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Background/Purpose The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

To assess the concurrent validity between logbooks and a single-item rehabilitation adherence measurement for patients with stroke. Agreement between caregivers and patients and between caregivers and physical therapists regarding a single-item measurement was investigated, and its predictive validity was explored.Adherence to therapy is a primary determinant of treatment success. There are no standard instruments for measuring rehabilitation adherence available for stroke patients.Prospective longitudinal study.Seventy-five patients with stroke were recruited, measured four times and followed for 6 months. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used to ensure comprehensive reporting. Adherence was documented in logbooks, and single-item measurements were compared. Predictive validity was explored by assessing associations between adherence levels, self-care ability and health-related quality of life. The Spearman's correlation coefficients, weighted kappa, and generalised estimating equations statistics were used to explore the concurrent validity, measurement agreement, and predictive validity, respectively.Logbook records had a fair correlation (rThere was fair concurrent validity between logbooks and single-item rehabilitation adherence measurements and moderate and fair adherence measure agreement between caregivers and patients and caregivers and physical therapists, respectively. Logbooks and single-item rehabilitation adherence measurements had adequate predictive validity.Single-item rehabilitation adherence measurement is a workable and straightforward method to assess stroke patients' rehabilitation adherence in busy clinical care settings. Caregivers can represent stroke patients regarding their reported rehabilitation adherence.Patients were diagnosed with stroke in the study hospital. Rehabilitation physicians transferred patients to a research nurse who then screened them for the inclusion criteria and invited them and their family caregivers to participate in this study if they met the requirements. We also recruited seven physical therapists responsible for the physical therapy of the study participants. After participants signed informed consent, the research nurse encouraged participants to respond to research questions face to face, including rehabilitation adherence data, daily physical function, and quality of life. Each participant was measured four times at baseline and at 1, 3, and 6 months after inclusion in this study. Physical therapists had to score their patients' rehabilitation adherence levels before discharge.Not applicable.

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Small flexible force-sensing resistor (FSR) sensors can detect laryngeal excursion during swallowing, but the detected laryngeal excursion has not been correlated with videofluoroscopic swallowing study (VFSS) results. Here, we tested the correlation of temporal parameters between the laryngeal excursion recording by FSR sensor and the hyoid motion recording by VFSS under simultaneously swallowing test recordings. Swallowing measurements were recorded in a radiological suite by simultaneously using VFSS and FSR sensors to detect hyoid motion and laryngeal excursion, respectively. Volunteers sat with their head vertical to the Frankfort plane. Two FSR sensors, each for detecting thyroid cartilage excursion and thumb pressing, were placed. VFSS images and FSR sensor signals during single 5-mL barium liquid (30% wt/volume %) bolus swallowing were collected and analyzed for four swallows per participant. In total, 15 men (28.0 ± 4.1 years old); 14 women (28.4 ± 4.2 years old) were recruited. Temporal parameters between VFSS and noninvasive system demonstrated a strong correlation by Pearson’s correlation analysis: in men (R = 0.953–0.999) and in women (R = 0.813–0.982), except for VT1–V1 compared with FT1–F1, which demonstrated a moderate correlation in women (R = 0.648; all p p = 0.001). Therefore, this is the first study to simultaneous record VFSS and noninvasive signals by FSR sensor. The correlation of temporal parameters between these two tests was strong. This finding is valuable for future applications of this noninvasive swallowing study tool.

Background: Ankylosing spondylitis (AS) is an inflammatory autoimmune disorder that manifested with sacroiliitis at its early stage and developed extensive inflammation with syndesmophytes of the lumbar, thoracic and cervical spines at its later stage. In the present study, we characterized the trunk isometric strength in patients with AS with different disease severity, defined by the radiological images. Methods: In a cross-sectional study conducted in a university-affiliated hospital, thirty-eight male AS patients (23 in the early AS group whose radiological findings showed no syndesmophyte, Modified Stoke Ankylosing Spinal Score (m-SASSS

Ankylosing spondylitis (AS) is a chronic inflammatory disease that leads to spinal ankylosis. The receptor activator of the nuclear factor-kappa (RANK), RANK ligand, and osteoprotegerin (OPG) (RANK/RANKL/OPG) pathway plays critical roles in bone metabolism and the immune system. The current study was aimed at investigating whether six single-nucleotide polymorphisms (SNPs) within the RANK, RANKL, and OPG genes essential for bone homeostasis are associated with AS. Genotype distributions, allele and haplotype frequencies, were compared between 1120 AS patients and 1435 healthy controls and among AS patients with stratification by syndesmophyte formation, onset age, and HLA-B27 positivity. We found that RANKL SNPs were associated with AS syndesmophyte formation. Notably, the RANKL SNP haplotype rs7984870C/rs9533155G/rs9525641C was negatively associated with AS susceptibility and appeared to protect against syndesmophyte formation in AS. Functionally, RANKL promoter SNPs (rs9525641 C/T and rs9533155 G/C) affected DNA-protein complex formation and promoter activity in promoter reporter analyses. The OPG SNP haplotype rs2073618G/rs3102735T was significantly associated with HLA-B27 negativity in AS patients. Furthermore, AS patients with syndesmophyte formation had significantly lower levels of soluble RANKL levels than those without syndesmophyte formation. Our data suggested a role for RANKL in AS susceptibility and severity.

Background Type III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. Methods TaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan. The distributions of IFNL3/4 SNP genotypes and allele frequencies were compared between SLE patients and healthy controls and among SLE patients stratified by clinical phenotypes. ELISA was used to determine the serum IFN-λ3 concentrations of SLE patients. Results All major IFN3/4 SNP alleles were significantly associated with the risk for lupus nephritis (rs8099917T, PFDR = 0.0021, OR 1.75, 95% CI 1.24–2.47; rs12979860C, PFDR = 0.0034, OR 1.65, 95% CI 1.18–2.30; rs4803217C, PFDR = 0.0021, OR 1.76, 95% CI 1.25–2.48; and ss469415590TT, PFDR = 0.0021, OR 1.73, 95% CI 1.23–2.42) among SLE patients. Similarly, the major IFNL3/4 SNP haplotype rs8099917T-ss469415590TT-rs12979860C-rs4803217C (or T-TT-C-C) was a significant risk factor for lupus nephritis (P = 0.0015, OR 1.68, 95% CI 1.22–2.32). Additionally, all minor IFN3/4 SNP alleles were significantly associated with SLE susceptibility in nephritis-negative SLE patients as compared to normal healthy controls (rs8099917G, PFDR = 0.00177, OR 1.68, 95% CI 1.24–2.28; rs12979860T, PFDR = 0.00299, OR 1.58, 95% CI 1.18–2.32; rs4803217A, PFDR = 0.00176, OR 1.65, 95% CI 1.22–2.23; and ss469415590ΔG, PFDR = 0.00176, OR 1.70, 95% CI 1.26–2.29). Furthermore, the elevated serum levels of IFN-λ3 were significantly correlated with the complement depression and the high SLE disease activities in SLE patients. Conclusions IFN-λ3/4 genetic variants play a unique role in the development of lupus nephritis and SLE. Electronic supplementary material The online version of this article (10.1186/s13075-018-1683-z) contains supplementary material, which is available to authorized users.

Dysphagia is common among patients with Parkinson's disease. Swallowing and its coordination with respiration is extremely important to achieve safety swallowing. Different tools have been used to assess this coordination, however the results have been inconsistent. We aimed to investigate this coordination in patients with Parkinson's disease using a non-invasive method.Signals of submental muscle activity, thyroid cartilage excursion, and nasal airflow during swallowing were recorded simultaneously. Five different water boluses were swallowed three times, and the data were recorded and analyzed.Thirty-seven controls and 42 patients with early-stage Parkinson's disease were included. The rates of non-expiratory/expiratory pre- and post-swallowing respiratory phase patterns were higher in the patients than in the controls (P 0.001). The rates of piecemeal deglutition when swallowing 10-ml and 20-ml water boluses and overall were also significantly higher in the patients (all P 0.001). There were differences in oropharyngeal swallowing parameters between the patients and controls, including a pharyngeal phase delay with longer total excursion duration and excursion time in the patients swallowing small water boluses (1 ml, 3 ml and 5 ml), but no difference in the length of swallowing respiratory pause.Oropharyngeal swallowing and its coordination with respiration are affected in patients with early-stage Parkinson's disease, and safety compensation mechanisms were used more than efficiency during swallowing. The results of this study may serve as a baseline for further research into new treatment regimens and to improve the management of swallowing in patients with Parkinson's disease.

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115, OR, 14.90, 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017, OR, 1.69, 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33, OR, 28.79, 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

The objectives of this study are to investigate swallowing and its coordination with respiration in patients with obstructive sleep apnea (OSA). This is a prospective cohort study conducted in a tertiary referred Medical Center. A non-invasive method of assessing swallowing was used to detect the oropharyngeal swallowing parameters and the coordination with respiration during swallowing. The system used to assess swallowing detected: (1) movement of the larynx using a force-sensing resistor; (2) submental muscle activity using surface electromyography; and (3) coordination with respiration by measuring nasal airflow. Five sizes of water boluses (maximum 20 mL) were swallowed three times, and the data recorded and analyzed for each participant. Thirty-nine normal controls and 35 patients with OSA who fulfilled the inclusion criteria were recruited. The oropharyngeal swallowing parameters of the patients differed from the controls, including longer total excursion duration and shorter duration of submental muscles contraction. A longer swallowing respiratory pause (SRP), temporary coordination with respiration during swallowing, was demonstrated in the patients compared with the controls. The frequency of non-expiratory/expiratory pre- and postswallowing respiratory phase patterns of the patients was similar with the controls. There was significantly more piecemeal deglutition in OSA patients when clumping 10- and 20-mL water boluses swallowing together (p = 0.048). Oropharyngeal swallowing and coordination with respiration affected patients with OSA, and it could be detected using a non-invasive method. The results of this study may serve as a baseline for further research and help advance research methods in obstructive sleep apnea swallowing studies.

OBJECTIVE Human complement C4 is complex, with multiple layers of diversity. The aims of this study were to elucidate the copy number variations (CNVs) of C4A and C4B in relation to disease risk in systemic lupus erythematosus (SLE), and to compare the basis of race-specific C4A deficiency between East Asians and individuals of European descent. METHODS The East Asian study population included 999 SLE patients and 1,347 healthy subjects. Variations in gene copy numbers (GCNs) of total C4, C4A, and C4B, as well as C4-Long and C4-Short genes, were determined and validated using independent genotyping technologies. Genomic regions with C4B96 were investigated to determine the basis of the most basic C4B protein occurring concurrently with C4A deficiency. RESULTS In East Asians, high GCNs of total C4 and C4A were strongly protective against SLE, whereas low and medium GCNs of total C4 and C4A, and the absence of C4-Short genes, were risk factors for SLE. Homozygous C4A deficiency was infrequent in East Asian subjects, but had an odds ratio (OR) of 12.4 (P = 0.0015) for SLE disease susceptibility. Low serum complement levels were strongly associated with low GCNs of total C4 (OR 3.19, P = 7.3 × 10(-7) ) and C4B (OR 2.53, P = 2.5 × 10(-5) ). Patients with low serum complement levels had high frequencies of anti-double-stranded DNA antibodies (OR 4.96, P = 9.7 × 10(-17) ), hemolytic anemia (OR 3.89, P = 3.6 × 10(-10) ), and renal disease (OR 2.18, P = 8.5 × 10(-6) ). The monomodular-Short haplotype found to be prevalent in European Americans with C4A deficiency, which was in linkage disequilibrium with HLA-DRB1*0301, was scarce in East Asians. Instead, most East Asian subjects with C4A deficiency were found to have a recombinant haplotype with bimodular C4-Long and C4-Short genes, encoding C4B1 and C4B96, which was linked to HLA-DRB1*1501. DNA sequencing revealed an E920K polymorphism in C4B96. CONCLUSION C4 CNVs and deficiency of C4A both play an important role in the risk and manifestations of SLE in East Asian and European populations.

Table S1. Association of IFN3/4 locus SNP haplotypes (rs8099917-ss469415590-rs12979860-rs4803217) with lupus nephritis among SLE patients. Figure S1. Schematic illustration of IFNL3/4 locus SNP locations. Sizes of exons and distances between exons indicated as base pairs (bp). First exon (exon 1) of each gene starts from ATG start codon and last exon (exon 5) of each gene ends at stop codon. SNP rs8099917 located in IFNL4 promoter region (3945 bp upstream of translation starting site) and SNP rs4803217 in IFNL3 3′-UTR (52 bp downstream of translation termination codon). Two other SNPs (ss469415590 and rs12979860) are with IFNL4 gene. Figure S2. Pairwise LD patterns of four IFNL3/4 locus SNPs on chromosome 19 show coefficient of linkage disequilibrium D′ (red) and square of correlation coefficient between two indicator variables γ2 (black) of all subjects (A), SLE cases (B), and healthy controls (C), respectively. Darker colors indicate stronger LD. Figure S3. Association of IFN3 levels with SLE disease activity (SLEDAI) in replication cohort. A IFNL3 levels significantly (unpaired t test t = 3.783, P = 0.0003) increased in high SLEDAI SLE patients (SLEDAI ≥ 4, N = 40; IFNL3 concentration 8.450 ± 1.263 pg/ml) than in low SLEDAI patients (SLEDAI = 0, N = 40; IFNL3 concentration 3.260 ± 0.5365 pg/ml). B IFNL3 levels not significantly different (unpaired t test t = 1.650, P = 0.103) between nephritis-positive patients (N = 40; IFNL3 concentration 4.645 ± 1.039 pg/ml) and nephritis-negative patients (N = 40; IFNL3 concentration 7.065 ± 1.036 pg/ml). (DOCX 194 kb)

Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype distributions and HLA-C allele frequencies were compared in patients and controls and among patients with and without HLA-B27 positivity, early age onset and spinal syndesmophytes. HLA-C alleles were functionally characterized using 3D structural modelling with peptide simulation. This study discovered that the HLA-C*12:02:02 allele (43.42% vs. 3.31%; p < 0.00001 odds ratio (OR), 16.88; 95% confidence intervals (CI): 11.27–25.28) confers a strong risk for Taiwanese AS development. The 3D modelling results identified four unique amino acid polymorphisms, Ala73, Trp156, Arg219 and Met304, that may affect the function of the HLA-C*12:02:02 allele. KIR2DL5 (p = 0.0047; pFDR = 0.0423) and the KIR Bx haplotype (p = 0.0000275) were protective against Taiwanese AS, while KIR 2DS4/1D (22 base pair truncated deletion; p = 0.0044; pFDR = 0.1998) appeared to be a risk factor for it. KIR2DL5 combined with the HLA-C1/C2 heterozygous genotype showed a protective effect (AS 5.97% vs. normal 11.66%; p = 0.002; pFDR = 0.0127, OR, 0.48 95% CI: 0.33–0.70); in contrast, KIR 2DS4/1D combined with the HLA-C1C1 homozygous genotype (AS 45.33% vs. normal 35.92%; p = 0.002; pFDR = 0.0127, OR, 1.48 95% CI: 1.21–1.81) represented a risk factor for AS development. Our data suggested that interactions between KIRs and their cognate HLA-C ligands may contribute to the pathogenesis of AS.

IgG Fcγ receptors (FcγRs) mediate a variety of immune functions that are critical in immune responses. In humans, 5 classic low-affinity FcγRs (FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, and FcγRIIIB) are coded by 5 genes (FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B, respectively) in the FCGR cluster on chromosome 1. Activating FcγRs (FcγRIIA, FcγRIIC, FcγRIIIA, and FcγRIIIB) mediate immune cell activation promoting inflammation, while the classic inhibitory FcγRIIB dampens immune responses and restricts inflammation (1,2). Activating FcγRs mediate functions including immune complex clearance, phagocytosis, antigen presentation, antibody-dependent cellular cytotoxicity, and cytokine production (3). In contrast, the inhibitory FcγRIIB abrogates immune cell activation. FcγRIIB also plays a role in the maintenance of peripheral B cell tolerance and the prevention of autoimmunity (2). The variations in FcγR expression significantly affect IgG immune complex–mediated signal thresholds (3,4). Notably, proinflammatory and antiinflammatory cytokines could modulate the expression levels of activating and inhibitory FcγRs (5) that affect the threshold immune cell response to IgG immune complexes (6). FcγR-knockout mouse models indicate that both activating and inhibitory FcγRs influence the development of autoimmune diseases (7–9). The contributions of FcγR genes to autoimmune diseases have attracted substantial attention, and functional FcγR polymorphisms have been reported to play important roles in the pathogenesis of autoimmune diseases (4,10,11). Gene copy number variation (CNV) is a rich source of genetic heterogeneity (12,13). The FCGR cluster on chromosome 1q23 shows a complex pattern of CNVs. Among 5 FcγR genes in the cluster, 3 genes (FCGR3A, FCGR2C, and FCGR3B) have CNVs, while FCGR2A and FCGR2B do not have CNVs (14,15). CNVs play important roles in human disease pathogenesis (16). FCGR3B copy number deficiency is associated with autoimmune disease, including systemic lupus erythematosus (SLE) (17–19), Sjogren's syndrome (20), and systemic sclerosis (21). Although FCGR3B CNVs were reported to associate with rheumatoid arthritis (RA) (22–24), no association between RA and FCGR3B CNVs was observed in other studies (25,26). Moreover, no association between FCGR3A CNVs and RA was observed (24,27). In the current study, we investigated whether FCGR3A and FCGR3B CNVs are associated with susceptibility to SLE and RA in Taiwanese individuals. The results provide new insights into the role of FcγRIII family members in the pathogenesis of SLE and RA in an Asian population.

Objectives: To illustrate the clinical presentation, diagnosis, management, and outcome of unilateral right occipital condyle to C2 level spinal cord infarction.Setting: A teaching hospital in Taiwan.Findings: A 37-year-old man presented with acute-onset severe right neck pain before weakness developed in both right limbs. Early diagnosis was delayed due to mild intervertebral herniation of the C4–C5 disk. Magnetic resonance imaging revealed unilateral right occipital condyle to C2 level infarction. Angiography showed stenosis of the right vertebral artery (foraminal and intradural segments), and dissection of the left vertebral artery at the C1–C2 level. At discharge, he walked with assistance; 2 weeks later, he walked independently.Conclusions: An early diagnosis is difficult but important, as it facilitates appropriate treatment for better functional and survival outcomes. Accurate early diagnosis can be made with adequate knowledge of spinal cord infarction and high index of suspicion for this...

Chen C-C, Hong W-H, Wang C-M, Chen C-K, Wu KP-H, Kang C-F, Tang SF. Kinematic features of rear-foot motion using anterior and posterior ankle-foot orthoses in stroke patients with hemiplegic gait. Objective To evaluate the kinematic features of rear-foot motion during gait in hemiplegic stroke patients, using anterior ankle-foot orthoses (AFOs), posterior AFOs, and no orthotic assistance. Design Crossover design with randomization for the interventions. Setting A rehabilitation center for adults with neurologic disorders. Participants Patients with hemiplegia due to stroke (n=14) and able-bodied subjects (n=11). Interventions Subjects with hemiplegia were measured walking under 3 conditions with randomized sequences: (1) with an anterior AFO, (2) with a posterior AFO, and (3) without an AFO. Control subjects were measured walking without an AFO to provide a normative reference. Main Outcome Measures Rear-foot kinematic change in the sagittal, coronal, and transverse planes. Results In the sagittal plane, compared with walking with an anterior AFO or without an AFO, the posterior AFO significantly decreased plantar flexion to neutral at initial heel contact ( P =.001) and the swing phase ( P P =.002). In the coronal plane, the anterior AFO significantly increased maximal eversion to neutral (less inversion) at the stance phase ( P =.025), and decreased the maximal inversion angle at the swing phase when compared with using no AFO ( P =.005). The posterior AFO also decreased the maximal inversion angle at the swing phase as compared with no AFO ( P =.005). In the transverse plane, when compared with walking without an AFO, the anterior AFO and posterior AFO decreased the adduction angle significantly at initial heel contact ( P =.004). Conclusions For poststroke hemiplegic gait, the posterior AFO is better than the anterior AFO in enhancing rear-foot dorsiflexion during a whole gait cycle. The anterior AFO decreases rear-foot inversion in both the stance and swing phases, and the posterior AFO decreases the rear-foot inversion in the swing phase when compared with using no AFO.

Objective.To investigate the association of the functional FCRL3 single-nucleotide polymorphism (SNP) −169T/C with disease phenotypes and susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese.Methods.FCRL3 SNP −169T/C was genotyped in 573 patients with SLE, 670 patients with RA, and 758 controls. Genotype distributions and allele frequencies were compared among the 3 groups as aggregates or as stratified by clinical characteristics, autoantibody profile, and sex within patient groups.Results.Overall, FCRL3 SNP −169T/C was not associated with susceptibility to either SLE or RA. However, −169CC genotype was significantly reduced in leukopenia-positive SLE patients as compared to the leukopenia-negative SLE patients (CC vs CT+TT, p = 6 × 10−4, OR 0.444, 95% CI 0.279–0.708) and controls (p = 6.1 × 10−3, OR 0.583, 95% CI 0.396–0.857). On the other hand, −169TT genotypes were significantly more numerous in RA patients with non-destructive disease as compared with patients with destructive disease (CC+CT vs TT: p = 0.007, OR 1.672, 95% CI 1.149–2.432). The −169T allele frequency was also significantly increased in non-destructive RA compared with patients with destructive disease (C vs T: p = 0.010, OR 1.423, 95% CI 1.089–1.859). FCRL3 SNP −169TT homozygous donors were significantly more numerous among female cyclic citrullinated peptide (CCP)-negative RA patients versus female CCP-positive RA patients (CC+CT vs TT: p = 0.019, OR 1.64, 95% CI 1.085–2.479).Conclusion.The functional FCRL3 SNP −169T/C appears to play important roles in the development of certain phenotypes such as SLE leukopenia and RA disease severity in Taiwanese patients with SLE and RA.

Background Reviewing the literature on central neurocytoma revealed that functional outcomes traditionally have been assessed by KPS. However, KPS is not sufficiently sensitive to assess functional outcomes compared with the Barthel Index and the Functional Independence Measure (the FIM™ instrument). Discussion of other functional assessments and various aspects of central neurocytomas has never been documented clearly. Methods Nine case series of primary central neurocytomas received total or STR at our hospital. The clinical features, neuroradiologic findings, histopathologic features, and functional outcomes were listed and analyzed. Moreover, the functional outcomes were assessed using KPS, Barthel Index, and FIM™ instrument. The follow-up period ranged from 8 to 33 months after surgery. Results Patients with increased GFAP positivity or MIB-1 index greater than 3% did not have the worst scores in functional assessments. The functional outcomes of the cases presented here, including KPS, Barthel Index, and FIM™ instrument, were listed in Table 4. Most patients achieved good functional outcomes. The average KPS, Barthel Index, and FIM™ instrument were 86.25 ± 14.08 (range, 60-100), 86.88 ± 17.31 (range, 50-100), and 111 ± 17.02 (range, 78-126), respectively. Conclusion Most of the patients in this investigation achieved good ability to independently perform daily activity. Whether the high score of functional outcome was correlated with benign tumor course or 5-year survival rate remains uncertain. We recommend regular follow-up for detecting tumor growth or recurrence, although central neurocytomas are always benign.

Fcgamma receptors (FcgammaR) impact upon the development of inflammatory arthritis through immune complex stimulation and proinflammatory cytokine production. FcgammaRIIa, FcgammaRIotaIotaIotaa and FcRgammaIIIb polymorphisms were genotyped in 212 rheumatoid arthritis (RA) patients and 371 healthy control subjects using an allelic-specific polymerase chain reaction (PCR). No significant skewing in the distribution of FcgammaRIIa H/R131, FcgammaRIIIa F/V158 and FcgammaRIIIb NA1/NA2 was found between RA patients and healthy control subjects. However, a significant skewing distribution of the FcgammaRIIIa F/V158 polymorphism was observed between rheumatoid factor (RF)-positive versus RF-negative RA patients (P = 0.01). The low-affinity FcgammaRIIIa F158 allele seems to have a protective role in RF production, in comparison with the FcgammaRIIIa V158 allele (P = 0.004; OR = 0.485; 95% CI: 0.293-0.803). A high frequency of FcgammaRIIIa F/F158 was identified in RA patients with negative RF compared with RF-positive patients (for FF158 versus FV158 + VV158; P = 0.002; OR = 0.372; 95% CI: 0.194-0.713). In addition, no association was found between FcgammaRIIa H/R131, FcgammaRhoIIIa F/V158 and FcgammaRIIIb NA1/NA2 polymorphisms and other clinical parameters. The results of this study suggest that three activating FcgammaRs polymorphisms lack association with RA but FcgammaIIIa F/V158 polymorphism may influence RF production and IgG RF immune complex handling in Taiwanese RA patients.

Objective: To assess the effectiveness of neuromuscular electrical stimulation (NMES) on cough capacity and prevention of pulmonary complication in patients with acute cervical cord injury. Design: A randomized controlled trial. Subjects: Twenty-six tetraplegic patients with cervical spinal cord injury, 13 in the NMES therapy group and 13 in the control group. Methods: NMES was applied to the clavicular portion of the pectoralis major and abdominal muscle. Pulmonary function tests were performed before and after therapy, and at 3 months and 6 months follow-up. The pulmonary complications in this 6-month follow-up period were also recorded. Results: After the 4-week therapy, and at 3 months and 6 months follow-up testing, patients in the NMES therapy group displayed significant improvement in their peak expiratory flow, forced expiratory volume in 1 second, forced vital capacity, maximal expiratory pressure and maximal inspiratory pressure, compared with those in the control group (p B /0.05). Patients in the NMES therapy group also had fewer pulmonary complications in the follow-up period. Conclusion: NMES over the pectoralis and abdominal muscles might improve cough capacity and pulmonary function in cervical spinal cord injury with tetraplegia. This improvement might last for 6 months. With this improvement, pulmonary complications were reduced.

Summary Apoptosis is important in the pathogenesis of systemic lupus erythematosus (SLE). Several genome-wide scan studies have suggested chromosome 1q as a genetic susceptibility locus for SLE. This study investigated the association of apoptosis-related genes on chromosome 1q, Fas ligand (FasL), interleukin (IL)-10 and poly(ADP-ribose) polymerase (PARP), promoter microsatellite multi-allelic polymorphisms with SLE susceptibility and clinical characteristics in Taiwan. This study recruited 237 SLE patients and 304 healthy controls. FasL, IL-10 and PARP promoter microsatellite polymorphisms were genotyped employing gene scan. IL-10, located on 1q31–32, emerged as a significant susceptibility gene locus in Taiwanese SLE (T4 statistic = 0·01). IL-10 CA21 allele was the most common allele of 15 identified in Taiwanese, displaying skewed distribution of susceptibility in Taiwanese SLE patients. Conversely, the IL-10 CA20 allele showed a protective effect of SLE susceptibility. Additionally, the IL-10 CA26 allele displayed a negative significant association with ascites and IL-10 CA25 allele increased the occurrence of the anti-cardiolipin IgM antibody. This study identified five alleles of FasL and nine alleles of PARP of microsatellite polymorphisms in Taiwanese patients. FasL and PARP alleles displayed no skewing distribution between Taiwanese SLE patients and controls. However, FasL GT15 and PARP CA17 allele demonstrated a high discoid rash presentation (T4 statistic 0·01 and 0·03, respectively) and PARP CA12 allele displayed a significant association with anti-cardiolipin IgM antibody production (T4 statistic 0·02). IL-10, FasL and PARP microsatellite polymorphisms exhibited significant associations with SLE susceptibility and/or clinical characteristics in Taiwanese patients. Thus, SLE is a complex and multiple genetics determined autoimmune disease. Chromosome 1q23–42 is an important genetic locus for further SLE subphenotype susceptibility study.

Both botulinum toxin type A (BTA) injection and selective posterior rhizotomy (SPR) are well-recognized treatments for children with spastic cerebral palsy (CP); however, there has been no study in which the long-term effectiveness of these two approaches has been compared.The study population comprised 62 ambulatory children with spastic diplegic CP who were participating in the same rehabilitation program and 19 healthy volunteers. The children with CP were divided into the following three groups: BTA (22 cases), SPR (20 cases), and no treatment (20 cases); the healthy volunteers served as the control group. A computer-assisted gait analysis system was used to assess gait performance. Gait was assessed in the three groups of children at 1 week before treatment, and 3, 6, 12, and 20 months after treatment. Based on the analysis of walking velocity, cadence, and step length, the BTA group demonstrated rapid improvement posttreatment but the improvement became insignificant after 12 months even with repeated BTA injections at 4-month intervals. In contrast, the SPR group displayed initial deterioration of gait parameters during the first 3 months posttreatment and then improved continuously from 6 to 20 months. The control group did not display a significant change in gait.The findings suggest that the effectiveness of BTA injection is more short-lived and SPR initially decreases gait performance but is expected to improve gait performance at between 6 and 20 months after the procedure.

Objective: To assess the balance function of hemiplegic stroke patients and to investigate whether visual feedback rhythmic weight-shift training following acute stroke can decrease falls among patients with hemiplegic stroke. Design: A prospective study, using a Balance Master. Setting: Hospital-based rehabilitation units. Subjects: Fifty-two hemiplegic stroke patients (28 in the training group and 24 in the control group). Interventions: Conventional stroke rehabilitation programme plus visual feedback rhythmic weight-shift training. Training effect was evaluated by assessing the static and dynamic balance performance as well as comparing the occurrence of falls in the training and control groups at six-month follow-up. Main measures: Occurrence of falls; static balance in different sensory conditions; and dynamic balance performance, including on-axis velocity and directional control during rhythmic weight-shift. Results: Significant improvement in dynamic balance performance was found in hemiplegic patients in the training group. The improvement was sustained for six months. With regarding to static balance function, no significant improvement was found. At six-month follow-up, 5 of 28 patients (17.8%) in the training group had fallen, compared with 10 of 24 patients (41.7%) in the control group. The occurrence of falls decreased, although not statistically significantly (p = 0.059). Conclusions: Visual feedback rhythmic weight-shift training may improve dynamic balance function for hemiplegic stroke patients. The effects of training may be sustained for six months. The occurrence of falls decreased in the training group, but not statistically significantly.

Aim Previous studies have shown that the process of swallowing changes with aging, a phenomenon known as presbyphagia. These subtle and subclinical age-related changes make older adults more vulnerable to dysphagia during disease insults. However, there are limited studies of the swallowing process in older adults, because measurements are typically invasive or require exposure to X-rays. In the present study, we used integrated non-invasive measurements to determine aging-related changes of swallowing, and in the coordination of swallowing and respiration for a population of healthy participants. Methods The non-invasive system provided measurements of larynx movement with piezoelectric sensors, submental muscle activity with surface electromyography and respiration–swallowing coordination by measurement of nasal airflow. We recruited 112 healthy participants from the community, 35 in a young-age group (age 20–30 years), 38 in a middle-age group (age 31–50 years) and 39 in an old-age group (age 51–70 years). Results The oropharyngeal swallowing parameters of the old-age group had delayed onset latency and longer swallowing apnea duration relative to the other groups, and these differences were greater for larger boluses. The middle- and old-age groups had less expiratory–expiratory respiratory phase pattern than the young-age group. The probability of piecemeal deglutition was highest in the old-age group and lowest in the young-age group. These results show that the phases of oropharyngeal swallowing and the coordination of swallowing with respiration gradually change with aging. Conclusions We used integrated non-invasive measurements to document age-related changes in swallowing, and in the coordination of swallowing and respiration in healthy adults. Geriatr Gerontol Int 2015; 15: 736–744.

OBJECTIVE. A subgroup of patients benefiting most from robot-assisted therapy (RT) has not yet been described. We examined the predictors of improved outcomes after RT. METHOD. Sixty-six patients with stroke receiving RT were analyzed. The outcome measures were the Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and Stroke Impact Scale (SIS). The potential predictors were age, side of lesion, time since onset, Modified Ashworth Scale (MAS) scores, accelerometer data, Box and Block Test (BBT) scores, and kinematic parameters. RESULTS. BBT scores were predictive of FMA (29%) and MAL (9%−15%) improvements. Reduced shoulder flexion synergy, as measured by less shoulder abduction during forward reach, and MAS–distal were predictive of WMFT–function improvements. MAS–distal was predictive of SIS–physical improvements. Demographic variables did not predict outcomes. CONCLUSION. Manual dexterity was a valuable predictor of motor impairment and daily function after RT. Outcomes at different levels may have different predictors.

Toll-like receptors (TLRs), as innate immunity sensors, play critical roles in immune responses. Six SNPs of TLR3, TLR7, and TLR8 were genotyped to determine their associations with systemic lupus erythematosus (SLE) and clinical manifestations of SLE. TLR7 SNP rs3853839 was independently associated with SLE susceptibility in females (G vs. C: p = 0.0051). TLR7 rs3853839-G (G vs. C: p = 0.0100) and TLR8 rs3764880-G (recessive model: p = 0.0173; additive model: p = 0.0161) were associated with pericardial effusion in females relative to healthy females. Anti-SSA positive cases were more likely to have the dominant TLR7 rs179010-T allele than normal controls (p = 0.0435). TLR3 rs3775296-T was associated with photosensitivity (p = 0.0020) and anemia (p = 0.0082). The "G-G" haplotype of TLR7 rs3853839 and TLR8 rs3764880 increased risk of SLE in females (age adjusted p = 0.0032). These findings suggest that TLR variations that modify gene expression affect risk for SLE susceptibility, clinical phenotype development, and production of autoantibodies.

Salmonella infection is an important problem in immunocompromised patients. The synovium is a particular metastatic focus of Salmonella infection and can result in many disabilities of life. Systemic lupus erythematosus (SLE) patients were highly susceptible to Salmonella infection. In the past 6 years, 41 patients with Salmonella septic arthritis have been treated in our hospital. Eleven patients had an underlying systemic disease of SLE which presented with a distinctive clinical course. Alcoholic liver disease (six cases) was another common underlying systemic disease. The most frequent predisposing articular factor was avascular necrosis (16 cases). The hip joint was the most commonly involved site. Salmonella group B was the most common serotype (30/41). Seventy-three per cent (8/11) of the SLE group had involvement of two or more joints compared with only three out of 30 patients in the non-SLE group. The sex differentiation shows a predominance of young females (10/11) in the SLE group and middle-aged males in the non-SLE group. Moreover, in the SLE group, all 11 patients shared the risk of lupus nephritis and steroid use. Ten patients had Salmonella group B bacteraemia and five had urinary tract infections simultaneously. In the non-SLE group, there were 10 patients with a history of steroid use, three with antecedent enteritis, 12 with bacteraemia, and three with necrotising fasciitis. Seven patients in each of the groups had a recurrent course. However, three patients in the non-SLE group had died during the episode of septic arthritis.

Aim: To generate a descriptive theory grounded in the responses of family caregivers caring for their family stroke survivors with dysphagia during hospitalization. Design and Method: A qualitative study employing the grounded theory method was used. Fifteen family caregivers participated in comprehensive interviews. The interview data were analyzed using the constant comparative method. Findings: ‘Negotiating the maze: Confronting dysphagia with my stroke-afflicted family member’ was the core category guiding the care process for dysphagia family members among caregivers. After surviving stroke, the caregivers felt ‘more confusion less rejoicing’ as the antecedent condition. The following three interaction categories were identified: (1) ‘being overwhelmed by nasogastric (NG) tube issues’; (2) ‘searching for the right helper and information’; and (3) ‘food culture conflicts with the formula diet administered through the NG tube’. Additionally, ‘Maintaining positivity’ described the consequence of this process. Conclusions: This study highlights the critical perspective of family members who care for dysphagia stroke survivors in the hospital. Participants were under tremendous pressure during the disease treatment process. However, all attempted to maintain a positive attitude and treasured the chance to accompany their family members. Clinical Relevance: These findings can assist health professionals in charting the effects of dysphagia and in understanding the problems and needs according to the subjective perspectives of family caregivers. They can also provide a necessary foundation for comprehensive care interventions for family caregivers of stroke survivors with dysphagia.

Human complement C4 is complex with multiple layers of diversity. This study aims to elucidate the copy-number variations (CNVs) of C4A and C4B in disease risk of SLE, and compare the basis of race-specific C4A-deficiency in East-Asians (EA) and Europeans. Our study-populations included (a) 999 EA-SLE patients and 1,347 healthy subjects; and (b) 232 European SLE patients and 500 healthy subjects. Variations in gene copy-numbers (GCNs) for total C4, C4A, C4B, long and short genes were determined and validated by independent genotyping technologies. Genomic regions with C4B96 were investigated to determine the basis of the most basic C4B protein that is concurrent with C4A-deficiency. In EA, strong protective effects for high GCNs of total C4 and C4A against SLE were notable; low and medium GCNs of total C4 and C4A, and the absence of short genes were risk factors for SLE. Homozygous C4A-deficiency was infrequent but had an odds-ratio (OR) of 12.4 (p=0.0015) in SLE. Low serum complement levels were strongly associated with low GCNs of total C4 (OR=3.27, p=7.0×10−7) and C4B (OR=2.55, p=2.5×10−5). Patients with low complement had high frequencies of anti-dsDNA (OR=4.96, p=9.7×10−17), hemolytic anemia (OR=3.89, p=3.6×10−10) and renal disease (OR=2.18, p=8.5×10−6). The monomodular-short haplotype with C4A-deficiency and in linkage-disequilibrium with HLA-DRB1*0301 prevalent in Europeans was scarce in EA. Instead, most EA-subjects with C4A-deficiency shared a recombinant haplotype with bimodular-LS encoding C4B1 and C4B96, which was linked to HLA-DRB1*1501. DNA-sequencing revealed the E920K polymorphism for C4B96. In conclusion, C4 CNVs and C4A-deficiency are important in the risk and manifestations of East-Asian and European SLE.

Introduction Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese. Methods Four ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters. Results The SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P = 5.5 × 10-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P = 1.5 × 10-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P = 1.7 × 10-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P

Objectives To investigate the associations of paroxysmal supraventricular tachycardia (PSVT) and Wolff–Parkinson–White (WPW) syndrome with ankylosing spondylitis (AS). Methods We conducted a retrospective cohort study by reviewing the medical records of 1503 consecutive AS patients diagnosed at a tertiary medical center. The clinical and electrocardiographic (ECG) characteristics of 641 AS patients having 12-lead ECG available were further analyzed in a precise manner. Results Among the 641 AS patients with 12-lead ECG available for detecting cardiac abnormalities, 14 were identified as having PSVT, including 3 with WPW syndrome and 1 having a WPW (ventricular preexcitation) ECG pattern. A higher proportion of AS patients presented with PSVT (21.8/1000) compared with a general population-based study (2.25/1000). Also, AS patients demonstrated a higher prevalence of WPW syndrome or WPW pattern (6.24/1000) than found in general population-based studies (0.9 to 1.5/1000). Ankylosing spondylitis patients with PSVT or WPW syndrome had significantly higher rates of peripheral arthritis (78.6%; P = 0.002), acute anterior uveitis (64.3%; P = 0.003), bamboo spine (64.3%; P = 0.001), and other cardiovascular disorders (85.7%; P Conclusions Ankylosing spondylitis patients had a high probability of developing PSVT and WPW syndrome. Detailed ECG and electrophysiological examinations are required for early detection of PSVT and WPW syndrome for prompt resolution of potentially life-threatening complications in all AS patients, especially those presenting with the symptoms of palpitation, dizziness, dyspnea, or syncope.

A boy with autism, growth and developmental retardation was brought to our clinic. He was diagnosed with CHARGE syndrome. Subsequently, various therapies were introduced when he was 5 months old yet the developmental delays persisted. Gastrointestinal problems such as frequent post-prandial vomiting and severe constipation were noted as well. At the age of 42 months, the boy was subjected to a gluten and casein-free diet. Soybean milk and rice were substituted for cow's milk, bread and noodles. After 2.5 months, interpersonal relations including eye to eye contact and verbal communication improved. At 5.5 months the boy was capable of playing and sharing toys with his sibling and other children, behavior noted to be closer to that of an unaffected child. In addition, the decreased frequency of postprandial vomiting led to a significant increment in body weight, body height (from below the third percentile to the tenth percentile) and vitality after 11 months on the diet. In view of the lack of consensus on the benefits of dietary intervention in patients with autism, we are suggesting an adjuvant therapy that is simple, safe and economical. In addition, the therapy may be more feasible in Taiwan as opposed to western countries because of cultural factors such as dietary preference and product availability.

Objective.We investigated the etiological association and clinical characteristics of apical pulmonary fibrosis in ankylosing spondylitis (AS).Methods.We reviewed medical records of 2136 consecutive patients diagnosed with AS at a tertiary medical center. Clinical and radiographic characteristics were analyzed for evidence of apical lung fibrosis on chest radiographs.Results.Of 2136 patients with AS, 63 (2.9%) developed apical lung fibrosis, of which chronic infections were the cause in 41 and AS inflammation predisposed the fibrosis in 22 patients. Tuberculosis (TB) infection was considered to be the cause of apical lung fibrosis in 40 patients (63.5%) including 19 with bacteriologically-proven TB and 21 with chest radiographs suggestive of TB. Two were identified as having non-TB mycobacterial infection and one asAspergillusinfection. Lung cavity lesion appeared to be a crucial differentiator (p = 0.009, odds ratio 7.4, 95% CI 1.5–36.0) between TB infection and AS inflammation-induced apical fibrosis.Conclusion.Our study suggests that TB, instead ofAspergillus, is the most common pulmonary infection in patients with AS presenting with apical lung fibrosis. AS-associated apical lung fibrosis may mimic pulmonary TB infection. Thus, bacteriological survey and serial radiological followup of lung fibrocavitary lesions are critical for accurate diagnosis and treatment.