Drivers of change in physical activity over 18 months in incident Parkinson’s disease

BACKGROUND AND AIM: Physical activity (PA) is important to maintain a healthy lifestyle. Beneficial effects of activity have been reported for people with Parkinson's disease (PD), and there is evidence to suggest it may be neuroprotective. Most people with PD do not achieve the recommended levels of PA, although the reasons for this are unclear [1]. It is important to understand the drivers of PA especially in the early stages of the disease before the secondary effects of PD are established. The aim of this study was to examine change in PA over 18 months in an incident cohort of PD and to identify possible drivers of PA. METHODS: For this preliminary analysis 35 people with PD [mean (SD) age 67.4 (10.4) years; 14 females; UPDRS III 23(10)] were recruited through an ongoing longitudinal study (ICICLE-PD). PA was measured for 7 days at baseline and 18 months, using a uniaxial accelerometer (ActivPal TM1,10Hz). PA outcomes included: 1) pattern of accumulation of activity (alpha); 2) number of steps accumulated in walking bouts of 100 steps (long); and 3) variability of stepping bout duration. A range of cognitive, motor, affective and quality of life outcomes were measured, including PD questionnaire (PDQ), the Geriatric Depression Scale (GDS), UPDRSIII and the Activities Balance Self- Confidence Scale (ABC). Multiple regression analysis was used to identify independent predictors of change in PA. RESULTS: At 18 months, there was a non-significant trend for people with PD to accumulate more steps in shorter bouts and fewer in longer bouts. Results from multiple regression showed that younger age, less severe PDQ stigma and lower PDQ mobility scores were independent predictors of a decrease in the number of steps accumulated in long bouts (F (5, 34) = 7.00, p < 0.001), with the model explaining 47% of the variance. In addition, more severe PDQ stigma and mobility scores were independent predictors of a decrease in steps accumulated in moderate bouts, total time spent walking and alpha. Post-hoc analysis showed these findings were independent of change in working status and medication. There were no significant independent predictors of change in variability of bout duration or number of steps accumulated in short bouts. CONCLUSION: Age, stigma and mobility are significant drivers of change in PA in early PD. This behavioural change reflects an early response to PD, even in those whose levels of physical activity should arguably be least affected. Future analysis will be performed on a larger cohort and compared with aged-matched controls to gain a greater understanding of the motor and non-motor drivers of PA in PD

Combining the Petasis 3‑Component Reaction with Multiple Modes of Cyclization: A Build/Couple/Pair Strategy for the Synthesis of Densely Functionalized Small Molecules

A <i>build/couple/pair</i> strategy for the synthesis of complex and densely functionalized small molecules is presented. The strategy relies on synthetically tractable building blocks (build), that is, diversely substituted hydrazides, α-hydroxy aldehydes, and boronic acids, which undergo Petasis 3-component reactions (couple) to afford densely functionalized <i>anti</i>-hydrazido alcohols. The resulting scaffolds can subsequently be converted via chemoselective cyclization reactions (pair), including intramolecular Diels–Alder or Ru-alkylidene catalyzed ring-closing metathesis, into sets of structurally diverse heterocycles in good yields in only 3–4 steps

Build/Couple/Pair Strategy Combining the Petasis 3-Component Reaction with Ru-Catalyzed Ring-Closing Metathesis and Isomerization

A “build/couple/pair” pathway for the systematic synthesis of structurally diverse small molecules is presented. The Petasis 3-component reaction was used to synthesize <i>anti</i>-amino alcohols displaying pairwise reactive combinations of alkene moieties. Upon treatment with a ruthenium alkylidene-catalyst, these dienes selectively underwent ring-closing metathesis reactions to form 5- and 7-membered heterocycles and cyclic aminals via a tandem isomerization/<i>N</i>-alkyliminium cyclization sequence

Ruthenium Hydride/Brønsted Acid-Catalyzed Tandem Isomerization/<i>N</i>‑Acyliminium Cyclization Sequence for the Synthesis of Tetrahydro-β-carbolines

This paper describes an efficient tandem sequence for the synthesis of 1,2,3,4-tetrahydro-β-carbolines (THBCs) relying on a ruthenium hydride/Brønsted acid-catalyzed isomerization of allylic amides to <i>N</i>-acyliminium ion intermediates which are trapped by a tethered indole nucleophile. The methodology provides not only a convenient “aldehyde-free” alternative to the classical Pictet–Spengler reaction but also attractive possibilities for total synthesis, including rapid generation of molecular complexity and formation of quaternary stereogenic centers. TBHCs can also be accessed by harnessing the Suzuki cross-coupling reaction to the isomerization/<i>N</i>-acyliminium cyclization sequence. Finally, diastereo- and enantioselective versions of the title reaction have been examined using substrate control (with dr >15: 1) and asymmetric catalysis (ee up to 57%), respectively

Ruthenium Hydride/Brønsted Acid-Catalyzed Tandem Isomerization/<i>N</i>‑Acyliminium Cyclization Sequence for the Synthesis of Tetrahydro-β-carbolines

This paper describes an efficient tandem sequence for the synthesis of 1,2,3,4-tetrahydro-β-carbolines (THBCs) relying on a ruthenium hydride/Brønsted acid-catalyzed isomerization of allylic amides to <i>N</i>-acyliminium ion intermediates which are trapped by a tethered indole nucleophile. The methodology provides not only a convenient “aldehyde-free” alternative to the classical Pictet–Spengler reaction but also attractive possibilities for total synthesis, including rapid generation of molecular complexity and formation of quaternary stereogenic centers. TBHCs can also be accessed by harnessing the Suzuki cross-coupling reaction to the isomerization/<i>N</i>-acyliminium cyclization sequence. Finally, diastereo- and enantioselective versions of the title reaction have been examined using substrate control (with dr >15: 1) and asymmetric catalysis (ee up to 57%), respectively