T cell expressions of aberrant gene signatures and Co-inhibitory receptors (Co-IRs) as predictors of renal damage and lupus disease activity.

BACKGROUND: Systemic lupus erythematosus (SLE) is distinguished by an extensive range of clinical heterogeneity with unpredictable disease flares and organ damage. This research investigates the potential of aberrant signatures on T cell genes, soluble Co-IRs/ligands, and Co-IRs expression on T cells as biomarkers for lupus disease parameters. METHODS: Comparative transcriptome profiling analysis of non-renal and end-stage renal disease (ESRD) phenotypes of SLE was performed using CD4 + and CD8 + cDNA microarrays of sorted T cells. Comparing the expression of Co-IRs on T cells and serum soluble mediators among healthy and SLE phenotypes. RESULTS: SLE patients with ESRD were downregulated CD38, PLEK, interferon-γ, CX3CR1, FGFBP2, and SLCO4C1 transcripts on CD4 + and CD8 + T cells simultaneously and NKG7, FCRL6, GZMB/H, FcγRIII, ITGAM, Fas ligand, TBX21, LYN, granulysin, CCL4L1, CMKLR1, HLA-DRß, KIR2DL3, and KLRD1 in CD8 T cells. Pathway enrichment and PPI network analyses revealed that the overwhelming majority of Differentially Expressed Genes (DEGs) have been affiliated with novel cytotoxic, antigen presentation, and chemokine-cell migration signature pathways. CD8 + GZMK + T cells that are varied in nature, including CD161 + Mucosal-associated invariant T (MAIT) cells and CD161- aged-associated T (Taa) cells and CD161-GZMK + GZMB + T cells might account for a higher level of GZMK in CD8 + T cells associated with ESRD. SLE patients have higher TIGIT + , PD1 + , and lower CD127 + cell percentages on CD4 + T cells, higher TIM3 + , TIGIT + , HLA-DR + cell frequency, and lower MFI expression of CD127, CD160 in CD8 T cells. Co-IRs expression in T cells was correlated with soluble PD-1, PDL-2, and TIM3 levels, as well as SLE disease activity, clinical phenotypes, and immune-therapy responses. CONCLUSION: The signature of dysfunctional pathways defines a distinct immunity pattern in LN ESRD patients. Expression levels of Co-IRs in peripheral blood T cells and serum levels of soluble PD1/PDL-2/TIM3 can serve as biomarkers for evaluating clinical parameters and therapeutic responses.

Functional MICA Variants Are Differentially Associated with Immune-Mediated Inflammatory Diseases.

As the principal ligand for NKG2D, MICA elicits the recruitment of subsets of T cells and NK cells in innate immunity. MICA gene variants greatly impact the functionality and expression of MICA in humans. The current study evaluated whether MICA polymorphisms distinctively influence the pathogenesis of psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in Taiwanese subjects. The distributions of MICA alleles and levels of serum soluble NKG2D were compared between healthy controls and patients with PSO, RA, and SLE, respectively. The binding capacities and cell surface densities of MICA alleles were assessed by utilizing stable cell lines expressing four prominent Taiwanese MICA alleles. Our data revealed that MICA*010 was significantly associated with risks for PSO and RA (PFDR = 1.93 × 10-15 and 0.00112, respectively), while MICA*045 was significantly associated with predisposition to SLE (PFDR = 0.0002). On the other hand, MICA*002 was associated with protection against RA development (PFDR = 4.16 × 10-6), while MICA*009 was associated with a low risk for PSO (PFDR = 0.0058). MICA*002 exhibited the highest binding affinity for NKG2D compared to the other MICA alleles. Serum concentrations of soluble MICA were significantly elevated in SLE patients compared to healthy controls (p = 0.01). The lack of cell surface expression of the MICA*010 was caused by its entrapment in the endoplasmic reticulum. As a prevalent risk factor for PSO and RA, MICA*010 is deficient in cell surface expression and is unable to interact with NKG2D. Our study suggests that MICA alleles distinctively contribute to the pathogenesis of PSO, RA, and SLE in Taiwanese people.

Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis.

Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IR T cells and to assess the levels of serum soluble PD-1, PDL-2, and TIM3 in Taiwanese RA patients. METHODS: Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and TIM3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high-sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1/PDL-2/TIM3. RESULTS: In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT in CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 in CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests were revealed to be correlated with hsCRP: CD4/CD279 MFI, CD4/CD279%, CD4/TIM3%, CD8/TIM3%, CD8/TIM3 MFI, CD8/LAG3%, and CD8+HLA-DR+CD38+%. CD8/LAG3 and CD8/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4/CD127 MFI, CD8/CD279%, and CD8/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR (p = 0.0084, N = 46), DAS28-CRP (p = 0.007, N = 47), and hsCRP (p = 0.002, N = 56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% (p = 0.0089, N = 46) and CD8+ TIM3+% (p = 0.0305, N = 46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% (p < 0.0001, N = 31) and CD3+CD279+% (p = 0.0084, N = 30). CONCLUSIONS: Co-IR expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and TIM3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA.

Development of a tool for monitoring the jaw-opening pace and preliminary comparison the pace between young and old ages.

OBJECTIVES: Studies have demonstrated that high-speed jaw-opening exercises are effective in improving swallowing function. However, there has been no objective tool available for monitoring jaw-opening pace. This study aimed to develop an objective tool for monitoring and validating jaw-opening pace and compare it between young and old ages from different age groups. MATERIALS AND METHODS: A load cell plug-in jaw pad connected to an automatic recording and analysis system was used to record jaw-opening motions for offline analysis. We recruited 58 healthy volunteers from different age groups (20-39 y/o; 40-59y/o; 60-79y/o). During a 2-min recording session, each participant was instructed to fully open and close their jaw as quickly as possible while wearing a sensor. Bland-Altman plot, paired t-test and Pearson's correlation test were used to compare the number of jaw-opening motions between manual counting and automatic software analysis. The number of jaw-opening motions during the 2-min recording was compared between the three age groups. RESULTS: Automated analysis of jaw-opening pace was efficient and equally comparable with the traditional manual counting method across the three age groups. A declining trend in jaw-opening pace among the old age group was found but with no statistically significant difference. CONCLUSIONS: A jaw-opening motion monitoring tool with reliable automatic pace analysis software was validated in young and old ages. The jaw-opening pace demonstrated a tendency to decline with age. CLINICAL RELEVANCE: This monitoring tool can also be used to provide visual feedback during jaw-opening motion training in pace control.

Multi-Sensor Respiratory-Swallow Telecare System for Safe Feeding in Different Trunk Inclinations: System Development and Clinical Application.

Proper positioning is especially important to ensure feeding and eating safely. With many nursing facilities restricting visitations and close contact during the coronavirus pandemic, there is an urgent need for remote respiratory-swallow monitoring. This study aimed to develop a semiautomatic feeding telecare system that provides instant feedback and warnings on-site and remotely. It also aimed to analyze the effects of trunk positions on respiratory-swallow coordination. A signal collector with multiple integrated sensors for real-time respiratory-swallow monitoring and warning was developed. A repeated measures design was implemented to evaluate the effects of trunk inclination angles on the swallow-related functions. Significant differences in inclination angles were discovered for swallowing apnea (p = 0.045) and total excursion time of thyroid cartilage (p = 0.037), and pairwise comparisons indicated that these differences were mostly present at 5° to 45°. Alerts were triggered successfully when undesired respiratory patterns or piecemeal occurred. The results indicated that a care recipient can swallow more easily when sitting upright (5°) than when leaning backward (45°). This telecare system provides on-site and remote respiratory-swallow monitoring and alerting for residents in care facilities and can serve as a pipeline for the early screening of swallowing dysfunction.

Can rehabilitation adherence among stroke patients be measured using a single item?

AIMS AND OBJECTIVES: 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. BACKGROUND: Adherence to therapy is a primary determinant of treatment success. There are no standard instruments for measuring rehabilitation adherence available for stroke patients. DESIGN: Prospective longitudinal study. METHODS: 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. RESULTS: Logbook records had a fair correlation (rs  = .23, p = .04) with the single-item rehabilitation adherence measurements. There was moderate agreement (kappa = 0.42, p < .001) between caregiver and patient assessments and fair agreement (kappa = 0.29, p = .017) between caregiver and physical therapist assessments of patients' rehabilitation adherence levels. Perfect rehabilitation adherence, based on the logbook and single-item measurements, predicted better scores for self-care ability and quality of life than imperfect rehabilitation adherence during 6 months after inclusion. CONCLUSIONS: There 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. RELEVANCE TO CLINICAL PRACTICE: 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. PATIENT OR PUBLIC CONTRIBUTION: 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. TRIAL REGISTRATION DETAILS: Not applicable.

The correlation between two occlusal analyzers for the measurement of bite force.

BACKGROUND: Occlusal force represents masticatory function. Using quantifiable occlusal indicators provides a more objective occlusal force evaluation. In the recent dental practice, digital methods such as the Dental Prescale II (DP2, GC Corp., Tokyo, Japan) and T-scan (T-Scan III v8; Tekscan Inc.) are commonly used in clinics to evaluate treatment outcomes. The T-scan provides the relative bite force (%) compared to the maximal bite force on individual teeth or the unilateral arch. The DP2 can quantify occlusal force, measured in newtons (N), on the half arch or the overall bite, but it is difficult to identify the bite force on an individual tooth. It is difficult to select a device that fulfils all the requirements to record occlusal force. This study aimed to investigate the association between the bite measured by the DPS2 and T-scan to determine whether the measured bite force is comparable through calculation. METHODS: A total of 80 healthy adults, including 41 women and 39 men with a mean age of 38.2, were requested to bite pressure sensitive film sheets ten minutes apart. Linear regression analysis was used to estimate the measured bite force by the DP2 and T-scan. RESULTS: There was a significant positive correlation between the occlusal force measured by the DP2 and T-scan (P < 0.01) when intercept was equal to zero as confounders were adjused. These results provided the comparability of the measured occlusal forces determined by the DP2 and T-scan. CONCLUSION: The estimated bite force determined by DP2 and T-Scan is convertible using the linear equation from this study to increase the value for clinical applications. The estimated bite force from the two quantifiable occlusal indicators are comparable. The two commercially available quantifiable occlusal indicators can be fully adapted to all clinical requirements according to this result.

Functional ERAP1 Variants Distinctively Associate with Ankylosing Spondylitis Susceptibility under the Influence of HLA-B27 in Taiwanese.

Epistasis of ERAP1 single nucleotide variations (SNVs) and HLA-B27 has been linked to ankylosing spondylitis susceptibility (AS). The current study examined how prevalent ERAP1 allelic variants (SNV haplotypes) in Taiwan affect ERAP1 functions and AS susceptibility in the presence or absence of HLA-B27. Sanger sequencing was used to discover all ERAP1 coding SNVs and common allelic variants in Taiwanese full-length cDNAs from 45 human patients. For the genetic association investigation, TaqMan genotyping assays were utilized to establish the genotypes of ERAP1 SNVs in 863 AS patients and 1438 healthy controls. Ex vivo biological analysis of peripheral blood mononuclear cells from homozygous donors of two common-risk ERAP1 allelic variants was performed. Two common-risk ERAP1 allelic variants were also cloned and functionally studied. In Taiwanese, eleven frequent ERAP1 SNVs and six major ERAP1 allelic variants were discovered. We discovered that in Taiwanese, the most prevalent ERAP1-001 variant with 56E, 127R, 276I, 349M, 528K, 575D, 725R, and 730Q interacting with HLA-B27 significantly contributed to the development of AS. In HLA-B27 negative group, however, the second most prevalent ERAP1-002 variant with 56E, 127P, 276M, 349M, 528R, 575D, 725R, and 730E was substantially related with an increased risk of AS. Ex vivo and in vitro research demonstrated that ERAP1 allelic variants have a significant impact on ERAP1 functions, suggesting that ERAP1 plays a role in the development of AS. In an HLA-B27-dependent manner, common ERAP1 allelic variants are related with AS susceptibility.

Genetic effects of B3GNT2 on ankylosing spondylitis susceptibility and clinical manifestations in Taiwanese.

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.

MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese.

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.

Noninvasive Measurement of Tongue Pressure and Its Correlation with Swallowing and Respiration.

Tongue pressure plays a critical role in the oral and pharyngeal stages of swallowing, contributing considerably to bolus formation and manipulation as well as to safe transporting of food from the mouth to the stomach. Smooth swallowing relies not only on effective coordination of respiration and pharynx motions but also on sufficient tongue pressure. Conventional methods of measuring tongue pressure involve attaching a pressure sheet to the hard palate to monitor the force exerted by the tongue tip against the hard palate. In this study, an air bulb was inserted in the anterior oral cavity to monitor the pressure exerted by the extrinsic and intrinsic muscles of the tongue. The air bulb was integrated into a noninvasive, multisensor approach to evaluate the correlation of the tongue pressure with other swallowing responses, such as respiratory nasal flow, submental muscle movement, and thyroid cartilage excursion. An autodetection program was implemented for the automatic identification of swallowing patterns and parameters from each sensor. The experimental results indicated that the proposed method is sensitive in measuring the tongue pressure, and the tongue pressure was found to have a strong positive correlation with the submental muscle movement during swallowing.

Correlation of Temporal Parameters of Laryngeal Excursion by Using Force-Sensing Resistor Sensors with Hyoid Motion in Videofluoroscopic Swallowing Study.

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 < 0.001). Only VT1-V1 and FT1-F1 in women displayed a significant difference (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.

Does the M.D. Anderson Dysphagia Inventory correlate with dysphagia-limit and the Unified Parkinson Disease Rating Scale in early-stage Parkinson's disease?

BACKGROUND: Dysphagia is a common and critical condition that occurs in Parkinson's disease (PD), and it may appear in early stages. However, few reliable swallowing-related questionnaires are currently available. Therefore, finding efficient questionnaires for surveying dysphagia during the early stages of PD is necessary. PURPOSE: This prospective study aimed to identify the correlations between the M.D. Anderson Dysphagia Inventory (MDADI) with dysphagia limit (DL) and the Unified Parkinson Disease Rating Scale (UPDRS) in early-stage PD. METHODS: Forty-two patients with early-stage PD were recruited from a medical center. Data were collected for analysis of swallowing-related quality of life using the MDADI, symptom severity using the UPDRS, and DL using a noninvasive swallowing-respiration assessment system. RESULTS: Our results showed that the MDADI, including its composite and subscales, was not correlated with DL. The composite scores of the MDADI were moderately correlated with the total score of the UPDRS (r = -0.504; p < 0.05) as well as with the second and third sections of the UPDRS scores (r = -0.453 to -0.478; p < 0.05). These results indicated that the impaired MDADI score can predict symptom severity (UPDRS), especially in activities of daily life and motor function. CONCLUSION: The impaired MDADI for early-stage PD was determined, and decreased DL as a presentation of dysphagia could not be reflected by the MDADI. The MDADI may be used as a quick and convenient questionnaire for predicting the severity of early-stage PD, but not for the screening of early or subclinical dysphagia.

Using Wearable and Non-Invasive Sensors to Measure Swallowing Function: Detection, Verification, and Clinical Application.

BACKGROUND: A widely used method for assessing swallowing dysfunction is the videofluoroscopic swallow study (VFSS) examination. However, this method has a risk of radiation exposure. Therefore, using wearable, non-invasive and radiation-free sensors to assess swallowing function has become a research trend. This study addresses the use of a surface electromyography sensor, a nasal airflow sensor, and a force sensing resistor sensor to monitor the coordination of respiration and larynx movement which are considered the major indicators of the swallowing function. The demand for an autodetection program that identifies the swallowing patterns from multiple sensors is raised. The main goal of this study is to show that the sensor-based measurement using the proposed detection program is able to detect early-stage swallowing disorders, which specifically, are useful for the assessment of the coordination between swallowing and respiration. METHODS: Three sensors were used to collect the signals from submental muscle, nasal cavity, and thyroid cartilage, respectively, during swallowing. An analytic swallowing model was proposed based on these sensors. A set of temporal parameters related to the swallowing events in this model were defined and measured by an autodetection algorithm. The verification of this algorithm was accomplished by comparing the results from the sensors with the results from the VFSS. A clinical application of the long-term smoking effect on the swallowing function was detected by the proposed sensors and the program. RESULTS: The verification results showed that the swallowing patterns obtained from the sensors strongly correlated with the laryngeal movement monitored from the VFSS. The temporal parameters measured from these two methods had insignificant delays which were all smaller than 0.03 s. In the smoking effect application, this study showed that the differences between the swallowing function of smoking and nonsmoking participants, as well as their disorders, is revealed by the sensor-based method without the VFSS examination. CONCLUSIONS: This study showed that the sensor-based non-invasive measurement with the proposed detection algorithm is a viable method for temporal parameter measurement of the swallowing function.

Features of trunk muscle weakness in patients with ankylosing spondylitis: A cross-sectional study.

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 <3); and 15 in the syndesmophyte group, m-SASSS ≥24), and 22 healthy controls were recruited. All subjects received assessments of maximum isometric strength of trunk flexor and extensor muscles at a variety of trunk postures measured by an isokinetic device. RESULTS: Under all examined trunk postures, the syndesmophyte AS patient group had the lowest isometric trunk muscle strength among the three groups. The flexion/extension ratio, defined by the ratio between isometric trunk flexor and extensor strengths, was highest among the three groups. CONCLUSIONS: Trunk muscle strength significantly decreases in patients with syndesmophyte AS. The decrease of trunk muscle is inhomogeneous, which is more profound in extensor than in flexor muscles.

Association of Genetic Variants of RANK, RANKL, and OPG with Ankylosing Spondylitis Clinical Features in Taiwanese.

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.

Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese.

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.

Home-Based Orolingual Exercise Improves the Coordination of Swallowing and Respiration in Early Parkinson Disease: A Quasi-Experimental Before-and-After Exercise Program Study.

Introduction: The coordination of swallowing and respiration is important for safety swallowing without aspiration. This coordination was affected in Parkinson disease (PD). A noninvasive assessment tool was used to investigate the effect of an easy-to-perform and device-free home-based orolingual exercise (OLE) program on swallowing and respiration coordination in patients with early-stage PD. Materials and Methods: This study had a quasi-experimental before-and-after exercise program design. Twenty six patients with early-stage PD who were aged 62.12 ± 8.52 years completed a 12-week home-based OLE program. A noninvasive assessment tool was used to evaluate swallowing and respiration. For each patient, we recorded and analyzed 15 swallows (3 repeats of 5 water boluses: 1, 3, 5, 10, and 20 mL) before and after the home-based OLE program. Oropharyngeal swallowing and its coordination with respiration were the outcome measures. The frequency of piecemeal deglutition, pre- and post-swallowing respiratory phase patterns, and parameters of oropharyngeal swallowing and respiratory signals (swallowing respiratory pause [SRP], onset latency [OL], total excursion time [TET], excursion time [ET], second deflexion, amplitude, and duration of submental sEMG activity, and amplitude of laryngeal excursion) were examined. Results: The rate of piecemeal deglutition decreased significantly when swallowing 10- and 20-mL water boluses after the program. In the 1-mL water bolus swallowing trial, the rate of protective pre- and post-swallowing respiratory phase patterns was significantly higher after the program. For the parameters of oropharyngeal swallowing and respiratory signals, only the amplitude of laryngeal excursion was significantly lower after the program. Moreover, the volume of the water bolus significantly affected the SRP and duration of submental sEMG when patients swallowed three small water bolus volumes (1, 3, and 5 mL). Conclusion: The home-based OLE program improved swallowing and its coordination with respiration in patients with early-stage PD, as revealed using a noninvasive method. This OLE program can serve as a home-based program to improve swallowing and respiration coordination in patients with early-stage PD.

Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese.

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.

Non-invasive assessment determine the swallowing and respiration dysfunction in early Parkinson's disease.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.