0 (IQR 22.3-27.0) vs 18.5 (IQR 15.3-23.8); p< 0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (p< 0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse.

Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.

Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.

Anesthesiologists have long used multimodal analgesia for effective pain control. Opioid-sparing anesthetics are gaining popularity among practitioners in light of increasing concerns for both immediate opioid side effects and the long-term opioid misuse among susceptible patients. Currently, there is a critical gap in knowledge regarding outcomes after an opioid-free anesthetic (OFA) during general anesthesia. We hypothesized that an opioid-free general anesthetic will not be inferior to a traditional opioid anesthetic (OA) as measured by the perioperative outcomes of postanesthesia care unit (PACU) duration, 12-hour postoperative summed pain intensity (SPI12) scores, total morphine equivalent doses (MEDs) utilized in the 12-hour postoperative inpatient (MED12) and total MEDs utilized in the 90-day outpatient periods (MED90).

Patients were included if they were  ≥18 years old, met criteria for American Society of Anesthesiologists classification I-IV, received general endotracheal anesthesia from a singlach group. Additional research is needed to explore if these findings can be extrapolated to a larger more heterogeneous population. Our preliminary work suggests that eliminating patient exposure to opioids in the intraoperative period does not have a deleterious effect on perioperative patient outcomes.

Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but their association with response to TNF inhibitors (TNFi) is unclear. We examined associations between comorbidity history at TNFi initiation and 1) change in disease indices over time; 2) binary response definitions; 3) time-to-treatment-discontinuation.

We studied participants starting their first TNFi from a national axSpA register. Comorbidity categories were created from 14 physician-diagnosed conditions and compared against change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unit reduction) and BASDAI<4 at 6 months using logistic models; and time-to-treatment-discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education.

994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over ty burden.

Adult onset Still’s disease (AOSD) is a multifactorial systemic autoinflammatory disease. Neurological damage has been scarcely reported in AOSD. We aimed to characterize the clinical features of AOSD patients with neurological involvement.

Totally, 187 AOSD patients were admitted to Peking Union Medical College Hospital from January 2015 to August 2019. The complete medical records were reviewed in this retrospective study. Clinical features of 14 AOSD patients with neurological involvement were collected and compared with those without.

The prevalence of neurological involvement in AOSD inpatients was 7.5%. Median disease duration was 4.5 months with a range of 1 to 15 months. The frequent symptoms were fever (14, 100%), rash (13, 92.9%), liver dysfunction (11, 78.6%), arthralgia/arthritis (10, 71.4%), and lymphadenopathy (10, 71.4%). Four (28.6%) patients had macrophage activation syndrome (MAS). Aseptic meningitis was the most common presentation (64.3%) when the nervous system was involved. Other rare manifestations included cranial nerve palsy, encephalitis, and cerebral infarction. Rate of MAS, serum levels of lactate dehydrogenase and ferritin were significantly higher in AOSD patients with neurological involvement than in those without. All patients received high dose corticosteroid therapy and immunosuppressive agents, and two were given tocilizumab. Clinical remission was achieved in all of the 14 AOSD patients with neurological involvement.

Neurological involvement, particularly aseptic meningitis, is not a rare complication of AOSD. It is frequently complicated by MAS. There may be a potential relationship between neurological damages of AOSD and MAS.

Neurological involvement, particularly aseptic meningitis, is not a rare complication of AOSD. It is frequently complicated by MAS. There may be a potential relationship between neurological damages of AOSD and MAS.

Myocardial involvement (MCI) is known to increase morbidity and mortality in polymyositis (PM) and dermatomyositis (DM). This study aims to investigate whether complicating with ventricular arrhythmia (VA) predicts poor outcomes in patients with PM/DM-related myocardial involvement (PM/DM-MCI).

We reviewed all PM/DM-MCI patients admitted in Peking Union Medical College Hospital from October 1997 to April 2019. VA and the other possible risk factors for the composite end point, including death from any cause and rehospitalization for cardiac causes, were analysed.

A total of 75 PM/DM-MCI patients (44 PM and 31 DM) were enrolled, of which 27 (36%) met the composite end point during a median follow-up of 24 months. Independent prognostic factors for the composite end point includes VA (HR 4.215, 95% CI [1.737, 10.230]), NT-proBNP > 3415 pg/ml (HR 2.606, 95% CI [1.203, 5.646]), interstitial lung disease (HR 2.688, 95% CI [1.209, 5.978]), and anti-cardiac remodelling therapy (HR 0.302, 95% CI [0.115, 0.792]). The 3-year event-free survival rate of patients without VA was significantly higher than that of patients with VA (63.3% vs 40.7%, p = 0.034). Skin lesions (OR 0.163, 95% CI [0.051, 0.523]) and positive antimitochondrial antibody (OR 3.484, 95% CI [1.192, 10.183]) were independent predictors of VA.

VA provides prognostic insights for PM/DM-MCI patients and predicts poor outcome. Polymyositis and positive antimitochondrial antibody are closely associated with the presence of VA in PM/DM-MCI.

VA provides prognostic insights for PM/DM-MCI patients and predicts poor outcome. Polymyositis and positive antimitochondrial antibody are closely associated with the presence of VA in PM/DM-MCI.

To evaluate the persistence and effectiveness of tumor necrosis factor inhibitors (TNFi) vs non-TNFi among newly diagnosed JIA patients after initiation of biologic disease-modifying anti-rheumatic drug (bDMARD).

Using longitudinal patient-level data extracted from electronic medical records (EMR) in a large Midwestern pediatric hospital from 2009-2018, we identified JIA patients initiating TNFi and non-TNFi. Treatment effectiveness was assessed based on disease activity. Inverse probability of treatment weighting (IPTW) of propensity score was used to estimate the treatment effectiveness and Kaplan-Meier analysis were conducted to assess persistence.

Of 667 JIA patients, most (92.0%) were prescribed one of the class of TNFi as their initial biologic treatment. Etanercept was the most frequently prescribed (67.1%) treatment, followed by adalimumab (27.5%). Only around 5% of patients were prescribed off-label bDMARDs as their first-course treatment; however, >20% were prescribed off-label biologics as their second-course therapy. 7.3% of patients received four or more bDMARDs. The median persistence of the first-course bDMARD is 320 days, with TNFi being significantly longer than the non-TNFi (395 vs 320 days, p= 0.010). The cJADAS reduction was significant greater of TNFi users (6.6, 95% CI 5.7-7.5) compare to non-TNFi users (3.0, 95% CI 1.5-4.6, p< 0.0001) at 6-month follow-up visit.

Persistence was significantly longer among patients initiating TNFi as their first biologic therapy than those receiving non-TNFi. Patients with TNF therapy had significant greater reduction of cJADAS at the 6-month follow-up visit compared with patient in non-TNF cohort.

Persistence was significantly longer among patients initiating TNFi as their first biologic therapy than those receiving non-TNFi. Patients with TNF therapy had significant greater reduction of cJADAS at the 6-month follow-up visit compared with patient in non-TNF cohort.

SLE patients have elevated cardiovascular disease (CVD) risk, but it is unclear whether this risk is affected by choice of immunosuppressive drug. We compared CVD risks among SLE patients starting mycophenolate mofetil (MMF), cyclophosphamide (CYC), or azathioprine (AZA).

Using Medicaid Analytic eXtract (2000-2012), adult SLE patients starting MMF, CYC, or AZA were identified and propensity scores (PS) were estimated for receipt of MMF vs CYC and MMF vs AZA. We examined rates of first CVD event (primary outcome), all-cause mortality, and a composite of first CVD event and all-cause mortality (secondary outcomes). After 11 PS-matching, Fine-Gray regression models estimated subdistribution hazard ratios (HRSD) for risk of CVD events. Cox regression models estimated HRs for all-cause mortality. The primary analysis was as-treated; 6- and 12-month intention-to-treat (ITT) analyses were secondary.

We studied 680 PS-matched pairs of patients with SLE initiating MMF vs CYC and 1,871 pairs initiating MMF vs AZA. Risk of first CVD event was non-significantly reduced for MMF vs CYC (HRSD 0.72[95%CI 0.37-1.39]) and for MMF vs AZA (HRSD 0.88[95%CI 0.59-1.32]) groups. In the 12-month ITT, first CVD event risk was lower among MMF than AZA new users (HRSD 0.68 [95%CI 0.47-0.98]).

In this head-to-head PS-matched analysis, CVD event risks among SLE patients starting MMF vs CYC or AZA were not statistically reduced except in one 12-month ITT analysis of MMF vs AZA, suggesting longer term use may convey benefit. Further studies of potential cardioprotective benefit of MMF are necessary.

In this head-to-head PS-matched analysis, CVD event risks among SLE patients starting MMF vs CYC or AZA were not statistically reduced except in one 12-month ITT analysis of MMF vs AZA, suggesting longer term use may convey benefit. Further studies of potential cardioprotective benefit of MMF are necessary.

CYD-TDV demonstrated vaccine efficacy (VE) against symptomatic, virologically confirmed dengue of any serotype from month 13 to month 25 (VCD-DENV-AnyM13→M25) in the CYD14 (2-14-y-olds) and CYD15 (9-16-y-olds) phase 3 trials. Fifty percent plaque reduction neutralization test (PRNT50) titers are a potential surrogate for immunobridging VE to adults.

Using PRNT50 calibration datasets, we applied immunobridging approaches using baseline and/or M13 PRNT50 titers to estimate VE against VCD-DENV-AnyM0→M25 and against hospitalized VCD (HVCD)-DENV-AnyM0→M72 in hypothetical 18-45-y-old and 46-50-y-old CYD14 and CYD15 cohorts.

Baseline and M13 geometric mean PRNT50 titers were greater in 18-45-y-olds and in 46-50-y-olds vs 9-16-y-olds for most comparisons. Estimated VE (95% CIs against VCD-DENV-AnyM0→M25 ranged from 75.3% to 90.9% (52.5% to 100%) for 18-45-y-olds and 74.8% to 92.0% (53.4% to 100%) for 46-50-y-olds. Estimated VE (95% CIs) against HVCD-DENV-AnyM0→M72 ranged from 58.8% to 78.1% (40.9 to 98.9%) for 18-45-y-olds and 57.2% to 78.4% (40.5 to 97.6%) for 46-50-y-olds. Corresponding predictions among baseline-seropositive individuals yielded comparable or higher VE estimates.

VE M0→M25 against DENV-Any and VE against HVCD-DENV-AnyM0→M72 are both expected to be higher in 18-45 and 46-50-y-olds vs CYD14 and CYD15 9-16-y-olds.

VE M0→M25 against DENV-Any and VE against HVCD-DENV-AnyM0→M72 are both expected to be higher in 18-45 and 46-50-y-olds vs CYD14 and CYD15 9-16-y-olds.

Minimal clinically important difference (MCID) is determined when a patient or physician defines the minimal change that outweighs the costs and untoward effects of a treatment. These measurements are „anchored” to validated quality-of-life instruments or physician-rated, disease-activity indices. To capture the subjective clinical experience in a measurable way, there is an increasing use of MCID.

To review the overall concept, method of calculation, strengths, and weaknesses of MCID and its application in the neurosurgical literature.

Recent articles were reviewed based on PubMed query. To illustrate the strengths and limitations of MCID, studies regarding the measurement of pain are emphasized and their impact on subsequent publications queried.

MCID varies by population baseline characteristics and calculation method. In the context of pain, MCID varied based on the quality of pain, chronicity, and treatment options.

MCID evaluates outcomes relative to whether they provide a meaningful change to patients, incorporating the risks and benefits of a treatment. Using MCID in the process of evaluating outcomes helps to avoid the error of interpreting a small but statistically significant outcome difference as being clinically important.

MCID evaluates outcomes relative to whether they provide a meaningful change to patients, incorporating the risks and benefits of a treatment. Using MCID in the process of evaluating outcomes helps to avoid the error of interpreting a small but statistically significant outcome difference as being clinically important.

Brain metastases (BMs) occur in ∼1/3 of cancer patients and are associated with poor prognosis. Genomic alterations contribute to BM development; however, mutations that predispose and promote BM development are poorly understood.

To identify differences in genomic alterations between BM and primary tumors.

A retrospective cohort of 144BM patients were tested for genomic alterations (85 lung, 21 breast, 14 melanoma, 4 renal, 4 colon, 3 prostate, 4 others, and 9 unknown carcinomas) by a next-generation sequencing assay interrogating 315 genes. The differences in genomic alterations between BM and primary tumors from COSMIC and TCGA were evaluated by chi-square or Fisher’s exact test. Overall survival curves were plotted using the Kaplan-Meier method.

The comparison of BM and primary tumors revealed genes that were mutated in BM with increased frequency TP53, ATR, and APC (lung adenocarcinoma); ARID1A and FGF10 (lung small-cell); PIK3CG, NOTCH3, and TET2 (lung squamous); ERBB2, BRCA2, and AXL1 (breast cstem tumors could help our understanding of BM development and improve patient management.Plant mitochondria harbour complex metabolic routes that are interconnected with those of other cell compartments and changes in mitochondrial function remotely influence processes in different parts of the cell. This implies the existence of signals that convey information about mitochondrial function to the rest of the cell. Increasing evidence indicates that metabolic and redox signals are important for this process, but probably also changes in ion fluxes, protein relocalization and physical contacts with other organelles are involved. Besides possible direct effects of these signalling molecules on cellular functions, changes in mitochondrial physiology also affect the activity of different signalling pathways that modulate plant growth and stress responses. As a consequence, mitochondria influence the responses to internal and external factors that modify the activity of these pathways and associated biological processes. Acting through the activity of hormonal signalling pathways, mitochondria may also exert remote control over distant organs or plant tissues. In addition, an intimate cross-talk of mitochondria with energy signalling pathways, like those represented by Target of Rapamycin and Sucrose non-fermenting1-related protein kinase 1, can be envisaged. This review discusses available evidence on the role of mitochondria in shaping plant growth and stress responses through different signalling pathways.

To evaluate the safety and efficacy of abatacept treatment for refractory juvenile localized scleroderma (jLS) in a retrospective study.

A multicentre cohort study was performed to evaluate jLS subjects treated with abatacept with follow-up for 12 months to maximum of 24 months. Assessments at 6 month intervals included skin activity measures and physician global assessment of activity (PGA-A). Descriptive statistical analysis was performed.

Eighteen subjects were studied with median age 13.4 years, the majority had linear scleroderma subtype, and musculoskeletal involvement. All had previously failed methotrexate and/or mycophenolate mofetil (MMF) treatment and glucocorticoids. Abatacept was added to the subject’s maintenance DMARD treatment; 13 also received glucocorticoids at start of abatacept.No serious adverse events occurred. Skin activity and PGA-A scores declined in nearly all by 6 months and continued to improve from 6 to 12 months. At 12 months, 15 (83%) subjects were considered responders, two (11%) treatment failures, and one dropped out for adverse event. Response was sustained for 11 (61%) subjects to 18 months and 8 (44%) to 24 months. Overall, 4 (22%) subjects were treatment failures and 3 (16.7%) discontinued abatacept for adverse event. Active musculoskeletal problems improved in most affected subjects. Ten subjects were able to discontinue initial glucocorticoid and 6 concomitant DMARD treatment.

Abatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept’s efficacy.

Abatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept’s efficacy.Alveolar macrophages (AM) are the first-line lung defense against Mucorales in pulmonary mucormycosis. Since corticosteroid use is a known risk factor for mucormycosis, the aim of this study was to describe the role of corticosteroids on AM capacities to control Lichtheimia corymbifera spore growth using a new ex vivo model. An in vivo mouse model was developed to determine the acetate cortisone dose able to trigger pulmonary invasive infection. Then, in the ex vivo model, male BALB/c mice were pretreated with the corticosteroid regimen triggering invasive infection, before AM collection through bronchoalveolar lavage. AMs from corticosteroid-treated mice and untreated control AMs were then exposed to L. corymbifera spores in vitro (ratio 15). AM control of fungal growth, adherence/phagocytosis, and oxidative burst were assessed using optical densities by spectrophotometer, flow cytometry, and 2′, 7′-dichlorofluoresceine diacetate fluorescence, respectively. Cortisone acetate at 500 mg/kg, at D-3 and at D0, lAM phagocytosis inhibition and burst oxidative decrease.

The aim of this study was to describe the impact of corticosteroids on alveolar macrophage (AM) capacities to control Mucorales growth in a new murine ex vivo model. Corticosteroids enhanced fungal growth of L. corymbifera through AM phagocytosis inhibition and burst oxidative decrease.The genus Malassezia is part of the normal skin mycobiota of a wide range of warm-blooded animals. In this genus, M. cuniculi is the only species described from rabbits. However, Malassezia species are rarely studied in lagomorphs. In the present study, the presence of Malassezia was assessed in samples from the external ear canal of healthy rabbits of different breeds. Cytological and culture techniques, Sanger sequencing, and Next-generation sequencing (NGS) were used to describe the ear mycobiota in the samples. Although no growth was observed in the cultured plates, cytological examination revealed the presence of round cells similar to those of Malassezia yeasts. For metagenomics analysis, the D1/D2 domain of the large subunit of the ribosomal DNA (LSU rDNA) was PCR amplified and the resulting reads were mapped against a custom-made cured database of 26S fungal sequences. NGS analysis revealed that Basidiomycota was the most abundant phylum in all the samples followed by Ascomycota. Malassezia was the most common genus presenting the highest abundance in the external ear canal. Malassezia phylotype 131 and M. cuniculi were the main sequences detected in the external auditory canal of rabbits. The study included both lop-eared and erect-eared rabbits and no differences were observed in the results when comparing both groups. This is the first attempt to study the external ear canal mycobiome of rabbits of different breeds using NGS.

In the present study, the presence of Malassezia was assessed in samples from the external ear canal of healthy rabbits of different breeds. Cytological and culture techniques, Sanger sequencing, and Next-generation sequencing (NGS) were used to describe the ear mycobiota in the samples.

In the present study, the presence of Malassezia was assessed in samples from the external ear canal of healthy rabbits of different breeds. Cytological and culture techniques, Sanger sequencing, and Next-generation sequencing (NGS) were used to describe the ear mycobiota in the samples.

To estimate the incidence of COVID-19 hospitalisation in patients with inflammatory rheumatic disease (IRD); in patients with rheumatoid arthritis (RA) treated with specific DMARDs; and the incidence of severe COVID-19 infection among hospitalised patients with RA.

A nationwide cohort study from Denmark between 1 March to 12 August 2020. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with RA; spondyloarthritis including psoriatic arthritis; connective tissue disease; vasculitides; and non-IRD individuals.Further, the incidence of COVID-19 hospitalisation was estimated for patients with RA treated respectively non-treated with TNF-inhibitors, hydroxychloroquine, or glucocorticoids.Lastly, the incidence of severe COVID-19 infection (intensive care, acute respiratory distress syndrome, or death) among hospital-admitted patients was estimated for RA and non-IRD individudals.

Patients with IRD (n = 58,052) had an increased partially adjusted incidence of hospitalisation with COVID-19 compared with the 4.5 million people in the general population (HR 1.46, 95%CI 1.15 to 1.86) with strongest associations for patients with RA (n = 29,440, HR 1.72, 95%CI 1.29 to 2.30) and vasculitides (n = 4072, HR 1.82, 95%CI 0.91 to 3.64). There was no increased incidence of COVID-19 hospitalisation associated with TNF-inhibitor, hydroxychloroquine nor glucocorticoid use. COVID-19 admitted patients with RA had a HR of 1.43 (95% CI 0.80 to 2.53) for a severe outcome.

Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalisation.

Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalisation.

Identification of subgroups at greatest risk for suicide mortality is essential for prevention efforts and targeting interventions. Sexual minority individuals may have an increased risk for suicide compared with heterosexual individuals, but a lack of sufficiently powered studies with rigorous methods for determining sexual orientation has limited the knowledge on this potential health disparity.

To investigate suicide mortality among sexual minority veterans using Veterans Health Administration (VHA) electronic health record data.

This retrospective population-based cohort study used data on 8.1 million US veterans enrolled in the VHA after fiscal year 1999 that were obtained from VHA electronic health records from October 1, 1999 to September 30, 2017. Data analysis was carried out from March 1, 2020 to October 31, 2020.

Veterans with documentation of a minority sexual orientation. Documentation of sexual minority status was obtained through natural language processing of clinical notes and extractxual minority veterans (82.5 per 100 000 person-years) was higher than the rate in the general veteran population (37.7 per 100 000 person-years).

The results of this population-based cohort study suggest that sexual minority veterans have a greater risk for suicide than the general US population and the general veteran population. Further research is needed to determine whether and how suicide prevention efforts reach sexual minority veterans.

The results of this population-based cohort study suggest that sexual minority veterans have a greater risk for suicide than the general US population and the general veteran population. Further research is needed to determine whether and how suicide prevention efforts reach sexual minority veterans.

Active surveillance (AS) is now recognized as the preferred management option for most low-risk prostate cancers to minimize risks of overtreatment. Despite increasing use of AS in the US, wide regional variability has been observed, and these regional variations in contemporary practice have not been well described.

To explore variations between county and Surveillance, Epidemiology, and End Results (SEER) regions in AS in the US.

A cohort study using the SEER Prostate with Watchful Waiting (WW) database linked to the County Area Health Resource File for detailed county-level demographics and physician distribution data was conducted from January 2010 to December 2015. Analysis was performed in October 2020. A total of 79 825 men with clinically localized, low-risk prostate cancer eligible for AS or WW were included.

Multiple patient-, county-, and SEER region-level factors, including age, year of diagnosis, county-level densities of urologists, radiation oncologists, primary care physicians, and SEEice and may inform policies aimed at continuing to affect risk-appropriate care for men throughout the US.

Video learning prior to surgery is common practice for trainees and surgeons, and immersive virtual reality (IVR) simulators are of increasing interest for surgical training. The training effectiveness of IVR compared with video training in complex skill acquisition should be studied.

To evaluate whether IVR improves learning effectiveness for surgical trainees and to validate a VR rating scale through correlation to real-world performance.

This block randomized, intervention-controlled clinical trial included senior (ie, postgraduate year 4 and 5) orthopedic surgery residents from multiple institutions in Canada during a single training course. An intention-to-treat analysis was performed. Data were collected from January 30 to February 1, 2020.

An IVR training platform providing a case-based module for reverse shoulder arthroplasty (RSA) for advanced rotator cuff tear arthropathy. Participants were permitted to repeat the module indefinitely.

The primary outcome measure was a validated performanceentifier NCT04404010.

Health taxes are policy tools used to reduce harmful consumption of products and raise tax revenue, and they may also be associated with signaling (ie, informational and educational) factors that enhance their impact.

To examine changes in prices and volume sold of sweetened beverages following the implementation and repeal of the Cook County, Illinois, Sweetened Beverage Tax (SBT) compared with the comparison site of St Louis County and city, Missouri, which did not impose a tax.

This study used interrupted time series analyses to assess changes in price and volume sold of taxed (based on beverage type and sweetener status) and untaxed beverages in Cook County compared with St Louis following the implementation of the SBT on August 2, 2017, and its repeal effective December 1, 2017. Statistical analysis was performed from January to June 2020.

Implementation and repeal of the Cook County SBT.

Changes in taxed and untaxed beverage prices and volume sold. Nielsen food store scanner data were obtainede in volume sold from pretax to 8 months after repeal.

This study using interrupted time series analysis found no net change in volume sold of taxed beverages following the implementation and repeal of the Cook County SBT, suggesting the tax had no signaling association. Repeals of such taxes may fully reverse their associations with reduced demand and harms associated with sweetened beverage intake.

This study using interrupted time series analysis found no net change in volume sold of taxed beverages following the implementation and repeal of the Cook County SBT, suggesting the tax had no signaling association. Repeals of such taxes may fully reverse their associations with reduced demand and harms associated with sweetened beverage intake.

The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a psoriatic arthritis (PsA) dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders.

Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, one month (T1) and three months (T3).

We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI, and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (p< 0.001) and between clinical remission and non-remission groups (p< 0.001).

The DACTOS score performs well in real life, clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

The DACTOS score performs well in real life, clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

Cereal fiber modulates the gut microbiome and benefits metabolic health. The potential link between these effects is of interest.0.

The aim for this systematic review was to assess evidence surrounding the influence of cereal fiber intake on microbiome composition, microbiome diversity, short-chain fatty acid production, and risk factors for metabolic syndrome.

The MEDLINE, PubMed, CINAHL, and Cochrane Library databases were searched systematically, and quality of studies was assessed using the Cochrane Risk of Bias 2.0 tool. Evidence relating to study design, dietary data collection, and outcomes was qualitatively synthesized on the basis of fiber type.

Forty-six primary publications and 2 secondary analyses were included. Cereal fiber modulated the microbiome in most studies; however, taxonomic changes indicated high heterogeneity. Short-chain fatty acid production, microbiome diversity, and metabolic-related outcomes varied and did not always occur in parallel with microbiome changes. Poor dietary data were a further limitation.

Cereal fiber may modulate the gut microbiome; however, evidence of the link between this and metabolic outcomes is limited. Additional research is required with a focus on robust and consistent methodology.

PROSPERO registration no. CRD42018107117.

PROSPERO registration no. CRD42018107117.

An early acute marker of long-term neurological outcome would be useful to help guide clinical decision making and therapeutic effectiveness after severe traumatic brain injury (TBI). We investigated the utility of the Disability Rating Scale (DRS) as early as 1 wk after TBI as a predictor of favorable 6-mo Glasgow Outcome Scale extended (GOS-E).

To determine the predictability of a favorable 6-mo GOS-E using the DRS measured during weeks 1 to 4 of injury.

The study is a sub analysis of patients enrolled in the Epo Severe TBI Trial (n=200) to train and validate L1-regularized logistic regression models. DRS was collected at weeks 1 to 4 and GOS-E at 6 mo.

The average area under the receiver operating characteristic curve was 0.82 for the model with baseline demographic and injury severity variables and week 1 DRS and increased to 0.88 when including weekly DRS until week 4.

This study suggests that week 1 to 4 DRS may be predictors of favorable 6-mo outcome in severe TBI patients and thus useful both for clinical prognostication as well as surrogate endpoints for adaptive clinical trials.

This study suggests that week 1 to 4 DRS may be predictors of favorable 6-mo outcome in severe TBI patients and thus useful both for clinical prognostication as well as surrogate endpoints for adaptive clinical trials.

To evaluate serum concentration and activity of angiotensin-converting enzyme 2 (ACE2) in patients with connective tissue diseases (CTDs).

Serum samples from healthy subjects and patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (SS) and rheumatoid arthritis (RA) were collected. The concentration and activity of ACE2 were measured by ELISA and fluorometric method respectively, and analyzed for associations with clinical features and concurrent medications.

Totally 66 SLE, 55 SSc, 31 SS and 31 RA patients were involved. ACE2 concentration was significantly decreased in patients with either of the four CTDs compared with healthy subjects. The concentration was not linked to special clinical features expect that it was slightly lower in patients with lupus nephritis than those without. In SLE patients, ACE2 concentration elevated with the increase of glucocorticoids, and was not associated with other treatments. Different from the concentration, ACE2 activity was increased in CTD patients. A weak correlation of ACE2 activity with SLE disease activity index score was also observed.

The clinical significance of ACE2 concentration and activity looks quite different among CTD patients. Preliminary data suggests ACE2 levels are not affected by most of the treatments.

The clinical significance of ACE2 concentration and activity looks quite different among CTD patients. Preliminary data suggests ACE2 levels are not affected by most of the treatments.

Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were to study; 1) IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, 2) the fluctuation of IgA anti-CD74 levels in prospectively collected samples, 3) and to explore the relation between IgA anti-CD74 and radiographic spinal changes.

IgA anti-CD74 was analyzed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls. BASDAI, ASDAS, BASFI, and BASMI were assessed and spinal radiographs were scored for r-axSpA related changes with mSASSS. Previously donated samples, before inclusion in the Backbone study, were identified in the Medical Biobank of Northern Sweden.

A total of 155 patients comprising 69% men and 31% women, age (mean±SD) 55.5 ± 11.4 years, and 152 (98.1%) HLA-B27 positive, were included. The plasma level of IgA anti-CD74 was significantly higher in the patients, median (IQR), 12.9 (7.9-17.9) U/ml compared with controls 10.9 (7.2-14.6) U/ml, p= 0.003. IgA anti-CD74 was above the cut-off level of 20 U/ml in 36/155 (23.2%) patients and in 15/151 (9.9%) controls, p= 0.002. Multivariable logistic regression analyzes revealed that to have ≥1 syndesmophyte associated with IgA anti-CD74 (OR 5.64, 95% CI, 1.02-35.58, p= 0.048) adjusted for hsCRP, smoking, BMI, sex, and age. No distinct pattern of IgA anti-CD74 over time was revealed.

Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.

Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.Pneumocystis jirovecii pneumonia (PCP) is an opportunistic and life-threatening pulmonary infection with an increasing prevalence among individuals who are human immunodeficiency virus (HIV)-negative. Evidence regarding diagnostic testing of PCP in this patient population is insufficient. We evaluated the performance of serum (1, 3)-β-d-glucan (BDG) using the Fungitec G-test MK kit for diagnosing PCP in non-HIV patients. We retrospectively analyzed data from 219 non-HIV adult patients who underwent bronchoscopy and were tested for P. jirovecii DNA by PCR using lavage samples from the lower respiratory tract. Fifty PCP patients and 125 non-PCP patients were included. The most common underlying diseases were malignancies and systemic autoimmune diseases. Using the serum BDG Fungitec G-test MK test to diagnose PCP, the area under the receiver operating characteristic curve (AUC) was 0.924, whereas the modified cut-off value of 36.6 pg/mL had a sensitivity and specificity of 92.0% and 84.8%, respectively. The AUC for patients with systemic autoimmune diseases was 0.873, and the accuracy of serum BDG test declined when using methotrexate (MTX). In conclusion, the serum BDG test was useful for diagnosing PCP in non-HIV patients; however, the results should be carefully interpreted in case of MTX administration.

The Fungitec G-test MK kit for measuring serum (1, 3)-β-d-glucan (BDG) levels had a sufficient diagnostic performance for Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus-negative patients. However, the results should be carefully interpreted in case of MTX administration.

The Fungitec G-test MK kit for measuring serum (1, 3)-β-d-glucan (BDG) levels had a sufficient diagnostic performance for Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus-negative patients. However, the results should be carefully interpreted in case of MTX administration.Primary SS (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands leading to glandular dysfunction, resulting in dryness of the eyes, mouth and other mucosal surfaces. Systemic manifestations also occur in the majority of patients. There has been increasing interest in recent years, with a number of publications regarding the classification criteria, diagnostic tools, disease activity, damage, impact and potential treatments. This article reviews recent advances in the diagnosis and treatment of ocular and oral involvement in pSS. Recent stand-out developments include measurement of tear osmolarity as a marker in dry eye disease diagnosis, new devices measuring tear constituents and meibomian gland structure and treatment of its dysfunction. Lip biopsy is still valuable despite emerging evidence of non-invasive diagnostic techniques, notably salivary gland ultrasound.Post-embryonic organogenesis has uniquely equipped plants to become developmentally responsive to their environment, affording opportunities to remodel organism growth and architecture to an extent not possible in other higher order eukaryotes. It is this developmental plasticity that makes the field of plant-microbe interactions an exceptionally fascinating venue in which to study symbiosis. This review article describes the various ways in which mutualistic microbes alter the growth, development, and architecture of the roots of their plant hosts. We first summarize general knowledge of root development, and then examine how association of plants with beneficial microbes affects these processes. Working our way inwards from the epidermis to the pericycle, this review dissects the cell biology and molecular mechanisms underlying plant-microbe interactions in a tissue-specific manner. We examine the ways in which microbes gain entry into the root, and modify this specialized organ for symbiont accommodation, with a particular emphasis on the colonization of root cortical cells. We present significant advances in our understanding of root-microbe interactions, and conclude our discussion by identifying questions pertinent to root endosymbiosis that at present remain unresolved.

Base of thumb osteoarthritis (BTOA) is a common age-related disease which has a significant negative impact upon quality of life, while little is known about structure and pathways of interface services. Our aim was to assess disease burden, referral pathways, service structure and management pathways in UK interface services.

A structured questionnaire was carried out with a participating clinician at each centre to detail the local guidelines and management of BTOA. Five patients referred with BTOA were prospectively identified in each of 32 United Kingdom (UK) interface centres.

Most centres (72%) had a local guideline and a standardised treatment regime consisting of education (100%), joint protection (100%), range of motion exercises (84%), strengthening exercises (88%), splintage (100%) and use of assistive devices (78%). No centre routinely offered a steroid injection at the first appointment and no centre had a specific threshold for offering an injection. Injection delivery was variable. Most patients had not been referred previously (82%). Most patients used analgesia (72%) but a minority of patients had been treated with a splint (46%), therapy (43%) and steroid injection (27%) prior to their latest attendance.

Most BTOA patients newly referred to interface services have been treated with analgesics and have not received comprehensive multimodal intervention. The management of BTOA at interface services is standardised in terms of education, splintage and therapy. However, there is a lack of standardisation in terms of both the threshold for, timing and mode of delivery of injection therapy.

Most BTOA patients newly referred to interface services have been treated with analgesics and have not received comprehensive multimodal intervention. The management of BTOA at interface services is standardised in terms of education, splintage and therapy. However, there is a lack of standardisation in terms of both the threshold for, timing and mode of delivery of injection therapy.Pulmonary specimen pairs from five patients who presented with pulmonary colonization and later developed Pneumocystis Pneumonia (PcP) were retrospectively examined for P. jirovecii genotyping. A match of genotypes in pulmonary specimen pairs of three patients was observed, whereas a partial match and a mismatch were observed in the fourth and fifth patients, respectively. The genotyping results suggest that the colonization state can differ from PcP but can also represent the incubation period of PcP. Clinicians should not systematically rule out the treatment of putative colonized patients and should at least discuss the initiation of prophylaxis on a case-by-case basis.

To determine behavioral and genetic factors associated with incidence and age of progression to advanced age-related macular degeneration (AMD), geographic atrophy (GA), and neovascular disease (NV), and to quantify these effects.

Longitudinal analyses were conducted among 5421 eyes with nonadvanced AMD at baseline in 2976 participants in the Age-Related Eye Disease Study (mean age of 68.8 (±5.0), 56.1% female). Progression was confirmed based on two consecutive visits on the AMD severity scale. Separate analyses for progression and age of progression were performed. All analyses adjusted for correlation between eyes, demographic and behavioral covariates, baseline severity scale, and genetic variants.

A higher genetic risk score (GRS) including eight genetic variants was associated with a higher rate of progression to advanced AMD within each baseline severity scale, especially for the highest risk intermediate level AMD category, and smoking further increased this risk. When assessing age when progression to advanced disease occurred, smoking reduced age of onset by 3.9 years (P < 0.001), and higher body mass index (BMI) led to earlier onset by 1.7 years (P = 0.003), with similar results for GA and NV. Genetic variants associated with earlier age of progression were CFH R1201C (4.3 years), C3 K155Q (2.15 years), and ARMS2/HTRA1 (0.8 years per allele).

Rare variants in the complement pathway and a common risk allele in ARMS2/HTRA1, smoking, and higher BMI can lead to as much as 11.5 additional years of disease and treatment burden. Closer adherence to healthy lifestyles could reduce years of visual impairment.

Rare variants in the complement pathway and a common risk allele in ARMS2/HTRA1, smoking, and higher BMI can lead to as much as 11.5 additional years of disease and treatment burden. Closer adherence to healthy lifestyles could reduce years of visual impairment.

The purpose of this work was to test whether palisade endings express structural and molecular features of exocytotic machinery, and are associated with acetylcholine receptors, and enzymes for neurotransmitter breakdown.

Extraocular rectus muscles from six cats were studied. Whole-mount preparations of extraocular muscles (EOMs) were immunolabeled with markers for exocytotic proteins, including synaptosomal-associated protein of 25 kDa (SNAP25), syntaxin, synaptobrevin, synaptotagmin, and complexin. Acetylcholine receptors (AChRs) were visualized with α-bungarotoxin and with an antibody against AChRs, and acetylcholinesterase (AChE) was tagged with anti-AChE. Molecular features of multicolor labeled palisade endings were analyzed in the confocal scanning microscope, and their ultrastructural features were revealed in the transmission electron microscope.

All palisade endings expressed the exocytotic proteins SNAP25, syntaxin, synaptobrevin, synaptotagmin, and complexin. At the ultrastructural level, vehinery, suggesting neurotransmitter release. However, AChRs were not associated with palisade endings, so there is no binding site for acetylcholine, and, due to low/absent AChE activity, insufficient neurotransmitter removal. Thus, the present findings indicate that palisade endings belong to an effector system that is very different from that found in other skeletal muscles.

To investigate the functional role of immunoproteasome subunit β5i in pathologic retinal neovascularization (RNV) and its ability to link the immunoproteasome and autophagy.

Oxygen-induced retinopathy (OIR) was induced in wild-type (WT) and β5i knockout (KO) mouse pups on a C57BL/6J background. Proteasome catalytic subunit expression and proteasome activity were evaluated by quantitative real-time PCR (qPCR) and proteasome activity. Retinal vascular anatomy and neovascularization were characterized and quantified by retinal vascular flat-mount staining, fluorescence angiography, platelet endothelial cell adhesion molecule (PECAM) immunostaining, and hematoxylin and eosin staining. Correlation factors, including VEGF and ICAM-1, were detected by qPCR. Autophagy was examined by transmission electron microscopy (TEM). Autophagy biomarkers, including LC3, P62, ATG5, and ATG7, were measured by immunostaining and immunoblotting. The protein interaction between β5i and ATG5 was detected by immunoprecipitation.

nking the immunoproteasome and autophagy.

Müller glial-mesenchymal transition (GMT) is reported as the fibrogenic mechanism promoted by TGF-β-SNAIL axis in Müller cells transdifferentiated into myofibroblasts. Here we show the multifaceted involvement of TGF-β in diabetic fibrovascular proliferation via Müller GMT and VEGF-A production.

Surgically excised fibrovascular tissues from the eyes of patients with proliferative diabetic retinopathy were processed for immunofluorescence analyses of TGF-β downstream molecules. Human Müller glial cells were used to evaluate changes in gene and protein expression with real-time quantitative PCR and ELISA, respectively. Immunoblot analyses were performed to detect TGF-β signal activation.

Müller glial cells in patient fibrovascular tissues were immunopositive for GMT-related molecular markers, including SNAIL and smooth muscle protein 22, together with colocalization of VEGF-A and TGF-β receptors. In vitro administration of TGF-β1/2 upregulated TGFB1 and TGFB2, both of which were suppressed by inhibitors for nuclear factor-κB, glycogen synthase kinase-3, and p38 mitogen-activated protein kinase. Of the various profibrotic cytokines, TGF-β1/2 application exclusively induced Müller glial VEGFA mRNA expression, which was decreased by pretreatment with small interfering RNA for SMAD2 and inhibitors for p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Supporting these findings, TGF-β1/2 stimulation to Müller cells increased the phosphorylation of these intracellular signaling molecules, all of which were also activated in Müller glial cells in patient fibrovascular tissues.

This study underscored the significance of Müller glial autoinduction of TGF-β as a pathogenic cue to facilitate diabetic fibrovascular proliferation via TGF-β-driven GMT and VEGF-A-driven angiogenesis.

This study underscored the significance of Müller glial autoinduction of TGF-β as a pathogenic cue to facilitate diabetic fibrovascular proliferation via TGF-β-driven GMT and VEGF-A-driven angiogenesis.

We investigate the orientation tuning of interocular suppression using a dichoptic masking paradigm in adult controls and amblyopes.

Fourteen adults with anisometropic or mixed amblyopia and 10 control adults participated in our study. Contrast sensitivity was measured by presenting a target Gabor in the tested eye and mean luminance in the untested eye (monocular) and by presenting a target in the tested eye and a bandpass oriented filtered noise in the other eye (masked). Interocular suppression was defined as the thresholds difference between the monocular and masked conditions for each eye. Interocular suppression was measured under parallel and orthogonal suppression configurations. The peak spatial frequency of the target and mask was 0.25 c/d in experiment 1 (low), 1.31 c/d in experiment 2 (mid), and 6.87 c/d in experiment 3 (high).

The masking suppression induced by the amblyopic eye was less strong than that induced by the fellow eye. The suppression from the fellow eye was similar to that observed in the controls.