Marchernicholson2798
Determinant Factors associated with Three-Dimensional Aromaticity throughout Antiaromatic Cyclophanes.
BACKGROUND AND OBJECTIVES The ProMuscle in Practice intervention combines resistance exercise training and dietary protein intake for community-dwelling older adults, implemented by health care professionals (HCPs). This study aimed to evaluate implementation and context of this intervention in Dutch health care practice. RESEARCH DESIGN AND METHODS We conducted a randomized controlled multicenter intervention study in 5 Dutch municipalities. Eighty-two older adults received the 12-week intensive support intervention (resistance exercise training and individual dietary counseling) and the optional 12-week moderate support intervention (resistance exercise training and a nutrition course). Mixed method data were collected from both participants and HCPs (n = 37) on process indicators recruitment, dose received, acceptability, fidelity, applicability, and context. RESULTS Overall, the intervention was feasible to implement and accepted by participants and HCPs. About two thirds of participants continued with th Gerontological Society of America.MTX is the medication most commonly used for antirheumatic treatment in juvenile idiopathic arthritis. It has high efficacy, is usually well tolerated and has an excellent safety profile. However, frequently intolerance symptoms develop that manifest as nausea, feelings of disgust or abdominal complaints prior to or directly after administration of the medication. No obvious toxicity is causing these intolerance symptoms, but symptoms are strictly limited to MTX and not transferred to other medications. MTX intolerance causes a significant reduction of quality of life in affected patients, frequently puts the treating physician in difficult situations regarding treatment choice, and may lead to uncomfortable decisions whether or not to stop an otherwise effective drug. Conventional countermeasures such as antiemetics, change of route from subcutaneous to oral or vice versa, or taste masking usually have only a limited effect. In this review, we present the current knowledge on MTX intolerance, its clinical picture and commonly employed strategies. We also consider newer behavioural treatment strategies that may offer a more effective symptom control. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email journals.permissions@oup.com.OBJECTIVE To report a chronic recurrent multifocal osteomyelitis (CRMO)-like clinical phenotype with multisystem inflammation associated with a novel gene variant in the spectrum of IL-1-mediated diseases. METHODS A 3-year-old boy presented with recurrent episodes of fever, serositis, pancreatitis and high inflammatory markers with onset at age 13 months. At age 3 years, he started limping. TGF-beta family Imaging revealed multifocal pelvic bone inflammation suggestive of CRMO. Autoinflammation panel testing was non-contributory. Whole exome sequencing (WES) and advanced IL-1 pathway analysis was conducted. RESULTS WES identified a novel homozygous interleukin receptor 1 (IL1RN) variant (c.62C>G; p. Ser21*) (NM_173842.2). Functional analysis of IL1RN mRNA and IL-1 receptor antagonist (IL-1RA) protein confirmed the diagnosis of a deficiency of the IL-1 receptor antagonist (DIRA). Treatment with the nonselective IL-1 inhibitor anakinra resulting in rapid remission; switch to the selective IL-1β antagonist canakinumab led to a flare within 6 weeks. Re-start of anakinra recaptured remission, last documented at the recent 19-month follow-up. CONCLUSION This is the first report of a novel late-onset DIRA confirmed by advanced diagnostic testing. In patients with systemic inflammation and CRMO-like bone lesions, IL1RN testing should be considered; even in the absence of skin manifestations. Non-selective IL-1 inhibition is an effective therapy. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. TGF-beta family All rights reserved. For permissions, please email journals.permissions@oup.com.Bottlenose dolphins (Tursiops truncatus) are long-lived mammals that can develop chronic aging-associated conditions similar to humans, including metabolic syndrome. Initial studies suggest that these conditions may be attenuated in dolphins using a modified fish diet. Serum metabolomics, fatty acid panels, and blood-based health indices were compared between 20 dolphins on a modified, 50% wild-type diet (50% mullet, 25% capelin, and 25% squid and/or herring) and 10 dolphins on a baseline diet (75% capelin and 25% squid and/or herring). Blood samples were collected at Months 0, 1, 3 and 6. Dolphins on the modified diet had lower insulin (7.5 ± 4.0 and 14.8 ± 14.0 μIU/ml, P = 0.039), lower cholesterol (160 ± 26 and 186 ± 24 mg/dl, P = 0.015) and higher hematocrit (46 ± 3 and 44 ± 3%, P = 0.043) by Month 1 compared to controls. Dolphins with anemia (hemoglobin ≤ 12.5 g/dl, n = 6) or low-normal hemoglobin (12.5-13.5 g/dl, n = 3) before placed on the modified diet had normal hemoglobin concentrations (> 13.5 g/dl) by Month 3. The modified diet caused a significant shift in the metabolome, which included 664 known metabolites. Thirty prioritized metabolites at Months 1 and 3 were 100% predictive of dolphins on the modified diet. Among 25 prioritized lipids, 10 (40%) contained odd-chain saturated fatty acids (OCFAs); C150 was the highest-prioritized OCFA. Increased dietary intake of C150 (from 1.3 ± 0.4 to 4.5 ± 1.1 g/day) resulted in increased erythrocyte C150 concentrations (from 1.5 ± 0.3 to 5.8 ± 0.8 μg/ml, P less then 0.0001), which independently predicted raised hemoglobin. Further, increasing age was associated with declining serum C150 (R2 = 0.14, P = 0.04). While higher circulating OCFAs have been previously associated with lower risks of cardiometabolic diseases in humans, further studies are warranted to assess potential active roles of OCFAs, including C150, in attenuating anemia.The neurobiological traits that confer risk for addictions remain poorly understood. However, dopaminergic function throughout the prefrontal cortex, limbic system, and upper brainstem has been implicated in behavioral features that influence addiction vulnerability, including poor impulse control, and altered sensitivity to rewards and punishments (i.e., externalizing features). To test these associations in humans, we measured type-2/3 dopamine receptor (DA2/3R) availability in youth at high vs. low risk for substance use disorders (SUDs). In this study, N = 58 youth (18.5 ± 0.6 years) were recruited from cohorts that have been followed since birth. Participants with either high (high EXT; N = 27; 16 F/11 M) or low pre-existing externalizing traits (low EXT; N = 31; 20 F/11 M) underwent a 90-min positron emission tomography [18F]fallypride scan, and completed the Barratt Impulsiveness Scale (BIS-11), Substance Use Risk Profile scale (SURPS), and Sensitivity to Punishment (SP) and Sensitivity to Reward (SR) questionnaire.