Magnetocardiography at rest predicts cardiac death in patients with acute chest pain.

Introduction: Sudden cardiac arrest is a major cause of morbidity and mortality worldwide and remains a major public health problem for which better non-invasive prediction tools are needed. Primary preventive therapies, such as implantable cardioverter defibrillators, are not personalized and not predictive. Most of these devices do not deliver life-saving therapy during their lifetime. The individual relationship between fatal arrhythmias and cardiac function abnormalities in predicting cardiac death risk has rarely been explored. Methods: We retrospectively analyzed the measurements at rest for 191 patients with acute chest pain (ACP) magnetocardiographically. Our recently introduced analyses are able to detect inhomogeneities of the depolarization and repolarization. Moreover, electrically silent phenomena-intracellular ionic currents as well as vortex currents-can be measured and quantified. All included ACP patients were recruited in 2009 at Yonsei University Hospital and were followed up until 2022. Results: During half of the follow-up period (6.5 years), 11 patients died. Out of all the included nine clinical, eight magnetocardiographical, and nine newly introduced magnetoionographical parameters we tested in this study, three parameters revealed themselves to be outstanding at predicting death: heart rate-corrected QT (QTc) prolongation, depression of repolarization current IKr + IKs, and serum creatinine (all significant in Cox regression, p < 0.05). They clearly predicted cardiac death over the 6.5 years duration (sensitivity 90.9%, specificity 85.6%, negative predictive accuracy 99.4%). Cardiac death risk was more than ninefold higher in patients with low repolarization reserve and QTc prolongation in comparison with the remaining patients with ACP (p < 0.001). The non-parametric Kaplan-Meier statistics estimated significantly lower survival functions from their lifetime data (p < 0.001). Discussion: To the best of our knowledge, these are the first data linking magnetocardiographical and magnetoionographical parameters and subsequent significant fatal events in people, suggesting structural and functional components to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of new prevention strategies and herald those new non-invasive techniques as complementary risk stratification tools.

Cardiovascular Disease Risk Burden, Cognitive Impairments and Incident Dementia among Community-Dwelling Middle-Aged and Older Adults: An 8-Year Longitudinal Follow-up Study.

OBJECTIVES: To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up. DESIGN: A community-based longitudinal cohort study. SETTING: Yuanshan township in Yi-Lan County, Taiwan. PARTICIPANTS: A total of 889 community-dwelling residents aged 50 years or older. MEASUREMENTS: Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test. RESULTS: Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 [95% confidence interval (CI) 1.19-2.15], P=0.002), verbal memory (aOR 1.97 [1.43-2.70], P< 0.001) and language (aOR 1.99 [1.46-2.70], P< 0.001), as well as incident dementia (aOR 2.40 [1.33-4.33], P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment. CONCLUSIONS: Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment.

Long-term Cardiovascular Risks of Gonadotropin-releasing Hormone Agonists and Antagonists: A Population-based Cohort Study.

AIMS: Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. MATERIALS AND METHODS: Patients with PCa receiving GnRH agonists or antagonists during 2013-2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. RESULTS: In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0-81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7-5.0 years), 1115 patients (45.0%) had MACEPRONOUNCE and 344 (13.9%) had MACECVM. GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACEPRONOUNCE: Log-rank P = 0.308; MACECVM: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACEPRONOUNCE: Log-rank P = 0.569; MACECVM: Log-rank P = 0.615). CONCLUSIONS: GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors.

RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay.

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.

A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Live-streaming otolaryngology surgical procedures for virtual medical student rotations.

BACKGROUND: The coronavirus disease 2019 pandemic created challenges in surgical education that expedited the development of virtual learning. Virtual rotations have been one such solution. However, they require co-ordination and technological equipment to create a meaningful, interactive experience for students. METHODS: Various otolaryngology surgical procedures were live-streamed during a two-week virtual rotation for medical students. A mobile audiovisual cart comprising a computer mounted with a webcam and microphone/speaker were utilised to live-stream from four sources: video-assisted telescope operating monitor ('VITOM') exoscope, microscope, endoscope and room camera. A dedicated faculty member, who was not the operating surgeon, was present to facilitate students' understanding of the procedure. CONCLUSION: A wide breadth of otolaryngology surgical procedures were live-streamed via a mobile audiovisual computer, including views of the room, endoscopic views, microscopic views and open views via an exoscope (video-assisted telescope operating monitor). This virtual rotation set-up, along with the dedicated faculty facilitator, reduced the burden on the operating surgeon and enhanced students' learning experience.

Janus kinase inhibitors for treating active ankylosing spondylitis: a meta-analysis of randomized controlled trials.

OBJECTIVE: In this study, we aimed to assess the safety and efficacy of Janus kinase (JAK) inhibitors in patients with ankylosing spondylitis (AS). METHODS: We conducted a Bayesian network meta-analysis using direct and indirect data from randomized controlled trials (RCTs), and examined the safety and efficacy of JAK inhibitors in active AS patients exhibiting inadequate response or intolerance to two or more non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: RCTs included a total of 406 patients (203 experimental subjects and 203 controls) from three studies on upadacitinib, filgotinib, and tofacitinib. Assessment of SpondyloArthritis International Society 20% improvement (ASAS20), ASAS40, and ASAS5/6 responses were significantly higher in the JAK inhibitor group than in the placebo group. Other efficacy outcomes, such as ASAS partial remission, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), Ankylosing Spondylitis Disease Activity Score (ASDAS), Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) scores, and Bath Ankylosing Spondylitis Functional Index (BASFI) were also significantly higher in the JAK inhibitor group compared to the placebo group. The JAK inhibitors significantly improved disease activity (ASAS partial remission, BASDAI50, ASDAS), function (BASFI), and MRI outcomes (SPARCC MRI spine). However, the incidence of adverse events (AEs) and serious adverse events (SAEs), and the rate of withdrawal attributed to AEs did not differ between the JAK inhibitor and placebo groups. CONCLUSION: JAK inhibitors were effective in active AS patients exhibiting an inadequate response or intolerance to two or more NSAIDs, without the risk of SAEs; this suggests that based on our data, studies are warranted to further investigate the use of JAK inhibitors for treating AS.

Anti-diabetic effects of Protaetia brevitarsis in pancreatic islets and a murine diabetic model.

OBJECTIVE: In this study, the antidiabetic efficacy of Protaetia brevitarsis in alloxan-treated pancreatic islets and db/db mice was investigated. P. brevitarsis was tested for alloxan-mediated cytotoxicity and nitric oxide production in mice pancreatic islets. MATERIALS AND METHODS: The anti-diabetic effect of P. brevitarsis was also evaluated in db/db mice after 4 weeks of administration. Biochemical analysis, oral glucose tolerance test (OGTT), and pancreatic histological analysis were performed. RESULTS: P. brevitarsis displayed hypoglycemic activity in alloxan-treated mice pancreatic islets. Our results showed that P. brevitarsis protects pancreatic islets from cytotoxicity. Moreover, daily oral supplementation with P. brevitarsis for 4 weeks reduced plasma glucose levels without affecting body weight and food intake, elevated glucose tolerance in OGTT, improved blood lipid parameters, inhibited fat accumulation, and restored islet structure of db/db mice. CONCLUSIONS: The present study provided evidence for the anti­diabetic effect of P. brevitarsis in alloxan-treated pancreatic islets and db/db mice. These results suggest that P. brevitarsis may be used as an adjunctive anti-diabetic agent or as a functional food.

Noncontact Sensing of Contagion.

The World Health Organization (WHO) has declared COVID-19 a pandemic. We review and reduce the clinical literature on diagnosis of COVID-19 through symptoms that might be remotely detected as of early May 2020. Vital signs associated with respiratory distress and fever, coughing, and visible infections have been reported. Fever screening by temperature monitoring is currently popular. However, improved noncontact detection is sought. Vital signs including heart rate and respiratory rate are affected by the condition. Cough, fatigue, and visible infections are also reported as common symptoms. There are non-contact methods for measuring vital signs remotely that have been shown to have acceptable accuracy, reliability, and practicality in some settings. Each has its pros and cons and may perform well in some challenges but be inadequate in others. Our review shows that visible spectrum and thermal spectrum cameras offer the best options for truly noncontact sensing of those studied to date, thermal cameras due to their potential to measure all likely symptoms on a single camera, especially temperature, and video cameras due to their availability, cost, adaptability, and compatibility. Substantial supply chain disruptions during the pandemic and the widespread nature of the problem means that cost-effectiveness and availability are important considerations.

Comparative study of the efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib versus methotrexate for disease-modifying antirheumatic drug-naïve patients with rheumatoid arthritis.

An assessment of the relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to those of methotrexate (MTX) was performed in disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid arthritis (RA). We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) so as to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and MTX in DMARD-naïve RA patients. Four RCTs comprising 2185 patients met the inclusion criteria. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of achieving the American College of Rheumatology 20% (ACR20) response rate, followed by baricitinib 4 mg, tofacitinib 5 mg, filgotinib 200 mg, and MTX. Tofacitinib, baricitinib, upadacitinib, and filgotinib treatments achieved significantly higher ACR50 and ACR70 responses compared to MTX. Tofacitinib 5 mg had the highest probability of achieving the ACR50 and ACR70 response rates, followed by upadacitinib 15 mg, baricitinib 4 mg, filgotinib 200 mg, and MTX. The safety analysis based on serious adverse events, adverse events (AEs), and withdrawals due to AEs revealed no statistically significant differences between the respective intervention groups. In conclusion, tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for DMARD-naïve RA patients, suggesting a difference in efficacy and safety among the different JAK inhibitors.

Circulating interleukin-23 levels in ankylosing spondylitis and their correlation with disease activity : A meta-analysis.

OBJECTIVE: To systematically investigate the relationship between circulating interleukin-23 (IL­23) levels and ankylosing spondylitis (AS) and establish a correlation between these hematological indices and AS activity/severity. METHODS: We searched the Medline, Embase, and Cochrane databases; performed a meta-analysis comparing serum/plasma IL­23 levels in patients with AS to those of controls; and examined the correlation coefficients between serum/plasma IL­23 levels and AS activity. RESULTS: Ten studies including 1724 patients with AS and 1589 controls were included in this meta-analysis. This meta-analysis showed that circulating IL­23 levels were significantly higher in the AS than in the control group (standardized mean difference [SMD] 1.479; 95% confidence interval [CI] 0.308-2.650; p = 0.013). Stratification by ethnicity showed a significantly increased IL­23 level in the AS group in an Asian population (SMD 1.551; 95% CI 0.543-2.558; p = 0.003). Stratification by adjustment for age and sex revealed significantly higher IL­23 levels in the AS adjustment group. Subgroup analysis of sample size showed a significantly higher IL­23 level for a small (n < 150) sample number in the AS group. Meta-analysis of correlation coefficients revealed that the IL­23 level was positively associated with the Bath Ankylosing Spondylitis Metrology Index (BASMI; correlation coefficient 0.464; 95% CI 0.027-0.752; p = 0.038), erythrocyte sedimentation rate (ESR; correlation coefficient 0.258; 95% CI 0.076-0.422; p = 0.006), and C­reactive protein (CRP; correlation coefficient 0.291; 95% CI 0.053-0.498; p = 0.017). CONCLUSION: This meta-analysis demonstrated that the circulating IL­23 level is significantly higher in patients with AS, and a significant positive correlation exists between the circulating IL­23 level and BASMI, ESR, and CRP.

Comparative efficacy and safety of mycophenolate mofetil versus cyclophosphamide in patients with active antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of randomized trials.

OBJECTIVE: This study aimed to assess the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) in patients with active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We performed a meta-analysis of four randomized clinical trials (RCTs; 300 patients) to examine the relative efficacy and safety of MMF compared to CYC in patients with active AAV. RESULTS: There was no significant difference in remission at 6 months between MMF and CYC (odds ratio [OR] 1.311, 95% confidence interval [CI] 0.570-3.017, P = 0.524). Additionally, the relapse rate did not differ between the MMF and CYC groups (OR 1.331, 95% CI 0.497-3.568, P = 0.570). There was no significant difference in serious adverse event (SAE; OR 1.232, 95% CI 0.754-2.014, P = 0.404) and infection rates (OR 0.958, 95% CI 0.561-1.634, P = 0.873) between the MMF and CYC groups. Some heterogeneity was found in the meta-analysis of remission and relapse rates (I2 = 57.4%, 63.4%), but no between-study heterogeneity was found during the meta-analysis of SAE and infection rate. Egger's regression test showed no evidence of publication bias (Egger's regression test P-values >0.1). CONCLUSION: MMF was an equally effective alternative treatment to CYC and MMF was comparable to CYC in patients with active AAV in terms of safety, suggesting that MMF can be used as an alternative to CYC for remission induction in AAV.

Comparative efficacy and safety of secukinumab and ixekizumab in patients with active ankylosing spondylitis.

OBJECTIVE: Evaluation of the effectiveness and safety of secukinumab and ixekizumab in active ankylosing spondylitis (AS) patients. METHODS: A Bayesian network meta-analysis was conducted using direct and indirect data from five randomized controlled trials that examined the efficacy and safety of secukinumab 150 mg every 4 weeks and ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) in active AS patients. RESULTS: Data from 1433 patients were analyzed. The Assessment of Spondyloarthritis International Society evaluation 20% response rates (ASAS20) were significantly higher with secukinumab 150 mg, IXEQ2W, IXEQ2W, and adalimumab 40 mg (odds ratio [OR] 2.75, 95% Bayesian credible interval [CrI] 2.04-3.69; OR 2.59, 95% CrI 1.69-3.98; OR 2.45, 95% CrI 1.60-3.75; and OR 1.94, 95% CrI 1.13-3.37, respectively) compared to the placebo group. Efficacies of secukinumab and ixekizumab were numerically higher compared to adalimumab 40 mg, although there was no significant difference in the ASAS20 response rates. The ASAS40 response rate showed a pattern of distribution similar to the ASAS20 response rate, with the exception of the ixekizumab group, which was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ASAS40 response rate. Based on the SUCRA rating, secukinumab 150 mg had the highest probability of being the best ASAS20 response rate therapy, followed by IXEQ2W, IXEQ4W, adalimumab 40 mg, and placebo. There was no significant difference between the treatments regarding the number of serious adverse events (SAEs). CONCLUSION: Secukinumab and ixekizumab were effective in active AS treatment, without the risk of SAEs.

Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs.

OBJECTIVE: The relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib were assessed in patients with rheumatoid arthritis (RA) with inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in RA patients with inadequate responses to bDMARDs. RESULTS: Four RCTs comprising 1399 patients met the inclusion criteria. Tofacitinib, baricitinib, upadacitinib, and filgotinib achieved significant American College of Rheumatology 20% (ACR20) responses versus placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by filgotinib 200 mg, baricitinib 4 mg, filgotinib 100 mg, tofacitinib 5 mg, and placebo. The ranking in SUCRA based on the ACR50 response rate indicated that baricitinib 4 mg had the highest probability of achieving the ACR50 response rate, followed by filgotinib 200 mg, tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 100 mg, and placebo. Tofacitinib 5 mg showed a significantly higher ACR70 response rate than filgotinib 100 mg and upadacitinib 15 mg. Tofacitinib 5 mg, filgotinib 200 mg, and placebo showed a significantly lower serious adverse event rate than upadacitinib 15 mg. CONCLUSION: Tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for RA patients with an inadequate response to bDMARDs but with different efficacy and safety profiles.

Anifrolumab for the treatment of active systemic lupus erythematosus: a meta-analysis of randomized controlled trials.

We surveyed randomized controlled trials (RCTs) examining the efficacy and safety of anifrolumab 300 mg in patients with active systemic lupus erythematosus (SLE) despite receiving standard therapy, using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis performed to determine treatment efficacy and safety outcomes of three RCTs (459 patients and 468 controls) revealed that the BICLA responses were significantly higher in the anifrolumab group than in the placebo group (OR = 2.071, 95%CI 1.575-2.725, p < 0.001). Steroid reduction and CLASI reduction were also significantly higher in the anifrolumab group than in the placebo group (OR = 1.811, 95%CI = 1.308-2.506, p < 0.001; OR = 2.245, 95%CI = 1.437-3.506, p < 0.001). Compared with placebo, anifrolumab significantly increased the SRI7 and SRI8 responses in SLE patients (OR = 1.866, 95%CI = 1.372-2.536, p < 0.001; OR = 1.925, 95%CI = 1.387-2.672, p < 0.001). The SRI4, 5, and 6 responses also tended to be higher in the anifrolumab group than in the placebo group. Adverse event incidence was significantly higher in the anifrolumab group than in the placebo group (OR = 1.815, 95%CI = 1.262-2.611, p = 0.001); serious adverse events were significantly lower in the anifrolumab group than in the placebo group (OR = 0.679, 95%CI = 0.468-0.986, p = 0.042). Herpes zoster infection was significantly higher in the anifrolumab group than in the placebo group (OR = 4.089, 95%CI = 1.750-9.522, p = 0.001). Anifrolumab is effective for treating active SLE. However, anifrolumab increased the incidence of herpes zoster infection compared with placebo.

Sex-specific association of urate and levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND AND PURPOSE: As a major antioxidant, uric acid (UA) is known to be associated with the clinical progression of Parkinson's disease (PD). This study investigated whether baseline UA levels are associated with the risk for levodopa-induced dyskinesia (LID) in PD in a sex-dependent manner. METHODS: In all, 152 patients with de novo PD (78 males and 74 females) who were followed up for >2 years were enrolled. The effect of baseline serum UA levels on LID-free survival was assessed by Cox regression, separately for sex, whilst being adjusted for potential confounding factors. The optimal UA level cut-off value to determine the high-risk group for LID was set using Contal and O'Quigley's method. RESULTS: Levodopa-induced dyskinesia developed in 23 (29.5%) male patients and 30 (40.5%) female patients. Cox regression showed a significant interaction between UA level and sex. Higher UA levels were associated with a higher risk for LID in male PD patients (hazard ratio 1.380; 95% confidence interval 1.038-1.835; P = 0.027), although this relationship was not observed in female PD patients. The optimal UA level cut-off for LID in male PD was 7.2 mg/dl, and the high UA group had a 5.7-fold higher risk of developing LID than the low UA group. CONCLUSIONS: Contrary to a presumptive beneficial role of UA, the present study demonstrated that higher UA levels are associated with increased risk of LID occurrence in male patients with PD, suggesting a sex-dependent role of UA in LID.

[Melatonin Induces Apoptotic Cell Death in 3T3-L1 Preadipocytes].

Obesity is a major disease that causes significant complications. Inhibition of preadipocyte proliferation has the potential to prevent obesity and metabolic diseases. Melatonin is a pineal gland hormone that has various effects on cells and tissues. In this research, we investigated whether melatonin induces apoptosis in 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were cultured until confluence and then treated with 0, 10, 100, and 1000 µM melatonin for 1, 3, and 5 days. A cell viability assay kit was used for determining cell viability. Cell death marker proteins were assessed by Western blot analysis using GAPDH for control. Apoptotic morphological changes with nuclei fragmentation were observed using DAPI staining. Melatonin treatment decreased the phosphorylated extracellular signal-regulated kinases (p-ERK) activation while increasing the activation of caspase-3, 8, and 9. Furthermore, melatonin not only increased Bcl-2-associated X protein (Bax) but decreased B-cell lymphoma 2 (Bcl-2) expression as dose increases from 0 to 1000 µM. The melatonin treatment also suppressed the growth of preadipocytes with increasing concentration. These effects were attenuated by luzindole, a melatonin receptor antagonist and U0126, an inhibitor of p-ERK activation. In conclusion, melatonin can induce apoptosis of 3T3-L1 preadipocytes via p-ERK decrease.

Cognitive anosognosia is associated with frontal dysfunction and lower depression in Parkinson's disease.

BACKGROUND AND PURPOSE: Anosognosia refers to a deficit of self-awareness or impaired insight for cognitive and behavioral problems. Cognitive anosognosia was explored in de novo patients with Parkinson's disease (PD) and its relationship to cognitive function and neuropsychiatric symptoms was investigated. METHODS: The cross-sectional study enrolled 340 drug-naïve patients with PD. According to the presence of mild cognitive impairment (MCI) and subjective cognitive complaint, patients were classified as patients with cognitive anosognosia (PD-CA, n = 74), with normal cognitive recognition (PD-NR, n = 184) or with cognitive underestimation (PD-CU, n = 82). After controlling for covariates, cognitive performance and neuropsychiatric symptoms were compared between the PD groups. RESULTS: Cognitive anosognosia was found in 21.8% of patients with de novo PD. The PD-CA group showed poorer performance in all cognitive domains except for attention. Amongst PD patients with MCI, those with cognitive anosognosia showed lower composite z-scores in the Stroop color reading test than those without. The Beck Depression Inventory score in the PD-NR group was lower than that in the PD-CU group and higher than that in the PD-CA group. The Cognitive Complaints Interview score mediated the association between cognitive anosognosia and Beck Depression Inventory score. CONCLUSIONS: Cognitive anosognosia in PD was associated with greater frontal dysfunction and lower depression. Since cognitive anosognosia has a harmful impact on PD patients and their caregivers due to overestimation of their abilities in everyday life, early identification of cognitive anosognosia in PD is important in management and prognosis.