Association of Neurocognitive and Physical Function With Gait Speed in Midlife.

Importance: Gait speed is a well-known indicator of risk of functional decline and mortality in older adults, but little is known about the factors associated with gait speed earlier in life. Objectives: To test the hypothesis that slow gait speed reflects accelerated biological aging at midlife, as well as poor neurocognitive functioning in childhood and cognitive decline from childhood to midlife. Design, Setting, and Participants: This cohort study uses data from the Dunedin Multidisciplinary Health and Development Study, a population-based study of a representative 1972 to 1973 birth cohort in New Zealand that observed participants to age 45 years (until April 2019). Data analysis was performed from April to June 2019. Exposures: Childhood neurocognitive functions and accelerated aging, brain structure, and concurrent physical and cognitive functions in adulthood. Main Outcomes and Measures: Gait speed at age 45 years, measured under 3 walking conditions: usual, dual task, and maximum gait speeds. Results: Of the 1037 original participants (91% of eligible births; 535 [51.6%] male), 997 were alive at age 45 years, of whom 904 (90.7%) had gait speed measured (455 [50.3%] male; 93% white). The mean (SD) gait speeds were 1.30 (0.17) m/s for usual gait, 1.16 (0.23) m/s for dual task gait, and 1.99 (0.29) m/s for maximum gait. Adults with more physical limitations (standardized regression coefficient [ß], -0.27; 95% CI, -0.34 to -0.21; P < .001), poorer physical functions (ie, weak grip strength [ß, 0.36; 95% CI, 0.25 to 0.46], poor balance [ß, 0.28; 95% CI, 0.21 to 0.34], poor visual-motor coordination [ß, 0.24; 95% CI, 0.17 to 0.30], and poor performance on the chair-stand [ß, 0.34; 95% CI, 0.27 to 0.40] or 2-minute step tests [ß, 0.33; 95% CI, 0.27 to 0.39]; all P < .001), accelerated biological aging across multiple organ systems (ß, -0.33; 95% CI, -0.40 to -0.27; P < .001), older facial appearance (ß, -0.25; 95% CI, -0.31 to -0.18; P < .001), smaller brain volume (ß, 0.15; 95% CI, 0.06 to 0.23; P < .001), more cortical thinning (ß, 0.09; 95% CI, 0.02 to 0.16; P = .01), smaller cortical surface area (ß, 0.13; 95% CI, 0.04 to 0.21; P = .003), and more white matter hyperintensities (ß, -0.09; 95% CI, -0.15 to -0.02; P = .01) had slower gait speed. Participants with lower IQ in midlife (ß, 0.38; 95% CI, 0.32 to 0.44; P < .001) and participants who exhibited cognitive decline from childhood to adulthood (ß, 0.10; 95% CI, 0.04 to 0.17; P < .001) had slower gait at age 45 years. Those with poor neurocognitive functioning as early as age 3 years had slower gait in midlife (ß, 0.26; 95% CI, 0.20 to 0.32; P < .001). Conclusions and Relevance: Adults' gait speed is associated with more than geriatric functional status; it is also associated with midlife aging and lifelong brain health.

Functional characterization of the ecdysteroid UDP-glucosyl transferase gene of Helicoverpa armigera single-enveloped nucleopolyhedrovirus isolated in South Africa.

The ecdysteroid UDP-glucosyltransferase (egt) gene of a single enveloped nucleopolyhedrovirus was located using an Hz-SNPV gene-specific probe. This SNPV was found infecting a colony of Helicoverpa armigera (HaSNPV) in the Western Cape region of South Africa. The open reading frame of the HaSNPV-SA egt is 1.548 nucleotides long and encodes a predicted protein of 516 amino acids with a Mr of 58,897-kDa. The 5'-noncoding region contained an early transcription initiation motif (CAGT) and a baculovirus late transcription motif (ATAAG). A transcription enhancer sequence (GATA) was also identified. Two possible TATA boxes together with an AT rich region were also recognized. A putative signal peptide of 20 residues was present at the N-terminus of the predicted EGT sequence. A polyadenylation signal (AATAAA) was found downstream of the translation stop codon. Five Helicoverpa NPV EGT's that have an extremely high degree of nucleotide and amino acid sequence homology were used in this study. Single nucleotide polymorphisms (SNPs) within the gene were tabulated. The Helicoverpa NPV egts seem to be closely related to the egt genes of Mamestra configurata NPV (MacoNPV), Buzura suppressaria NPV (BusuSNPV) and Spodoptera exigua NPV (SeMNPV) with amino acid identities of approximately 50%. The Helicoverpa NPV EGTs show ten conserved motifs with other EGTs. A phylogenetic tree of 27 baculovirus EGTs and a human UDP-glucoronosyltransferase was constructed using Neighbour-joining within CLUSTAL X. That a secreted and active EGT is encoded by HaSNPV-SA was confirmed by assay of infected cell culture medium.