Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Early-Life Social Determinants of SCA6 Age at Onset, Severity, and Progression.

SCA6 patients with the same size CAG repeat allele can vary significantly in age at onset (AAO) and clinical progression. The specific external factors affecting SCA6 have yet to be investigated. We assessed the effect of early life events on AAO, severity, and progression in SCA6 patients using a social determinant of health approach. We performed a survey of biological and social factors in SCA6 patients enrolled in the SCA6 Network at the University of Chicago. AAO of ataxia symptoms and patient-reported outcome measure (PROM) of ataxia were used as primary outcome measures. Least absolute shrinkage and selection operation (LASSO) regressions were used to identify which early life factors are predictive of SCA6 AAO, severity, and progression. Multiple linear regression models were then used to assess the degree to which these determinants influence SCA6 health outcomes. A total of 105 participants with genetically confirmed SCA6 completed the assessments. SCA6 participants with maternal difficulty during pregnancy, active participation in school sports, and/or longer CAG repeats were determined to have earlier AAO. We found a 13.44-year earlier AAO for those with maternal difficulty in pregnancy than those without (p = 0.008) and a 12.31-year earlier AAO for those active in school sports than those who were not (p < 0.001). Higher education attainment was associated with decreased SCA6 severity and slower progression. Early life biological and social factors can have a strong influence on the SCA6 disease course, indicating that non-genetic factors can contribute significantly to SCA6 health outcomes.

Consensus Paper: Cerebellum and Reward.

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs.

Cognitive, Emotional, and Other Non-motor Symptoms of Spinocerebellar Ataxias.

PURPOSE OF REVIEW: Spinocerebellar ataxias (SCAs) are autosomal dominant degenerative syndromes that present with ataxia and brain stem abnormalities. This review describes the cognitive and behavioral symptoms of SCAs in the context of recent knowledge of the role of the cerebellum in higher intellectual function. RECENT FINDINGS: Recent studies suggest that patients with spinocerebellar ataxia can display cognitive deficits even early in the disease. These have been given the term cerebellar cognitive affective syndrome (CCAS). CCAS can be tracked using newly developed rating scales. In addition, patients with spinocerebellar ataxia also display impulsive and compulsive behavior, depression, anxiety, fatigue, and sleep disturbances. This review stresses the importance of recognizing non-motor symptoms in SCAs. There is a pressing need for novel therapeutic interventions to address these symptoms given their deleterious impact on patients' quality of life.

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV.

BACKGROUND: Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). METHODS: From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS: During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSION: Combinations of short-course rifapentine-based regimens and InSTI-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

The Role of the Cerebellum in Learning to Predict Reward: Evidence from Cerebellar Ataxia.

Recent findings in animals have challenged the traditional view of the cerebellum solely as the site of motor control, suggesting that the cerebellum may also be important for learning to predict reward from trial-and-error feedback. Yet, evidence for the role of the cerebellum in reward learning in humans is lacking. Moreover, open questions remain about which specific aspects of reward learning the cerebellum may contribute to. Here we address this gap through an investigation of multiple forms of reward learning in individuals with cerebellum dysfunction, represented by cerebellar ataxia cases. Nineteen participants with cerebellar ataxia and 57 age- and sex-matched healthy controls completed two separate tasks that required learning about reward contingencies from trial-and-error. To probe the selectivity of reward learning processes, the tasks differed in their underlying structure: while one task measured incremental reward learning ability alone, the other allowed participants to use an alternative learning strategy based on episodic memory alongside incremental reward learning. We found that individuals with cerebellar ataxia were profoundly impaired at reward learning from trial-and-error feedback on both tasks, but retained the ability to learn to predict reward based on episodic memory. These findings provide evidence from humans for a specific and necessary role for the cerebellum in incremental learning of reward associations based on reinforcement. More broadly, the findings suggest that alongside its role in motor learning, the cerebellum likely operates in concert with the basal ganglia to support reinforcement learning from reward.

Ataxias: Hereditary, Acquired, and Reversible Etiologies.

A variety of etiologies can cause cerebellar dysfunction, leading to ataxia symptoms. Therefore, the accurate diagnosis of the cause for cerebellar ataxia can be challenging. A step-wise investigation will reveal underlying causes, including nutritional, toxin, immune-mediated, genetic, and degenerative disorders. Recent advances in genetics have identified new genes for both autosomal dominant and autosomal recessive ataxias, and new therapies are on the horizon for targeting specific biological pathways. New diagnostic criteria for degenerative ataxias have been proposed, specifically for multiple system atrophy, which will have a broad impact on the future clinical research in ataxia. In this article, we aim to provide a review focus on symptoms, laboratory testing, neuroimaging, and genetic testing for the diagnosis of cerebellar ataxia causes, with a special emphasis on recent advances. Strategies for the management of cerebellar ataxia is also discussed.

Influence of daptomycin dose and fosfomycin susceptibility on outcome of vancomycin-resistant Enterococcus faecium bloodstream infections treated with daptomycin and fosfomycin combination.

OBJECTIVES: Synergistic combinations of daptomycin and ß-lactam antibiotics are currently recommended for treatment of VRE bloodstream infection (BSI). The efficacy of these combinations is jeopardized by VRE inherently resistant to ß-lactam antibiotics. The combination of daptomycin and fosfomycin is recommended as an alternative therapy for VRE BSI; however, clinical data to support use of this combination are lacking. PATIENTS AND METHODS: We conducted a prospective observational multicentre study of patients treated with a combination of daptomycin and fosfomycin for VRE BSI during 2016-20. The primary outcome was 28 day mortality. Multivariable logistic regression was performed for outcome analysis. RESULTS: The study included 106 patients from 1112 VRE BSI episodes. The overall 28 day mortality was 40.6%. The median (IQR) daptomycin dose was 10.18 mg/kg (9.43-10.70). The fosfomycin dose was 16 g/day (8-22.5). Ninety-six isolates were available for MIC testing. The fosfomycin MIC was 32 mg/L in 6 (6.3%), 64 mg/L in 68 (70.8%) and ≥128 mg/L in 22 (22.9%) isolates. Independent of Charlson comorbidity index and Pitt bacteraemia score, fosfomycin MIC ≥128 mg/L [adjusted OR (aOR) = 3.05; 95% CI = 1.01-9.19; P = 0.047] and daptomycin dose (aOR = 0.64; 95% CI = 0.43-0.97; P = 0.04) predicted mortality. CONCLUSIONS: Higher daptomycin dose and susceptibility to fosfomycin were independently associated with lower mortality in patients with VRE BSI. Our results suggest that higher doses of daptomycin are indicated for VRE BSI, whether or not it is used in combination with fosfomycin. The combination was less effective for patients with fosfomycin-resistant isolates.

Influence of daptomycin doses on the outcomes of VRE bloodstream infection treated with high-dose daptomycin.

OBJECTIVES: The CLSI recommended high-dose daptomycin (8-12 mg/kg) for treating Enterococcus faecium bloodstream infections (BSI). The current study was designed to determine the safety and efficacy of increasing the daptomycin dose for VRE BSI patients receiving ≥8 mg/kg. METHODS: We conducted a multicentre prospective observational study of patients who received a ≥8 mg/kg dose of daptomycin for treatment of VRE BSI. The primary outcome was 28 day mortality. RESULTS: A total of 661 patients were included. The 28 day mortality rate was 45.1%. The survivors received higher doses of daptomycin than non-survivors (10.1 versus 9.8 mg/kg; P < 0.001). An increase in the daptomycin dose independently predicted lower mortality [adjusted OR (aOR) = 0.85; 95% CI = 0.73-0.99; P = 0.03]. Eighty-six survivors (23.7%) and 43 non-survivors (14.4%) received a ≥11 mg/kg dose of daptomycin (P = 0.003). The 8 to <11 and ≥11 mg/kg doses of daptomycin differed in the 28 day mortality in the higher MIC group (≥2 mg/L) (49.4% versus 33.3%; P = 0.004), but not in the lower MIC group (≤1 mg/L) (29.3% versus 29.4%; P = 0.99). A dose of ≥11 mg/kg was associated with a higher (3.9%) rate of highly elevated creatine kinase (>2000 U/L) compared with 1.1% with 8 to <11 mg/kg (P = 0.04). CONCLUSIONS: The efficacy of daptomycin is dose dependent. A high daptomycin dose, especially at ≥11 mg/kg, improved survival in patients with VRE BSI, but was associated with highly elevated creatine kinase. We recommend a ≥11 mg/kg dose of daptomycin be considered for treatment of VRE BSI, particularly for isolates with higher MICs.

Design of Transverse Brachiation Robot and Motion Control System for Locomotion between Ledges at Different Elevations.

Bio-inspired transverse brachiation robots mimic the movement of human climbers as they traverse along ledges on a vertical wall. The constraints on the locomotion of these robots differ considerably from those of conventional brachiation robots due primarily to the need for robust hand-eye coordination. This paper describes the development of a motion control strategy for a brachiation robot navigating between wall ledges positioned on a level plane or at different elevations. We based our robot on a four-link arm-body-tail system performing a four-phase movement, including a release phase, body reversal phase, swing-up phase, and grasping phase. We designed a gripper that uses passive wrist joint motion to grasp the ledge during the tail swing. We also developed a dynamic model by which to coordinate the swing-up movement, define the phase switching conditions, and time the grasping action of the grippers. In experiments, the robot proved highly effective in traversing between wall ledges of the same or different elevations.

Combined intravenous immunoglobulin and baricitinib treatment for severe COVID-19 with rhabdomyolysis: A case report.

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world. The severity of COVID-19 ranges from asymptomatic carriers to severe acute respiratory distress syndrome (ARDS). Accumulating evidence has shown that COVID-19 may be associated with multiple organ complications including cardiac injury, viral myositis and neurological deficits. Numerous laboratory biomarkers including lymphocytes, platelets, lactate dehydrogenase and creatine kinase (CK) have been associated with the prognostic outcomes of patients with COVID-19. However, dynamic correlations between levels of biomarkers and clinical course have not been studied. Herein, we report a 74-year-old female patient with severe COVID-19 which progressed to ARDS requiring intubation and mechanical ventilation. The laboratory findings showed lymphopenia, hypogammaglobulinemia, and elevated inflammatory biomarkers and CK. She received intensive therapy with hydroxychloroquine, lopinavir/ritonavir, and azithromycin with limited effects. Immunomodulatory treatments with high dose intravenous immunoglobulin and baricitinib were prescribed with satisfactory biochemical, radiographic and clinical recovery. We found an interesting correlation between serum CK elevation and inflammatory biomarkers, which reflected clinical improvement. This case demonstrates that inflammatory biomarkers, cytokines, and CK level correlated with disease severity and treatment response, and combined use of intravenous immunoglobulin and baricitinib is a potential treatment in patients with severe COVID-19.

National Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).

A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.

Early Seroreversion After 2 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Patients: Incidence and Associated Factors.

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)-positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV-positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV-positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case-control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow-up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow-up of 611 days. In a case-control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292-2.323, per 10-kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067-7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020-0.154) and 0.837 (95% CI, 0.704-0.979, per 100-cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two-dose HAV vaccination occurred in 3.9% of HIV-positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV-positive adults with predictors of early seroreversion.

Cerebellar Volume Is Associated with Cognitive Decline in Mild Cognitive Impairment: Results from ADNI.

Alzheimer's disease (AD) is a disease with dysfunctional brain network. Previous studies found the cerebellar volume changes over the course of AD disease progression; however, whether cerebellar volume change contributes to the cognitive decline in AD, or its earlier disease stage (i.e., mild cognitive impairment [MCI]) remains unclear. In ADNI, cognitive function was assessed using Alzheimer's Disease Assessment Scale-Cognitive Behavior section (ADAS-Cog). We used linear regression and linear mixed effects models to examine whether cerebellar volume is associated with either baseline cognition or with cognitive changes over time in MCI or in AD. We used logistic regression to assess the relationship between cerebellar volume and disease progression to MCI and AD. We found that cerebellar volume is associated with cognition in patients with MCI, after adjusting for age, gender, education, hippocampal volume, and APOE4 status. Consistently, cerebellar volume is associated with increased odds of the disease stages of MCI and AD when compared to controls. However, cerebellar volume is not associated with cognitive changes over time in either MCI or AD. In summary, cerebellar volume may contribute to cognition level in MCI, but not in AD, indicating that the cerebellar network might modulate the cognitive function in the early stage of the disease. The cerebellum may be a potential target for neuromodulation in treating MCI.

Survival of Patients With Vancomycin-Resistant Enterococcus faecium Bacteremia Treated With Conventional or High Doses of Daptomycin or Linezolid Is Associated With the Rate of Bacterial Clearance.

OBJECTIVES: Vancomycin-resistant enterococci are important pathogens for healthcare-associated infections. Although linezolid is bacteriostatic and daptomycin is rapidly bactericidal against vancomycin-resistant enterococci in vitro, it is not clear whether they differ in their effect on bacterial clearance in patients with vancomycin-resistant enterococci bloodstream infections. DESIGN: Prospective observational study. SETTING: Two university hospitals and research laboratory. PATIENTS: Patients with vancomycin-resistant enterococci bloodstream infection proven by blood cultures were prospectively enrolled from January 2010 to July 2015. INTERVENTIONS: Sequential blood samples were collected. Real-time quantitative polymerase chain reaction was used to monitor bacterial loads. MEASUREMENTS AND MAIN RESULTS: One hundred eight patients with vancomycin-resistant enterococci bloodstream infection were enrolled. Quantitative polymerase chain reaction assays were performed on 465 blood isolates. We found this method to be closely correlated with colony-forming units and more sensitive than culture. Sixty-three patients (58.3%) received "conventional dose" daptomycin (6-9 mg/kg), 15 (13.9%) received high-dose daptomycin (≥ 9 mg/kg), and 30 (27.8%) were treated with linezolid (600 mg every 12 hr) as sole agents. The initial mean bacterial load was 1.03 log10 copies/mL and unrelated to survival. Survivors had a more rapid early bacterial clearance than nonsurvivors (Δ log10 copies/mL/d; -0.16 vs 0.31; p = 0.02). Multivariable logistic regression showed that a slower early bacterial clearance independently predicted increased mortality (odds ratio, 3.21; 95% CI, 1.03-10.02; p = 0.045). Conventional dose daptomycin was associated with a significantly slower rate of bacterial clearance than high-dose daptomycin (Δ log10 copies/mL/d; -0.04 vs -0.41; p < 0.001) and linezolid (-0.04 vs -0.56; p = 0.043). CONCLUSIONS: We found that survivors of vancomycin-resistant enterococci bloodstream infection had a significantly more rapid early bacterial clearance by quantitative polymerase chain reaction than nonsurvivors. High-dose daptomycin and linezolid were associated with more rapid bacterial clearance than conventional dose daptomycin. These results support recommendations that conventional dose daptomycin not be used for the treatment of patients with vancomycin-resistant enterococci bloodstream infection.

Serum antigliadin antibodies in cerebellar ataxias: a systematic review and meta-analysis.

BACKGROUND: Gluten sensitivity refers to prominent immunological responses to gluten, usually in conjunction with elevated levels of serum antigliadin antibody (AGA). The association between AGA and cerebellar ataxias has been inconsistently reported. METHODS: We performed a systematic literature search and a meta-analysis to study the weighted pooled OR of idiopathic cerebellar ataxia (IDCA) cases to controls or to hereditary ataxia (HA) for AGA seropositivity using fixed effect model. RESULTS: Eleven studies were included, with a total of 847 IDCA cases, 1654 controls and 445 HA cases. IDCA cases had fourfold higher odds than controls (OR 4.28, 95% CI 3.10 to 5.90) and twofold higher odds than HA cases (OR 2.23, 95% CI 1.45 to 3.44) of having AGA seropositivity. Sensitivity analysis excluding the most weighted study, which accounted for 69% of the total weight, still showed similar associations (IDCA vs controls, OR 3.18, 95% CI 1.79 to 5.67 and IDCA vs HA, OR 1.72, 95% CI 1.03 to 2.86, respectively). The subgroup analysis showed that, when compared with controls, IDCA cases of both East Asian and Western countries had approximately threefold to fourfold higher odds to have AGA seropositivity (OR 3.41, 95% CI 1.67 to 6.97 and OR 4.53, 95% CI 3.16 to 6.49, respectively), suggesting the lack of ethnic heterogeneity. The odds of AGA seropositivity for HA cases was not significantly higher than controls (OR 1.41, 95% CI 0.82 to 2.44). CONCLUSION: Our study indicates the association between AGA and IDCA, across different geographic regions.

Development and Performance Evaluation of Image-Based Robotic Waxing System for Detailing Automobiles.

Waxing is an important aspect of automobile detailing, aimed at protecting the finish of the car and preventing rust. At present, this delicate work is conducted manually due to the need for iterative adjustments to achieve acceptable quality. This paper presents a robotic waxing system in which surface images are used to evaluate the quality of the finish. An RGB-D camera is used to build a point cloud that details the sheet metal components to enable path planning for a robot manipulator. The robot is equipped with a multi-axis force sensor to measure and control the forces involved in the application and buffing of wax. Images of sheet metal components that were waxed by experienced car detailers were analyzed using image processing algorithms. A Gaussian distribution function and its parameterized values were obtained from the images for use as a performance criterion in evaluating the quality of surfaces prepared by the robotic waxing system. Waxing force and dwell time were optimized using a mathematical model based on the image-based criterion used to measure waxing performance. Experimental results demonstrate the feasibility of the proposed robotic waxing system and image-based performance evaluation scheme.

Effect of Daptomycin Dose on the Outcome of Vancomycin-Resistant, Daptomycin-Susceptible Enterococcus faecium Bacteremia.

Background: Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection (BSI) are limited. Daptomycin, although not currently approved for this indication, is frequently used for the treatment of VRE-BSI. Its optimal dose still needs to be determined. Methods: We conducted a prospective, observational, cohort study during 2010-2015. We included patients who received a daptomycin dose of ≥6 mg/kg for the treatment of VRE-BSI caused by daptomycin-susceptible VRE. The primary endpoint was 14-day mortality, and multivariable logistic regression was performed for outcome analysis. Results: We included 112 patients treated with daptomycin for VRE-BSI and with evaluable clinical outcomes. The daptomycin minimum inhibitory concentration (MIC) was 4 mg/L in 78 (69.6%) and ≤2 mg/L in 34 (30.4%) isolates. The overall mortality was 40/112 (35.7%). The unadjusted mortality was 18/36 (50.0%) for a daptomycin dose of <7 mg/kg, 17/51 (33.3%) for a dose of 7-9 mg/kg, and 5/25 (20%) for a dose of ≥9 mg/kg (P = .05). The best outcomes were associated with a daptomycin dose of ≥9 mg/kg compared to doses of <7 mg/kg (adjusted odds ratio [aOR], 10.57; 95% confidence interval [CI], 2.25-49.62; P=.003) and 7-9 mg/kg (aOR, 5.01; 95% CI, 1.14-21.98; P=.03). There was no significant difference in mortality with respect to the daptomycin MIC. There was no association between daptomycin dose and elevated creatinine kinase. Conclusion: Higher daptomycin doses (≥9 mg/kg) were associated with lower mortality in patients with VRE-BSI. Our results suggest that higher daptomycin doses need to be considered for VRE-BSI treatment.

Deep brain stimulation and climbing fiber synaptic pathology in essential tremor.

Essential tremor (ET) patients have abnormal climbing fiber (CF) synapses in the parallel fiber territory in the cerebellum, and these abnormal CF synapses are inversely correlated with tremor severity. We therefore examined CF synaptic pathology in ET cases with and without thalamic deep brain stimulation (DBS) and assessed the association with tremor severity. We found that CF synaptic pathology was inversely correlated with tremor severity in ET cases without DBS, and this correlation disappeared in ET cases with DBS. Our data suggest that DBS might have effects in modulating excitatory synapses in ET cerebellum, in addition to its symptomatic effects on tremor. Ann Neurol 2016;80:461-465.