Left and Right Cortical Activity Arising from Preferred Walking Speed in Older Adults.

Cortical activity and walking speed are known to decline with age and can lead to an increased risk of falls in the elderly. Despite age being a known contributor to this decline, individuals age at different rates. This study aimed to analyse left and right cortical activity changes in elderly adults regarding their walking speed. Cortical activation and gait data were obtained from 50 healthy older individuals. Participants were then grouped into a cluster based on their preferred walking speed (slow or fast). Analyses on the differences of cortical activation and gait parameters between groups were carried out. Within-subject analyses on left and right-hemispheric activation were also performed. Results showed that individuals with a slower preferred walking speed required a higher increase in cortical activity. Individuals in the fast cluster presented greater changes in cortical activation in the right hemisphere. This work demonstrates that categorizing older adults by age is not necessarily the most relevant method, and that cortical activity can be a good indicator of performance with respect to walking speed (linked to fall risk and frailty in the elderly). Future work may wish to explore how physical activity training influences cortical activation over time in the elderly.

Structure of Escherichia coli O157:H7 bacteriophage CBA120 tailspike protein 4 baseplate anchor and tailspike assembly domains (TSP4-N).

Four tailspike proteins (TSP1-4) of Escherichia coli O157:H7 bacteriophage CBA120 enable infection of multiple hosts. They form a branched complex that attaches to the tail baseplate. Each TSP recognizes a different lipopolysaccharide on the membrane of a different bacterial host. The 335 N-terminal residues of TSP4 promote the assembly of the TSP complex and anchor it to the tail baseplate. The crystal structure of TSP4-N335 reveals a trimeric protein comprising four domains. The baseplate anchor domain (AD) contains an intertwined triple-stranded ß-helix. The ensuing XD1, XD2 and XD3 ß-sheet containing domains mediate the binding of TSP1-3 to TSP4. Each of the XD domains adopts the same fold as the respective XD domains of bacteriophage T4 gp10 baseplate protein, known to engage in protein-protein interactions via its XD2 and XD3 domains. The structural similarity suggests that XD2 and XD3 of TSP4 also function in protein-protein interactions. Analytical ultracentrifugation analyses of TSP4-N335 and of domain deletion proteins showed how TSP4-N335 promotes the formation of the TSP quaternary complex. TSP1 and TSP2 bind directly to TSP4 whereas TSP3 binding requires a pre-formed TSP4-N335:TSP2 complex. A 3-dimensional model of the bacteriophage CBA120 TSP complex has been developed based on the structural and ultracentrifuge information.

Validation of an Embedded Motion-Capture and EMG Setup for the Analysis of Musculoskeletal Disorder Risks during Manhole Cover Handling.

Musculoskeletal disorders in the workplace are a growing problem in Europe. The measurement of these disorders in a working environment presents multiple limitations concerning equipment and measurement reliability. The aim of this study was to evaluate the use of inertial measurement units against a reference system for their use in the workplace. Ten healthy volunteers conducted three lifting methods (snatching, pushing, and pulling) for manhole cover using a custom-made tool weighting 20 and 30 kg. Participants' back and dominant arm were equipped with IMU, EMG, and reflective markers for VICON analysis and perception of effort was estimated at each trial using a Visual Analog Scale (VAS). The Bland-Altman method was used and results showed good agreement between IMU and VICON systems for Yaw, Pitch and Roll angles (bias values < 1, -4.4 < LOA < 3.6°). EMG results were compared to VAS results and results showed that both are a valuable means to assess efforts during tasks. This study therefore validates the use of inertial measurement units (IMU) for motion capture and its combination with electromyography (EMG) and a Visual Analogic Scale (VAS) to assess effort for use in real work situations.

Retrograde tibial nailing of far distal tibia fractures: a biomechanical evaluation of double- versus triple-distal interlocking.

OBJECTIVES: Retrograde tibial nailing using the Distal Tibia Nail (DTN) is a novel surgical option in the treatment of distal tibial fracture. Its unique retrograde insertion increases the range of surgical options in far distal fractures of the tibia beyond the use of plating. The aim of this study was to assess the feasibility of the DTN for far distal tibia fractures where only double rather than triple-distal locking is possible due to fracture localisation and morphology. METHODS: Six Sawbones® were instrumented with a DTN and an AO/OTA 43-A3 fracture simulated. Samples were tested in two configurations: first with distal triple locking, second with double locking by removing one distal screw. Samples were subjected to compressive (350 N, 600 N) and torsional (± 8 Nm) loads. Stiffness construct and interfragmentary movement were quantified and compared between double and triple-locking configurations. RESULTS: The removal of one distal screw resulted in a 60-70% preservation of compressive stiffness, and 90% preservation of torsional stiffness for double locking compared to triple locking. Interfragmentary movement remained minimal for both compressive and torsional loading. CONCLUSIONS: The DTN with a distal double locking can, therefore, be considered for far distal tibia fractures where nailing would be preferred over plating.

A comparative biomechanical study of the Distal Tibia Nail against compression plating for the osteosynthesis of supramalleolar corrective osteotomies.

The Distal Tibia Nail (DTN; Mizuho, Japan) has demonstrated higher biomechanical stiffness to locking plates in previous research for A3 distal tibia fractures. It is here investigated as a fixation option for supramalleolar corrective osteotomies (SMOT). Sixteen Sawbones tibiae were implanted with either a DTN (n = 8) or Medial Distal Tibia Plate (MDTP; n = 8) and a SMOT simulated. Two surgical outcome scenarios were envisaged: "best-case" representing an intact lateral cortex, and "worst-case" representing a fractured lateral cortex. All samples were subjected to compressive (350 N, 700 N) and torsional (± 4 Nm, ± 8 Nm) testing. Samples were evaluated using calculated construct stiffness from force-displacement data, interfragmentary movement and Von Mises' strain distribution. The DTN demonstrated a greater compressive stiffness for the best-case surgical scenario, whereas the MDTP showed higher stiffness (p < 0.05) for the worst-case surgical scenario. In torsional testing, the DTN proved more resistant to torsion in the worst-case surgical setup (p < 0.05) for both ± 4 Nm and ± 8 Nm. The equivalent stiffness of the DTN against the MDTP supports the use of this implant for SMOT fixation and should be considered as a treatment option particularly in patients presenting vascularisation problems where the MDTP is an inappropriate choice.

Computational models in the service of X-ray and cryo-electron microscopy structure determination.

Critical assessment of structure prediction (CASP) conducts community experiments to determine the state of the art in computing protein structure from amino acid sequence. The process relies on the experimental community providing information about not yet public or about to be solved structures, for use as targets. For some targets, the experimental structure is not solved in time for use in CASP. Calculated structure accuracy improved dramatically in this round, implying that models should now be much more useful for resolving many sorts of experimental difficulties. To test this, selected models for seven unsolved targets were provided to the experimental groups. These models were from the AlphaFold2 group, who overall submitted the most accurate predictions in CASP14. Four targets were solved with the aid of the models, and, additionally, the structure of an already solved target was improved. An a posteriori analysis showed that, in some cases, models from other groups would also be effective. This paper provides accounts of the successful application of models to structure determination, including molecular replacement for X-ray crystallography, backbone tracing and sequence positioning in a cryo-electron microscopy structure, and correction of local features. The results suggest that, in future, there will be greatly increased synergy between computational and experimental approaches to structure determination.

Structure and function of bacteriophage CBA120 ORF211 (TSP2), the determinant of phage specificity towards E. coli O157:H7.

The genome of Escherichia coli O157:H7 bacteriophage vB_EcoM_CBA120 encodes four distinct tailspike proteins (TSPs). The four TSPs, TSP1-4, attach to the phage baseplate forming a branched structure. We report the 1.9 Å resolution crystal structure of TSP2 (ORF211), the TSP that confers phage specificity towards E. coli O157:H7. The structure shows that the N-terminal 168 residues involved in TSPs complex assembly are disordered in the absence of partner proteins. The ensuing head domain contains only the first of two fold modules seen in other phage vB_EcoM_CBA120 TSPs. The catalytic site resides in a cleft at the interface between adjacent trimer subunits, where Asp506, Glu568, and Asp571 are located in close proximity. Replacement of Asp506 and Asp571 for alanine residues abolishes enzyme activity, thus identifying the acid/base catalytic machinery. However, activity remains intact when Asp506 and Asp571 are mutated into asparagine residues. Analysis of additional site-directed mutants in the background of the D506N:D571N mutant suggests engagement of an alternative catalytic apparatus comprising Glu568 and Tyr623. Finally, we demonstrate the catalytic role of two interacting glutamate residues of TSP1, located in a cleft between two trimer subunits, Glu456 and Glu483, underscoring the diversity of the catalytic apparatus employed by phage vB_EcoM_CBA120 TSPs.

Structure and tailspike glycosidase machinery of ORF212 from E. coli O157:H7 phage CBA120 (TSP3).

Bacteriophage tailspike proteins mediate virion absorption through reversible primary receptor binding, followed by lipopolysaccharide or exopolysaccharide degradation. The Escherichia coli O157:H7 bacteriophage CBA120 genome encodes four distinct tailspike proteins, annotated as ORFs 210 through 213. Previously, we reported the crystal structure of ORF210 (TSP1). Here we describe the crystal structure of ORF212 (TSP3) determined at 1.85 Å resolution. As observed with other tailspike proteins, TSP3 assembles into a trimer. Each subunit of TSP3 has an N-terminal head domain that is structurally similar to that of TSP1, consistent with their high amino acid sequence identity. In contrast, despite sharing a ß-helix fold, the overall structure of the C-terminal catalytic domain of TSP3 is quite different when compared to TSP1. The TSP3 structure suggests that the glycosidase active site resides in a cleft at the interface between two adjacent subunits where three acidic residues, Glu362 and Asp383 on one subunit, and Asp426 on a second subunit, are located in close proximity. Comparing the glycosidase activity of wild-type TSP3 to various point mutants revealed that catalysis requires the carboxyl groups of Glu362 and Asp426, and not of Asp383, confirming the enzyme employs two carboxyl groups to degrade lippopolysaccharide using an acid/base mechanism.

A comparison of health-related quality of life (HRQoL) across four systemic autoimmune rheumatic diseases (SARDs).

OBJECTIVES: To compare physical and mental health-related quality of life (HRQoL) across four systemic autoimmune rheumatic diseases (SARD). METHODS: Incident subjects enrolled in four SARD cohorts, namely systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM) were studied. The outcomes of interest were baseline Short Form Health Survey physical (PCS) and mental (MCS) component summary scores. Multivariate analysis was conducted to determine whether PCS and MCS scores differed across SARD type. RESULTS: The study included 118 SLE (93% women, mean age 36 years), 108 SSc (79% women, mean age 55), 64 RA (63% women, mean age 58) and 25 IIM (68% women, mean age 49) subjects. Mean PCS scores were 38.9 ± 12.2 in SLE, 37.1 ± 13.3 in RA, 35.0 ± 13.6 in SSc and 28.0 ± 15.4 in IIM. Mean MCS scores were 45.0 ± 13.3 in RA, 44.4 ± 14.7 in SSc, 40.1 ± 14.3 in SLE and 33.6 ± 18.7 in IIM. SARD type was an independent predictor of HRQoL with, in some cases, the magnitude of the differences reaching one standard deviation (IIM worse PCS scores compared to SLE (ß -12.23 [95% CI -18.11, -6.36; p<0.001]); IIM worse MCS scores compared to SSc (ß -11.05 [95% CI -17.53, -4.58; p = 0.001]) and RA (ß -11.72 [95% CI -18.62, -4.81; p = 0.001]). CONCLUSIONS: Cross-SARD research provides a novel approach to gain greater understanding of commonalities and differences across rheumatic diseases. The differences observed warrant further research into correlates and trajectories over time.

Is the novel olecranon tension plate a valid alternative to tension band wiring of olecranon fractures? A biomechanical study on cadaver bones.

INTRODUCTION: Tension band wiring (TBW) used for olecranon fractures is afflicted with a high rate of complications. The aim of this study was to compare the stability of the TBW versus an alternative, novel low-profile olecranon tension plate (OTP) with angular stable screws in a simulated complex fracture model. MATERIALS AND METHODS: Nine fresh-frozen pairs of cadaver proximal ulnae with an oblique osteotomy and an additional wedge fragment simulating an unstable fracture were tested. The TBW and OTP were implanted pairwise. The elbow motion was simulated in a single-muscle model and ranged from full extension to 90° of flexion. The pulling force of the triceps tendon ranged from 50 to 200 N. The displacement of the fracture fragments was measured with a video motion analysis system over 304 cycles. Data were assessed statistically using the Wilcoxon signed-rank test. RESULTS: The cyclic loading tests showed mean loosening of the fracture fragments at the articular surface of 0.56 mm using TBW (SD 0.65) and 0.15 mm for OTP (SD 0.39). There was no statistical significance in loosening between the two constructs (p = 0.31). No plate breakage or screw loosening occurred. CONCLUSIONS: The low-profile OTP, using the principles of pre-tensioning, lag, cortical, and angular stable screws together, demonstrated similar stability after olecranon fracture fixation when compared with the TBW technique and a lag screw in the olecranon fracture model with a third wedge fragment.

Treatment of distal intraarticular tibial fractures: A biomechanical evaluation of intramedullary nailing vs. angle-stable plate osteosynthesis.

In factures of the distal tibia with simple articular extension, the optimal surgical treatment remains debatable. In clinical practice, minimally invasive plate osteosynthesis and intramedullary nailing are both routinely performed. Comparative biomechanical studies of different types of osteosynthesis of intraarticular distal tibial fractures are missing due to the lack of an established model. The goal of this study was first to establish a biomechanical model and second to investigate, which are the biomechanical advantages of angle-stable plate osteosynthesis and intramedullary nailing of distal intraarticular tibial fractures. Seven 4(th) generation biomechanical composite tibiae featuring an AO 43-C2 type fracture were implanted with either osteosynthesis technique. After primary lag screw fixation, 4-hole Medial Distal Tibial Plate (MDTP) with triple proximal and quadruple distal screws or intramedullary nailing with double proximal and triple 4.0mm distal interlocking were implanted. The stiffness of the implant-bone constructs and interfragmentary movement were measured under non-destructive axial compression (350 and 600 N) and torsion (1.5 and 3Nm). Destructive axial compression testing was conducted with a maximal load of up to 1,200 N. No overall superior biomechanical results can be proclaimed for either implant type. Intramedullary nailing displays statistically superior results for axial loading in comparison to the MDTP. Torsional loading resulted in non-statistically significant differences for the two-implant types with higher stability in the MDTP group. From a biomechanical view, the load sharing intramedullary nail might be more forgiving and allow for earlier weight bearing in patients with limited compliance.

Crystal structure of ORF210 from E. coli O157:H1 phage CBA120 (TSP1), a putative tailspike protein.

Bacteriophage tailspike proteins act as primary receptors, often possessing endoglycosidase activity toward bacterial lipopolysaccharides or other exopolysaccharides, which enable phage absorption and subsequent DNA injection into the host. Phage CBA120, a contractile long-tailed Viunalikevirus phage infects the virulent Escherichia coli O157:H7. This phage encodes four putative tailspike proteins exhibiting little amino acid sequence identity, whose biological roles and substrate specificities are unknown. Here we focus on the first tailspike, TSP1, encoded by the orf210 gene. We have discovered that TSP1 is resistant to protease degradation, exhibits high thermal stability, but does not cleave the O157 antigen. An immune-dot blot has shown that TSP1 binds strongly to non-O157:H7 E. coli cells and more weakly to K. pneumoniae cells, but exhibits little binding to E. coli O157:H7 strains. To facilitate structure-function studies, we have determined the crystal structure of TSP1 to a resolution limit of 1.8 Å. Similar to other tailspikes proteins, TSP1 assembles into elongated homotrimers. The receptor binding region of each subunit adopts a right-handed parallel ß helix, reminiscent yet not identical to several known tailspike structures. The structure of the N-terminal domain that binds to the virion particle has not been seen previously. Potential endoglycosidase catalytic sites at the three subunit interfaces contain two adjacent glutamic acids, unlike any catalytic machinery observed in other tailspikes. To identify potential sugar binding sites, the crystal structures of TSP1 in complexes with glucose, α-maltose, or α-lactose were determined. These structures revealed that each sugar binds in a different location and none of the environments appears consistent with an endoglycosidase catalytic site. Such sites may serve to bind sugar units of a yet to be identified bacterial exopolysaccharide.

Impact of Friedreich's Ataxia on health-care resource utilization in the United Kingdom and Germany.

BACKGROUND: Friedreich's Ataxia (FRDA) is a neurodegenerative disorder that causes progressive damage to the central and peripheral nervous systems having a significant impact upon quality of life. With little information in the literature, cross-sectional observational studies were conducted in the UK and Germany to collect data on resource use and the burden of the disease on individuals and their caregivers. METHODS: Cross-sectional observational studies were conducted in the UK and Germany to estimate the burden of FRDA on individuals and on the respective healthcare systems. A total of 75 individuals in the UK and 28 in Germany were recruited to the study. Participants in both countries were asked to complete a Patient and Caregiver Information Form (PCIF), regarding access to, and use of, healthcare resources, and the impact FRDA has on their lifestyle. In Germany, doctors were asked to complete a Patient Record Form (PRF). Analyses of annual direct and indirect resource utilization were conducted for both countries while costs were calculated for the UK only. These figures were compared to the costs associated with Parkinson's disease; one of the most common neurodegenerative conditions and the one most similar in terms of disease progression. RESULTS: The results showed that the annual burden of FRDA is significant and falls on the health and social care sectors, on society, on caregivers and on the individuals themselves. In the UK FRDA had a total annual cost per person of between £11,818 and £18,774 depending on whether the cost of long-term unemployment was included.Typically the largest component of direct costs is associated with professional care. Given the high proportion of children and young adults recruited and the long disease duration, (typically 40-50 years for FRDA, compared with 20 years for Parkinson's disease), these figures may underestimate the true burden of the disease. CONCLUSION: It is hoped that these estimates of resource utilization, can help in understanding the previously unquantified burden of FRDA. Given the long disease duration, management strategies should seek to minimise the impact of the condition on individuals and their caregivers, while maximising quality of life.