Preventing Loss of Independence through Exercise (PLIÉ): A Pilot Trial in Older Adults with Subjective Memory Decline and Mild Cognitive Impairment.

BACKGROUND: Preventing Loss of Independence through Exercise (PLIÉ) is a group movement program initially developed for people with mild-to-moderate dementia that integrates principles from several well-established traditions to specifically address the needs of people with cognitive impairment. OBJECTIVE: To investigate whether PLIÉ would benefit cognitive and behavioral outcomes and functional brain connectivity in older adults with milder forms of cognitive impairment. METHODS: Participants (≥55 y) with subjective memory decline (SMD) or mild cognitive impairment (MCI) were assessed with tests of cognitive and physical function, self-report questionnaires, and resting state functional magnetic resonance imaging (rs-fMRI) on a 3 Tesla scanner before and after participating in twice weekly PLIÉ classes for 12 weeks at the San Francisco Veterans Affairs Medical Center. RESULTS: Eighteen participants completed the pre-post intervention pilot trial. We observed significant improvements on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog; effect size 0.34, p = 0.002) and enhanced functional connections between the medial prefrontal cortex (mPFC) and other nodes of the default mode network (DMN) after PLIÉ. Improvements (i.e., lower scores) on ADAS-cog were significantly correlated with enhanced functional connectivity between the mPFC and left lateral parietal cortex (Spearman's ρ= -0.74, p = 0.001) and between the mPFC and right hippocampus (Spearman's ρ= -0.83, p = 0.001). After completing PLIÉ, participants reported significant reductions in feelings of social isolation and improvements in well-being and interoceptive self-regulation. CONCLUSION: These preliminary findings of post-PLIÉ improvements in DMN functional connectivity, cognition, interoceptive self-regulation, well-being and reduced feelings of social isolation warrant larger randomized, controlled trials of PLIÉ in older adults with SMD and MCI.

Synthesis of ABBV-168, a 2'-Bromouridine for the Treatment of Hepatitis C.

ABBV-168 is a dihalogenated nucleotide under investigation for the treatment of hepatitis C virus. Three synthetic routes aimed at achieving the stereoselective installation of the C2' gem-Br,F substitution and subsequent Vorbruggen glycosylation were explored to prepare the penultimate nucleoside intermediate. Development culminated in a route to ABBV-168 featuring a de novo chromatography-free furanose synthesis, protecting group-directed Vorbruggen glycosylation, and highly selective phosphoramidation to furnish the API.

Effects of low-level laser therapy on bone healing and signs of pain in dogs following tibial plateau leveling osteotomy.

OBJECTIVE To assess the effect of low-level laser therapy (LLLT) on markers of synovial inflammation and signs of pain, function, bone healing, and osteoarthritis following tibial plateau leveling osteotomy (TPLO) in dogs with spontaneous cranial cruciate ligament rupture (CCLR). ANIMALS 12 client-owned dogs with unilateral CCLR. PROCEDURES All dogs were instrumented with an accelerometer for 2 weeks before and 8 weeks after TPLO. Dogs were randomly assigned to receive LLLT (radiant exposure, 1.5 to 2.25 J/cm2; n = 6) or a control (red light; 6) treatment immediately before and at predetermined times for 8 weeks after TPLO. Owners completed a Canine Brief Pain Inventory weekly for 8 weeks after surgery. Each dog underwent a recheck appointment, which included physical and orthopedic examinations, force plate analysis, radiography and synoviocentesis of the affected joint, and evaluation of lameness and signs of pain, at 2, 4, and 8 weeks after surgery. Select markers of inflammation were quantified in synovial fluid samples. Variables were compared between the 2 groups. RESULTS For the control group, mean ground reaction forces were greater at 2 and 4 weeks after TPLO and owner-assigned pain scores were lower during weeks 1 through 5 after TPLO, compared with corresponding values for the LLLT group. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the LLLT protocol used had no beneficial effects on signs of pain or pelvic limb function following TPLO. Further research is necessary to evaluate the effects of LLLT and to determine the optimum LLLT protocol for dogs with CCLR.

Pharmacokinetic Analysis of an Oral Multicomponent Joint Dietary Supplement (Phycox®) in Dogs.

Despite the lack of safety, efficacy and pharmacokinetic (PK) studies, multicomponent dietary supplements (nutraceuticals) have become increasingly popular as primary or adjunct therapies for clinical osteoarthritis in veterinary medicine. Phycox® is a line of multicomponent joint support supplements marketed for joint health in dogs and horses. Many of the active constituents are recognized anti-inflammatory and antioxidant agents. Due to a lack of PK studies in the literature for the product, a pilot PK study of select constituents in Phycox® was performed in healthy dogs. Two novel methods of analysis were developed and validated for quantification of glucosamine and select polyphenols using liquid chromatography-tandem mass spectrometry. After a single oral (PO) administrated dose of Phycox®, a series of blood samples from dogs were collected for 24 h post-dose and analyzed for concentrations of glucosamine HCl, hesperetin, resveratrol and naringenin. Non-compartmental PK analyses were carried out. Glucosamine was detected up to 8 h post-dose with a Tmax of 2 h and Cmax of 9.69 µg/mL. The polyphenols were not found at detectable concentrations in serum samples. Co-administration of glucosamine in the Phycox® formulation may enhance the absorption of glucosamine as determined by comparison of glucosamine PK data in the literature.

Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis.

Multicomponent nutraceuticals are becoming increasingly popular treatments or adjunctive therapies for osteoarthritis in veterinary medicine despite lack of evidence of efficacy for many products. The objective of this study was to evaluate the anti-inflammatory and antioxidant activities of a commercially available C-phycocyanin-based nutraceutical and select constituent ingredients in an in-vitro model of canine osteoarthritis. Normal canine articular chondrocytes were used in an in-vitro model of osteoarthritis. Inflammatory conditions were induced using interleukin-1ß. The nutraceutical preparation as a whole, its individual constituents, as well as carprofen were evaluated at concentrations of 0 to 250 µg/mL for reduction of the following inflammatory mediators and indicators of catabolism of the extracellular matrix: prostaglandin E2 (PGE2), tumor necrosis factor-α (TFN-α), interleukin-6 (IL-6), metalloproteinase-3 (MMP-3), nitric oxide, and sulfated glycosaminoglycans (sGAGs). Validated, commercially available assay kits were used for quantitation of inflammatory mediators. The antioxidant capacities, as well as cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and lipoxygenase (LOX) inhibitory activities of the whole nutraceutical preparation and select constituents, were also assessed using validated commercially available assay kits. The antioxidant capacity of the nutraceutical and constituents was concentration-dependent. The nutraceutical and constituents appear to display anti-inflammatory activity primarily through the inhibition of COX-2. The nutraceutical displayed similar strength to carprofen in reducing TNF-α, IL-6, MMP-3, nitric oxide, and sGAGs at select concentration ranges. The C-phycocyanin (CPC)-based nutraceutical and constituents may be able to mediate 3 primary pathogenic mechanisms of osteoarthritis: inflammation, chondral degeneration, and oxidative stress in vitro. The nutraceutical may be clinically useful in veterinary medicine and its efficacy should be further investigated in vivo.

Les neutraceutiques à composés multiples deviennent de plus en plus populaires en médecine vétérinaire comme traitement ou thérapie alternative pour soigner l'ostéoarthrite, et ce malgré le manque d'évidence de l'efficacité de plusieurs produits. L'objectif de la présente étude était d'évaluer l'activité anti-inflammatoire et anti-oxydante d'un neutraceutique à base de C-phycocyanine disponible commercialement, et d'ingrédients constitutifs sélectionnés dans un modèle in vitro d'ostéoarthrite canine. Des chondrocytes articulaires canins normaux furent utilisés dans un modèle in vitro d'ostéoarthrite. Des conditions inflammatoires ont été induites en utilisant de l'interleukine-1ß. La préparation neutraceutique complète, ses constituants individuels, de même que du caprofène furent évalués à des concentrations de 0 à 250 µg/mL pour la réduction des médiateurs de l'inflammation suivants et des indicateurs du catabolisme de la matrice extracellulaire: prostaglandine E2 (PGE2), facteur-α nécrosant des tumeurs (TNF-α), interleukine-6 (IL-6), métalloprotéinase-3 (MMP-3), oxyde nitreux, et les glycosaminoglycans sulfatés (sGAGs). Des trousses commerciales validées furent utilisées pour la quantification des médiateurs de l'inflammation. Les capacités anti-oxydantes, de même que l'activité inhibitrice envers la cyclo-oxygénase 1 (COX-1), la cyclo-oxygénase-2 (COX-2), et la lipoxygénase (LOX) de la préparation neutraceutique complète et de constituants sélectionnés furent également évaluées au moyen de de trousses commerciales disponibles commercialement. La capacité anti-oxydante du neutraceutique et des constituants était dépendante de la concentration. Le neutraceutique et les constituants semblent manifester leur activité anti-inflammatoire principalement via l'inhibition de COX-2. Dans des écarts de concentrations sélectionnés, le neutraceutique a démontré une capacité similaire au carprofène en réduisant TNF-α, IL-6, MMP-3, oxyde nitreux, et sGAGs. Le neutraceutique à base de C-phycocyanine (CPC) et ses constituants peuvent être en mesure de médier trois mécanismes pathogéniques primaires de l'ostéo-arthrite: l'inflammation, la dégénération chondrale, et le stress oxydatif in vitro. Le neutraceutique pourrait être cliniquement utile en médecine vétérinaire et son efficacité devrait être investigué plus à fond in vivo.(Traduit par Docteur Serge Messier).