Six-Minute Walk Test Performance in Persons With Multiple Sclerosis While Using Passive or Powered Ankle-Foot Orthoses

Objective To determine whether a powered ankle-foot orthosis (AFO) that provides dorsiflexor and plantar flexor assistance at the ankle can improve walking endurance of persons with multiple sclerosis (MS). Design Short-term intervention. Setting University research laboratory. Participants Participants (N=16) with a neurologist-confirmed diagnosis of MS and daily use of a prescribed custom unilateral passive AFO. Interventions Three 6-minute walk tests (6MWTs), 1 per footwear condition: shoes (no AFO), prescribed passive AFO, and portable powered AFO (PPAFO). Assistive devices were worn on the impaired limb. Main Outcome Measures Distance walked and metabolic cost of transport were recorded during each 6MWT and compared between footwear conditions. Results Each participant completed all three 6MWTs within the experimental design. PPAFO use resulted in a shorter 6MWT distance than did a passive AFO or shoe use. No differences were observed in metabolic cost of transport between footwear conditions. Conclusions The current embodiment of this PPAFO did not improve endurance walking performance during the 6MWT in a sample of participants with gait impairment due to MS. Further research is required to determine whether expanded training or modified design of this powered orthosis can be effective in improving endurance walking performance in persons with gait impairment due to MS

Effect of SCBA Design and Firefighting Induced Fatigue on Balance, Gait and Safety of Movement

Here we presented a report for the Fire Service documenting an examination of the effect of SCBA and firefighting induced fatigue on firefighters’ gait, balance, and safety of movement. More detailed, peer-reviewed scientific reports can be found in academic literature and are available at the Illinois Fire Service Institute. Fireground operations are inherently dangerous, with overexertion/ strain and slips, trips, and falls being the two leading causes of injury. 26.5% of fireground injuries are a result of overexertion or strain, conditions which may be accelerated by the fact that firefighting activities can induce near maximal heart rates and elevated core temperatures. The high levels of effort and exertion needed to complete such activities may be made worse by the firefighter’s turnout gear and self-contained breathing apparatus (SCBA). Anecdotal evidence suggests a trend in the Fire Service toward extended duration SCBA (greater than 30-min), which may further increase the physical demand on the firefighter. Further, nearly 23% of fireground injuries are the result of a slip, trip, and/or fall. These injuries often occur while or following firefighting activities, and may often be a result of the fatigue those activities have induced in the firefighter. Extended duration SCBA are typically heavier and may reduce the time before the firefighter becomes fatigued. Thirty firefighters were recruited to take part in repeated-measures study to examine the effects of SCBAs and duration of work cycle have on physiological strain, balance, gait, and safety of movement. Firefighters completed seven different conditions with various SCBA (30, 45, and 60-minute standard cylindrical SCBA and a low-profile 45-min prototype) and durations of simulated firefighting (one or two bouts) in a heated environmental chamber (117°F (47°C)). Four activities were performed (stair climb, hose advance, secondary search, and overhaul) on two-minute work-rest cycles. Subjects also completed an obstacle course designed to test their gait and functional balance prior to, and immediately after the simulated firefighting activities. Following firefighting activity firefighters had elevated heart rates and core temperatures. The firefighters also generally performed worse in the obstacle course. The size of the SCBA had a minimal impact on the firefighters, though it did decrease the performance on a Functional Balance Test. The low-profile prototype SCBA impacted the firefighters in a similar manner as the traditional cylindrical SCBA, though firefighters generally took longer to pass through a 16-inch on-center stud space. When firefighters completed multiple bouts of simulated firefighting activity heart rates and core temperatures were elevated relative to a single bout while the number of repetitions performed during each activity decreased. Performance during the obstacle course was also more negatively impacted following a second bout of activity than after a single bout.U.S. Department of Homeland Security through the Assistance to Firefighters Grant Program (Research and Development grant: EMW-2010-FP-01606)Ope

Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners

<p>Abstract</p> <p>Background</p> <p>Enzymes in the radical SAM (rSAM) domain family serve in a wide variety of biological processes, including RNA modification, enzyme activation, bacteriocin core peptide maturation, and cofactor biosynthesis. Evolutionary pressures and relationships to other cellular constituents impose recognizable grammars on each class of rSAM-containing system, shaping patterns in results obtained through various comparative genomics analyses.</p> <p>Results</p> <p>An uncharacterized gene cluster found in many Actinobacteria and sporadically in Firmicutes, Chloroflexi, Deltaproteobacteria, and one Archaeal plasmid contains a PqqE-like rSAM protein family that includes Rv0693 from <it>Mycobacterium tuberculosis</it>. Members occur clustered with a strikingly well-conserved small polypeptide we designate "mycofactocin," similar in size to bacteriocins and PqqA, precursor of pyrroloquinoline quinone (PQQ). Partial Phylogenetic Profiling (PPP) based on the distribution of these markers identifies the mycofactocin cluster, but also a second tier of high-scoring proteins. This tier, strikingly, is filled with up to thirty-one members per genome from three variant subfamilies that occur, one each, in three unrelated classes of nicotinoproteins. The pattern suggests these variant enzymes require not only NAD(P), but also the novel gene cluster. Further study was conducted using SIMBAL, a PPP-like tool, to search these nicotinoproteins for subsequences best correlated across multiple genomes to the presence of mycofactocin. For both the short chain dehydrogenase/reductase (SDR) and iron-containing dehydrogenase families, aligning SIMBAL's top-scoring sequences to homologous solved crystal structures shows signals centered over NAD(P)-binding sites rather than over substrate-binding or active site residues. Previous studies on some of these proteins have revealed a non-exchangeable NAD cofactor, such that enzymatic activity <it>in vitro </it>requires an artificial electron acceptor such as N,N-dimethyl-4-nitrosoaniline (NDMA) for the enzyme to cycle.</p> <p>Conclusions</p> <p>Taken together, these findings suggest that the mycofactocin precursor is modified by the Rv0693 family rSAM protein and other enzymes in its cluster. It becomes an electron carrier molecule that serves <it>in vivo </it>as NDMA and other artificial electron acceptors do <it>in vitro</it>. Subclasses from three different nicotinoprotein families show "only-if" relationships to mycofactocin because they require its presence. This framework suggests a segregated redox pool in which mycofactocin mediates communication among enzymes with non-exchangeable cofactors.</p

Egress Efficacy of Persons with Multiple Sclerosis During Simulated Evacuations

Expedited evacuation of commercial and residential structures in the event of an emergency may be more difficult for persons with physical movement disorders. There is a need to better characterize the impact of such disorders and provide movement data to improve evacuee and responder safety. We undertook a pilot, feasibility study that investigated the ability of persons with multiple sclerosis (MS) and controls without MS to walk along a 48 m long path that included five different door configurations with various opening hardware and closure mechanisms, both before and after a six-minute walk, simulating a long evacuation path. Persons with MS took longer to complete the evacuation circuit (102 vs. 31 s) and to pass through each door (average 4.8 vs. 1.4 s) compared to controls. During the six-minute walk, persons with MS had decreased walking speed (0.7 vs. 1.9 m/s). The MS population demonstrated more conservative gait biomechanics throughout the simulation, i.e., wider, shorter and slower steps. Timing and biomechanical differences between populations and the potential fatigue induced through an extended evacuation can be used to improve understanding of movement in populations with disabilities, and incorporate these data into estimation of flow rates during evacuation.Funding support for MB was provided by the National Science Foundation Engineering Research Center for Compact and Efficient Fluid Power (0540834), with additional support from the Foundation of the Consortium of Multiple Sclerosis Centers’ Multiple Sclerosis Workforce of the Future program.Ope

Force-Controlled Balance Perturbations Associated with Falls in Older People: A Prospective Cohort Study

Balance recovery from an unpredictable postural perturbation can be a challenging task for many older people and poor recovery could contribute to their risk of falls. This study examined associations between responses to unpredictable perturbations and fall risk in older people. 242 older adults (80.064.4 years) underwent assessments of stepping responses to multi-directional force-controlled waist-pull perturbations. Participants returned monthly falls calendars for the subsequent 12 months. Future falls were associated with lower force thresholds for stepping in the posterior and lateral but not anterior directions. Those with lower posterior force thresholds for stepping were 68% more likely to fall at home than those with higher force thresholds for stepping. These results suggest that amount of force that can be withstood following an unpredictable balance perturbation predicts future falls in community-dwelling older adults. Perturbations in the posterior direction best discriminated between future fallers and non-fallers

A two-component protease in Methylorubrum extorquens with high activity toward the peptide precursor of the redox cofactor pyrroloquinoline quinone

Pyrroloquinoline quinone is a prominent redox cofactor in many prokaryotes, produced from a ribosomally synthesized and post-translationally modified peptide PqqA via a pathway comprising four conserved proteins PqqB?E. These four proteins are now fairly well-characterized and span radical SAM activity (PqqE), aided by a peptide chaperone (PqqD), a dual hydroxylase (PqqB), and an eight-electron, eight-proton oxidase (PqqC). A full description of this pathway has been hampered by a lack of information regarding a protease/peptidase required for the excision of an early, cross-linked di-amino acid precursor to pyrroloquinoline quinone. Herein, we isolated and characterized a two-component heterodimer protein from the ?-proteobacterium Methylobacterium (Methylorubrum) extorquens that can rapidly catalyze cleavage of PqqA into smaller peptides. Using pulldown assays, surface plasmon resonance, and isothermal calorimetry, we demonstrated the formation of a complex PqqF/PqqG, with a K-D of 300 nm. We created a molecular model of the heterodimer by comparison with the Sphingomonas sp. A1 M16B Sph2681/Sph2682 protease. Analysis of time-dependent patterns for the appearance of proteolysis products indicates high specificity of PqqF/PqqG for serine side chains. We hypothesize that PqqF/PqqG initially cleaves between the PqqE/PqqD-generated cross-linked form of PqqA, with nonspecific cellular proteases completing the release of a suitable substrate for the downstream enzyme PqqB. The finding of a protease that specifically targets serine side chains is rare, and we propose that this activity may be useful in proteomic analyses of the large family of proteins that have undergone post-translational phosphorylation at serine.National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM118117, GM124002, 1S10OD020062-01

Nitric Oxide Releasing Materials Triggered by Near-Infrared Excitation Through Tissue Filters

Novel materials for the phototherapeutic release of the bioregulator nitric oxide (nitrogen monoxide) are described. Also reported is a method for scanning these materials with a focused NIR beam to induce photouncaging while minimizing damage from local heating. The new materials consist of poly(dimethylsiloxane) composites with near-infrared-to-visible upconverting nanoparticles (UCNPs) that are cast into a biocompatible polymer disk (PD). These PDs are then impregnated with the photochemical nitric oxide precursor Roussin's black salt (RBS) to give UCNP_RBS_PD devices that generate NO when irradiated with 980 nm light. When the UCNP_RBS_PD composites were irradiated with NIR light through filters composed of porcine tissue, physiologically relevant NO concentrations were released, thus demonstrating the potential of such devices for minimally invasive phototherapeutic applications

Physiological response to firefighting activities of various work cycles using extended duration and prototype SCBA

Firefighters’ self-contained breathing apparatus (SCBA) protects the respiratory system during firefighting but increases the physiological burden. Extended duration SCBA (>30 min) have increased air supply, potentially increasing the duration of firefighting work cycles. To examine the effects of SCBA configuration and work cycle (length and rest), 30 firefighters completed seven trials using different SCBA and one or two bouts of simulated firefighting following work cycles common in the United States. Heart rate, core temperature, oxygen consumption, work output and self-reported perceptions were recorded during all activities. Varying SCBA resulted in few differences in these parameters. However, during a second bout, work output significantly declined while heart rates and core temperatures were elevated relative to a single bout. Thirty seven per cent of the subjects were unable to complete the second bout in at least one of the two-bout conditions. These firefighters had lower fitness and higher body mass than those who completed all assigned tasks. Practitioner Summary: The effects of extended duration SCBA and work/rest cycles on physiological parameters and work output have not been examined. Cylinder size had minimal effects, but extended work cycles with no rest resulted in increased physiological strain and decreased work output. This effect was more pronounced in firefighters with lower fitness.This work was supported by the Department of Homeland Security Fire Prevention and Safety, Federal Emergency Management Agency [grant number EMW-2010-FP-01606].Ope