Semantic Memory Functional MRI and Cognitive Function After Exercise Intervention in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer\u27s disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed an fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged 0.048 to 0.0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD

Zebrafish Cytosolic Carboxypeptidases 1 and 5 Are Essential for Embryonic Development

The cytosolic carboxypeptidases (CCPs) are a subfamily of metalloenzymes within the larger M14 family of carboxypeptidases that have been implicated in the post-translational modification of tubulin. It has been suggested that at least four of the six mammalian CCPs function as tubulin deglutamylases. However, it is not yet clear whether these enzymes play redundant or unique roles within the cell. To address this question, genes encoding CCPs were identified in the zebrafish genome. Analysis by quantitative polymerase chain reaction indicated that CCP1, CCP2, CCP5, and CCP6 mRNAs were detectable between 2 h and 8 days postfertilization with highest levels 5–8 days postfertilization. CCP1, CCP2, and CCP5 mRNAs were predominantly expressed in tissues such as the brain, olfactory placodes, and pronephric ducts. Morpholino oligonucleotide-mediated knockdown of CCP1 and CCP5 mRNA resulted in a common phenotype including ventral body curvature and hydrocephalus. Confocal microscopy of morphant zebrafish revealed olfactory placodes with defective morphology as well as pronephric ducts with increased polyglutamylation. These data suggest that CCP1 and CCP5 play important roles in developmental processes, particularly the development and functioning of cilia. The robust and similar defects upon knockdown suggest that each CCP may have a function in microtubule modification and ciliary function and that other CCPs are not able to compensate for the loss of one

Cover zone properties influencing acoustic emission due to corrosion

The deterioration of reinforced concrete is a serviceability problem world-wide. The cover zone plays an important role in the durability and serviceability of concrete and provides the initial barrier to aggressive species. The research presented investigates the potential of acoustic emission (AE) as a means of identifying corrosion at an early stage, before any significant cover damage has occurred. The purpose of part of the study was to identify the influential cover zone factors that affect the magnitude of the acoustic emission measurements per gram of steel loss. Prisms with various combinations of strength, cover thickness, aggregate and rebar diameters were studied to ascertain the important variables likely to be encountered on reinforced structures. The experimental results confirmed that early corrosion, verified by internal visual inspection and mass loss, can be detected by AE and before any external signs of cracking. They also show that the most influential parameter affecting the AE measurement is concrete strength, being exponentially related to the AE Energy. Material properties such as cover thickness had a negligible effect on AE Energy during the initial stages of reinforcement corrosion, whereas from this initial work, the rebar diameter indicated a promising relationship with AE Energy per gram of steel loss

Influence of diurnal and seasonal temperature variations on the detection of corrosion in reinforced concrete by acoustic emission

Chloride rich reinforced concrete prisms were coupled to chloride free prisms and exposed to diurnal and seasonal temperature cycles typical of those found in the UK. Acoustic Emissions (AE) and galvanic currents were continuously monitored and correlated with ambient temperature. AE and galvanic currents were found to emulate the evolution of temperature in the diurnal cycles, although no specific relationship between AE and galvanic current could be obtained. The influence of seasonal variations in galvanic current had no obvious influence on AE Energy per second over the range of corrosion rates studied. The findings suggest that AE is more sensitive to short term (diurnal) changes in corrosion rates than the longer (seasonal) effects. It was hypothesised that this is due to transitory changes in the internal microclimate of the concrete

Condition monitoring of reinforced concrete structures at risk from reinforcement corrosion

The corrosion of reinforced concrete structures is a major issue in the UK and worldwide, both structurally and from a maintenance management aspect. Damage induced by the corrosion of the steel can dramatically reduce the designed service life of the structure through loss of bond between the steel and concrete, or from localised loss of section of the corroding rebars. Failure to manage the maintenance of reinforced concrete may result in the premature replacement of the structure or in extreme cases, structural failure. Avoiding such scenarios can be aided through improved detection and monitoring of corrosion in concrete. In addition, combining this with a condition management tool, capable of benchmarking, index testing and prioritising areas of the concrete structure(s) for remedial action, would provide robust facilities management techniques for structural assets. This paper suggests how the results of a novel non-destructive corrosion detection technique, currently being developed, could be incorporated into a condition-monitoring tool for the facilities management of structures. The development of protocols based on laboratory and field data enable the formation of a condition-monitoring tool forming part of a longterm maintenance strategy for estate owners and managers

Electrochemical behaviour of steel reinforced concrete during accelerated corrosion testing

Corrosion of reinforcing steel presents a major durability issue worldwide and is the focus of much research activity. The long time periods involved in replicating reinforcement corrosion within laboratories has resulted in a number of accelerated test methods being developed. The basis of this research presented in this paper was to examine the impressed current technique often used to induce reinforcement corrosion. The suitability of the technique to model chloride induced corrosion was investigated by examining the electrochemical nature of the test method. Corrosion was induced in prisms of differing characteristic strengths and cover thicknesses by applying a current for between 3 and 17 days. The gravimetrical and theoretical mass losses are compared and a modified expression based on Faraday’s law relating the electrical current to the mass loss is also proposed which accounts for the localised nature of chloride-induced corrosion. It was found that the technique is a suitable method to simulate reinforcement corrosion

Risk-based investigation of steel reinforcement corrosion using the AeCORR technique

The use of a non-destructive acoustic evaluation technique as a Risk Based Inspection tool to detect the corrosion of steel reinforcement in concrete is presented in this paper. It offers the potential to save time and money for facilities owners and users. Recent research has demonstrated that AE has the ability to identify corrosion activity in concrete before conventional NDT methods, enabling faster intervention and increasing the repair options available. Monitoring a structure using the AeCORR technique, currently being researched and under development in the field, can create a digital map of part of a structure enabling an unbiased reference point for that structure for future maintenance tests as well as being able to distinguish areas of active corrosion. This paper reviews the principles and development of the new AeCORR technique for detecting and estimating the scale of corrosion induced damage and its ability as a tool to index test parts of structures

Feedback from activity trackers improves daily step count after knee and hip arthroplasty: A randomized controlled trial

Background: Commercial wrist-worn activity monitors have the potential to accurately assess activity levels and are being increasingly adopted in the general population. The aim of this study was to determine if feedback from a commercial activity monitor improves activity levels over the first 6 weeks after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods: One hundred sixty-three consecutive subjects undergoing primary TKA or THAwere randomized into 2 groups. Subjects received an activity tracker with the step display obscured 2 weeks before surgery and completed patient-reported outcome measures (PROMs). On day 1 after surgery, participants were randomized to either the “feedback (FB) group” or the “no feedback (NFB) group.” The FB group was able to view their daily step count and was given a daily step goal. Participants in the NFB group wore the device with the display obscured for 2 weeks after surgery, after which time they were also able to see their daily step count but did not receive a formal step goal. The mean daily steps at 1, 2, 6 weeks, and 6 months were monitored. At 6 months after surgery, subjects repeated PROMs and daily step count collection. Results: Of the 163 subjects, 95 underwent THA and 68 underwent TKA. FB subjects had a significantly higher (P \u3c .03) mean daily step count by 43% in week 1, 33% in week 2, 21% in week 6, and 17% at 6 months, compared with NFB. The FB subjects were 1.7 times more likely to achieve a mean 7000 steps per day than the NFB subjects at 6 weeks after surgery (P ¼ .02). There was no significant difference between the groups in PROMs at 6 months. Ninety percent of FB and 83% of NFB participants reported that they were satisfied with the results of the surgery (P ¼ .08). At 6 months after surgery, 70% of subjects had a greater mean daily step count compared with their preoperative level. Conclusion: Subjects who received feedback from a commercial activity tracker with a daily step goal had significantly higher activity levels after hip and knee arthroplasty over 6 weeks and 6 months, compared with subjects who did not receive feedback in a randomized controlled trial. Commercial activity trackers may be a useful and effective adjunct after arthroplasty

Biochemical and genetic analysis of Ecm14, a conserved fungal pseudopeptidase

© 2020, The Author(s). Background: Like most major enzyme families, the M14 family of metallocarboxypeptidases (MCPs) contains a number of pseudoenzymes predicted to lack enzyme activity and with poorly characterized molecular function. The genome of the yeast Saccharomyces cerevisiae encodes one member of the M14 MCP family, a pseudoenzyme named Ecm14 proposed to function in the extracellular matrix. In order to better understand the function of such pseudoenzymes, we studied the structure and function of Ecm14 in S. cerevisiae. Results: A phylogenetic analysis of Ecm14 in fungi found it to be conserved throughout the ascomycete phylum, with a group of related pseudoenzymes found in basidiomycetes. To investigate the structure and function of this conserved protein, His6-tagged Ecm14 was overexpressed in Sf9 cells and purified. The prodomain of Ecm14 was cleaved in vivo and in vitro by endopeptidases, suggesting an activation mechanism; however, no activity was detectable using standard carboxypeptidase substrates. In order to determine the function of Ecm14 using an unbiased screen, we undertook a synthetic lethal assay. Upon screening approximately 27,000 yeast colonies, twenty-two putative synthetic lethal clones were identified. Further analysis showed many to be synthetic lethal with auxotrophic marker genes and requiring multiple mutations, suggesting that there are few, if any, single S. cerevisiae genes that present synthetic lethal interactions with ecm14Δ. Conclusions: We show in this study that Ecm14, although lacking detectable enzyme activity, is a conserved carboxypeptidase-like protein that is secreted from cells and is processed to a mature form by the action of an endopeptidase. Our study and datasets from other recent large-scale screens suggest a role for Ecm14 in processes such as vesicle-mediated transport and aggregate invasion, a fungal process that has been selected against in modern laboratory strains of S. cerevisiae