Interest in the role of sex as a biological variable has increased, including a mandate for the study of both sexes in NIH-funded research. As sex differences exist in both human chronic pain ...conditions and rodent models of nociception, it is critical to understand the impact of sex in nociceptive assays. Choice-based thermal nociceptive tests permit the study of avoidance responses to thermal stimuli compared to traditional nociceptive assays, which measure nocifensive reactions. However, to date no comparison of male and female responses to choice-based tests has been published. Herein, we examined the effect of sex on two choice-based thermal nociceptive tests, the thermal gradient test and the temperature place preference test, in adult rats. The activation of a 10 °C-to-47 °C thermal gradient results in an increase in time spent in the 10 °C zone in females, compared to a reduction in males. Additionally, in a temperature place preference test pairing a surface temperature of 22 °C with either 5 °C, 10 °C, 47 °C, or 50 °C, females appeared to have overall greater tolerance for non-ambient temperatures. Males spent less than 50% of their time in every non-22 °C zone, whereas in females this was only observed when testing 5 °C and 50 °C. Together, these results suggest that male rats show more avoidance behavior than females to both hot and cold non-ambient temperatures when given free access to multiple zones, including at milder temperatures than those typically used to evoke a nociceptive response in traditional hot and cold plate tests.
•Female rats show increased preference for the cold zone in a thermal gradient test.•In thermal preference tests, both males and females show avoidance at 5 ° and 50 °C.•In thermal preference tests, only males avoid 10 ° and 47 °C zones.
Abstract
Objectives
To determine whether the introduction of biological DMARDs (bDMARDs) was associated with reduced incidences of total hip and knee arthroplasty (THA/TKA) among patients with RA ...compared with OA.
Methods
Using a population-based cohort in British Columbia, Canada, RA and OA patients diagnosed between 1995 and 2007 were divided into semi-annual cohorts according to diagnosis date. For each cohort, we calculated 8-year incidence rates of THA and TKA. We compared levels and trends of THA/TKA incidence in RA/OA patients diagnosed during pre-bDMARDs (1995–2001) and post-bDMARDs (2003–2007) periods using interrupted time-series analysis, adjusting for baseline characteristics. Adjusted 8-year total joint arthroplasty incidence estimated for RA/OA cohorts diagnosed five years after bDMARDs introduction were compared with expected rates assuming no bDMARDs introduction, based on extrapolation of pre-bDMARDs trends.
Results
We identified 60 227 RA and 288 260 OA incident cases. For cohorts diagnosed pre-bDMARDs, 8-year THA/TKA incidence rates increased over time in both RA and OA. For cohorts diagnosed post-bDMARDs, these rates decreased over time in RA but continued to increase for OA. For RA, differences between the post- and pre-bDMARDs secular trends in incidence rates were −0.49 (P = 0.002) for THA and −0.36 (P = 0.003) for TKA, compared with +0.40 (P = 0.006) and +0.54 (P < 0.001), respectively, for OA. For RA cohorts diagnosed five years after bDMARDs introduction, 8-year incidences were 26.9% and 12.6% lower for THA and TKA, respectively, than expected rates. In contrast, corresponding rates in OA were higher by 11.7% and 16.6%, respectively.
Conclusion
Arthritis onset after bDMARDs introduction is associated with a significant reduction in THA/TKA incidence in RA, but not in OA. The reduction reflects a significant improvement in RA treatment during the biological era.
To review the reliability and validity of the CAGE questionnaire across different patient populations and discuss its role in the detection of alcohol-related problems.
The Cochrane Database for ...Systematic Reviews, Medline, Embase, and Psychinfo were searched. No systematic reviews were found on the Cochrane Database. Search of the other databases yielded one systematic review and one meta-analysis, on different aspects of CAGE. Three articles on reliability and 16 on validity of CAGE were found and used. Studies generally yielded Level II evidence.
CAGE has demonstrated high test-retest reliability (0.80-0.95), and adequate correlations (0.48-0.70) with other screening instruments. The questionnaire is a valid tool for detecting alcohol abuse and dependence in medical and surgical inpatients, ambulatory medical patients, and psychiatric inpatients (average sensitivity 0.71, specificity 0.90). Its performance in primary care patients has been varied, while it has not performed well in white women, prenatal women, and college students. Furthermore, it is not an appropriate screening test for less severe forms of drinking.
CAGE is short, feasible to use, and easily applied in clinical practice. However, users should be aware of its limitations when interpreting the results. A positive screen should be followed by a proper diagnostic evaluation using standard clinical criteria.
Summary
Chronic liver damage is associated with unique changes in the hemostatic system. Patients with liver disease often show a precariously rebalanced hemostatic system, which is easily tipped ...towards bleeding or thrombotic complications by otherwise benign stimuli. In addition, some clinical studies have shown that hemostatic system components contribute to the progression of liver disease. There is a strong basic science foundation for clinical studies with this particular focus. Chronic and acute liver disease can be modeled in rodents and large animals with a variety of approaches, which span chronic exposure to toxic xenobiotics, diet‐induced obesity, and surgical intervention. These experimental approaches have now provided strong evidence that, in addition to perturbations in hemostasis caused by liver disease, elements of the hemostatic system have powerful effects on the progression of experimental liver toxicity and disease. In this review, we cover the basis of the animal models that are most often utilized to assess the impact of the hemostatic system on liver disease, and highlight the role that coagulation proteases and their targets play in experimental liver toxicity and disease, emphasizing key similarities and differences between models. The need to characterize hemostatic changes in existing animal models and to develop novel animal models recapitulating the coagulopathy of chronic liver disease is highlighted. Finally, we emphasize the continued need to translate knowledge derived from highly applicable animal models to improve our understanding of the reciprocal interaction between liver disease and the hemostatic system in patients.
The distribution of mercury and methylmercury (MeHg) in sediment, mudflats, and marsh soils of the Hg-contaminated tidal Penobscot River was investigated, along with biogeochemical controls on ...production. Average total Hg in surface samples (0–3 cm) ranged from 100 to 1200 ng/g; average MeHg ranged from 5 to 50 ng/g. MeHg was usually highest at or near the surface except in highly mobile mudflats. Although total Hg concentrations in the Penobscot are elevated, it is the accumulation of MeHg that stands out in comparison to other ecosystems. Surface soils in the large Mendall Marsh, about 17 km downstream from the contamination source, contained particularly high %MeHg (averaging 8%). In Mendall marsh soil porewaters, MeHg often accounted for more than half of total Hg.
Salt marshes are areas of particular concern in the Penobscot River, for they are depositional environments for a Hg-contaminated mobile pool of river sediment, hot spots for net MeHg production, and sources of risk to marsh animals. We hypothesized that exceptionally low mercury partitioning between the solid and aqueous phases (with log Kd averaging ~4.5) drives high MeHg in Penobscot marshes. The co-occurrence of iron and sulfide in filtered soil porewaters, sometimes both above 100 μM, suggests the presence of nanoparticulate and/or colloidal metal sulfides. These colloids may be stabilized by high concentrations of aromatic and potentially sulfurized dissolved organic matter (DOM) in marsh soils. Thus, Hg in Penobscot marsh soils appears to be in a highly available for microbial methylation through the formation of DOM-associated HgS complexes. Additionally, low partitioning of MeHg to marsh soils suggests high MeHg bioavailability to animals. Overall, drivers of high MeHg in Penobscot marshes include elevated Hg in soils, low partitioning of Hg to solids, high Hg bioavailability for methylation, rapidly shifting redox conditions in surface marsh soils, and high rates of microbial activity.
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•Penobscot methylmercury (MeHg) > other Hg-contaminated ecosystems•Salt marshes are areas of particular concern for MeHg risk in the Penobscot.•Penobscot salt marsh soil chemistry is particularly favorable for MeHg accumulation.•HgS colloids in marsh porewaters enhance Hg availability for methylation.•Low partitioning of MeHg to marsh soils suggests high bioavailability to animals.
Waterfowl wintering along the lower Penobscot River, Maine continue to be exposed to elevated Hg concentrations from the HoltraChem chlor-alkali plant that operated along the river between 1967 and ...2000. In American black ducks (Anas rubripes) total Hg in duck breast muscle increased with residence time on contaminated marshes, reaching means of 0.82±0.21μg/g ww (wet weight) by the end of the fall hunting season, and prompting Maine to issue a human consumption advisory on duck breast muscle. Methyl Hg comprised over 99% of the total Hg in breast muscle. The ratio of Hg concentrations in blood and muscle were strongly correlated and approached 1:1 after extended residence times. Primary feather (P1) total Hg concentrations averaged 2.2±1.3μg/g fw (fresh weight), verifying low Hg exposure during feather growth on distant breeding grounds the preceding summer. Mercury concentrations in black ducks, following winter residence along the lower Penobscot exceeded levels associated with reproductive toxicity. Carry-over of Hg to summer breeding grounds may limit the subsequent reproductive success of black ducks.
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•Mercury (Hg) exceeds safe consumption limits in waterfowl during the fall hunting season along the lower Penobscot River, Maine•Primary feather Hg concentrations document low mercury exposure on breeding grounds•Mercury concentrations increase with residence time during fall and winter•Mercury concentrations in duck blood and breast muscle are strongly correlated•By spring, Hg concentrations in ducks exceed levels associated with reproductive toxicity and may carry-over to summer breeding grounds
Abstract
Objective
To identify magnetic resonance imaging (MRI) predictors (cartilage C, osteophytes O and meniscus M scores) of prevalent and 3-year incident medial tibiofemoral (MTF) and lateral ...tibiofemoral (LTF) knee joint tenderness and patellofemoral (PF) grind.
Methods
Population-based knee pain cohort aged 40–79 was assessed at baseline (
N
= 255), 3- and 7-year follow-up (
N
= 108 × 2 = 216). COM scores were measured at 6/8/6 subregions respectively. Age-sex-BMI adjusted logistic models predicted prevalence versus relevant COM predictors (medial, lateral or patellar / trochlear groove scores). Fully adjusted models also included all relevant COM predictors. Binary generalized estimating equations models predicting 3-year incidence were also adjusted for individual follow-up time between cycles.
Results
Significant predictors of prevalent MTF tenderness: medial femoral cartilage (fully adjusted odds ratio aOR 1.84; 95% confidence interval CI 1.11, 3.05), female (aOR = 3.05; 1.67, 5.58), BMI (aOR = 1.53 per 5 units BMI; 1.10, 2.11). Predictors of prevalent LTF tenderness: female (aOR = 2.18; 1.22, 3.90). There were no predictors of prevalent PF grind in the fully adjusted model. However, medial patellar osteophytes was predictive in the age-sex-BMI adjusted model. There were no predictors of 3-year incident MTF tenderness. Predictors of 3-year incident LTF tenderness: female (aOR = 3.83; 1.25, 11.77). Predictors of 3-year incident PF grind: lateral patellar osteophytes (aOR = 4.82; 1.69, 13.77). In the age-sex-BMI adjusted model, patellar cartilage was also a predictor.
Conclusion
We explored potential MRI predictors of prevalent and 3-year incident MTF/LTF knee joint tenderness and PF grind. These findings could guide preemptive strategies aimed at reducing these symptoms in the present and future (3-year incidence).
Objective To develop a whole-joint, unidimensional, irreversible, and fine-grained MRI knee osteoarthritis (OA) severity score, based on cartilage, osteophytes and meniscus (OA-COM), and to predict ...progression across different severity states using OA-COM as outcome and clinical variables as predictors. Methods Population-based knee pain cohort aged 40-79 was assessed at baseline and 7-year follow-up. OA-COM score was defined as the sum of MRI scores for cartilage, osteophytes and menisci, measured at 6, 8 and 6 sites, total score 0-54. To anchor severity levels, we fit cross-sectional logistic models using OA-COM to predict Kellgren-Lawrence (KL) grades in subsets at or one point below each grade. OA-COM threshold scores were selected on sensitivity, specificity, positive and negative predictive value. We developed longitudinal logistic models for OA-COM progression over each threshold over 7 years. Potential predictors included age, sex, BMI, malalignment, physical exam effusion, quadriceps weakness, and crepitus, selected on area under the receiver operating characteristic curve (AUC) and Akaike's Information Criterion (AIC). Results Optimal OA-COM thresholds were 12, 18, 24 and 30, for KL grades 1 to 4. Significant predictors of progression (depending on threshold) included physical exam effusion, malalignment and female sex, with other selected predictors age, BMI and crepitus. Conclusion OA-COM (0-54 range) is a whole-joint, unidimensional, irreversible, and fine-grained MRI OA severity score reflecting cartilage, osteophytes and menisci. OA-COM scores 12, 18, 24 and 30 are equivalent to KL grades 1 to 4, while offering fine-grained differentiation of states between KL grades, and within pre-radiographic disease (KL = 0) or late-stage disease (KL = 4). In modeling, several clinical variables predicted progression across different states over 7 years.
The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint ...replacement surgery, and prevention of OA by reducing obesity and overweight.
We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons.
Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades).
In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere.
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