interventionists could consult with caregivers: (a) to observe the persistence and positive affect (mastery motivation) of children during different activities, (b) to figure out the possible barriers to participation in those activities, and (c) to demonstrate appropriate caregiver-child interactions.Interventionists are encouraged to support children's mastery motivation and quality of maternal teaching behaviors to enhance participation in daily activities.

Dementia is highly comorbid with gait disturbance, and both conditions negatively impact the ability of elderly people to conduct daily living activities. The ambulatory status of older adults with dementia may cause variable functional disability, which is crucial for the progression of dementia. The present study investigated the association between ambulatory status with functional disability in elderly people and dementia by using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). In total, 34,040 older adults with mild-to-advanced dementia were analyzed and categorized according to their ambulatory status into three groups: Nonambulatory, assisted ambulatory, and ambulatory. In general, poor ambulatory status was associated with both greater severity of dementia and functional disability. The study participants were further segregated according to their ages and dementia severity levels, which demonstrated that the WHODAS 2.0 domains of functioning for getting along, life activities, and participation (domains 4, 5&ndash, 1, and 6) were all associated with ambulatory status. In addition, nonambulatory status was significantly associated with institution residency among older adults with dementia. In conclusion, the present study clearly demonstrated the role of ambulatory status in functional disability in older adults with dementia, and the association persisted among older adults of different ages and severities of dementia. This finding indicates the importance of maintaining walking ability in the management of dementia in older adults.

Dementia is a common nonmotor condition among people with moderate or advanced Parkinson&rsquo, s disease (PD). Undoubtedly, profound motor symptoms cause remarkable impairment in daily activities, however, dementia-related disabilities have not been thoroughly investigated, especially not with consideration of differences according to sex. The present study used the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) to compare the functional disability between men and women with PD (PwP) with and without dementia. This study employed a registry of disability evaluation and functional assessment using the Taiwan Data Bank of Persons with Disability between July 2012 and October 2018. To investigate dementia-related disability in PwP, 1:1 matching by age and Hoehn-Yahr stage was conducted, which resulted in the inclusion of 1605 study participants in each group. The present study demonstrated that among the six major domains of WHODAS 2.0, the section of &ldquo, Getting alone with others&rdquo, was significantly worse in both genders of PwP with dementia, however, a greater disability in fulfilling activities of daily living was only noted in male PwP with dementia but not in their female counterparts. Neither the inability to provide self-care nor participation were significantly different between the sexes. Our findings suggested that deteriorating social relationships were a dementia-related disability in all PwP at the moderate and advanced disease stages. Regarding the performance of activities of daily living, deterioration was related to dementia only in male PwP. Such disabilities could indicate cognitive impairment in people with moderate or advanced PD and could be used as an indicator for the early detection of dementia in PwP by healthcare professionals through the easier functional assessment of the WHODAS 2.0.

STUDY OBJECTIVES: This study aimed to explore the effects of a single bout of light-intensity walking on sleep in older women with mild sleep impairment. METHODS: A total of 40 women aged 55 years or older with mild sleep impairment were randomized to either a treadmill walking session for 50 minutes or a quiet-rest control. All participants completed the study (mean age: 60.4 ± 4.7 years). Sleep quality was assessed by ActiGraph for 2 nights before (pretest) and 2 nights after exercise (posttest). A mixed-design analysis of variance was used with group as the between-subjects factor and time point as the within-subjects factor. RESULTS: No significant group difference in demographic variables, body mass index, physical and mental status, and eight sleep parameters were observed at baseline. Significant group-time interactions existed for sleep latency (P < .001) and sleep efficiency (P = .025). After the intervention, the walking group reduced sleep latency by 3.3 minutes (P = .001) and also had greater sleep efficiency (increase 3.8%, P = .008), but no significant change was found in the control group. No significant group-time interactions were present for the other six sleep parameters (activity counts, total sleep time, wake after sleep onset, number and length of awakenings, or time in bed). CONCLUSIONS: A single session of light-intensity walking led to a modest reduction in sleep latency and improvement of sleep efficiency in older women with mild sleep impairment. CITATION: Chen LJ, Stevinson C, Fang SH, Taun CY, Ku PW. Effects of an acute bout of light-intensity walking on sleep in older women with sleep impairment: a randomized controlled trial. J Clin Sleep Med. 2019;15(4):581–586.

The objective of this study was to analyze retrospectively the clinical efficacy and fungal clearance of long-pulsed 1064-nm Nd:YAG laser for treating onychomycosis and explore the inhibitory effects of laser on the fungus pathogen-induced onychomycosis in vitro. We performed a systematic retrospective analysis of clinical patients (162 effected nails) of onychomycosis treatment applying laser with or without topical ketoconazole ointment and followed up 3 months after treatment. Trichophyton rubrum- and Trichophyton mentagrophytes-induced onychomycosis was irradiated with laser superimposed for different cumulative energy, respectively; then, the areas of fungus colonies and growth curve in different days were showed, and changes in ultrastructures were observed under SEM and TEM. The clinical effective rate and fungal clearance rate in the combined group were higher than those in the laser group; however, there was no significant difference between the two groups. In vitro, the areas of T. rubrum colonies were significantly reduced at days 1, 3, and 5 after irradiation with cumulative laser energy ≥ 6400 J/cm2. When irradiated with cumulative laser energy ≥ 25600 J/cm2, significant difference in the areas of T. mentagrophytes colonies was found at day 5. And ultrastructure of the two strains before and after laser irradiation was damaged at different degrees. This study confirmed that long-pulsed 1064-nm Nd:YAG laser is effective for treating onychomycosis, and the laser irradiation can inhibit the colony growth of T. rubrum and T. mentagrophytes and change their cellular ultrastructures. The mechanism of laser treatment of onychomycosis may be related to direct damage of fungus pathogen.

BackgroundMaternal shift work is associated with preterm delivery, small-for-gestational-age new-borns, childhood obesity and future behavioural problems. However, the adverse effects on and interactions of maternal shift work with infant neurodevelopment remain uncertain. Therefore, we examined the associations between maternal-shift-work status and infant neurodevelopmental parameters.MethodsThe Taiwan Birth Cohort Study is a nationwide birth cohort study following representatively sampled mother–infant pairs in 2005. The participants’ development and exposure conditions were assessed by home interviews with structured questionnaires at 6 and 18 months of age. Propensity scores were calculated with predefined covariates for 1:1 matching. Multivariate conditional logistic regression and the Cox proportional-hazards model were used to examine the association between maternal-shift-work status and infant neurodevelopmental-milestone-achievement status.ResultsIn this study, 5637 term singletons were included, with 2098 cases selected in the propensity-score-matched subpopulation. Persistent maternal shift work was associated with increased risks of delays in gross-motor neurodevelopmental milestones [aOR = 1.36, 95% confidence interval (CI) = 1.06–1.76 for walking steadily], fine-motor neurodevelopmental milestones (aOR = 1.39, 95% CI = 1.07–1.80 for scribbling) and social neurodevelopmental milestones (aOR = 1.35, 95% CI = 1.03–1.76 for coming when called upon). Moreover, delayed gross-motor and social development were identified in the propensity-score-matched sub-cohort.ConclusionsThis study shows negative associations between maternal shift work and delayed neurodevelopmental-milestone achievement in the gross-motor, fine-motor and social domains at 18 months. Future research is necessary to elucidate the possible underlying mechanisms and long-term health effects.

Lung adenocarcinoma (LA) is the most commonly occurring histological type of non‑small cell lung cancer. Diagnosis and treatment of LA remain a major clinical challenge. In the present study, to identify early LA biomarkers, extracellular vesicles (EVs) were separated from the plasma samples from 153 patients with LA and 75 healthy controls. microRNA (miRNA) expression profiling was performed at the screening stage (5 patients with LA vs. 5 controls), followed by verification at the validation stage (40 patients with LA vs. 20 controls) using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The four disordered miRNAs (miR‑505‑5p, miR‑486‑3p, miR‑486‑3p and miR‑382‑3p) identified in the plasma EVs were further evaluated at the testing stage (108 patients with LA vs. 50 controls) by RT‑qPCR. It was revealed that miR‑505‑5p was upregulated, whereas miR‑382‑3p was downregulated, in the EVs from patients with LA. Furthermore, miR‑505‑5p was also upregulated in tumor tissues, compared with adjacent non‑tumor control tissues. Subsequently, the direct targets of miR‑505‑5p were predicted using bioinformatics analyses, and verified by luciferase assay and immunoblotting. The present study determined that miR‑505‑5p functions as an oncogene, promoting lung cancer cell proliferation and inhibiting cancer cell apoptosis via the targeting of tumor protein P53‑regulated apoptosis‑inducing protein 1 (TP53AIP1). Finally, it was confirmed that miR‑505‑5p in plasma EVs could be delivered to lung cancer cells, inhibiting cell apoptosis and promoting cell proliferation by targeting TP53AIP1. In conclusion, the present study indicated that miRNA‑505‑5p functions as an oncogene that may be used as a novel biomarker for the diagnosis and treatment of LA.

Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR‐135a‐5p, as well as those between miR‐135a‐5p and 3′ untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual‐luciferase reporter gene assay. The expression of miR‐135a‐5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR‐135a‐5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv‐shGAS5 and Lv‐miR‐135a‐5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR‐135a‐5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR‐135a‐5p. After the treatment of Lv‐shGAS5 and Lv‐miR‐135a‐5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR‐135a‐5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.

This study assesses the functioning and disability related to Parkinson&rsquo, s disease using the Functioning Disability Evaluation Scale-Adult Version (FUNDES-Adult), based on the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in a large-scale database, this study describes, discusses and clarifies the predictive factor of not being in an ambulatory status. Of 7455 patients included in this study, 3561 were not ambulatory and 3894 were ambulatory or assisted ambulatory. Patients with poor walking status revealed higher FUNDES-Adult scores in all domains. Age, modified Hoehn&ndash, Yahr stage, living in an institution and the standardized score of FUNDES-Adult domains 1 and 2 were positive independent predictors of the not ambulatory status. The FUNDES-Adult could evaluate multifaceted disability and predict the walking status in patients with Parkinson&rsquo, s disease.

// Zu-Guang Xia 1, * , Hua-Fang Yin 2, * , Ying Long 3, * , Lei Cheng 1 , Ling-Jun Yu 4 , Wei-Jian Guo 1 , Xiao-Dong Zhu 1 , Jin Li 1 , Ya-Nong Wang 5 , Ya-Jun Yang 6, 7 , Jiu-Cun Wang 6, 7 , Li Jin 6, 7 , Li-Xin Qiu 1 , Yongyue Wei 8 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 Department of Medical Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangsu, China 3 Department of Medical Oncology, Wanzai City Hospital, Jiangxi, China 4 Department of Informatics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China 5 Department of Gastric Cancer & Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 6 Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China 7 Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China 8 Department of Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Li-Xin Qiu, email: mdqiulixin@hotmail.com Yongyue Wei, email: ywei@njmu.edu.cn Keywords: gastric cancer, genetic susceptibility, miR-146a, polymorphism Received: January 30, 2016 Accepted: March 31, 2016 Published: April 18, 2016 ABSTRACT The single nucleotide polymorphism (SNP) rs2910164 G>C within miR-146a has been reported that is associated with the increased risk of gastric cancer (GCa). However, the results are inconclusive, espicially among Asian populations, which probably due to small sample size in each single study. To validate this association and get a more precise estimation, we conducted a large GCa study including 1,125 cases and 1,196 controls in an eastern Chinese population. Our results showed that this SNP was not associated with GCa risk in either of the three genetic models [co-dominant model: CG vs. CC, odds ratio (OR) = 0.99, 95% confidence interval (95%CI): 0.83-1.19; GG vs. CC, OR = 1.03, 95%CI: 0.81-1.32; dominant model: (CG+GG) vs. CC, OR = 1.00, 95%CI = 0.84-1.19; recessive model: GG vs. (CG+CC), OR = 1.04, 95%CI = 0.83-1.29]. Stratified analysis by age, gender, smoking status, drinking status, or tumor location confirmed this non-significant association. In summary, these results suggest that the miR-146a SNP rs2910164 may not be a risk factor for GCa in this Chinese population. Larger and well-designed, preferably prospective studies are needed to further confirm our findings.

To analyse the disability status of elderly Taiwanese dementia patients by using the World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0).We enrolled 12 126 disabled elderly (65 years) patients with dementia during July 2012-January 2014 from the Taiwan Data Bank of Persons with Disability. Trained interviewers evaluated the standardised scores in the six WHODAS 2.0 domains. Student's t test was used for comparing WHODAS 2.0 scores of male and female dementia patients with different age groups.The study population comprised 12 126 patients; 7612 were women and 4514 were men. The WHODAS 2.0 scores showed that the dementia patients had global activity limitation and participation restriction in all domains. Dementia-induced disability was prominent in male patients in all of the domains of the WHODAS 2.0. The domains of life activities, getting along with people and cognition were more strongly affected than the other domains. However, women experienced more rapid functional decline than men did as they aged.The data analysed in this large-scale, population-based study revealed crucial information on dementia-induced disability in elderly patients on the basis of the WHODAS 2.0 framework. Implications for rehabilitation Dementia patients have global functional disability in all domains of WHODAS 2.0 and multidisciplinary team is needed for rehabilitation programme intervention for these patients. When considering the rehabilitation resource and strategy, the domains of cognition, activities of daily living and life activities should be focussed. When dementia patients aged 65-75 years old, male patients got more restriction of function than female and more medical resource allocation for disabled male patients is recommended. With ageing, female dementia patients exhibited more rapid functional decline than male patients did and more budget about rehabilitation for maintain functional and dementia progression is crucial for female patients.

To assess activity and participation for children in Taiwan&rsquo, s Disability Eligibility Determination System (DEDS), we developed a questionnaire, the Functioning Disability Evaluation Scale (FUNDES-Child), based on the Child and Adolescent Scale of Participation (CASP). The study follows a methodology research design to investigate the construct validity of the frequency and independence dimensions of FUNDES-Child 7.0. Two samples were randomly stratified from the databank of 13,835 children and youth with disabilities aged 6.0&ndash, 17.9 years to examine structural validity by exploratory factor analysis (EFA, n = 4111, mean age of 11.3 &plusmn, 3.5) and confirmatory factor analysis (CFA, n = 4823, mean age of 11.4 &plusmn, 3.5)). EFA indicated a 4-factor structure for the frequency dimension (51.3% variance explained) and a 2-factor structure for the independence dimension (53.6% variance explained). The CFA indicated that the second-order factor structures of both dimensions were more parsimonious with adequate fit indices (Goodness fit Index, GFI, Normed Fit Index, NFI, Comparative Fit Index, CFI, and Tucker-Lewis Index, TLI &ge, 0.95, Root Mean Square Error of Approximation, RMSEA &lt, 0.06). Results provide evidence that the participation part of FUNDES-Child 7.0 has acceptable structural validity for use in Taiwan&rsquo, s DEDS. Utility of FUNDES-Child 7.0 in rehabilitation, welfare, and educational services needs further study.

Aims: Mastery motivation refers to a child’s persistent attempts to solve problems and learn skills. The purpose of this longitudinal study was to examine whether children’s mastery motivation-medi...

BACKGROUND: The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status. RESULTS: At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population. CONCLUSIONS: The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence. ispartof: MICROBIOME vol:6 issue:1 ispartof: location:England status: published

To improve the clinical diagnosis of neural autoimmune diseases, we developed an in-house muscle-specific kinase (MuSK) antibody cell-based assay (CBA) and compared its performance with RIA, ELISA, and other CBAs. Sera from patients with myasthenia gravis (MG) and other autoimmune diseases were analyzed. We found 46 (18.3%) MuSK-CBA Ab positive cases among 251 AChR-Ab negative cases [patients] and 4 (0.6%) MuSK-CBA Ab positive cases [among] the 624 AChR-Ab positive samples. Comparing these with available clinic assays, our highly specific CBA method is more sensitive than commercial ELISA and IFA(indirect immunofluorescence assay).

This study aims to investigate major complications or symptoms of pregnant women, causes of maternal near-miss, and issues that are relevant to severe maternal disease. A retrospective analysis was performed in the “maternal individual investigation form,” which included all critical maternity patients admitted to the First Affiliated Hospital of Anhui Medical University from January 1, 2012 to September 31, 2015. A total of 14,014 pregnant patients who delivered at 28 to 42 weeks of gestation were included. Eight thousand eighty-six patients experienced complications or symptoms, and top 7 of these were postpartum hemorrhage, hypertension during pregnancy, diabetes, anemia, hepatopathy, nephroma, and connective tissue disease, of which the morbidity were 11.92%, 10.15%, 9.34%, 8.57%, 3.13%. 0.56%, and 0.55%, respectively. Delivery times, gestational weeks, and informal pregnancy examinations had significant correlation with maternal near-miss (P .05). Two hundred sixty-five patients had severe maternal diseases (maternal near miss), and the top 5 causes for severe maternal morbidity were massive blood transfusion, thrombocytopenia, clinical feature of shock, uterus removal induced by uterus infection or bleeding, and coagulation dysfunction, of which the morbidity were 24.15%, 18.87%, 13.58%, 9.43%, and 6.79%, respectively. Delivery times, gestational weeks, and informal pregnancy examinations should be considered in maternal near miss patients. Moreover, hypertensive disorders during pregnancy, postpartum hemorrhage, anemia, thrombocytopenia, hepatopathy, and cardiopathy were the principal causes of maternal near miss. Therefore, the monitoring of these principal causes of severe maternity near miss is important for reducing the maternal morbidity and mortality.

OBJECTIVE: This study aimed to investigate the correlation of serum uric acid (SUA) with risk and dilatation diameter of ascending aortic dilatation (AAD) in Behçet's disease (BD) patients. METHODS: Seventeen BD patients complicated with AAD and 20 BD patients without AAD were consecutively enrolled and categorized into AAD group and control group, respectively. Ascending aortic dilatation was determined by two‐dimensional doppler echocardiographic examination, and AAD was defined as a diameter of ascending aorta ≥3.8 and

Doppler ultrasonography is useful in monitoring intra-operative PV flow in LDLT. A retrospective cohort study included 550 pediatric recipients (