How do neurons age? A focused review on the aging of the microtubular cytoskeleton.

Aging is the leading risk factor for Alzheimer's disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer's disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer's disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain regions that are worthy of further investigation. Additionally, longitudinal studies of neuronal/cytoskeletal aging should also investigate whether these age-related changes contribute not just to vulnerability to disease but also to the decline in nervous system function and behavioral output that all organisms experience. This will highlight the utility, if any, of cytoskeletal fortification for the promotion of healthy neuronal aging and potential protection against age-related neurodegenerative disease. This review seeks to summarize what is currently known about the physiological aging of the neuron and microtubular cytoskeleton in the hope of uncovering mechanisms underpinning age-related risk to disease.

Tau-mediated axonal degeneration is prevented by activation of the WldS pathway.

Tauopathy is characterized by neuronal dysfunction and degeneration occurring as a result of changes to the microtubule-associated protein tau. The neuronal changes evident in tauopathy bear striking morphological resemblance to those reported in models of Wallerian degeneration. The mechanisms underpinning Wallerian degeneration are not fully understood although it can be delayed by the expression of the slow Wallerian degeneration (WldS) protein, which has also been demonstrated to delay axonal degeneration in some models of neurodegenerative disease. Given the morphological similarities between tauopathy and Wallerian degeneration, this study investigated whether tau-mediated phenotypes can be modulated by co-expression of WldS. In a Drosophila model of tauopathy in which expression of human 0N3R tau protein leads to progressive age-dependent phenotypes, WldS was expressed with and without activation of the downstream pathway. The olfactory receptor neuron circuit OR47b was used for these studies in adults, and the larval motor neuron system was employed in larvae. Tau phenotypes studied included neurodegeneration, axonal transport, synaptic deficits and locomotor behaviour. Impact on total tau was ascertained by assessing total, phosphorylated and misfolded tau levels by immunohistochemistry. Activation of the pathway downstream of WldS completely suppressed tau-mediated degeneration. This protective effect was evident even if the pathway downstream of WldS was activated several weeks after tau-mediated degeneration had become established. Though total tau levels were not altered, the protected neurons displayed significantly reduced MC1 immunoreactivity suggestive of clearance of misfolded tau, as well as a trend for a decline in tau species phosphorylated at the AT8 and PHF1 epitopes. In contrast, WldS expression without activation of the downstream protective pathway did not rescue tau-mediated degeneration in adults or improve tau-mediated neuronal dysfunction including deficits in axonal transport, synaptic alterations and locomotor behaviour in tau-expressing larvae. This collectively implies that the pathway mediating the protective effect of WldS intersects with the mechanism(s) of degeneration initiated by tau and can effectively halt tau-mediated degeneration at both early and late stages. Understanding the mechanisms underpinning this protection could identify much-needed disease-modifying targets for tauopathies.

Improving curriculum delivery: Using a results informed quality improvement model for teen behavioral health education.

Adolescence is a critical developmental stage to establish healthy decision-making processes and behavior patterns. Many interventions such as evidence-based curricula have been implemented to guide adolescents to avoid risk-taking behaviors and improve health and medical knowledge and outcomes. This study presents a participatory approach informed by the three-stage (3S) quality improvement process model to improve the quality of curriculum delivery, based on the results indicating outcomes achieved, needs for improvement, and quality assurance for maintaining the expected outcomes of an evidence-based curricula. Tests were conducted before and after the intervention. Using threshold levels and measures of change in the tests, instructors participated in guided discussion and analysis of the data to identify where and how instructional improvements should be made and where outcomes were being achieved as expected. This method was used to diagnose variation in the results and delivery and identify root causes informing actions to improve curriculum delivery and outcomes. After the facilitated discussions, pre- and post-tests from subsequent classes were analyzed. The results showed improved test item scores ranging from 2 to 69.5% and seven of 18 items obtained statistical significance following the implementation of the model described. Overall, an increase in the mean percent correct of 17.1% was found.

Airborne transmission may have played a role in the spread of 2015 highly pathogenic avian influenza outbreaks in the United States.

The unprecedented 2015 outbreaks of highly pathogenic avian influenza (HPAI) H5N2 in the U.S. devastated its poultry industry and resulted in over $3 billion economic impacts. Today HPAI continues eroding poultry operations and disrupting animal protein supply chains around the world. Anecdotal evidence in 2015 suggested that in some cases the AI virus was aerially introduced into poultry houses, as abnormal bird mortality started near air inlets of the infected houses. This study modeled air movement trajectories and virus concentrations that were used to assess the probability or risk of airborne transmission for the 77 HPAI cases in Iowa. The results show that majority of the positive cases in Iowa might have received airborne virus, carried by fine particulate matter, from infected farms within the state (i.e., intrastate) and infected farms from the neighboring states (i.e., interstate). The modeled airborne virus concentrations at the Iowa recipient sites never exceeded the minimal infective doses for poultry; however, the continuous exposure might have increased airborne infection risks. In the worst-case scenario (i.e., maximum virus shedding rate, highest emission rate, and longest half-life), 33 Iowa cases had > 10% (three cases > 50%) infection probability, indicating a medium to high risk of airborne transmission for these cases. Probability of airborne HPAI infection could be affected by farm type, flock size, and distance to previously infected farms; and more importantly, it can be markedly reduced by swift depopulation and inlet air filtration. The research results provide insights into the risk of airborne transmission of HPAI virus via fine dust particles and the importance of preventative and containment strategies such as air filtration and quick depopulation of infected flocks.

Comparison of Athletes and Nonathletes Undergoing Thoracic Outlet Decompression for Neurogenic Thoracic Outlet Syndrome.

BACKGROUND: Neurogenic thoracic outlet syndrome (NTOS) is the most common form of thoracic outlet syndrome (TOS) and may occur from injury, occupational stress, or athletic endeavors. Although most patients with NTOS will improve after first-rib resection and scalenectomy (FRRS), the prognostic risk factors for success remain unclear. Athletes are a very motivated and disciplined demographic and therefore should be a group more likely to respond to FRRS for NTOS than nonathletes. We hypothesized that athletes would do better after FRRS than nonathletes despite the added physical stress that sporting activity imposes. METHODS: We reviewed our office records for all patients treated for TOS from July 2009 to May 2014 and extracted demographic, historical, procedural, and follow-up data. We contacted these patients to complete a survey to assess patient-centered outcomes of FRRS and compared athlete versus nonathlete survey responses. RESULTS: Five hundred sixty-four patients had FRRS for NTOS, and 184 (33%) responded to the survey. Of the 184 who responded, 97 were athletes (53%) and 87 were nonathletes (47%). Survey results suggested that 87% were improved in pain medication use (athletes 93% vs. nonathletes 80%, P = 0.013), 77% would undergo FRRS on the contralateral side if needed (athletes 75% vs. nonathletes 79%, P = 0.49), 73% had resolution of TOS symptoms (athletes 80% vs. nonathletes 65%, P = 0.02), and 86% could perform activities of daily living without limitation (athletes 95% vs. nonathletes 77%, P = 0.0004). Although 24% of respondents required another non-TOS procedure (athletes 27% vs. nonathletes 22%, P = 0.6), 89% felt that they had made the right decision (athletes 93% vs. nonathletes 80%, P = 0.09). Multivariable analysis of age, race, gender, previous surgery, preoperative physical therapy, preoperative narcotic use, and athletic status confirmed that athletic status was a significant predictor for improvement in pain medication use, complete TOS resolution, and the ability to perform activities of daily living. CONCLUSIONS: Most patients undergoing FRRS for NTOS are improved and satisfied with the result and indicate they made the correct choice to have FRRS. Although being an athlete was an independent variable for better outcomes in activity and pain medication use, their satisfaction after FRRS was similar to that in nonathletes. Further investigation is needed to determine if these findings are due to physical and/or psychosocial factors.

Midterm and long-term follow-up in competitive athletes undergoing thoracic outlet decompression for neurogenic thoracic outlet syndrome.

BACKGROUND: Neurogenic thoracic outlet syndrome (NTOS) results from compression of the brachial plexus by the clavicle, first rib, and scalene muscles and may develop secondary to repetitive motion of the upper extremity. Athletes routinely perform repetitive motions, and sports requiring significant arm and shoulder use may put the participant at increased risk for NTOS. Competitive athletes who develop NTOS may require first rib resection and scalenectomy (FRRS) for symptomatic relief. However, the effectiveness of FRRS has not previously been studied in this vulnerable population. METHODS: This is a cross-sectional study of competitive athletes with NTOS who received FRRS by the senior author between 2009 and 2014. Eligible patients were contacted by phone and invited to complete a nine-item survey assessing the long-term effects of FRRS on pain medication use, postoperative physical therapy duration, patient satisfaction, symptom relief, activities of daily living, athletic performance, time to return of athletic performance, and need for other operations. Multivariate analyses of the following risk factors were performed: age, pectoralis minor release, preoperative narcotic use, athletic shutdown, and involvement in a throwing sport. RESULTS: There were 232 competitive athletes who met the inclusion criteria, and 67 of these (age, 14-48 years; 35 male; 99% white) responded to the survey. The average time between surgery and survey completion was 3.9 years (range, 2.2-7.0 years). The most frequent sports conducted by this group were baseball and softball (n = 44 [66%]), volleyball (n = 7 [10%]), and cheerleading and gymnastics (n = 5 [7%]), ranging from high-school to professional levels. The survey results revealed that 96% were improved in pain medication use, 75% would undergo FRRS on the contralateral side if needed, 82% had resolution of symptoms, and 94% were able to perform activities of daily living without limitation; 70% returned to the same or better level of athletic activity after FRRS, and this occurred within 1 year in 50%. Multivariate regression analysis identified younger age as a predictor of the length of physical therapy and preoperative narcotics use as a predictor of symptom resolution. CONCLUSIONS: At our center, >40% of patients requiring FRRS for NTOS are competitive athletes. The results of this study show that the majority of them are able to return to their precompetitive state after FRRS, and few experience limitations in their daily living activities. Half can return to competition at or exceeding their premorbid ability level within 6 months of surgery. The majority are pleased with their decision to undergo FRRS. Further investigation is needed to identify predictive factors for successful return to competitive athletics.

Measuring change in disproportionality and disparities: three diagnostic tools.

At present there are few examples of sustained reductions in disproportionate minority contact with the juvenile justice and child welfare systems. This article describes the use of three instruments that have been used to measure levels of racial and ethnic disproportionality and disparities: The Disproportionality Diagnostic Tool, Ecomap and Racial Equity Scorecard. Using a combination of community and public agency data, these tools measure and track change over time on racial and ethnic disproportionality and disparities. Study results indicated a reduction in racial and ethnic disproportionality and disparities and demonstrated the utility of all three instruments for targeting efforts and assessing improvements in child welfare over time.

Evaluating multisystemic efforts to impact disproportionality through key decision points.

Working in four communities, Casey Foundation/Center for the Study of Social Policy (CSSP) Alliance on Racial Equity (the Alliance) have developed a Racial Equity Scorecard for measuring disproportionality at key decision points for use in impacting disproportionality in the child welfare system. The four communities include King County, Washington; Guilford County, North Carolina; Ramsey County, Minnesota; and Woodbury County, Iowa. Data from one site--Woodbury County, Iowa--are used as an example. This article provides the background and method for identification and measurement of key decision points in the child welfare system to track change effected by multisystemic approaches to reduce disproportionality. Interpretation of the results in the scorecard is provided and recommendations for future interventions based on the data are discussed.

Comparative analysis of two community-based efforts designed to impact disproportionality.

Children of color are overrepresented in child welfare in Iowa at a rate double their percentage of the population. In 2005 the Iowa Department of Human Services implemented two pilot demonstration projects to address overrepresentation of Native American and African American children in the child welfare system. The projects, called the Minority Youth and Families Initiative (MYFI), included ongoing evaluation. Results obtained over two years indicate improved worker and participant alliance, family functioning, and outcomes for children. Findings are discussed and recommendations are provided for further improvements in practice, research, and evaluation to reduce racial disparities the child welfare system.