Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment

Cortical atrophy is a biomarker of Alzheimer’s disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. V̇O2peak increased an average of 8.49%, which was comparable between MCI and healthy elders. Overall, cortical thickness was stable except for a significant decrease in the right fusiform gyrus in both groups. However, improvement in cardiorespiratory fitness due to the intervention (V̇O2peak) was positively correlated with cortical thickness change in the bilateral insula, precentral gyri, precuneus, posterior cingulate, and inferior and superior frontal cortices. Moreover, MCI participants exhibited stronger positive correlations compared to healthy elders in the left insula and superior temporal gyrus. A 12-week moderate intensity walking intervention led to significantly improved fitness in both MCI and healthy elders. Improved V̇O2peak was associated with widespread increased cortical thickness, which was similar between MCI and healthy elders. Thus, regular exercise may be an especially beneficial intervention to counteract cortical atrophy in all risk groups, and may provide protection against future cognitive decline in both healthy elders and MCI

Entropy and Barrier-Hopping Determine Conformational Viscoelasticity in Single Biomolecules

Biological macromolecules have complex and non-trivial energy landscapes, endowing them a unique conformational adaptability and diversity in function. Hence, understanding the processes of elasticity and dissipation at the nanoscale is important to molecular biology and also emerging fields such as nanotechnology. Here we analyse single molecule fluctuations in an atomic force microscope (AFM) experiment using a generic model of biopolymer viscoelasticity that importantly includes sources of local `internal' conformational dissipation. Comparing two biopolymers, dextran and cellulose, polysaccharides with and without the well-known `chair-to-boat' transition, reveals a signature of this simple conformational change as minima in both the elasticity and internal friction around a characteristic force. A calculation of two-state populations dynamics offers a simple explanation in terms of an elasticity driven by the entropy, and friction by barrier-controlled hopping, of populations on a landscape. The microscopic model, allows quantitative mapping of features of the energy landscape, revealing unexpectedly slow dynamics, suggestive of an underlying roughness to the free energy.Comment: 25 pages, 7 figures, naturemag.bst, modified nature.cls (naturemodified.cls

Adult Foot and Ankle Trauma at Schroeder Mounds (11He177): A Late Woodland Period Site in Illinois

Foot and ankle trauma in adults may be accidental or caused by physical activities that increase the likelihood of injury. Little is known about the organization of labor or health of the presumed forager-farmers of the later Late Woodland (~AD 900-1150) period mortuary site of Schroeder Mounds (Henderson County, Illinois). In order to better understand the physical activities or hazards of the individuals from this site, thirty-seven adult skeletons preserving at least one essentially complete mid (metatarsals) and hind (tarsals) foot were examined for reactive changes that are consistent with traumatic injury. This data is compared to published reports from other Illinois Late Woodland sites. The study is comprised of 17 females, 14 males, and 6 skeletally unsexable adults. In the Schroeder Mounds sample, there were six cases of foot/ankle pathology (6/37, 13.5%), five of which (3/17, 17.6% females; 2/14, 14.3% males) are diagnostically traumatic injuries (5/37, 13.5%). A sixth case is a likely congenital foreshortening of a metatarsal (brachymetatarsia). There is no significant difference between the sexes in the frequency of ankle/foot trauma (p=1.000, Fisher’s test). However, given the small sample size, the results are tentative. The trauma pattern of the Schroeder mounds cases consists of the clinically infrequent tarsometatarsal (Lisfranc joint complex) high-energy misstep injuries, a vertical jump/fall (Pilon fracture), and stress (“march”) fractures of the metatarsal shafts. These injuries are consistent with a highly active and/or mobile community where trauma hazards are arguably equally experienced by both adult males and females

The effect of relative plasma plume delay on the properties of complex oxide films grown by multi-laser multi-target combinatorial pulsed laser deposition

We report the effects of relative time delay of plasma plumes on thin garnet crystal films fabricated by dual-beam, combinatorial pulsed laser deposition. Relative plume delay was found to affect both the lattice constant and elemental composition of mixed Gd3Ga5O12 (GGG) and Gd3Sc2Ga5O12 (GSGG) films. Further analysis of the plasmas was undertaken using a Langmuir probe, which revealed that for relative plume delays shorter than ~200 µs, the second plume travels through a partial vacuum created by the first plume, leading to higher energy ion bombardment of the growing film. The resulting in-plane stresses are consistent with the transition to a higher value of lattice constant normal to the film plane that was observed around this delay value. At delays shorter than ~10 µs, plume propagation was found to overlap, leading to scattering of lighter ions from the plume and a change in stoichiometry of the resultant films

Speech and language therapy versus placebo or no intervention for speech problems in Parkinson's disease

Parkinson's disease patients commonly suffer from speech and vocal problems including dysarthric speech, reduced loudness and loss of articulation. These symptoms increase in frequency and intensity with progression of the disease). Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids

Low fruit and vegetable consumption is associated with low knowledge of the details of the 5-a-day fruit and vegetable message in the UK: findings from two cross-sectional questionnaire studies.

BACKGROUND: This project aimed to understand the details of the 5-a-day fruit and vegetable (FV) message (which foods are included, portion sizes, the need for variety, reasons for consumption) least known by UK consumers, and most associated with low FV consumption. METHODS: Study 1 assessed FV consumption, knowledge of the details of the message, and relationships between these, using a short questionnaire administered face-to-face to an opportunity sample of one large UK city. Study 2 assessed the same variables using a comprehensive postal questionnaire administered across the UK to a representative population sample. RESULTS: Five hundred and seven respondents completed Study 1 and 247 respondents completed Study 2. The majority of individuals in both studies were aware of the 5-a-day message and could recount this correctly. In both studies, however, knowledge of the details of the message was low, and lower knowledge was associated with lower FV consumption. Respondents had lowest knowledge of the details of the message related to portion sizes and the need for variety. However, FV consumption was not independently associated with knowledge of any one aspect of the message. CONCLUSIONS: These findings suggest that, although most of the UK population sampled were aware of the 5-a-day FV message and could recount this correctly, details of the 5-a-day FV message were not well known, and that FV consumption was related to this knowledge. These findings suggest that strategies to increase FV consumption will benefit from increasing UK consumers' knowledge of the details of the 5-a-day FV message

Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence

Viral immune evasion strategies target key aspects of the host antiviral response. Recently, it has been recognized that Toll-like receptors (TLRs) have a role in innate defense against viruses. Here, we define the function of the vaccinia virus (VV) protein A46R and show it inhibits intracellular signalling by a range of TLRs. TLR signalling is triggered by homotypic interactions between the Toll-like-interleukin-1 resistance (TIR) domains of the receptors and adaptor molecules. A46R contains a TIR domain and is the only viral TIR domain-containing protein identified to date. We demonstrate that A46R targets the host TIR adaptors myeloid differentiation factor 88 (MyD88), MyD88 adaptor-like, TIR domain-containing adaptor inducing IFN-beta (TRIF), and the TRIF-related adaptor molecule and thereby interferes with downstream activation of mitogen-activated protein kinases and nuclear factor kappaB. TRIF mediates activation of interferon (IFN) regulatory factor 3 (IRF3) and induction of IFN-beta by TLR3 and TLR4 and suppresses VV replication in macrophages. Here, A46R disrupted TRIF-induced IRF3 activation and induction of the TRIF-dependent gene regulated on activation, normal T cell expressed and secreted. Furthermore, we show that A46R is functionally distinct from another described VV TLR inhibitor, A52R. Importantly, VV lacking the A46R gene was attenuated in a murine intranasal model, demonstrating the importance of A46R for VV virulence

Stigma as a fundamental hindrance to the United States opioid overdose crisis response.

Alexander Tsai and co-authors discuss the role of stigma in responses to the US opioid crisis