Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, affecting 9% of women, and it is responsible for significant morbidity and occupational absence. Clinical assessment is used for ...initial diagnosis and nerve conduction (NC) studies are currently the principal test used to confirm the diagnosis. Sensitivity of NC studies is >85% and specificity is >95%. There is now good evidence that US can be used as an alternative to NC studies to diagnose CTS. US can assess the anatomy of the median nerve and also identify pathology of the surrounding structures that may compress the nerve. Median nerve enlargement (cross-sectional area ≥10 mm(2) at the level of the pisiform bone or tunnel inlet) is the most commonly used parameter to diagnose CTS on US, and sensitivity has been reported to be as high as 97.9% using this parameter. US may also be used to guide therapeutic corticosteroid injection into the carpal tunnel--thus avoiding median nerve injury--and to objectively monitor the response to treatment. There is now sufficient evidence to propose a new paradigm for the diagnosis of CTS that incorporates US. US is proposed as the initial diagnostic test in CTS based on similar sensitivity and specificity to NC studies but higher patient acceptability, lower cost and additional capability to assess carpal tunnel anatomy and guide injection.
Objective
To investigate a role for insulin‐resistant pathways in inflammation and therapeutic targeting for disease modification in rheumatoid arthritis (RA).
Methods
RA disease activity and ...cardiovascular risk factors, including insulin resistance and body mass index (BMI), were assessed in an Irish RA cohort. Glucose transporter 1 (GLUT‐1) and GLUT‐4 activity in RA and osteoarthritis (OA) synovial tissue was examined using immunohistochemistry. Spontaneous release of proinflammatory mediators from ex vivo RA synovial explants and primary synovial fibroblast (SF) cell culture supernatants was quantified by enzyme‐linked immunosorbent assay. Phosphorylated AMP‐activated protein kinase (p‐AMPK) and GLUT‐1 protein expression was analyzed by Western blotting. Cellular glycolytic and oxidative phosphorylation was assessed using extracellular flux analysis.
Results
Insulin resistance was independently associated with both BMI (unstandardized coefficient B 0.113 95% confidence interval (95% CI) 0.059–0.167; P < 0.001) (n = 61) and swollen joint count in 28 joints (SJC28) (B 0.114 95% CI 0.032–0.197; P = 0.008) (n = 61). Increased GLUT‐1 expression in RA synovium (n = 26) versus OA synovium (n = 16) was demonstrated (P = 0.0003), with increased expression in the lining, sublining, and vascular regions. In contrast, decreased GLUT‐4 expression in the RA lining layer (n = 21) versus the OA lining layer (n = 8) was observed (P = 0.0358). Decreased GLUT‐1 protein expression was observed in parallel with increased p‐AMPK protein expression in SFs in the presence of metformin (n = 4). Metformin increased glycolytic activity and decreased oxidative phosphorylation in RASFs (n = 7) (P < 0.05 for both). Metformin or aminoimidazole carboxamide ribonucleotide presence decreased spontaneous production of interleukin‐6 (IL‐6), IL‐8, and monocyte chemotactic protein 1 in RA synovial explants and SFs (n = 5–7).
Conclusion
Insulin resistance is significantly associated with BMI and synovitis in RA, suggesting distinct interplay between glucose availability and inflammation in RA. Furthermore, the effect of metformin on proinflammatory mechanisms suggests a role for AMPK‐modifying compounds in the treatment of RA.
•Vergence–accommodation conflicts that vary quickly cause more visual discomfort than conflicts that vary slowly.•We tested three temporal frequencies of conflict modulation: 0.01, 0.05, and ...0.25Hz.•At 0.01 and 0.05Hz, visual discomfort due to natural and S3D viewing did not differ significantly.•At 0.25Hz, visual discomfort due to S3D viewing was significantly worse than that due to natural viewing.
Stereoscopic (S3D) displays create conflicts between the distance to which the eyes must converge and the distance to which the eyes must accommodate. Such conflicts require the viewer to overcome the normal coupling between vergence and accommodation, and this effort appears to cause viewer discomfort. Vergence–accommodation coupling is driven by the phasic components of the underlying control systems, and those components respond to relatively fast changes in vergence and accommodative stimuli. Given the relationship between phasic changes and vergence–accommodation coupling, we examined how the rate of change in the vergence–accommodation conflict affects viewer discomfort. We used a stereoscopic display that allows independent manipulation of the stimuli to vergence and accommodation. We presented stimuli that simulate natural viewing (i.e., vergence and accommodative stimuli changed together) and stimuli that simulate S3D viewing (i.e., vergence stimulus changes but accommodative stimulus remains fixed). The changes occurred at 0.01, 0.05, or 0.25Hz. The lowest rate is too slow to stimulate the phasic components while the highest rate is well within the phasic range. The results were consistent with our expectation: somewhat greater discomfort was experienced when stimulus distance changed rapidly, particularly in S3D viewing when the vergence stimulus changed but the accommodative stimulus did not. These results may help in the generation of guidelines for the creation and viewing of stereo content with acceptable viewer comfort.
Dosimetry models can be used to predict the dose of inhaled material, but they require several parameters including particle size distribution. The reported particle size distributions for aerosols ...from electronic nicotine delivery system (ENDS) products vary widely and don't always identify a specific product. A low-flow cascade impactor was used to determine the particle size distribution mass median aerodynamic diameter (MMAD); geometric standard deviation (GSD) from 20 different cartridge based ENDS products. To assess losses and vapor phase amount, collection efficiency of the system was measured by comparing the collected mass in the impactor to the difference in ENDS product mass. The levels of nicotine, glycerin, propylene glycol, water, and menthol in the formulations of each product were also measured. Regardless of the ENDS product formulation, the MMAD of all tested products was similar and ranged from 0.9 to 1.2 μm with a GSD ranging from 1.7 to 2.2. There was no consistent pattern of change in the MMAD and GSD as a function of number of puffs (cartridge life). The collection efficiency indicated that 9%–26% of the generated mass was deposited in the collection system or was in the vapor phase. The particle size distribution data are suitable for use in aerosol dosimetry programs.
•ENDS product formulation did not affect the MMAD or GSD.•MMAD and GSD were not affected by puff count.•Vapor phase and losses range from 9% to 26% of the generated mass.•Particle size distribution data are suitable for use in aerosol dosimetry programs.
A unique adult human mouth/throat physical model has been developed to study e-cigarette aerosol dynamics during inhalation. The 3D printed physical model was created from the CT scan of a 28 yr. old ...healthy male. Internal walls of the physical model were lined with a thin layer of cotton gauze that can be saturated with water to replicate the high relative humidity conditions in a human Oral/Pharyngeal cavity. Aerosol hygroscopic growth and deposition inside the physical model from a cartomizer style e-cigarette using a prototype e-liquid formulation was determined by measuring cumulative aerosol mass from five puffs (gravimetric) and for individual constituents (propylene glycol, glycerol, and nicotine) from a single puff (GC/MS analysis). Measurements were taken at constant temperature of 37 °C under both wet and dry inner wall conditions for a for a 3-sec. 55 mL puff. The condition of holding aerosol inside the physical model without airflow for a duration of 3-sec. was also included. For the same puffing conditions of 3-sec puff of 55 mL and a 3-sec. puff hold time, dry wall conditions resulted in a mean aerosol mass loss of 20.9 ± 3.8%, while the total aerosol mass was increased by 150.9 ± 19% under wet wall condition when compared to total aerosol mass entering the physical model entrance. The dramatic increase is due to water vapor uptake by the aerosol particles when flowing through the wetted physical model. Aerosol evolution of individual chemical constituent analysis appeared to vary as a function of volatility.
Advances in the high-throughput omic technologies have made it possible to profile cells in a large number of ways at the DNA, RNA, protein, chromosomal, functional, and pharmacological levels. A ...persistent problem is that some classes of molecular data are labeled with gene identifiers, others with transcript or protein identifiers, and still others with chromosomal locations. What has lagged behind is the ability to integrate the resulting data to uncover complex relationships and patterns. Those issues are reflected in full form by molecular profile data on the panel of 60 diverse human cancer cell lines (the NCI-60) used since 1990 by the U.S. National Cancer Institute to screen compounds for anticancer activity. To our knowledge, CellMiner is the first online database resource for integration of the diverse molecular types of NCI-60 and related meta data.
CellMiner enables scientists to perform advanced querying of molecular information on NCI-60 (and additional types) through a single web interface. CellMiner is a freely available tool that organizes and stores raw and normalized data that represent multiple types of molecular characterizations at the DNA, RNA, protein, and pharmacological levels. Annotations for each project, along with associated metadata on the samples and datasets, are stored in a MySQL database and linked to the molecular profile data. Data can be queried and downloaded along with comprehensive information on experimental and analytic methods for each data set. A Data Intersection tool allows selection of a list of genes (proteins) in common between two or more data sets and outputs the data for those genes (proteins) in the respective sets. In addition to its role as an integrative resource for the NCI-60, the CellMiner package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types.
CellMiner is a relational database tool for storing, querying, integrating, and downloading molecular profile data on the NCI-60 and other cancer cell types. More broadly, it provides a template to use in providing such functionality for other molecular profile data generated by academic institutions, public projects, or the private sector. CellMiner is available online at (http://discover.nci.nih.gov/cellminer/).
The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach.
...Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared.
We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate.
Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.
Survival of children with in-hospital cardiac arrest that does not respond to conventional cardiopulmonary resuscitation (CPR) is poor. We report on survival and early neurological outcomes of ...children with heart disease supported with rapid-response extracorporeal membrane oxygenation (ECMO) to aid cardiopulmonary resuscitation (ECPR).
Children with heart disease supported with ECPR were identified from our ECMO database. Demographic, CPR, and ECMO details associated with mortality were evaluated using multivariable logistic regression. Pediatric overall performance category and pediatric cerebral performance category scores were assigned to ECPR survivors to assess neurological outcomes. There were 180 ECPR runs in 172 patients. Eighty-eight patients (51%) survived to discharge. Survival in patients who underwent ECPR after cardiac surgery (54%) did not differ from nonsurgical patients (46%). Survival did not vary by cardiac diagnosis and CPR duration did not differ between survivors and nonsurvivors. Factors associated with mortality included noncardiac structural or chromosomal abnormalities (OR, 3.2; 95% CI, 1.3-7.9), use of blood-primed ECMO circuit (OR, 7.1; 95% CI, 1.4-36), and arterial pH <7.00 after ECMO deployment (OR, 6.0; 95% CI, 2.1-17.4). Development of end-organ injury on ECMO and longer ECMO duration were associated with increased mortality. Of pediatric overall performance category/pediatric cerebral performance category scores assigned to survivors, 75% had scores ≤2, indicating no to mild neurological injury.
ECPR may promote survival in children with cardiac disease experiencing cardiac arrest unresponsive to conventional CPR with favorable early neurological outcomes. CPR duration was not associated with mortality, whereas patients with metabolic acidosis and noncardiac structural or chromosomal anomalies had higher mortality.
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