Subtherapeutic hydroxychloroquine concentration is associated with increased disease activity and greater organ damage in lupus.

OBJECTIVE: To investigate the effects of the serum HCQ concentration on clinical manifestations, disease activity and organ damage in a longitudinal cohort of SLE patients. METHODS: The 338 SLE patients were assessed with respect to their demographic data, clinical and laboratory findings, Physician's Global Assessment (PGA), adjusted mean SLEDAI-2000 (AMS) and SLICC Damage Index (SDI) annually for 5 consecutive years. Patients were divided into two groups according to their serum HCQ concentration at baseline: subtherapeutic (<500 ng/ml) and therapeutic (≥500 ng/ml) groups. The impact of the HCQ concentration on the clinical outcomes was evaluated in a longitudinal analysis using a generalized estimating equation (GEE). RESULTS: Of the 338 patients, 287 (84.9%) were in the subtherapeutic group at baseline. This group had a higher incidence of newly developed LN (P = 0.036) and had been prescribed higher mean and cumulative doses of prednisolone (P = 0.003 and P = 0.013, respectively) than the therapeutic group. In multivariable analyses based on GEE, the subtherapeutic group had a higher AMS score (ß = 1.398, 95% CI 0.607, 2.189; P < 0.001), higher PGA score (ß = 0.328, 95% CI 0.215, 0.441; P < 0.001) and higher SDI score (ß = 0.366, 95% CI 0.061, 0.671; P = 0.019) across all 5 years. CONCLUSION: The subtherapeutic HCQ concentration was associated with the development of new-onset LN, and had significant associations with disease activity and cumulative organ damage in SLE patients over time.

Ramosetron as an add-on therapy for refractory fibromyalgia: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study aimed to assess the efficacy and safety of intravenous ramosetron for pain relief in patients with fibromyalgia (FM) unresponsive to conventional treatments. METHODS: . In this prospective, double-blind, placebo-controlled trial, 80 FM patients were randomly allocated to receive either placebo (n = 40) or ramosetron (n = 40) at a dosage of 0.3 mg/day intravenously for five consecutive days. The primary outcome was the reduction in pain intensity at the end of the treatment period, evaluated using a visual analogue scale (VAS). Secondary outcome measures included the FM Impact Questionnaire, Beck Depression Inventory (BDI), Multi-Dimensional Health Assessment Questionnaire (MDHAQ), EQ-5D, and State-Trait Anxiety Inventory on days 5 (end of treatment), 7, 10, and 28. Safety was continuously monitored throughout the study. RESULTS: . At the end of the treatment phase, the ramosetron group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (1.18 ± 1.60 vs 0.54 ± 1.59, p< 0.05). Additionally, the ramosetron group exhibited significant improvements in BDI (4.42 ± 5.18 vs 1.33 ± 4.87, p< 0.05) and MDHAQ pain scale (0.37 ± 0.74 vs 0.04 ± 0.52, p< 0.05) scores. However, these improvements in pain VAS and BDI scores were not sustained through day 28. The safety profile of ramosetron was favorable, with gastrointestinal symptoms, particularly constipation, being the most commonly reported adverse events. CONCLUSIONS: . Intravenous administration of ramosetron provided safe and effective short-term relief of pain intensity in FM patients with inadequate response to standard treatments.

Recent Advances in Microscale Electroporation.

Electroporation (EP) is a commonly used strategy to increase cell permeability for intracellular cargo delivery or irreversible cell membrane disruption using electric fields. In recent years, EP performance has been improved by shrinking electrodes and device structures to the microscale. Integration with microfluidics has led to the design of devices performing static EP, where cells are fixed in a defined region, or continuous EP, where cells constantly pass through the device. Each device type performs superior to conventional, macroscale EP devices while providing additional advantages in precision manipulation (static EP) and increased throughput (continuous EP). Microscale EP is gentle on cells and has enabled more sensitive assaying of cells with novel applications. In this Review, we present the physical principles of microscale EP devices and examine design trends in recent years. In addition, we discuss the use of reversible and irreversible EP in the development of therapeutics and analysis of intracellular contents, among other noteworthy applications. This Review aims to inform and encourage scientists and engineers to expand the use of efficient and versatile microscale EP technologies.

Unveiling nurses' end-of-life care experiences: Moral distress and impacts.

BACKGROUND: Nurses providing care to patients with end-of-life or terminal illnesses often encounter ethically challenging situations leading to moral distress. However, existing quantitative studies have examined moral distress using instruments that address general clinical situations rather than those specific to end-of-life care. Furthermore, qualitative studies have often been limited to participants from a single unit or those experiencing moral distress-induced circumstances. A comprehensive and integrated understanding of the overarching process of moral distress is vital to discern the unique circumstances surrounding end-of-life care and its consequential impacts. RESEARCH OBJECTIVES: To explore the moral distress experiences of nurses who are frequently involved in caring for patients with end-of-life or terminal illnesses and apply it to two existing theories: the model of moral distress and the ecological model. RESEARCH DESIGN: A qualitative descriptive approach was employed. PARTICIPANTS AND RESEARCH CONTEXT: Seven focus group interviews involving 30 nurses were performed. The subsequent transcriptions underwent rigorous content analysis. ETHICAL CONSIDERATIONS: We obtained Institutional Review Board approval from a university. Focus group interviews were conducted with nurses who agreed to participate and signed the consent form. FINDINGS: The moral distress-inducing factors and nurses' perceived impact of moral distress were identified and categorized based on moral distress theories and ecological models. A total of 15 categories and 30 subcategories across the following 4 domains were derived: (1) intrapersonal, (2) interpersonal, (3) organizational, and (4) structural factors. CONCLUSIONS: End-of-life-specific circumstances induced moral distress among nurses, with both negative and positive impacts identified. Effective organizational and policy support is essential to manage conflicts, form a healthy organizational culture, provide training, and prevent unnecessary expenses due to the negative consequences of moral distress.

Folate deficiency is associated with increased radiographic severity of osteoarthritis in knee joints but not in hand joints.

OBJECTIVES: No previous studies have explored the effect of folate deficiency on the severity of osteoarthritis (OA). Therefore, we investigated the relationship between folate level and features on knee and hand radiographs in a large, population-based OA cohort. METHODS: Among 9,260 subjects enrolled in the Dong-gu study, 2,489 who had knee and hand joint radiographs were included. Of these, subjects with a history of amputation or total knee replacement were excluded. Serum folate levels were measured using blood samples collected at the time of enrolment and stored. A semi-quantitative system was used to grade the severity of hand and knee x-ray changes. Linear regression was performed to assess relationships between serum folate levels and knee and hand radiographic scores after adjusting for age, sex, body mass index, smoking, alcohol consumption, education, physical activity, occupation, vitamin D, and ferritin. RESULTS: A total of 2,322 subjects were recruited. After adjusting for confounders, participants with folate deficiency (<4 ng/mL) had higher total (p<0.001), osteophyte (p<0.001), joint space narrowing (p=0.002), tibial attrition (p<0.001), and sclerosis (p=0.005) scores for knee joint radiographs compared to participants with a normal folate level. After adjusting for confounders, the radiographic scores for hand joints did not differ between the groups. CONCLUSIONS: Folate deficiency is associated with increased radiographic severity of OA in knee joints, but not in hand joints. Further studies are needed to explore the differential effects of folate on the severity of knee and hand OA.

Development and Modification of a Culturally Tailored Education Program to Prevent Breast Cancer in Korean Immigrant Women in New York City.

Breast cancer (BC) is the most common cancer in Korean American (KA) women. In view of its high prevalence in these women, their low screening rates, and the cultural influence of BC risk factors in their lifestyles, we developed a community-based culturally tailored BC prevention program, the Korean Breast Cancer Risk Reduction Program (KBCRRP). Guided by the PRECEDE-PROCEDE and health belief models, the KBCRRP was developed to achieve four goals: (1) healthy weight, (2) physically active lifestyle, (3) healthy diet, and (4) BC screening and adherence. KBCRRP combines effective multicomponent strategies for BC screening and a group-based lifestyle intervention incorporating traditional Korean health beliefs and is tailored for BC risk reduction. In this paper, we provide an overview of the program, the process of program development, implementation, and evaluation, and modification during the COVID-19 pandemic. The initial program involved 8 weeks of in-person group education sessions led by interdisciplinary healthcare professionals and 16 weeks of follow-up involving smartphone applications, phone calls, and text messaging from trained lifestyle coaches. Participants received opportunities to obtain free mammography during the program. After feasibility testing, the program was modified by incorporating participants' feedback. During the COVID-19 pandemic, we provided the program using the Zoom video platform. Participants' recruitment and retention during the pandemic was successful, reflecting the fact that virtual delivery of group-based education was a feasible and acceptable alternative to in-person sessions. Collaboration with community organizations serving the target population is the key to developing and sustaining a successful community-based educational program.

Is spiritual well-being related to survival time of inpatients with advanced cancer? An East Asian cohort study.

OBJECTIVES: It has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries. METHODS: This international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors. RESULTS: A total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5-19.5) in Japan, 23.0 days (95% CI 19.9-26.1) in Korea, and 15.0 days (95% CI 13.0-17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01-1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00-1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77-1.35; p = 0.89). SIGNIFICANCE OF RESULTS: SWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer.

Metabotropic Glutamate Receptor 5 in Natural Killer Cells Attenuates Liver Fibrosis by Exerting Cytotoxicity to Activated Stellate Cells.

BACKGROUND AND AIMS: The important roles of glutamate and metabotropic glutamate receptor 5 (mGluR5) in HSCs have recently been reported in various liver diseases; however, the mechanism linking the glutamine/glutamate metabolism and mGluR5 in liver fibrosis remains unclear. Here, we report that mGluR5 activation in natural killer (NK) cells attenuates liver fibrosis through increased cytotoxicity and interferon-γ (IFN-γ) production in both mice and humans. APPROACH AND RESULTS: Following 2-week injection of carbon tetrachloride (CCl4 ) or 5-week methionine-deficient and choline-deficient diet, liver fibrosis was more aggravated in mGluR5 knockout mice with significantly decreased frequency of NK cells compared with wild-type mice. Consistently, NK cell-specific mGluR5 knockout mice had aggravated CCl4 -induced liver fibrosis with decreased production of IFN-γ. Conversely, in vitro activation of mGluR5 in NK cells significantly increased the expression of anti-fibrosis-related genes including Ifng, Prf1 (perforin), and Klrk1 (killer cell lectin like receptor K1) and the production of IFN-γ through the mitogen-activated extracellular signal-regulated kinase/extracellular signal-related kinase pathway, contributing to the increased cytotoxicity against activated HSCs. However, we found that the uptake of glutamate was increased in activated HSCs, resulting in shortage of extracellular glutamate and reduced stimulation of mGluR5 in NK cells. Consequently, this could enable HSCs to evade NK cell cytotoxicity in advanced liver fibrosis. In vivo, pharmacologic activation of mGluR5 accelerated CCl4 -induced liver fibrosis regression by restoring NK cell cytotoxicity. In humans, mGluR5 activation enhanced the cytotoxicity of NK cells isolated from healthy donors, but not from patients with cirrhosis with significantly reduced mGluR5 expression in NK cells. CONCLUSIONS: mGluR5 plays important roles in attenuating liver fibrosis by augmenting NK cell cytotoxicity, which could be used as a potential therapeutic target for liver fibrosis.

Non-adherence to methotrexate was associated with high disease activity and poor health-related outcomes during a 4-year follow-up of rheumatoid arthritis patients.

OBJECTIVES: Although methotrexate (MTX) is the first-line drug for management of rheumatoid arthritis (RA), non-adherence to MTX is highly prevalent and under-recognised. Here, we investigated adherence to MTX and its impact on clinical outcomes during follow-up in patients with RA. METHODS: In total, 367 RA patients were included in this study, with patient visits conducted annually for 4 consecutive years. Adherence was defined by the medication possession ratio during the follow-up period. We divided the patients into two groups; patients who took ≥80% of their prescribed MTX doses and those who did not. In a prospective cohort, the generalised estimating equations were used to identify longitudinal associations between drug adherence and clinical outcomes including disease activity, physical function, and quality of life. RESULTS: Of the 367 RA patients, 8.7% were found to have taken MTX <80% during the period of follow up. After adjustment for confounders, non-adherence to MTX was significantly associated with higher DAS28-ESR during the follow-up period (coefficient ß=0.989, 95%; CI: 0.603-1.375; p<0.001). In addition, non-adherence to MTX was a significant predictor of RAPID3 (coefficient ß=1.847; 95% CI: 0.221-3.472; p=0.026) and EQ-5D (coefficient ß= -0.051; 95% CI: -0.090-0.012; p=0.010) after adjustment for confounding factors. CONCLUSIONS: Non-adherence to MTX was significantly associated with worse clinical outcomes, as evidenced by higher disease activity, poorer physical function, and lower health-related quality of life during a 4-year follow-up of RA patients.

Comparison of the accuracy of clinicians' prediction of survival and Palliative Prognostic Score: an East Asian cross-cultural study.

PURPOSE: No study has been conducted to compare the clinicians' prediction of survival (CPS) with Palliative Prognostic Scores (PaP) across countries. We aimed to compare the performance of the CPS in PaP (PaP-CPS), the PaP without the CPS, and the PaP total scores in patients with advanced cancer in three East Asian countries. METHODS: We compared the discriminative accuracy of the three predictive models (the PaP-CPS [the score of the categorical CPS of PaP], the PaP without the CPS [sum of the scores of only the objective variables of PaP], and the PaP total score) in patients admitted to palliative care units (PCUs) in Japan, Korea, and Taiwan. We calculated the area under the receiver operating characteristic curve (AUROC) for 30-day survival to compare the discriminative accuracy of these three models. RESULTS: We analyzed 2,072 patients from three countries. The AUROC for the PaP total scores was 0.84 in patients in Japan, 0.76 in Korea, and 0.79 in Taiwan. The AUROC of the PaP-CPS was 0.82 in patients in Japan, 0.75 in Korea, and 0.78 in Taiwan. The AUROC of the PaP without the CPS was 0.75 in patients in Japan, 0.66 in Korea, and 0.67 in Taiwan. CONCLUSION: The PaP total scores and the PaP-CPS consistently showed similar discriminative accuracy in predicting 30-day survival in patients admitted to PCUs in Japan, Korea, and Taiwan. It may be sufficient for experienced clinicians to use the CPS alone for estimating the short-term survival (less than one month) of patients with far-advanced cancer. The PaP may help to improve prognostic confidence and further reduce subjective variations.

Liquid-based thin-prep cytology study of lacrimal drainage system in primary acquired nasolacrimal duct obstruction.

PURPOSE: We investigated the cytologic findings of primary acquired nasolacrimal duct obstruction (PANDO) based on the thin-prep cytology method using sheath-guided dacryoendoscopy. METHODS: A retrospective review was conducted of 66 cases from 50 patients who were diagnosed with PANDO. Slit-lamp examination, the lacrimal irrigation test, and dacryocystography were performed for the evaluation of PANDO. The dacryocystography (DCG) findings were classified into primary and secondary change. Each patient was treated with transcanalicular dacryoplasty using catheter sheath-guided dacryoendoscopy (RUIDO Fiberscope, Fiber Tech Co., Ltd., Tokyo, Japan) and obtained cytologic specimens. The liquid-based thin-prep cytology method was used for the analysis of histopathology. RESULTS: The cellular detection rate was as follows: epithelial cells with 56 cases (84.8%), 33 cases (50.0%) with inflammatory cells, 1 case (1.5%) with mucin, and bacterial colonies with 2 cases (3.0%). In the dacryoendoscopic findings, all cases of a presence of pus were related to the detection of the columnar epithelium (p = 0.026), while there was no statical significance according to the presence of an epithelial cell. In the DCG findings, the PANDOs with the secondary change showed a higher detection rate than those with the primary change (p = 0.005), and columnar epithelial cells were observed (p = 0.011). The detection rate of inflammatory cells was 50.0% (33/66) and all inflammatory cells were lymphocytes but it was not correlated with clinical findings. One case of mucin (1.5%) and 2 cases of bacterial colonies (3.0%) were presented using liquid-based thin-prep cytology analysis. The overall success rate of transcanalicular dacryoplasty and silicone intubation was 86.4%. CONCLUSION: Liquid based thin prep cytology can be used to analyze histopathological changes of lacrimal passage in PANDO without invasive biopsy. These cytologic findings of lacrimal passage provide a better understanding of the pathogenesis of lacrimal passage in patients with PANDO.

Cognitive impairment and edentulism among older adults: an observational study using claims data.

BACKGROUND: The scientific link between mastication strength and cognitive function has not yet been strongly corroborated in population studies. Utilizing large-scale claims, we aim to investigate the association between edentulism and cognitive impairment in older American adults. METHODS: Using de-identified claims from a commercial insurer from 2015-2019, we conducted a retrospective cohort study using multilevel regression models to evaluate the association between denture status and clinically diagnosed cognitive impairment. Secondary analysis included symptomatic cognitive impairment in the outcome. RESULTS: Adjusting for individual-level risk factors, denture status was significantly associated with clinical cognitive impairment with odds ratios of 1.13 (95%CI: 1.02-1.25) and 1.26, (95%CI: 1.09-1.45) for complete dentures on one or both jaws, respectively. Including symptomatic cognitive impairment in the analysis did not substantially change our fundamental findings. CONCLUSION: Prevention and treatment of oral diseases should be considered a key component in preserving the overall wellness of older adults.

Comparison of three different definitions of low disease activity in patients with systemic lupus erythematosus and their prognostic utilities.

OBJECTIVES: Three definitions of low-level disease activity in patients with SLE have been proposed by different groups. These include minimal disease activity (MDA), low disease activity (LDA) and the lupus low disease activity state (LLDAS). We investigated the performance of these definitions in SLE patients. METHODS: We recruited 299 SLE patients who were followed up annually for 4 consecutive years. We compared the three definitions of low disease activity via longitudinal analysis; we used a generalized, linear-mixed effects model and generalized estimating equations. RESULTS: The LLDAS was significantly associated with a lower SLICC/ACR damage index (ß coefficient=-0.064, 95% CI: -0.129, -0.002, P=0.050), reduced flare (odds ratio = 0.090, 95% CI: 0.034, 0.239, P<0.001), an improved SF-36 physical component score (ß coefficient=0.782, 95% CI: 0.046, 1.519, P=0.037), and an improved SF-36 mental component score (ß coefficient=1.522, 95% CI: 0.496, 2.547, P=0.004). Neither the MDA nor the LDA were associated with these variables. CONCLUSION: The LLDAS definition performs better than the MDA and LDA definitions, showing that LLDAS is associated with less organ damage and flare, and a better quality of life, during follow-up.

Uric acid as a risk factor for progression to chronic kidney disease in patients with lupus nephritis: results from the KORNET registry.

OBJECTIVES: Little is known regarding the effect of hyperuricaemia on the progression of kidney function in patients with lupus nephritis (LN). Thus, we investigated the effect of uric acid (UA) on the long-term outcome of patients with biopsy-proven LN. METHODS: Data were obtained from KORNET, a prospective longitudinal systemic lupus erythematosus registry in the Republic of Korea. All 137 patients with LN included in this study had undergone a kidney biopsy and were subsequently treated with immunosuppressants. The patients were divided into two groups: UA ≤7 mg/dL and >7 mg/dL; their sociodemographic, clinical, treatment-related data, and outcomes were compared. Cox-proportional regression analyses were performed to identify independent predictors of renal outcome in patients with LN. RESULTS: Among the 137 patients, 37 (27.0%) had UA >7 mg/dL. This higher UA group included fewer women, but more patients with hypertension, proliferative type LN, and a chronicity index >12. The 24-h urinary protein excretion and the creatinine level were higher in this group; haemoglobin, platelet, and albumin levels were lower. During 85.0 months of follow-up, complete remission at 1 year was less frequent in the higher UA group, whereas chronic kidney disease (CKD) and end-stage renal disease were more prevalent. In the Cox proportional hazards regression analysis, UA >7 mg/dL was a signi cant predictor of progression to CKD in patients with LN (hazard ratio=2.437; p=0.020). CONCLUSIONS: Our findings suggest that hyperuricaemia at LN onset is an independent risk factor that predicts the development of CKD in patients with LN.

Association between maternal periodontal disease and adverse pregnancy outcomes: an analysis of claims data.

BACKGROUND: While a number of studies have explored the link between periodontal disease and adverse pregnancy outcomes, both epidemiological studies and intervention trials have reached contradictory results with relatively small sample sizes. Utilizing large-scale claims data, we aim to investigate the association between maternal periodontal disease and adverse pregnancy outcomes. OBJECTIVE: Utilizing large-scale claims data, we aim to investigate the association between maternal periodontal disease and adverse pregnancy outcomes. METHODS: Using de-identified claims data from a national commercial insurer in the USA, records of all observed pregnancies from 2015 to 2019 were included in this retrospective cohort study. Adverse pregnancy outcomes, including low birthweight (LBW) of the newborn, preterm birth (PTB) and spontaneous abortion, were primary outcomes. To evaluate the association between periodontal disease and pregnancy outcomes, logistic mixed-effect model was estimated with periodontal disease status, age, existing clinical conditions of mothers and geographic location as covariates. RESULTS: Out of 748 792 observed pregnancy records, 18.66% resulted in adverse pregnancy outcomes; 5.92% in LBW, 14.46% in PTB and 2.22 % in spontaneous abortion. Adjusting for individual-level risk factors, periodontal disease was significantly associated with maternal complications with odds ratios of 1.19 (95% CI:1.15, 1.24) for any adverse pregnancy outcomes, 1.10 (95% CI:1.03, 1.17) for LBW, 1.15 (95% CI:1.10, 1.19) for PTB and 1.34 (95% CI:1.23, 1.46) for spontaneous abortions. CONCLUSIONS: Maternal periodontal disease may be associated with an increased risk of maternal complications and neonatal morbidity. A timely diagnosis and treatment of periodontal disease during pregnancy should be encouraged by considering oral health as part of routine prenatal care.

A meaning-centered spiritual care training program for hospice palliative care teams in South Korea: development and preliminary evaluation.

BACKGROUND: Spirituality is a fundamental, intrinsic aspect of human beings and should be a core component of quality palliative care. There is an urgent need to train hospice palliative care teams (HPCTs) to enhance their ability to provide spiritual care. This study aimed to develop and evaluate a meaning-centered, spiritual care training program (McSCTP) for HPCTs (McSCTP-HPCTs). METHODS: The modules' content was informed by Viktor Frankl's meaning-centered logotherapy with its emphasis on spiritual resources, as well as the spiritual care model of the Interprofessional Spiritual Care Education Curriculum (ISPEC). Following development, we conducted a pilot test with four nurses. We used the results to inform the final program, which we tested in an intervention involving 13 members of HPCTs. We took measurements using self-administered questionnaires at three points before and after the intervention. Using descriptive statistics, the Mann-Whitney U test, and the Kruskal-Wallis test, we analyzed the participants' demographic and career-related characteristics, as well as the degree of variance between three outcome variables: compassion fatigue (CF), spiritual care competencies (SCCs), and spiritual care therapeutics (SCT). RESULTS: We divided the McSCTP-HPCTs into five modules. Module I: The HPCTs' SCC evaluation, understanding the major concepts of spiritual care and logotherapy; Modules II-IV: Meaning-centered interventions (MCIs) related to spiritual needs (existential, relational, and transcendental/religious); Module V: The process of meaning-centered spiritual care. The preliminary evaluation revealed significant differences in all three outcome variables at the posttest point (CF, p = 0.037; SCCs, p = 0.005; SCT, p = 0.002). At the four-week follow-up test point, we only found statistical significance with the SCCs (p = 0.006). CONCLUSIONS: The McSCTP-HPCTs is suitable for use in clinical settings and provides evidence for assessing the SCCs of HPCTs.

Altered distribution and enhanced osteoclastogenesis of mucosal-associated invariant T cells in gouty arthritis.

OBJECTIVE: This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. METHODS: Patients with GA (n = 61), subjects with hyperuricaemia (n = 11) and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of M-CSF and RANK ligand. RESULTS: Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17 and TNF-α production were preserved. Expression levels of CD69, PD-1 and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with MSU crystals, suggesting that deposition of MSU crystals might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e. IL-6, IL-17 and TNF-α) and facilitated osteoclastogenesis. CONCLUSION: This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients.

Adaptive 3D Model-Based Facial Expression Synthesis and Pose Frontalization.

Facial expressions are one of the important non-verbal ways used to understand human emotions during communication. Thus, acquiring and reproducing facial expressions is helpful in analyzing human emotional states. However, owing to complex and subtle facial muscle movements, facial expression modeling from images with face poses is difficult to achieve. To handle this issue, we present a method for acquiring facial expressions from a non-frontal single photograph using a 3D-aided approach. In addition, we propose a contour-fitting method that improves the modeling accuracy by automatically rearranging 3D contour landmarks corresponding to fixed 2D image landmarks. The acquired facial expression input can be parametrically manipulated to create various facial expressions through a blendshape or expression transfer based on the FACS (Facial Action Coding System). To achieve a realistic facial expression synthesis, we propose an exemplar-texture wrinkle synthesis method that extracts and synthesizes appropriate expression wrinkles according to the target expression. To do so, we constructed a wrinkle table of various facial expressions from 400 people. As one of the applications, we proved that the expression-pose synthesis method is suitable for expression-invariant face recognition through a quantitative evaluation, and showed the effectiveness based on a qualitative evaluation. We expect our system to be a benefit to various fields such as face recognition, HCI, and data augmentation for deep learning.

Cost-effectiveness of malaria preventive treatment for HIV-infected pregnant women in sub-Saharan Africa.

BACKGROUND: Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. METHODS: A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. RESULTS: Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. CONCLUSION: In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.

HAQ score is an independent predictor of sustained remission in patients with rheumatoid arthritis.

We assessed potential predictors of sustained remission for 2 years according to the Disease Activity Score in 28 joints (DAS28)-CRP in patients with rheumatoid arthritis (RA). We obtained data for 290 RA outpatients, from July 2009 to September 2012. Sociodemographic data and answers to questionnaires were collected in face-to-face interviews. Remission was defined according to DAS28-CRP. Sustained remission was defined as meeting criteria for remission in the annual assessment for two consecutive years. Predictive factors of sustained remission according to DAS28-CRP were assessed by univariate and multivariate analyses. Of the 290 RA patients, the baseline remission level, according to DAS28-CRP, was 54.5%. During 2 years of follow-up, the sustained remission rate was 24.5%. RA patients who achieved sustained remission, according to DAS28-CRP, were younger, and had a shorter duration of symptoms, longer period of education, higher monthly income, lower Health Assessment Questionnaire (HAQ) score, lower physician global assessment, lower patient global assessment, lower patient pain assessment, and higher EQ-5D at baseline. Multivariate analyses showed that the baseline HAQ score was independently associated with sustained remission for 2 years according to DAS28-CRP (OR 0.298, 95% CI 0.115-0.770; p = 0.012). A lower HAQ score at baseline was an independent predictor of sustained remission at 2 years, according to DAS28-CRP. Thus, HAQ scores could be useful when stratifying patients according to risk for flare-ups in the clinic.