Gender and sex differences in occupation-specific infectious diseases: a systematic review.

Occupational infectious disease risks between men and women have often been attributed to the gendered distribution of the labour force, with limited comparative research on occupation-specific infectious disease risks. The objective of this study was to compare infectious disease risks within the same occupations by gender. A systematic review of peer-reviewed studies published between 2016 and 2021 was undertaken. To be included, studies were required to report infectious disease risks for men, women or non-binary people within the same occupation. The included studies were appraised for methodological quality. A post hoc power calculation was also conducted. 63 studies were included in the systematic review. Among high-quality studies with statistical power (9/63), there was evidence of a higher hepatitis risk for men than for women among patient-facing healthcare workers (HCWs) and a higher parasitic infection risk for men than for women among farmers (one study each). The rest of the high-quality studies (7/63) reported no difference between men and women, including for COVID-19 risk among patient-facing HCWs and physicians, hepatitis risk among swine workers, influenza risk among poultry workers, tuberculosis risk among livestock workers and toxoplasmosis risk among abattoir workers. The findings suggest that occupational infectious disease risks are similarly experienced for men and women within the same occupation with a few exceptions showing a higher risk for men. Future studies examining gender/sex differences in occupational infectious diseases need to ensure adequate sampling by gender.

Differences between men and women in their risk of work injury and disability: A systematic review.

BACKGROUND: Health responses associated with occupational exposures can vary between men and women. AIMS: This study reviewed the work injury and disability risks associated with similar types of occupational exposures for men and women within and across occupations. MATERIALS & METHODS: A systematic review was undertaken of observational studies published between 2009 and 2019. Studies were required to empirically compare men and women for associations between occupational exposures and work injury or disability outcomes. Included studies were appraised for methodological quality and medium to high rated studies were compared for risk differences between men and women. RESULTS: Of 14,006 records identified, 440 articles were assessed for methodological quality, and 33 medium to high rated studies were included and reviewed. Among all occupations, the association between physical exposures, job demands, noise, and repetitive tasks, and injury risk were stronger among men. The relationship between repetitive tasks and sickness absence was stronger among women. Most studies examining psychological exposures found no risk differences for men and women across occupations. Men were at higher injury risk in certain occupations in primary and secondary industry sectors involving physical exposures and some chemical/biological exposures. Women were at higher injury risk for the physical demands and repetitive tasks of health care and aluminum production occupations. CONCLUSION: This review found that men and women can have different work injury and disability risks, both across and within the same occupations, for some physical exposures and to a lesser extent for some chemical and biological exposures. These differences might be a result of occupation-specific task differences.

Comparison Considerations Toward Investigating the Factors of Load and Age Group on the Maximum Reach Envelope.

OBJECTIVE: The objectives were to compare cylindrical and spherical coordinate representations of the maximum reach envelope (MRE) and apply these to a comparison of age and load on the MRE. BACKGROUND: The MRE is a useful measurement in the design of workstations and quantifying functional capability of the upper body. As a dynamic measure, there are human factors that impact the size, shape, and boundaries of the MRE. METHOD: Three-dimensional reach measures were recorded using a computerized potentiometric system for anthropometric measures (CPSAM) on two adult groups (aged 18-25 years and 35-70 years). Reach trials were performed holding .0, .5, and 1 kg. RESULTS: Three-dimensional Cartesian coordinates were transformed into cylindrical (r, θ, Z) and spherical (r, θ, ϕ) coordinates. Median reach distance vectors were calculated for 54 panels within the MRE as created by incremented banding of the respective coordinate systems. Reach distance and reach area were compared between the two groups and the loaded conditions using a spherical coordinate system. Both younger adults and unloaded condition produced greater reach distances and reach areas. CONCLUSIONS: Where a cylindrical coordinate system may reflect absolute reference for design, a normalized spherical coordinate system may better reflect functional range of motion and better compare individual and group differences. Age and load are both factors that impact the MRE. APPLICATION: These findings present measurement considerations for use in human reach investigation and design.

Integrating Safety and Health Promotion in Workplaces: A Scoping Review of Facilitators, Barriers, and Recommendations.

BACKGROUND: Growing evidence supports the integration and coordination of occupational health and safety and workplace health promotion activities instead of these coexisting as siloed efforts. Identifying implementation challenges and how these can be overcome is an important step to achieving truly integrated worker health efforts. We conducted a scoping review to identify the barriers and facilitators to integrated worker health approaches and described recommendations for implementing these efforts. METHOD: Peer-reviewed articles and gray literature from 2008 to 2019 were searched from the following electronic databases: EMBASE, Ovid Medline, PsycINFO, and ABI/INFORM. References from relevant articles and key informant suggestions also were collected. Data were extracted from documents if they focused on the occupational health and safety and health promotion of workers and described outcomes associated with integrated worker health approaches or outlined considerations relevant to the implementation of these approaches. RESULTS: Fifty-one documents met the inclusion criteria and were reviewed. Barriers and facilitators to implementing integrated worker health approaches were found at the extraorganizational, organizational, worker, and program levels, with limited resource availability the most reported barrier and support from leadership the most reported facilitator. Ten broad recommendations were identified and highlighted gaining leadership support, demonstrating leadership commitment, developing worker-centric approaches, and building capacity for workers. CONCLUSION: In reviewing the literature, we found clear and consistent recommendations relevant for integrated worker health approaches. Further research is needed to better understand how these recommendations apply to diverse workforces and organizations with varied resources.

Combining SPR with atomic-force microscopy enables single-molecule insights into activation and suppression of the complement cascade.

Activation and suppression of the complement system compete on every serum-exposed surface, host or foreign. Potentially harmful outcomes of this competition depend on surface molecules through mechanisms that remain incompletely understood. Combining surface plasmon resonance (SPR) with atomic force microscopy (AFM), here we studied two complement system proteins at the single-molecule level: C3b, the proteolytically activated form of C3, and factor H (FH), the surface-sensing C3b-binding complement regulator. We used SPR to monitor complement initiation occurring through a positive-feedback loop wherein surface-deposited C3b participates in convertases that cleave C3, thereby depositing more C3b. Over multiple cycles of flowing factor B, factor D, and C3 over the SPR chip, we amplified C3b from ∼20 to ∼220 molecules·µm-2 AFM revealed C3b clusters of up to 20 molecules and solitary C3b molecules deposited up to 200 nm away from the clusters. A force of 0.17 ± 0.02 nanonewtons was needed to pull a single FH molecule, anchored to the AFM probe, from its complex with surface-attached C3b. The extent to which FH molecules stretched before detachment varied widely among complexes. Performing force-distance measurements with FH(D1119G), a variant lacking one of the C3b-binding sites and causing atypical hemolytic uremic syndrome, we found that it detached more uniformly and easily. In further SPR experiments, KD values between FH and C3b on a custom-made chip surface were 5-fold tighter than on commercial chips and similar to those on erythrocytes. These results suggest that the chemistry at the surface on which FH acts drives conformational adjustments that are functionally critical.

Infraspinatus Isolation During External Rotation Exercise at Varying Degrees of Abduction.

CONTEXT: External rotation (ER) strengthening exercises are a common component of shoulder injury prevention and rehabilitation programs. They are primarily intended to target the infraspinatus muscle, based on its role in glenohumeral stabilization and inferior humeral glide. ER also recruits the posterior deltoid, which can be undesirable due to its role in subacromial space narrowing. OBJECTIVE: To determine the angle of humeral abduction that maximizes the infraspinatus to posterior deltoid activation ratio (INFRA/PD) during ER. DESIGN: Within-subjects repeated-measures controlled lab trial. PARTICIPANTS: A total of 10 healthy participants (5 males, 5 females) aged 21 (0.67) years participated in the study. INTERVENTION: 7 consecutive repetitions of ER at 7 different abduction angles ranging from 0° to 90°, with resistance normalized to 3% body mass. MAIN OUTCOME MEASURES: Surface electromyography was performed on the infraspinatus, middle deltoid, and posterior deltoid. Surface electromyography data were processed to determine absolute muscle activation as well as INFRA/PD at each abduction angle. Group means were compared between abduction angles using 1-way analysis of variance. RESULTS: Abduction significantly reduced overall infraspinatus activity but increased posterior deltoid activity (P < .01). Average and peak INFRA/PD decreased as the angle of abduction increased (P < .001 and P < .01, respectively). CONCLUSION: Our findings suggest that ER should be performed in 0° of abduction to maximize infraspinatus isolation. Slight abduction, such as placing a towel under the humerus, as recommended by some clinicians, may improve patient comfort, but did not increase infraspinatus isolation in this study.

Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin-Targeting Thiazole Analogue of Bisebromoamide.

Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid-phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT116) cells was explored by reverse phase protein array (RPPA) analysis, which showed a dose-dependent response in IRS-1 expression. Alanine scanning reveals a structural dependence to the cytotoxicity, actin targeting and pathway inhibition, and allows a new readily synthesised lead to be proposed.

MHC-mismatched chimerism is required for induction of transplantation tolerance in autoimmune nonobese diabetic recipients.

In nonautoimmune recipients, induction of mixed and complete chimerism with hematopoietic progenitor cells from MHC (HLA)-matched or -mismatched donors are effective approaches for induction of organ transplantation immune tolerance in both animal models and patients. But it is still unclear whether this is the case in autoimmune recipients. With the autoimmune diabetic NOD mouse model, we report that, although mixed and complete MHC-mismatched chimerism provide immune tolerance to donor-type islet and skin transplants, neither mixed nor complete MHC-matched chimerism does. The MHC-mismatched chimerism not only tolerizes the de novo developed, but also the residual pre-existing host-type T cells in a mismatched MHC class II-dependent manner. In the MHC-mismatched chimeras, the residual host-type peripheral T cells appear to be anergic with upregulation of PD-1 and downregulation of IL-7Rα. Conversely, in the MHC-matched chimeras, the residual host-type peripheral T cells manifest both alloreactivity and autoreactivity; they not only mediate insulitis and sialitis in the recipient, but also reject allogeneic donor-type islet and skin grafts. Interestingly, transgenic autoreactive BDC2.5 T cells from Rag1(+/+), but not from Rag1(-/-), NOD mice show alloreactivity and mediate both insulitis and rejection of allografts. Taken together, MHC-mismatched, but not MHC-matched, chimerism can effectively provide transplantation immune tolerance in autoimmune recipients.

Selective and Efficient Generation of ortho-Brominated para-Substituted Phenols in ACS-Grade Methanol.

The mono ortho-bromination of phenolic building blocks by NBS has been achieved in short reaction times (15-20 min) using ACS-grade methanol as a solvent. The reactions can be conducted on phenol, naphthol and biphenol substrates, giving yields of >86% on gram scale. Excellent selectivity for the desired mono ortho-brominated products is achieved in the presence of 10 mol % para-TsOH, and the reaction is shown to be tolerant of a range of substituents, including CH3, F, and NHBoc.

Thymic damage, impaired negative selection, and development of chronic graft-versus-host disease caused by donor CD4+ and CD8+ T cells.

Prevention of chronic graft-versus-host disease (cGVHD) remains a major challenge in allogeneic hematopoietic cell transplantation (HCT) owing to limited understanding of cGVHD pathogenesis and lack of appropriate animal models. In this study, we report that, in classical acute GVHD models with C57BL/6 donors and MHC-mismatched BALB/c recipients and with C3H.SW donors and MHC-matched C57BL/6 recipients, GVHD recipients surviving for >60 d after HCT developed cGVHD characterized by cutaneous fibrosis, tissue damage in the salivary gland, and the presence of serum autoantibodies. Donor CD8(+) T cells were more potent than CD4(+) T cells for inducing cGVHD. The recipient thymus and de novo-generated, donor-derived CD4(+) T cells were required for induction of cGVHD by donor CD8(+) T cells but not by donor CD4(+) T cells. Donor CD8(+) T cells preferentially damaged recipient medullary thymic epithelial cells and impaired negative selection, resulting in production of autoreactive CD4(+) T cells that perpetuated damage to the thymus and augmented the development of cGVHD. Short-term anti-CD4 mAb treatment early after HCT enabled recovery from thymic damage and prevented cGVHD. These results demonstrate that donor CD8(+) T cells cause cGVHD solely through thymic-dependent mechanisms, whereas CD4(+) T cells can cause cGVHD through either thymic-dependent or independent mechanisms.

Administration of anti-CD20 mAb is highly effective in preventing but ineffective in treating chronic graft-versus-host disease while preserving strong graft-versus-leukemia effects.

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome, and donor B cells play important roles in augmenting its pathogenesis. B cell-depleting anti-CD20 mAb has been administered before or after cGVHD onset for preventing or treating cGVHD in the clinic. Although administration before onset appeared to be more effective, the effect is variable and sometimes minimal. Here, we used 2 mouse cGVHD models to evaluate the preventive and therapeutic effect of anti-CD20 mAb. With the model of DBA/2 donor to MHC-matched BALB/c recipient, 1 intravenous injection of anti-CD20 mAb (40 mg/kg) the following day or on day 7 after hematopoietic cell transplantation when serum autoantibodies were undetectable effectively prevented induction of cGVHD and preserved a strong graft-versus-leukemia (GVL) effect. The separation of GVL effect from GVHD was associated with a significant reduction of donor CD4(+) T cell proliferation and expansion and protection of host thymic medullary epithelial cells. Anti-CD20 mAb administration also prevented expansion of donor T cells and induction of cGVHD in another mouse model of C57BL/6 donor to MHC-mismatched BALB/c recipients. In contrast, administration of anti-CD20 mAb after GVHD onset was not able to effectively deplete donor B cells or ameliorate cGVHD in either model. These results indicate that administration of anti-CD20 mAb before signs of cGVHD can prevent induction of autoimmune-like cGVHD while preserving a GVL effect; there is little effect if administered after cGVHD onset. This provides new insights into clinical prevention and therapy of cGVHD with B cell-depleting reagents.

Depletion of host CCR7(+) dendritic cells prevented donor T cell tissue tropism in anti-CD3-conditioned recipients.

We reported previously that anti-CD3 mAb treatment before hematopoietic cell transplantation (HCT) prevented graft-versus-host disease (GVHD) and preserved graft-versus-leukemia (GVL) effects in mice. These effects were associated with downregulated donor T cell expression of tissue-specific homing and chemokine receptors, marked reduction of donor T cell migration into GVHD target tissues, and deletion of CD103(+) dendritic cells (DCs) in mesenteric lymph nodes (MLN). MLN CD103(+) DCs and peripheral lymph node (PLN) DCs include CCR7(+) and CCR7(-) subsets, but the role of these DC subsets in regulating donor T cell expression of homing and chemokine receptors remain unclear. Here, we show that recipient CCR7(+), but not CCR7(-), DCs in MLN induced donor T cell expression of gut-specific homing and chemokine receptors in a retinoid acid-dependent manner. CCR7 regulated activated DC migration from tissue to draining lymph node, but it was not required for the ability of DCs to induce donor T cell expression of tissue-specific homing and chemokine receptors. Finally, anti-CD3 treatment depleted CCR7(+) but not CCR7(-) DCs by inducing sequential expansion and apoptosis of CCR7(+) DCs in MLN and PLN. Apoptosis of CCR7(+) DCs was associated with DC upregulation of Fas expression and natural killer cell but not T, B, or dendritic cell upregulation of FasL expression in the lymph nodes. These results suggest that depletion of CCR7(+) host-type DCs, with subsequent inhibition of donor T cell migration into GVHD target tissues, can be an effective approach in prevention of acute GVHD and preservation of GVL effects.

Donor B cells in transplants augment clonal expansion and survival of pathogenic CD4+ T cells that mediate autoimmune-like chronic graft-versus-host disease.

We reported that both donor CD4(+) T and B cells in transplants were required for induction of an autoimmune-like chronic graft-versus-host disease (cGVHD) in a murine model of DBA/2 donor to BALB/c recipient, but mechanisms whereby donor B cells augment cGVHD pathogenesis remain unknown. In this study, we report that, although donor B cells have little impact on acute GVHD severity, they play an important role in augmenting the persistence of tissue damage in the acute and chronic GVHD overlapping target organs (i.e., skin and lung); they also markedly augment damage in a prototypical cGVHD target organ, the salivary gland. During cGVHD pathogenesis, donor B cells are activated by donor CD4(+) T cells to upregulate MHC II and costimulatory molecules. Acting as efficient APCs, donor B cells augment donor CD4(+) T clonal expansion, autoreactivity, IL-7Rα expression, and survival. These qualitative changes markedly augment donor CD4(+) T cells' capacity in mediating autoimmune-like cGVHD, so that they mediate disease in the absence of donor B cells in secondary recipients. Therefore, a major mechanism whereby donor B cells augment cGVHD is through augmenting the clonal expansion, differentiation, and survival of pathogenic CD4(+) T cells.

Factors Associated With Timeliness and Equity of Access to Outpatient MRI Examinations.

OBJECTIVE: The role of MRI in guiding patients' diagnosis and treatment is increasing. Therefore, timely MRI performance prevents delays that can impact patient care. We assessed the timeliness of performing outpatient MRIs using the socio-ecological model approach and evaluated multilevel factors associated with delays. METHODS: This institutional review board-approved study included outpatient MRI examinations ordered between October 1, 2021, and December 31, 2022, for performance at a large quaternary care health system. Mean order-to-performed (OtoP) interval (in days) and prolonged OtoP interval (defined as >10 days) for MRI orders with an expected date of 1 day to examination performance were measured. Logistic regression was used to assess patient-level (demographic and social determinants of health), radiology practice-level, and community-level factors associated with prolonged OtoP interval. RESULTS: There were 126,079 MRI examination orders with expected performance within 1 day placed during the study period (56% of all MRI orders placed). After excluding duplicates, there were 97,160 orders for unique patients. Of the MRI orders, 48% had a prolonged OtoP interval, and mean OtoP interval was 18.5 days. Factors significantly associated with delay in MRI performance included public insurance (odds ratio [OR] = 1.11, P < .001), female gender (OR = 1.11, P < .001), radiology subspecialty (ie, cardiac, OR = 1.71, P < .001), and patients from areas that are most deprived (ie, highest Area Deprivation Index quintile, OR = 1.70, P < .001). DISCUSSION: Nearly half of outpatient MRI orders were delayed, performed >10 days from the expected date selected by the ordering provider. Addressing multilevel factors associated with such delays may help enhance timeliness and equity of access to MRI examinations, potentially reducing diagnostic errors and treatment delays.

Reducing intravenous contrast utilization for CT: A health-system wide intervention with sustained impact.

OBJECTIVE: To determine the volume of intravenous iodinated contrast media utilized for CT before, during, and after the global iohexol shortage over a total of 17 months at a multisite health system. METHODS: This retrospective study included all patients who underwent CT at a large health system with 12 sites. Standardized contrast doses for 13 CT examinations were implemented 5/23/22. Mean contrast utilization per CT encounter was compared between 3 periods (pre-intervention 1/1/22-5/22/22; intervention 5/23/22-9/11/22; post-intervention 9/12/23-6/30/23). Contrast doses and CT encounter data were extracted from the enterprise data warehouse. Categorical variables were compared with a chi-squared test and continuous variables were compared with a two-tailed t-test. Multivariable linear regression assessed significance, with coefficients noted to determine magnitude and direction of effect. RESULTS: Pre-intervention, there were 152,009 examinations (87,722 with contrast, 57.7%), during the intervention 120,031 examinations (63,217 with contrast, 52.7%), and post-intervention 341,862 examinations (194,231 with contrast, 56.8%). Pre-intervention, mean contrast dose was 89.3 mL per exam, which decreased to 78.0 mL following standardization (Δ of -12.7%) (p<0.001). This decrease continued throughout the intervention and persisted in the post-intervention period (80.4 mL; Δ -10.0%, p<0.001). On multivariable analysis, patient weight, sex, and performing site were all associated with variations in contrast dose. Most but not all sites (9/12) sustained the decreased contrast media dose in the post-intervention period. DISCUSSION: Implementing standardized contrast media dosing for commonly performed CT examinations led to a rapid decrease in contrast media utilization which persisted over 1 year.

Pathophysiological insights derived by natural history and motor function of spinal muscular atrophy.

OBJECTIVE: To examine the natural history of spinal muscular atrophy (SMA) to gain further insight into the clinical course and pathogenesis. STUDY DESIGN: Survival pattern, age of onset, and ambulatory status were retrospectively analyzed in 70 patients with SMA with deletions of the survival motor neuron 1 genes that presented to a specialized neuromuscular clinic. The Kaplan-Meier method was used to obtain survival curves. Hammersmith Functional Motor Scale-Expanded and abductor pollicis brevis compound muscle action potential amplitudes were assessed in 25 of the surviving cohort and correlated with survival motor neuron 2 copy number. RESULTS: Survival probabilities at ages 1, 2, 4, 10, 20, and 40 years were 40%, 25%, 6%, and 0%, respectively, for patients with SMA type 1; 100%, 100%, 97%, 93%, 93%, and 52% for patients with SMA type 2 and all patients with SMA type 3 were alive (age range 7-33 years). There were significant associations between age of onset and long-term outcome, specifically survival in SMA type 1 (P < .01) and Hammersmith Functional Motor Scale-Expanded (P < .0001), and compound muscle action potential (P = .001) in SMA types 2 and 3. Motor function in patients with long-standing SMA reduced over prolonged periods or remained stable. Survival motor neuron 2 copy number related to continuing changes in motor function with age. CONCLUSION: The natural history of SMA suggests considerable early loss of motor neurons, with severity related to differences in the number of remaining motor neurons. As the ensuing chronic course in milder phenotypes suggests relative stability of remaining motor neurons, the maximal therapeutic window presents early.

Host APCs augment in vivo expansion of donor natural regulatory T cells via B7H1/B7.1 in allogeneic recipients.

Foxp3(+) regulatory T (Treg) cells include thymic-derived natural Treg and conventional T-derived adaptive Treg cells. Both are proposed to play important roles in downregulating inflammatory immune responses. However, the mechanisms of Treg expansion in inflammatory environments remain unclear. In this study, we report that, in an autoimmune-like graft-versus-host disease model of DBA/2 (H-2(d)) donor to BALB/c (H-2(d)) recipients, donor Treg cells in the recipients predominantly originated from expansion of natural Treg cells and few originated from adaptive Treg cells. In vivo neutralization of IFN-γ resulted in a marked reduction of donor natural Treg expansion and exacerbation of graft-versus-host disease, which was associated with downregulation of host APC expression of B7H1. Furthermore, host APC expression of B7H1 was shown to augment donor Treg survival and expansion. Finally, donor Treg interactions with host APCs via B7.1/B7H1 but not PD-1/B7H1 were demonstrated to be critical in augmenting donor Treg survival and expansion. These studies have revealed a new immune regulation loop consisting of T cell-derived IFN-γ, B7H1 expression by APCs, and B7.1 expression by Treg cells.

Financial incentives to promote employment of persons with disabilities: a scoping review of when and how they work best.

PURPOSE: To assess the state of evidence on the use of financial incentives to employ, retain, and promote persons with disabilities. MATERIALS AND METHODS: We completed a scoping review of the peer-reviewed literature published from 1990 to 31 March 2022. Inclusion criteria were - populations with a disability; employment, retention, or promotion; and use of financial incentives targeted at employers. Articles were excluded if incentive was targeted solely at persons with disabilities. RESULTS: Seventeen articles met the inclusion criterion and were collated based on their study designs, type of incentive investigated, employment sector, and jurisdiction. We identified seven common themes that are relevant contextual and situational factors associated with the use of financial incentives to employ, retain, and promote persons with disabilities. CONCLUSIONS: While the literature identified the fact that financial incentives are widely used, the current state of the literature is modest and insufficient to make strong statements about the evidence on how and when financial incentives work well or do not work well. The themes identified allude to a subset of contextual factors requiring consideration for incentive use; however, evaluative research is still required to substantiate best practices for their use.Implications for rehabilitationFinancial incentives for the recruitment, retention, and promotion of workers with disabilities take many different forms and can incent different behaviours based on their form and context.Workers with disabilities are as diverse as workers without disabilities, consequently the supports required will differ from situation to situation.In some cases, a worker with a disability may require several types of supports, at a point in time, or over their employment journey.Employer knowledge and experience are important considerations in the use of financial incentives, as are employer skills in recruitment, retention, and promotion of workers with disabilities.

Dysfunction of axonal membrane conductances in adolescents and young adults with spinal muscular atrophy.

Spinal muscular atrophy is distinct among neurodegenerative conditions of the motor neuron, with onset in developing and maturing patients. Furthermore, the rate of degeneration appears to slow over time, at least in the milder forms. To investigate disease pathophysiology and potential adaptations, the present study utilized axonal excitability studies to provide insights into axonal biophysical properties and explored correlation with clinical severity. Multiple excitability indices (stimulus-response curve, strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle) were investigated in 25 genetically characterized adolescent and adult patients with spinal muscular atrophy, stimulating the median motor nerve at the wrist. Results were compared with 50 age-matched controls. The Medical Research Council sum score and Spinal Muscular Atrophy Functional Rating Scale were used to define the strength and motor functional status of patients with spinal muscular atrophy. In patients with spinal muscular atrophy, there were reductions in compound muscle action potential amplitude (P < 0.0005) associated with reduction in stimulus response slope (P < 0.0005), confirming significant axonal loss. In the patients with mild or ambulatory spinal muscular atrophy, there was reduction of peak amplitude without alteration in axonal excitability; in contrast, in the non-ambulatory or severe spinal muscular atrophy cohort prominent changes in axonal function were apparent. Specifically, there were steep changes in the early phase of hyperpolarization in threshold electrotonus (P < 0.0005) that correlated with clinical severity. Additionally, there were greater changes in depolarizing threshold electrotonus (P < 0.0005) and prolongation of the strength-duration time constant (P = 0.001). Mathematical modelling of the excitability changes obtained in patients with severe spinal muscular atrophy supported a mixed pathology comprising features of axonal degeneration and regeneration. The present study has provided novel insight into the pathophysiology of spinal muscular atrophy, with identification of functional abnormalities involving axonal K(+) and Na(+) conductances and alterations in passive membrane properties, the latter linked to the process of neurodegeneration.

Musculoskeletal disorder risk assessment tool use: A Canadian perspective.

Canadian ergonomics professionals from the Association of Canadian Ergonomists (ACE) and Board of Canadian Registered Safety Professionals (BCRSP) participated in a web-based survey of their awareness, use, and factors influencing use of ergonomics musculoskeletal disorder (MSD) risk assessment tools. A total of 791 respondents (21.0% response rate) participated in the survey. Certified ergonomics professionals represented an important subpopulation of MSD risk assessment tool users, however; the vast majority (86.4%) of users within Canada were certified safety professionals. Average tool use varied between ACE and BCRSP groups, where ACE respondents on average use more tools than BCRSP respondents, however the top 10 tools used were similar between the groups. Over 45% of assessment tools were learned at school and average tool use was not influenced by years of experience or continuing education.