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Abstract This exploratory study aimed to examine the impact of abatacept treatment on bone structure in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). RA patients initiating either abatacept or newly introduced csDMARDs were enrolled in this prospective, non-randomized, two-group study. Bone structure in the 2nd and 3rd metacarpal heads was assessed using HR-pQCT at 0, 6, and 12 months after enrollment. Synovitis was evaluated using musculoskeletal ultrasound and MRI. The adjusted mean between-group differences (abatacept–csDMARDs group) were estimated using a mixed-effect model. Thirty-five patients (abatacept group: n = 15; csDMARDs group: n = 20) were analyzed. Changes in erosion volume, depth and width were numerically smaller in the abatacept group compared to the csDMARDs group (adjusted mean between-group differences: − 1.86 mm3, − 0.02 mm, and − 0.09 mm, respectively). Over a 12-month period, 5 erosions emerged in the csDMARDs group, while only 1 erosion appeared in the abatacept group. Compared to csDMARDs, abatacept better preserved bone microarchitecture; several components of bone microarchitecture were significantly worsened at 6 months in the csDMARDs group, but were not deteriorated at 6 months in the abatacept group. Changes in synovitis scores were similar between the two treatment groups. Our results indicate that abatacept prevented the progression of bone erosion including new occurrence, and also prevented worsening of bone strength independently with synovitis compared to csDMARDs including MTX. Thus, abatacept treatment may provide benefits not only in inhibiting the progress of bone erosion but also in preventing bone microarchitectural deterioration.

BackgroundFatty infiltration (FI) of rotator cuff muscles in patients with rotator cuff tears is an important imaging factor for determining surgical indications. However, the associations between FI grade and the size or location of adjacent rotator cuff tears are not well-known. This study aimed to primarily determine whether tear size and location, especially for the SSc tendon, are associated with FI of adjacent rotator cuff muscles. The secondary aim was to clarify which patient factors are associated with rotator cuff muscle FI in rotator cuff tear cases.MethodsThis study examined 373 shoulders of 348 patients (264 males and 109 females; mean age of 62.8 years) who underwent arthroscopic rotator cuff surgery. The FI grades of the supraspinatus (SSP), infraspinatus (ISP), and subscapularis (SSc) muscles were assessed using preoperative magnetic resonance imaging (MRI) using the Goutallier classification modified by Fuchs. According to the preoperative MRI and intraoperative findings, the tear size of the posterior–superior rotator cuff (SSP–ISP) was classified using a modified six-grade scale of the Cofield classification, and that of the SSc tear was classified using a six-grade scale according to the Lafosse classification. Age at surgery, sex, body mass index (BMI), presence of diabetes mellitus (DM) or hyperlipidemia (HL), trauma history, and duration of symptoms were investigated.ResultsThe FI grades of the SSP, ISP, and SSc were significantly associated with the size of the tears in those muscles (all P

Abstract Background Dengue virus serotype 2 (DENV-2) was the major serotype in the 2015 dengue outbreak in Taiwan, while DENV-1 and DENV-3 were dominant between 2005 and 2014. We aimed to investigate whether DENV-2 contributed to disease severity and mortality in the outbreak in Kaohsiung city, Taiwan. Methods We collected serum samples from dengue patients to detect the presence of DENV and determine the serotypes by using quantitative reverse transcription-polymerase chain reaction. Our cohorts comprised 105 DENV-1-infected cases and 1,550 DENV-2-infected cases. Demographic data, DENV serotype, and comorbidities were covariates for univariate and multivariate analyses to explore the association with severity and mortality. Results The results suggested that DENV-1 persisted and circulated, while DENV-2 was dominant during the dengue outbreak that occurred between September and December 2015. However, DENV-2 did not directly contribute to either severity or mortality. Aged patients and patients with diabetes mellitus (DM) or moderate to severe chronic kidney disease (CKD) had a higher risk of developing severe dengue. The mortality of dengue patients was related to a higher Charlson comorbidity index score and severe dengue. Among DENV-2-infected patients and older patients, preexisting anti-dengue IgG, DM, and moderate to severe CKD were associated with severe dengue. Moreover, female sex and severe dengue were associated with a significantly higher risk of death. Conclusions Our findings highlight the importance of timely serological testing in elderly patients to identify potential secondary infections and focus on the meticulous management of elderly patients with DM or moderate to severe CKD to reduce dengue-related death.

Background: Accurately identifying risk factors that predict fatality in dengue is crucial for patient triage and clinical management. Our objective was to identify predictors of death associated with dengue and investigate the clinical characteristics and risk factors among patients with chronic kidney disease (CKD) who died from dengue. Methods: A multicenter longitudinal observation study conducted from 2008 to 2019. Results: A total of 1272 patients (113 who died and 1186 who recovered) diagnosed with dengue were included. Old age, CKD, and an elevated white blood cell count at hospital presentation were identified as independent predictors of in-hospital mortality among individuals infected with the dengue virus. In a subgroup analysis of 138 patients with CKD infected with dengue virus, 64 (46.3%) patients died, with 46 (33.3%) patients dying within 7 days after symptom onset. Among 64 fatal dengue patients with CKD, 34.4% were in stages 2 and 3 of kidney disease, 51.5% were in stages 4 and 5, and 14.1% had end stage renal disease as per the classification by Kidney Disease Improving Global Outcomes. Multivariate analysis revealed that initial altered consciousness, pulmonary edema, and leukocytosis during hospitalization were independently associated with in-hospital mortality in CKD patients infected with the dengue virus. Leukocytosis during hospitalization and severe hepatitis were independent risk factors for death within 7 days after dengue illness onset in CKD patients. Conclusions: This study offers valuable insights into predictors linked to fatality in dengue and reinforces the importance of optimizing patient triage to improve the quality of care.

Abstract Background The risks of metal release due to fretting and corrosion at the head–neck junction and consequent adverse local tissue reaction (ALTR) have concerns in metal-on-polyethylene (MoP) total hip arthroplasty (THA). Although trunnions have become thinner in diameter to increase the range of motion, it has remained unclear whether this change affects metal release and ALTR in vivo. This study aimed to investigate serum metal concentrations and the prevalence of ALTR in MoP THA with a 9/10-mm stem trunnion. Patients and methods A consecutive series of 37 hips that underwent THA using MoP grafted with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) with a 9/10-mm trunnion stem were retrospectively reviewed. Serum metal levels were assessed and compared with those in MoP THA with a 10/12-mm trunnion stem. ALTR was diagnosed with serum metal levels and cross-sectional images. The factors associated with serum metal levels were also assessed. Results The median serum cobalt and chromium levels were 1.5 μg/L and 1.0 μg/L in the 9/10-mm group and 0.2 μg/L and 0.4 μg/L in the 10/12-mm group, respectively. ALTR was found in 5 hips of 3 patients. Revision surgery was performed in 4 hips, and all stem trunnions and femoral heads showed severe corrosion. Postoperative walking ability was associated with serum metal levels. Conclusion It was found that a 9/10-mm stem trunnion with MoP grafted with PMPC had high risks of metal release in primary THA. Careful follow-up and cross-sectional imaging are needed to detect ALTR for early revision.

Abstract Background This exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods In this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety. Results In total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2–3 metacarpal heads at 6 months was − 0.57 mm (− 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs − 0.22 mm (− 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: − 0.35 mm [− 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2–3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%). Conclusions Although the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. Japan Registry for Clinical Trials, jRCTs071180018

Chronic kidney disease (CKD) negatively affects bone strength; however, the osteoporotic conditions in patients with CKD are not fully understood. Moreover, the changes in bone microstructure between pre-dialysis and dialysis are unknown. High-resolution peripheral quantitative computed tomography (HR-pQCT) reveals the three-dimensional microstructures of the bone. We aimed to evaluate bone microstructures in patients with different stages of CKD. This study included 119 healthy men and 40 men admitted to Nagasaki University Hospital for inpatient education or the initiation of hemodialysis. The distal radius and tibia were scanned with HR-pQCT. Patient clinical characteristics and bone microstructures were evaluated within 3 months of initiation of hemodialysis (in patients with CKD stage 5 D), patients with CKD stage 4–5, and healthy volunteers. Cortical bone parameters were lower in the CKD group than in healthy controls. Tibial cortical and trabecular bone parameters (cortical thickness, cortical area, trabecular volumetric bone mineral density, trabecular-bone volume fraction, and trabecular thickness) differed between patients with CKD stage 5 D and those with CKD stage 4–5 (p

The proper treatment of hadronic resonances plays an important role for many aspects of heavy ion collisions. We expect this to be the case also for hadronization, due to the large degeneracies of excited states, and the abundant production of hadrons from their decays. We show how a comprehensive treatment of excited meson states can be incorporated into quark recombination, and in extension, into Hybrid Hadronization. We discuss in detail the quantum mechanics of forming excited states, utilizing the Wigner distribution functions of angular momentum eigenstates of isotropic 3-D harmonic oscillators. We describe how resonance decays can be handled, based on a set of minimal assumptions, by creating an extension of hadron decays in PYTHIA 8. Finally, we present a study of hadron production by jets using PYTHIA and Hybrid Hadronization with excited mesons up to orbital angular momentum L = 4. We find that states up to L = 2 are produced profusely by quark recombination.

Abstract Background Kneeling is necessary for certain religious and ceremonial occasions, crouching work, and gardening, which many people take part in worldwide. However, there have been few reports about kneeling activities. The purpose of this study was to clarify the kinematics of kneeling. Methods The subjects were 15 healthy young males. Kneeling activity was analysed within a knee flexion angle from 100° to maximum flexion (maxflex, mean ± SD = 161.3 ± 3.2°). The kinematic and contact point (CP) analyses were performed using a 2D/3D registration method, in which a 3D bone model created from computed tomography images was matched to knee lateral fluoroscopic images and analysed on a personal computer. Results In the kinematic analysis, the femur translated 37.5 mm posteriorly and rotated 19.8° externally relative to the tibia during the knee flexion phase. During the knee extension phase, the femur translated 36.4 mm anteriorly, which was almost the same amount as in the knee flexion phase. However, the femur rotated only 7.4° internally during the knee extension phase. In the CP analysis, the amount of anterior translation of the CP in the knee extension phase was greater in the medial CP and smaller in the lateral CP than that of posterior translation in the knee flexion phase. Conclusions In kneeling, there was a difference in the rotational kinematics between the flexion phase and the extension phase. The kinematic difference between the flexion and extension phases may have some effect on the meniscus and articular cartilage.

Abstract Background Dengue epidemics is affected by vector-human interactive dynamics. Infectious disease prevention and control emphasize the timing intervention at the right diffusion phase. In such a way, control measures can be cost-effective, and epidemic incidents can be controlled before devastated consequence occurs. However, timing relations between a measurable signal and the onset of the pandemic are complex to be discovered, and the typical lag period regression is difficult to capture in these complex relations. This study investigates the dynamic diffusion pattern of the disease in terms of a probability distribution. We estimate the parameters of an epidemic compartment model with the cross-infection of patients and mosquitoes in various infection cycles. We comprehensively study the incorporated meteorological and mosquito factors that may affect the epidemic of dengue fever to predict dengue fever epidemics. Results We develop a dual-parameter estimation algorithm for a composite model of the partial differential equations for vector-susceptible-infectious-recovered with exogeneity compartment model, Markov chain Montel Carlo method, and boundary element method to evaluate the epidemic periodicity under the effect of environmental factors of dengue fever, given the time series data of 2000–2016 from three cities with a population of 4.7 million. The established computer model of “energy accumulation-delayed diffusion-epidemics” is proven to be effective to predict the future trend of reported and unreported infected incidents. Our artificial intelligent algorithm can inform the authority to cease the larvae at the highest vector infection time. We find that the estimated dengue report rate is about 20%, which is close to the number of official announcements, and the percentage of infected vectors increases exponentially yearly. We suggest that the executive authorities should seriously consider the accumulated effect among infected populations. This established epidemic prediction model of dengue fever can be used to simulate and evaluate the best time to prevent and control dengue fever. Conclusions Given our developed model, government epidemic prevention teams can apply this platform before they physically carry out the prevention work. The optimal suggestions from these models can be promptly accommodated when real-time data have been continuously corrected from clinics and related agents.

Background: Intracranial hemorrhage (ICH) or infarction in dengue cases is rare but very challenging for clinicians. We report these uncommon complications of dengue patients and focused on the significant factors associated with ICH or infarction in dengue patients. Methods: This investigation was a retrospective study of 182 adult dengue patients who received brain computed tomography at three Taiwan hospitals during the 2014 and 2015 dengue outbreaks. This included 13 hemorrhage cases, 26 infarction cases and 143 cases without brain infarction or hemorrhage. Results: Among them, 13 (7.14%) suffered from ICH (6 had subdural hemorrhage, 3 had subarachnoid hemorrhage, 1 had subdural and subarachnoid hemorrhage, and 3 had intracerebral hemorrhage) and 26 (14.3%) had brain infarction. The overall mortality rate was 4/13 (30.8%) in the ICH group and 3/26 (11.5%) in the infarction group. The significant variables from the univariate analysis, including difference between 2014 and 2015, age, history of cerebrovascular accident, bone pain, arthralgia, dizziness, altered consciousness, and a higher Charlson comorbidity score. Multivariate analysis revealed that significant risk factors for ICH/infarction in dengue cases were the year of occurrence, 2014 vs. 2015 (p 4 (p = 0.01, OR = 3.764, 95% CI = 1.364–10.386) and altered consciousness (p 4, especially in the year that a higher frequency of infarction/ICH was observed.

The searching for potential quantum chromodynamics (QCD) phase transition signals is a fundamental goal of on-going experiments on heavy-ion collisions, which is critical to understanding the properties of strongly interacting matter under extreme conditions, the inner structure of compact stars, gravitational waves emitted from neutron star mergers, etc. In particular, the beam energy scan program carried out at the Relativistic Heavy-Ion Collider (RHIC) provides a unique tool that enables studies into the QCD phase diagram and the conjectured QCD critical point. Besides the event-by-event fluctuation of conserved charges, which has been widely accepted as a useful study of the QCD critical point, the production of light nuclei can serve as a sensitive observable to the QCD phase transitions in high-energy heavy-ion collisions. The density fluctuation and correlation among nucleons are automatically encoded in the production of light nuclei in heavy-ion collisions. This study aims to demonstrate how to probe QCD phase transition with light nuclei production in heavy-ion collisions. The progress of studies in this area over the last few years is reviewed. The nucleon coalescence model provides a suitable tool for the study of the effects of density fluctuation/correlation on light nuclei production. A transport model based on the Nambu-Jona-Lasinio (NJL) model is developed to simulate the occurrence of the first-order chiral phase transition in heavy-ion collisions. Within the coalescence model for light nuclei production, the yield ratio NtNp/Nd2 of protons (p), deuterons(d), and tritons (t) is shown to be sensitive to the nucleon density fluctuation and correlation and can function as a good probe to the non-smooth QCD phase transition. The production of light nuclei in heavy-ion collisions encodes the information about baryon density fluctuations and correlations, and enhancements of the yield ratio NtNp/Nd2 could serve as an indicator for the occurrence of a first-order or second-order QCD phase transition.

Global travel and climate change have drastically increased the number of countries with endemic or epidemic dengue. The largest dengue outbreak in Taiwan, with 43,419 cases and 228 deaths, occurred in 2015. Practical and cost-effective tools for early prediction of clinical outcomes in dengue patients, especially the elderly, are limited. This study identified the clinical profile and prognostic indicators of critical outcomes in dengue patients on the basis of clinical parameters and comorbidities. A retrospective cross-sectional study was conducted in a tertiary hospital from 1 July 2015 to 30 November 2015. Patients diagnosed with dengue were enrolled, and the initial clinical presentations, diagnostic laboratory data, details of the underlying comorbidities, and initial management recommendations based on 2009 World Health Organization (WHO) guidelines were used to evaluate prognostic indicators of critical outcomes in dengue patients. Dengue patients from another regional hospital were used to evaluate accuracy. A group B (4 points) classification, temperature < 38.5 °C (1 point), lower diastolic blood pressure (1 point), prolonged activated partial thromboplastin time (aPTT) (2 points), and elevated liver enzymes (1 point) were included in the scoring system. The area under the receiver operating characteristic curve of the clinical model was 0.933 (95% confidence interval [CI]: 0.905–0.960). The tool had good predictive value and clinical applicability for identifying patients with critical outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have originated in Wuhan City, Hubei Province, China, in December 2019. Infection with this highly dangerous human-infecting coronavirus via inhalation of respiratory droplets from SARS-CoV-2 carriers results in coronavirus disease 2019 (COVID-19), which features clinical symptoms such as fever, dry cough, shortness of breath, and life-threatening pneumonia. Several COVID-19 waves arose in Taiwan from January 2020 to March 2021, with the largest outbreak ever having a high case fatality rate (CFR) (5.95%) between May and June 2021. In this study, we identified five 20I (alpha, V1)/B.1.1.7/GR SARS-CoV-2 (KMUH-3 to 7) lineage viruses from COVID-19 patients in this largest COVID-19 outbreak. Sequence placement analysis using the existing SARS-CoV-2 phylogenetic tree revealed that KMUH-3 originated from Japan and that KMUH-4 to KMUH-7 possibly originated via local transmission. Spike mutations M1237I and D614G were identified in KMUH-4 to KMUH-7 as well as in 43 other alpha/B.1.1.7 sequences of 48 alpha/B.1.1.7 sequences deposited in GISAID derived from clinical samples collected in Taiwan between 20 April and July. However, M1237I mutation was not observed in the other 12 alpha/B.1.1.7 sequences collected between 26 December 2020, and 12 April 2021. We conclude that the largest COVID-19 outbreak in Taiwan between May and June 2021 was initially caused by the alpha/B.1.1.7 variant harboring spike D614G + M1237I mutations, which was introduced to Taiwan by China Airlines cargo crew members. To our knowledge, this is the first documented COVID-19 outbreak caused by alpha/B.1.1.7 variant harboring spike M1237I mutation thus far. The largest COVID-19 outbreak in Taiwan resulted in 13,795 cases and 820 deaths, with a high CFR, at 5.95%, accounting for 80.90% of all cases and 96.47% of all deaths during the first 2 years. The high CFR caused by SARS-CoV-2 alpha variants in Taiwan can be attributable to comorbidities and low herd immunity. We also suggest that timely SARS-CoV-2 isolation and/or sequencing are of importance in real-time epidemiological investigations and in epidemic prevention. The impact of D614G + M1237I mutations in the spike gene on the SARS-CoV-2 virus spreading as well as on high CFR remains to be elucidated.

Abstract Purpose Although a cementless modular prosthesis has shown reliable results, cases of unstable fixation and revision due to aseptic loosening were observed in our institute. The purpose of this study was to clarify the causes of unstable fixation of the prosthesis. Methods A total of 144 patients (154 hips) who underwent total hip arthroplasty using the modular prosthesis were retrospectively investigated. For the cohort study, 97 patients (104 hips) were included. The femoral component survival rate and sleeve fixation were assessed at a minimum follow-up of 5 years. Patients were divided into 2 groups, including stable and unstable fixation groups, by sleeve fixation. Clinical and radiographic outcomes were compared. Results The Kaplan-Meier survival rate at 9 years was 93% with revision for any reason as the endpoint in study cohort. The reasons for revision were recurrent dislocation (1 hip) and aseptic loosening of the stem (5 hips). A total of 88 hips (84.6%) showed stable fixation, and 16 hips (15.4%) showed unstable fixation at final follow-up. There was no significant difference in clinical outcomes between the 2 groups at final follow-up. The canal flare index was significantly higher, and the canal filling ratio was significantly lower in the unstable fixation group. Conclusion Although the modified modular prosthesis was useful for treating anatomically difficult patients, we need to pay attention to both proximal/distal mismatch of the intramedullary canal and the canal filling ratio to achieve stable fixation and good long-term results.

Abstract Background Older patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to that in non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has the higher SGLT2 selectivity, affects bone metabolism by using high-resolution, peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture. Methods/design This is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are older (age ≥ 60 years) individuals with T2DM with HbA1c levels at 7.0–8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or the control group (taking metformin) in a 1:1 ratio to compare the groups’ changes in bone microarchitecture of the radius and tibia which are analyzed by HR-pQCT before and at 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019. Discussion The reason that we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have a neutral effect on bone. This trial should reveal the effect of luseogliflozin on bone metabolism in older patients with T2DM. Trial registration The study was registered with the University Hospital Medical Information Network ( UMIN000036202 ) on 1 April 2019 and with the Japan Registry of Clinicla Trials ( jRCTs071180061 ) on 14 March 2019.

Purpose The purpose of this study was to establish an algorithm for measuring bone erosions at metacarpophalangeal (MCP) joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), to investigate the precision of measurements, and to assess longitudinal changes in bone erosions among patients with rheumatoid arthritis (RA). Methods The 2nd and 3rd MCP joints were scanned at a voxel size of 60.7 μm using second-generation HR-pQCT. Bone erosions on MCP joints were identified using a semi-automated algorithm we developed, and each erosion parameter was measured. Measurement reproducibility was evaluated in 19 healthy subjects using intraclass correlation coefficients (ICCs) and root mean square percent coefficient of variance (RMS%CV). Finally, longitudinal changes in bone erosions over a period of 12 months were assessed in 26 patients with RA based on the calculated least significant change (LSC). Results Reproducibilities for measurement parameters regarding bone erosions with our algorithm were good (all ICCs ≥ 0.98; all RMS%CVs < 5%). No erosion parameters showed significant changes after 12 months of treatment in terms of median values in all erosions, while both progression and repair of erosions were observed individually (e.g., erosion volume: progression, 26% (+0.62 mm3); repair, 34% (-0.85 mm3); no change, 40%). Conclusions The measurement algorithm developed for bone erosions at MCP joints showed good reproducibility. Both progression and repair of bone erosions were observed in patients with RA even after 12 months of appropriate treatment. Our algorithm may be useful to investigate the etiology of RA and assess drug efficacy.

A brief review of some topics in hadron production from heavy ion collisions is given. They include charged pion ratio as a probe of nuclear symmetry energy, in-medium effects on pion production, en- hanced Λc/D0 ratio, Λ local polarization, and X(3872) production.

Background: In Southeast Asia, Japanese encephalitis (JE) is an important cause of viral encephalitis which may cause severe neurological sequelae. JE affects mostly children; therefore, clinical presentations and prognosis of adult JE patients are seldom addressed. This study aimed to describe the clinical characteristics and prognostic factors for the outcome of adult JE patients. Methods: Medical records of adult JE patients with acute encephalitis syndrome during 2001–2018 from five medical centers in southern Taiwan were reviewed. Clinical characteristics, brain images, and prognostic factors for outcomes were analyzed. Patients were divided into the good outcome (GO) group and poor outcome (PO) group according to their Glasgow Coma Scale (GCS) scores (GCS >8 vs. ≤ 8) at discharge. Results: Sixty-eight patients (men, 61.8%; median age, 50 years) were included. Summer is the epidemic season, and the number of cases peaked in June. The most common symptoms at initial presentation were altered consciousness and fever (both 94.1%), followed by headache (51.4%). The most commonly involved brain regions were thalamus (55.7%) and basal ganglion (37.7%). The median GCS score at nadir was 8, and the median time from onset to nadir was five days. Fifty-two patients were included in the GO group, while 16 were included in the PO group. On multivariate analysis, flaccidity, rigidity, and elevated CSF protein level were identified as independent prognostic factors for PO. Conclusion: Initial clinical presentations of abnormal muscle tone including flaccidity, rigidity and high CSF protein levels are independent prognostic factors for PO in adult JE patients. Keywords: Adult, Japanese encephalitis, Outcome, Prognostic factor

Objectives: This study examined the epidemiological, clinical, and immunological characteristics of the 2015 dengue outbreak in Taiwan. Methods: Clinical data were collected from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients. A phylogenetic tree was used to analyze the source of the outbreak strain. Paired plasma samples from DF/DHF patients were used for antibody-dependent enhancement (ADE) assay and cytokine multiplex biometric immunoassay to validate the immunological mechanism. Results: This outbreak mainly occurred in two of the southern cities of Taiwan: Tainan (n = 22 777; 52%) and Kaohsiung (n = 19 784; 45%). A high DHF death rate was noted (34.6%). The case (DHF) and control (DF) study indicated that older age (>60 years), type II diabetes, and hypertension were risk factors correlated with the development of DHF (p

Abstract Background The purpose of this study was to compare radiological features between high tibial osteotomy (HTO) and tibial condylar valgus osteotomy (TCVO), in order to define the radiological indication criteria for TCVO. Methods Thirty-two cases involving 35 knees that had undergone HTO and the same number that had undergone TCVO for knee osteoarthritis were retrospectively evaluated. Characteristics of both groups did not differ significantly. Lower limb alignment, bone morphology, joint congruity, and joint instability were measured in standing full-length leg and knee radiographs obtained before and after surgery. Results Radiological features in the TCVO group included greater frequencies of advanced knee OA grade, varus lower limb malalignment, depression of the medial tibial plateau, and varus-valgus joint instability compared to the HTO group before surgery. However, tibial morphology, alignment of the lower limb, and joint instability improved to comparable levels after surgery in both groups. Conclusions TCVO appears preferable in cases with advanced knee OA, destroyed or inclined medial tibial plateau, widened and subluxated lateral joint, and high varus-valgus joint instability.

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, causes joint destruction, and leads to physical disability. Advances in the treatment of RA, such as biologic disease-modifying anti-rheumatic drugs (DMARDs), have provided better clinical outcomes, including the achievement of remission for patients with RA, but some patients cannot receive these treatments because of their side effects and high cost, and not all patients achieve remission. Although the efficacy of denosumab, which is a human IgG2 monoclonal antibody with a high affinity for the receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), in the treatment of RA has been reported in clinical trials, the efficacy of denosumab in both preventing joint destruction and improving disease activity has not been evaluated in a real-world setting. Methods/design This open-label, randomized, parallel-group study will compare the continued use of conventional synthetic DMARDs (csDMARDs) alone with the combined use of csDMARDs and denosumab in patients whose RA is treated with csDMARDs. In total, 44 patients with RA will be randomly assigned to receive additional treatment with denosumab or to continue RA treatment without additional denosumab. The duration of the intervention will be 12 months. To analyze bone erosion and bone micro-architecture precisely, high-resolution peripheral quantitative computed tomography (HR-pQCT) will be performed every 6 months. The primary endpoint is changes in the depth of bone erosion as measured by HR-pQCT from baseline to 6 months. Important secondary endpoints are the changes from baseline in the width and volume of bone erosion as measured by HR-pQCT and changes from baseline in the depth of bone erosion at 12 months. Changes in bone micro-architecture will also be analyzed as an exploratory endpoint. Discussion The results of this study are expected to provide strong evidence regarding the usefulness of denosumab for the treatment of RA. Moreover, by using HR-pQCT, this study will also reveal the effect of denosumab not only on bone erosion but also on bone micro-architecture. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000030575 on December 26, 2017.

Background/Purpose: : The increasing trend of ceftriaxone resistant non-typhoidal Salmonella (NTS) worldwide is of serious concern, however, data is lacked in southern Taiwan. Methods: Salmonella isolates were collected at a regional hospital in Kaohsiung during 2004–2013. Ceftriaxone resistant NTS isolates were further characterized for beta-lactamases, typed by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and their plasmids were analyzed by PCR replicon typing and plasmid mutilocus sequence typing. Results: Among 528 NTS isolates, the most common serogroup is serogroup B (44.9%), followed by serogroup D, and serogroup C. Eleven (2.1%) isolates were resistant to ceftriaxone and were distributed in three peak periods (2010, 2011, and 2013). PFGE and MLST revealed the ten serogroup B isolates were of two clones. Beta-lactamase genes were detected in 10 of the 11 isolates, including CMY-2 (5 isolates), TEM-1 (2), CTX-M-14 (1), and 2 isolates carried both TEM-1 and CMY-2. Plasmid incompatibility types were identified in 9 (81.8%) isolates; three were IncI1, three was IncHI2, one was IncFIB and two had both replicons of IncI1 and IncHI2. The only ESBL gene blaCTM-X-14 was found in an isolate with plasmid belonged to IncHI2, which has not been reported in NTS in Taiwan before. Most MLST types and plasmid MLST types of NTS isolates in this study are different from those in northern Taiwan. Conclusion: Though clonal spread of ceftriaxone resistant NTS was suggested by PFGE and MLST, plasmid characterization and beta-lactamase detection revealed their plasmid types and beta-lactamase types were different. Keywords: Salmonella, Ceftriaxone, Resistance, ESBL, Plasmid

Background/purpose: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. Methods: We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18–64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002–2011. Results: Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01–0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33–9.99). Conclusion: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications. Keywords: Elderly, Scrub typhus, Acute Q fever, Murine typhus, Complications

Primary culture of skeletal muscle stem cells (MuSCs) is indispensable to study the dynamics of muscle regeneration and homeostasis. Here we describe the modified pre-plating method for isolating MuSCs in culture with greatly improved purity, yield, and procedure time. The protocol is based on the distinct adhesion characteristics of MuSCs. We reduced the procedure time to 2.5 days to obtain highly purified MuSCs through a newly employed re-plating step, which repeats incubation and cell-suspension. The re-plating step efficiently traps remaining fibroblastic cells, but not MuSCs, on a collagen-coated dish. Additionally, we confirmed that MuSCs can be isolated from small amounts of human/mouse muscle tissues, enabling us to perform experiments with amount-limited specimens. Thus, our method can be performed with basic laboratory equipment suitable for most facilities and without sophisticated MuSC handling techniques.

The article discusses the topic of designing the optimal distribution of workstations within a production plant. A review focused on publications on this subject in the Scopus database, covering the years 1975–2017. The article presents a facility layout problem and basic principles of optimisation methods for the distribution of workstations within the factory. The author proposes a methodology for designing the optimal distribution of workstations using available optimisation methods and computer simulation. Also, directions for further research are indicated.

Abstract Background Fibroblast-like synovial cells (FLS) have multilineage differentiation potential including osteoblasts. We aimed to investigate the role of microRNAs during the osteogenic differentiation of rheumatoid arthritis (RA)-FLS. Methods RA-FLS were differentiated in osteogenic medium for 21 days. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) staining and Alizarin Red staining. MicroRNA (miRNA) array analysis was performed to investigate the differentially expressed miRNAs during osteogenic differentiation. Expression of miR-218-5p (miR-218) during the osteogenic differentiation was determined by quantitative real-time PCR. Transfections with an miR-218 precursor and inhibitor were used to confirm the targets of miR-218 and to analyze the ability of miR-218 to induce osteogenic differentiation. Secreted Dickkopf-1 (DKK1) from FLS transfected with miR-218 precursor/inhibitor or roundabout 1 (ROBO1) knockdown FLS established using ROBO1-small interfering RNA (siRNA) were measured by ELISA. Results The miRNA array revealed that 12 miRNAs were upregulated and 24 miRNAs were downregulated after osteogenic differentiation. We observed that the level of miR-218 rose in the early phase of osteogenic differentiation and then decreased. Pro-inflammatory cytokines modified the expression of miR-218. The induction of miR-218 in RA-FLS decreased ROBO1 expression, and promoted osteogenic differentiation. Both the overexpression of miR-218 and the knockdown of ROBO1 in RA-FLS decreased DKK1 secretion. Conclusion We identified miR-218 as a crucial inducer of the osteogenic differentiation of RA-FLS. MiR-218 modulates the osteogenic differentiation of RA-FLS through the ROBO1/DKK-1 axis. The induction of the osteogenic differentiation of proliferating RA-FLS through the provision of miR-218 into RA-FLS or by boosting the cellular reservoir of miR-218 might thus become a therapeutic strategy for RA.

Abstract Background The anterior cruciate ligament-deficient (ACLD) knee requires appropriate treatment for the patient to return to sports. The purpose of this study was to clarify the kinematics of the anterior cruciate ligament-deficient knee in squatting motion before and after double-bundle anterior cruciate ligament reconstruction (DB-ACLR) using a 2D/3D registration technique. Methods The subjects of this study were 10 men with confirmed unilateral ACL rupture who underwent DB-ACLR. Computed tomography (CT) of the knee joints was performed before DB-ACLR. Fluoroscopic imaging of the knee motion in squatting before and after DB-ACLR was also performed. The 2D/3D registration technique is a method of calculating positional relationships by projecting the 3D bone model created from the CT data onto the image extracted from the fluoroscopic images. The tibial anteroposterior (AP) and rotational positions were analyzed with reference to the femur. Results The tibial AP position of the ACLD knees was significantly anterior to the contralateral knees (p = 0.015). The tibial rotational position of the ACLD knees was significantly internally rotated compared to the contralateral knees (p

Abstract: Aim of the study: A novel topical paste used for fracture healing (FH), consisting of the extracts of six herbs, Radix Dipsaci, Ramulus Sambucus Williamsii, Rhizoma Notoginseng, Flos Carthami, Rhizoma Rhei and Fructus Gardeniae, was developed according to the classical theory of traditional Chinese medicine. This study aimed to determine the effectiveness of this formula, and some of its important chemical components in the promotion of fracture healing. The transdermal transport of FH was also examined. Materials and methods: The osteogenic, angiogenic and nitric oxide suppressing effects of FH and its important chemical marker components were assessed by using osteoblastosacroma UMR-106 cells, human umbilical vein endothelial cells (HUVEC) and murine macrophage RAW264.7 cells, respectively. The bone healing effects of the FH paste and its transdermal absorption were determined using a rabbit fracture model. The callus sizes, bone specific alkaline phosphatase levels and biomechanical properties of the healed bone were assessed. Results: FH significantly increased the cell proliferation in UMR-106 and HUVEC cells and inhibited the nitric oxide production in murine macrophage in dose-dependent manner. Its important chemical components asperosaponin VI, ginsenoside Rg1 and emodin were shown to be acting positively in the respective in vitro studies. FH paste significantly improved the bone healing in the rabbit fracture model, as was indicated by the increases in callus size at weeks 2–5, and the elevations in bone specific alkaline phosphatase activities at weeks 5–6. The analysis using LC/MS/MS also showed the presence of important chemical marker components of the FH formula in the plasma after 8 weeks of topical treatment. Conclusion: This study presents the first scientific evidence of the efficacy of a herbal paste in the promotion of fracture healing. There were evidences of transdermal transport of the chemical components, control the inflammation through nitric oxide inhibition, promotion of angiogenesis, and bone healing in the in vitro tests, as well as in the experimental animal. [ABSTRACT FROM AUTHOR]

Objective: To prospectively investigate and detect early cerebral metabolic changes in patients with end-stage renal disease (ESRD) by using in vivo proton MR spectroscopy (MRS).Methods: We enrolled 32 patients with ESRD and 32 healthy controls between the ages of 26 and 50 years. Short echo time single-voxel proton MRS was acquired from volumes of interest (VOIs) located in the frontal grey and white matter, temporal white matter and basal ganglia. The choline/phospatidylcholine (Cho), myo-inositol (mI), N-acetylaspartate (NAA) and total creatine (tCr) peaks were measured and the metabolic ratios with respect to tCr were calculated.Results: In the ESRD group, significant elevations of the Cho/tCr and mI/tCr ratios were observed for the frontal grey matter, frontal white matter, temporal white matter and basal ganglia as compared with controls. There was no significant difference in the NAA/tCr ratios at all VOIs between the ESRD patients and the healthy controls.Conclusions: Proton MRS is a useful and non-invasive imaging tool for the detection of early cerebral metabolic changes in neurologically presymptomatic ESRD patients. [ABSTRACT FROM AUTHOR]

Angiostrongyliasis in humans causes a range of symptoms from mild headache and myalgia to neurological complications, coma and death. Infection is caused by the consumption of raw or undercooked intermediate or paratenic hosts infected with Angiostrongylus cantonensis or via contaminated vegetables or water. We describe a cluster of cases involved in the shared meal of wild raw monitor lizard in the Lao PDR. Seven males, aged 22–36 years, reported headaches, abdominal pain, arthralgia, myalgia, nausea/vomiting, diarrhea, neurological effects and loss of appetite. Five were admitted to hospital. The final diagnosis was made by clinical presentation and case history, and positive A. cantonensis PCR for two cases. All hospitalized patients recovered fully following supportive treatment. The remaining two individuals sought local home remedies and made full recovery. Whilst most published reports concern infections via consumption of molluscs, few detailed reports exist on infections that result from the consumption of reptiles and there exists little awareness in Lao PDR. This case cluster, which originates from a single meal, highlights the potential public health risk of the consumption of raw and wild-caught meat in Lao PDR and the Southeast Asia region. Without specific diagnostics, clinical history and the consideration of recent food consumption are important when evaluating patients.