Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Convergent functional genomic studies of omega-3 fatty acids in stress reactivity, bipolar disorder and alcoholism

Omega-3 fatty acids have been proposed as an adjuvant treatment option in psychiatric disorders. Given their other health benefits and their relative lack of toxicity, teratogenicity and side effects, they may be particularly useful in children and in females of child-bearing age, especially during pregnancy and postpartum. A comprehensive mechanistic understanding of their effects is needed. Here we report translational studies demonstrating the phenotypic normalization and gene expression effects of dietary omega-3 fatty acids, specifically docosahexaenoic acid (DHA), in a stress-reactive knockout mouse model of bipolar disorder and co-morbid alcoholism, using a bioinformatic convergent functional genomics approach integrating animal model and human data to prioritize disease-relevant genes. Additionally, to validate at a behavioral level the novel observed effects on decreasing alcohol consumption, we also tested the effects of DHA in an independent animal model, alcohol-preferring (P) rats, a well-established animal model of alcoholism. Our studies uncover sex differences, brain region-specific effects and blood biomarkers that may underpin the effects of DHA. Of note, DHA modulates some of the same genes targeted by current psychotropic medications, as well as increases myelin-related gene expression. Myelin-related gene expression decrease is a common, if nonspecific, denominator of neuropsychiatric disorders. In conclusion, our work supports the potential utility of omega-3 fatty acids, specifically DHA, for a spectrum of psychiatric disorders such as stress disorders, bipolar disorder, alcoholism and beyond

Relationship of unilateral total hip arthroplasty (THA) to contralateral and ipsilateral knee joint degeneration - a longitudinal 3T MRI study from the Osteoarthritis Initiative (OAI).

ObjectiveTo evaluate the association of prevalent unilateral total hip arthroplasty (THA) with worsening of degenerative knee abnormalities and clinical outcomes in the ipsilateral and contralateral knee.MethodsBoth knees of 30 individuals in the Osteoarthritis Initiative (OAI) with unilateral THA (n = 14 left, n = 16 right) at baseline were assessed at baseline and at 4-year follow-up for Whole-organ MR Imaging Scores (WORMS), cartilage T2 relaxation times (only available for right knees), Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores and upper leg isometric strength. Right knees of 30 individuals without THA were analyzed as controls. Contralateral knees were compared to ipsilateral knees with paired t-tests and to control knees with multivariate regression analysis adjusting for covariates.ResultsIn paired analyses, compared to ipsilateral knees, contralateral knees had higher WORMS total (P = 0.008) and cartilage scores (P = 0.007) at baseline. Over 4 years contralateral knees worsened more on WORMS total score (P = 0.008). Cartilage T2 values were higher in knees contralateral to the THA (baseline, P = 0.02; follow-up, P < 0.001). Contralateral knees had greater declines in knee extension strength (P = 0.04) and had a trend for greater worsening in WOMAC pain, stiffness, function and total scores (P = 0.04-0.09). Similar results were found comparing contralateral knees with control knees in multivariate regression models.ConclusionsPrevalent unilateral THA is associated with an greater progression of degenerative findings for the knee contralateral to THA

Relationship of unilateral total hip arthroplasty (THA) to contralateral and ipsilateral knee joint degeneration - a longitudinal 3T MRI study from the Osteoarthritis Initiative (OAI)

Objective: To evaluate the association of prevalent unilateral total hip arthroplasty (THA) with worsening of degenerative knee abnormalities and clinical outcomes in the ipsilateral and contralateral knee. Methods: Both knees of 30 individuals in the Osteoarthritis Initiative (OAI) with unilateral THA (n = 14 left, n = 16 right) at baseline were assessed at baseline and at 4-year follow-up for Whole-organ MR Imaging Scores (WORMS), cartilage T2 relaxation times (only available for right knees), Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores and upper leg isometric strength. Right knees of 30 individuals without THA were analyzed as controls. Contralateral knees were compared to ipsilateral knees with paired t-tests and to control knees with multivariate regression analysis adjusting for covariates. Results: In paired analyses, compared to ipsilateral knees, contralateral knees had higher WORMS total (P = 0.008) and cartilage scores (P = 0.007) at baseline. Over 4 years contralateral knees worsened more on WORMS total score (P = 0.008). Cartilage T2 values were higher in knees contralateral to the THA (baseline, P = 0.02; follow-up, P < 0.001). Contralateral knees had greater declines in knee extension strength (P = 0.04) and had a trend for greater worsening in WOMAC pain, stiffness, function and total scores (P = 0.04-0.09). Similar results were found comparing contralateral knees with control knees in multivariate regression models. Conclusions: Prevalent unilateral THA is associated with an greater progression of degenerative findings for the knee contralateral to THA

Weight loss over 48 months is associated with reduced progression of cartilage T2 relaxation time values: Data from the osteoarthritis initiative

Purpose To assess whether changes in knee cartilage MR-based T2 relaxation times are associated with weight loss in individuals with risk factors for knee osteoarthritis (OA) compared with controls with stable weight. Materials and Methods One hundred twenty-seven individuals with risk factors for knee OA were studied: 62 subjects had a body mass index (BMI) decrease≥10% over 48 months and 65 controls had a BMI change <3%. Cartilage segmentation from five knee compartments at baseline and 48-month follow-up was performed, and T2 maps were generated. The association of change in T2 values over 48 months in the weight-loss group versus the control group was assessed using multiple linear regression models. Results Weight loss was associated with significantly smaller increases in cartilage T2 in the medial femoral condyle (P = 0.035) and overall medial compartment (P = 0.006) compared with the controls. In a subgroup analysis comparing weight-loss subjects who were obese (BMI≥30 kg/m ) and overweight (BMI 25-30 kg/m ) at baseline, obesity was associated with smaller increases in cartilage T2 values in the medial femoral condyle (P = 0.022), lateral femoral condyle (P = 0.015), patella (P = 0.002), and globally across all compartments (P = 0.002). Conclusion A decrease in BMI of ≥ 10% was associated with a slower progression of T2 values in individuals with risk factors for OA, suggesting a beneficial impact of weight loss on cartilage matrix degeneration. J. Magn. Reson. Imaging 2015;41:1272-1280. 2

Weight loss over 48 months is associated with reduced progression of cartilage T2 relaxation time values: Data from the osteoarthritis initiative

Purpose To assess whether changes in knee cartilage MR-based T2 relaxation times are associated with weight loss in individuals with risk factors for knee osteoarthritis (OA) compared with controls with stable weight. Materials and Methods One hundred twenty-seven individuals with risk factors for knee OA were studied: 62 subjects had a body mass index (BMI) decrease≥10% over 48 months and 65 controls had a BMI change <3%. Cartilage segmentation from five knee compartments at baseline and 48-month follow-up was performed, and T2 maps were generated. The association of change in T2 values over 48 months in the weight-loss group versus the control group was assessed using multiple linear regression models. Results Weight loss was associated with significantly smaller increases in cartilage T2 in the medial femoral condyle (P = 0.035) and overall medial compartment (P = 0.006) compared with the controls. In a subgroup analysis comparing weight-loss subjects who were obese (BMI≥30 kg/m2) and overweight (BMI 25-30 kg/m2) at baseline, obesity was associated with smaller increases in cartilage T2 values in the medial femoral condyle (P = 0.022), lateral femoral condyle (P = 0.015), patella (P = 0.002), and globally across all compartments (P = 0.002). Conclusion A decrease in BMI of ≥ 10% was associated with a slower progression of T2 values in individuals with risk factors for OA, suggesting a beneficial impact of weight loss on cartilage matrix degeneration. J. Magn. Reson. Imaging 2015;41:1272-1280

Racial differences in biochemical knee cartilage composition between African-American and Caucasian-American women with 3 T MR-based T2 relaxation time measurements--data from the Osteoarthritis Initiative.

ObjectiveTo determine whether knee cartilage composition differs between African-American and Caucasian-American women at risk for Osteoarthritis (OA) using in vivo 3 T MRI T2 relaxation time measurements.MethodsRight knee MRI studies of 200 subjects (100 African-American women, and 100 closely matched Caucasian-American women) were selected from the Osteoarthritis Initiative (OAI). Knee cartilage was segmented in the patellar (PAT), medial and lateral femoral (MF/LF), and medial and lateral tibial compartments (MT/LT)). Mean T2 relaxation time values per compartment and per whole joint cartilage were generated and analyzed spatially via laminar and grey-level co-occurrence matrix (GLCM) texture methods. Presence and severity of cartilage lesions per compartment were graded using a modified WORMS grading. Statistical analysis employed paired t- and McNemar testing.ResultsWhile African-American women and Caucasian-Americans had similar WORMS cartilage lesion scores (P = 0.970), African-Americans showed significantly lower mean T2 values (∼1 ms difference; ∼0.5SD) than Caucasian-Americans in the whole knee cartilage (P < 0.001), and in the subcompartments (LF: P = 0.001, MF: P < 0.001, LT: P = 0.019, MT: P = 0.001) and particularly in the superficial cartilage layer (whole cartilage: P < 0.001, LF: P < 0.001, MF: P < 0.001, LT: P = 0.003, MT: P < 0.001). T2 texture parameters were also significantly lower in the whole joint cartilage of African-Americans than in Caucasian-Americans (variance: P = 0.001; contrast: P = 0.018). In analyses limited to matched pairs with no cartilage lesions in a given compartment, T2 values remained significantly lower in African-Americans.ConclusionUsing T2 relaxation time as a biomarker for the cartilage collagen network, our findings suggest racial differences in the biochemical knee cartilage composition between African-American and Caucasian-American women

Racial differences in biochemical knee cartilage composition between African-American and Caucasian-American women with 3 T MR-based T2 relaxation time measurements - data from the Osteoarthritis Initiative

Objective: To determine whether knee cartilage composition differs between African-American and Caucasian-American women at risk for Osteoarthritis (OA) using in vivo 3 T MRI T2 relaxation time measurements. Methods: Right knee MRI studies of 200 subjects (100 African-American women, and 100 closely matched Caucasian-American women) were selected from the Osteoarthritis Initiative (OAI). Knee cartilage was segmented in the patellar (PAT), medial and lateral femoral (MF/LF), and medial and lateral tibial compartments (MT/LT)). Mean T2 relaxation time values per compartment and per whole joint cartilage were generated and analyzed spatially via laminar and grey-level co-occurrence matrix (GLCM) texture methods. Presence and severity of cartilage lesions per compartment were graded using a modified WORMS grading. Statistical analysis employed paired t- and McNemar testing. Results: While African-American women and Caucasian-Americans had similar WORMS cartilage lesion scores (P = 0.970), African-Americans showed significantly lower mean T2 values (~1 ms difference; ~0.5SD) than Caucasian-Americans in the whole knee cartilage (P < 0.001), and in the subcompartments (LF: P = 0.001, MF: P < 0.001, LT: P = 0.019, MT: P = 0.001) and particularly in the superficial cartilage layer (whole cartilage: P < 0.001, LF: P < 0.001, MF: P < 0.001, LT: P = 0.003, MT: P < 0.001). T2 texture parameters were also significantly lower in the whole joint cartilage of African-Americans than in Caucasian-Americans (variance: P = 0.001; contrast: P = 0.018). In analyses limited to matched pairs with no cartilage lesions in a given compartment, T2 values remained significantly lower in African-Americans. Conclusion: Using T2 relaxation time as a biomarker for the cartilage collagen network, our findings suggest racial differences in the biochemical knee cartilage composition between African-American and Caucasian-American women