Plasma for prevention and treatment of glycocalyx degradation in trauma and sepsis.

The endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients. Overall, the literature suggesting the use of plasma as a therapy for endothelial glycocalyx degradation is non-clinical basic science or exploratory. Plasma is an established therapy in the resuscitation of patients with hemorrhage for restoration of coagulation factors. However, plasma also contains other bioactive components, including sphingosine-1 phosphate, antithrombin, and adiponectin, which may protect and restore the endothelial glycocalyx, thereby helping to maintain or restore vascular homeostasis. This narrative review begins by describing the endothelial glycocalyx in health and disease: we discuss the overlapping disease mechanisms in trauma and sepsis that lead to its damage and introduce plasma transfusion as a potential therapy for prevention and treatment of endothelial glycocalyx degradation. Second, we review the literature on plasma as an exploratory therapy for endothelial glycocalyx degradation in trauma and sepsis. Third, we discuss the safety of plasma transfusion by reviewing the adverse events associated with plasma and other blood product transfusions, and we examine modern transfusion precautions that have enhanced the safety of plasma transfusion. We conclude that the literature proposes that plasma may have the potential to prevent and treat endothelial glycocalyx degradation in trauma and sepsis, indicating the need for further research.

Well-Being as a predictor of academic success in student veterans and factor validation of the PERMA + 4 well-being measurement scale.

Objective: The study sought to test whether well-being predicts academic performance for student service members/veterans (SSM/Vs) and to assess the factor structure of the PERMA + 4 measurement scale for use in this student population. Participants: Post-9/11 SSM/Vs (N = 199) from seven colleges and universities in the U.S. completed an online survey. Methods: A cross-sectional survey research design was used to assess PERMA + 4 and academic success. The PERMA + 4 framework and the measurement scale were examined using confirmatory factor analysis (CFA), and logistic regressions to determine if PERMA + 4 predicted academic performance in SSM/Vs. Results: Findings indicate that PERMA + 4 is a predictor of SSM/Vs academic performance, and CFA confirmed the factor structure of PERMA + 4 for use with SSM/Vs. Conclusions: The findings suggest that screening for the building blocks of well-being in SSM/Vs with a validated and comprehensive multidimensional instrument could be useful for mitigating transition challenges into college life and informing appropriate supports.

Building Program Evaluation Capacity Through an Online Training for Graduate Students at Schools and Programs of Public Health.

OBJECTIVES: Program evaluation is an essential function for public health professionals that is necessary to acquire funding for public health programs and support evidenced-based practice, but coverage of program evaluation principles and methodology within the master of public health (MPH) curriculum is inconsistent and may not adequately prepare students to conduct program evaluation activities postgraduation, especially on culturally responsive program evaluation. We examined the effectiveness of an online training course on program evaluation topics. METHODS: In July 2021, we recruited current and recently graduated MPH students from accredited US universities to measure the effectiveness of a 1-hour online training course in program evaluation. We distributed pre- and postsurveys to eligible participants. We assessed program evaluation skills on a 4-point Likert scale to determine improvements in knowledge (from 4 = extremely knowledgeable to 1 = not knowledgeable), attitudes (from 4 = strongly agree to 1 = strongly disagree), and self-efficacy (from 4 = strongly agree to 1 = strongly disagree). RESULTS: Among 80 MPH students who completed the survey, respondents indicated mean (SD) increases from presurvey to postsurvey in knowledge (from 2.13 [0.66] to 3.24 [0.54]) and attitudes (from 3.61 [0.51] to 3.84 [0.30]) toward program evaluation and in self-efficacy in conducting program evaluation (from 2.92 [0.71] to 3.44 [0.52]). CONCLUSION: The course may be an effective approach for training public health professionals about program evaluation. Our results provide a basis for revising the way program evaluation is taught and practical recommendations for integrating program evaluation competencies within public health curricula, such as by incorporating a self-paced training course for continuing education.

Momentary PERMA: An Adapted Measurement Tool for Studying Well-Being in Daily Life.

PERMA is a multidimensional framework that explains well-being through five hedonic and eudaimonic psychological elements-Positive emotions, Engagement, Relationships, Meaning, Accomplishment. Soon after the PERMA framework was proposed, PERMA-Profiler was introduced as a validated assessment tool for measuring these five elements of well-being from a global perspective. The current study aimed to shed further light onto the measurement of PERMA elements, extending it beyond global evaluations, to daily life assessments and the examination of individual differences in their dynamic characteristics. We introduce mPERMA (momentary PERMA), as an EMA-adapted version of the PERMA-Profiler measure, to assess well-being in daily life. Using data collected in an Ecological Momentary Assessment (EMA) study (N = 160), we first demonstrate the factor structure of mPERMA through a multilevel factor analysis and next examine within-person means and the dynamics of change (e.g., intra-individual variability) in the PERMA elements. Findings revealed that mPERMA displays convergent validity with two global measures of hedonic and eudaimonic well-being, namely Flourishing and Subjective Well-Being. Moreover, dynamical characteristics of the five elements of well-being measured over time, map onto their corresponding hedonic or eudaimonic global measures of well-being. Results of this paper present how dynamical features of well-being in daily life provide novel insights into predicting global well-being. Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-023-00684-w.

Assessment of Cell Viability in Electrically Excitable Muscle Cells Through Intact Twitch Stimulation.

Muscle cells (i.e. skeletal muscle fibers) are fully viable and functional when their excitation-contraction (EC) coupling machinery is intact. This involves intact membrane integrity with polarized membrane, functional ion channels for action potential generation and conduction, an intact electro-chemical interface at the level of the fiber's triad, followed by sarcoplasmic reticulum Ca2+ release, and subsequent activation of the chemico-mechanical interface at the level of the contractile apparatus. The ultimate end result is then a visible twitch contraction upon a brief electrical pulse stimulation. For many biomedical studies involving single muscle cells, intact and viable myofibers are of utmost importance. Thus, a simple global screening method that involves a brief electrical stimulus applied to single muscle fibers and assessment of visible contraction would be of high value. In this chapter, we describe step-by-step protocols to (i) obtain intact single muscle fibers from freshly dissected muscle tissue using an enzymatic digestion procedure and (ii) provide a workflow for the assessment of twitch response of single fibers that can be ultimately classified as viable. For this, we have prepared a unique stimulation pen for which we provide the fabrication guide for do-it-yourself rapid prototyping to eliminate the need for expensive specialized commercial equipment.

Classifying the unclassifiable-a Delphi study to reach consensus on the fibrotic nature of diseases.

BACKGROUND: Traditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity. AIM: A Delphi study was performed to reach consensus on which diseases may be described as fibrotic. METHODS: Participants were asked to rate a list of diseases, sub-grouped according to eight body regions, as 'fibrotic manifestation always present', 'can develop fibrotic manifestations', 'associated with fibrotic manifestations' or 'not fibrotic nor associated'. Classifications of 'fibrotic manifestation always present' and 'can develop fibrotic manifestations' were merged and termed 'fibrotic'. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification. RESULTS: After consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement. CONCLUSION: Using a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies.

Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle.

Introduction: It has been proposed that an increased susceptivity to oxidative stress caused by the absence of the protein dystrophin from the inner surface of the sarcolemma is a trigger of skeletal muscle necrosis in the destructive dystrophin deficient muscular dystrophies. Here we use the mdx mouse model of human Duchenne Muscular Dystrophy to test the hypothesis that adding the antioxidant NAC at 2% to drinking water for six weeks will treat the inflammatory phase of the dystrophic process and reduce pathological muscle fiber branching and splitting resulting in a reduction of mass in mdx fast-twitch EDL muscles. Methods: Animal weight and water intake was recorded during the six weeks when 2% NAC was added to the drinking water. Post NAC treatment animals were euthanised and the EDL muscles dissected out and placed in an organ bath where the muscle was attached to a force transducer to measure contractile properties and susceptibility to force loss from eccentric contractions. After the contractile measurements had been made the EDL muscle was blotted and weighed. In order to assess the degree of pathological fiber branching mdx EDL muscles were treated with collagenase to release single fibers. For counting and morphological analysis single EDL mdx skeletal muscle fibers were viewed under high magnification on an inverted microscope. Results: During the six-week treatment phase NAC reduced body weight gain in three- to nine-week-old mdx and littermate control mice without effecting fluid intake. NAC treatment also significantly reduced the mdx EDL muscle mass and abnormal fiber branching and splitting. Discussion: We propose chronic NAC treatment reduces the inflammatory response and degenerative cycles in the mdx dystrophic EDL muscles resulting in a reduction in the number of complexed branched fibers reported to be responsible for the dystrophic EDL muscle hypertrophy.

Early Versus Delayed Microdiscectomy for Chronic Sciatica Lasting 4-12 Months Secondary to Lumbar Disc Herniation: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVES: To compare the effect of delaying surgery on clinical outcome in patients with chronic sciatica secondary to lumbar disc herniation. METHODS: Patients with sciatica lasting 4-12 months and lumbar disc herniation at the L4-L5 or L5-S1 level were randomized to undergo microdiscectomy (early surgery) or to receive 6 months of nonoperative treatment followed by surgery if needed (delayed surgery). Outcomes were leg pain, Oswestry Disability Index score (ODI), back pain, SF-36 physical component (PCS) and mental component (MCS) summary scores, employment, and satisfaction measured preoperatively and at 6 weeks, 3 months, 6 months, and 1 year after surgery. RESULTS: Of the 64 patients in the early surgery group, 56 underwent microdiscectomy an average of 3 ± 2 weeks after enrollment. Of the 64 patients randomized to nonoperative care, 22 patients underwent delayed surgery an average of 53 ± 24 weeks after enrollment. The early surgery group experienced less leg pain than the delayed surgery group, which was the primary outcome, at 6 months after surgery (early surgery 2.8 ± .4 vs delayed surgery 4.8 ± .7; difference, 2.0; 95% confidence interval, .5-3.5). The overall estimated mean difference between groups significantly favored early surgery for leg pain, ODI, SF36-PCS, and back pain. The adverse event rate was similar between groups. CONCLUSIONS: Patients presenting with chronic sciatica treated with delayed surgery after prolonging standardized non-operative care have inferior outcomes compared to those that undergo expedited surgery.

Regularization of a Mathematical Model of the Wheatley Heart Valve.

This note considers the mathematical model published in the Journal of Biomechanical Engineering by McKee et al. [McKee, S., Cuminato, J. A., Stewart, I. W., and Wheatley, D. J., 2021, "A Mathematical Representation of the Wheatley Heart Valve," ASME J. Biomech. Eng., 143(8), p. 081006]. The model presented there suffers from the fact that there is a line discontinuity in the first derivative producing what appears to be a kink in each of the leaflets. This note is concerned with regularizing the shape of the valve while holding to Wheatley's essential idea [Wheatley, D. J., 2016, "Heart Valve," U.S. Patent No. 9,259,313, UK Patent No. 2,982,340 (2017), European Patent No. 2,979,666 (2017)].

Calcium and strontium contractile activation properties of single skinned skeletal muscle fibres from elderly women 66-90 years of age.

The single freshly skinned muscle fibre technique was used to investigate Ca2+- and Sr2+-activation properties of skeletal muscle fibres from elderly women (66-90 years). Muscle biopsies were obtained from the vastus lateralis muscle. Three populations of muscle fibres were identified according to their specific Sr2+-activation properties: slow-twitch (type I), fast-twitch (type II) and hybrid (type I/II) fibres. All three fibre types were sampled from the biopsies of 66 to 72 years old women, but the muscle biopsies of women older than 80 years yielded only slow-twitch (type I) fibres. The proportion of hybrid fibres in the vastus lateralis muscle of women of circa 70 years of age (24%) was several-fold greater than in the same muscle of adults (< 10%), suggesting that muscle remodelling occurs around this age. There were no differences between the Ca2+- and Sr2+-activation properties of slow-twitch fibres from the two groups of elderly women, but there were differences compared with muscle fibres from young adults with respect to sensitivity to Ca2+, steepness of the activation curves, and characteristics of the fibre-type dependent phenomenon of spontaneous oscillatory contractions (SPOC) (or force oscillations) occurring at submaximal levels of activation. The maximal Ca2+ activated specific force from all the fibres collected from the seven old women use in the present study was significantly lower by 20% than in the same muscle of adults. Taken together these results show there are qualitative and quantitative changes in the activation properties of the contractile apparatus of muscle fibres from the vastus lateralis muscle of women with advancing age, and that these changes need to be considered when explaining observed changes in women's mobility with aging.

Absence of the Z-disc protein α-actinin-3 impairs the mechanical stability of Actn3KO mouse fast-twitch muscle fibres without altering their contractile properties or twitch kinetics.

BACKGROUND: A common polymorphism (R577X) in the ACTN3 gene results in the complete absence of the Z-disc protein α-actinin-3 from fast-twitch muscle fibres in ~ 16% of the world's population. This single gene polymorphism has been subject to strong positive selection pressure during recent human evolution. Previously, using an Actn3KO mouse model, we have shown in fast-twitch muscles, eccentric contractions at L0 + 20% stretch did not cause eccentric damage. In contrast, L0 + 30% stretch produced a significant ~ 40% deficit in maximum force; here, we use isolated single fast-twitch skeletal muscle fibres from the Actn3KO mouse to investigate the mechanism underlying this. METHODS: Single fast-twitch fibres are separated from the intact muscle by a collagenase digest procedure. We use label-free second harmonic generation (SHG) imaging, ultra-fast video microscopy and skinned fibre measurements from our MyoRobot automated biomechatronics system to study the morphology, visco-elasticity, force production and mechanical strength of single fibres from the Actn3KO mouse. Data are presented as means ± SD and tested for significance using ANOVA. RESULTS: We show that the absence of α-actinin-3 does not affect the visco-elastic properties or myofibrillar force production. Eccentric contractions demonstrated that chemically skinned Actn3KO fibres are mechanically weaker being prone to breakage when eccentrically stretched. Furthermore, SHG images reveal disruptions in the myofibrillar alignment of Actn3KO fast-twitch fibres with an increase in Y-shaped myofibrillar branching. CONCLUSIONS: The absence of α-actinin-3 from the Z-disc in fast-twitch fibres disrupts the organisation of the myofibrillar proteins, leading to structural weakness. This provides a mechanistic explanation for our earlier findings that in vitro intact Actn3KO fast-twitch muscles are significantly damaged by L0 + 30%, but not L0 + 20%, eccentric contraction strains. Our study also provides a possible mechanistic explanation as to why α-actinin-3-deficient humans have been reported to have a faster decline in muscle function with increasing age, that is, as sarcopenia reduces muscle mass and force output, the eccentric stress on the remaining functional α-actinin-3 deficient fibres will be increased, resulting in fibre breakages.

The Leader Vitality Scale: Development, Psychometric Assessment, and Validation.

One of the most important units of analysis for positive organizational psychology research is leaders and future leaders in the workplace. Leaders often have a large responsibility for and influence on the well-being and performance of their followers. They also face the unique challenge of serving their followers and the organization while needing to maintain their own vitality and well-being. Vitality can provide a foundation of energy resources to a leader to serve at their full capacity. This study develops and empirically examines a new three factor scale to measure leader vitality which includes physical, psychological, and emotional components. In study 1, a total of 175 participants (including n = 128 leaders) completed the Leader Vitality Scale (LVS) and other positive psychology related measures. Exploratory factor analysis and then confirmatory factor analysis showed that the LVS is hierarchical with three distinct factors, with overall vitality as the higher-order factor. Correlational tests with two established vitality scales for general use showed that the LVS is positively related to existing scales, demonstrating convergent validity. In study 2, data was gathered from 92 top level leaders in the C-Suite (n = 25), vice presidents (n = 23), directors (n = 21), and managers (n = 23) of organizations across the United States. Results showed that LVS scores significantly correlated with life satisfaction, positive emotions, positive functioning at work, and psychological capital. Overall, these findings suggest that the LVS is a valid measure for assessing leader vitality, and can used in future studies of well-being and positive functioning at work.

Sarcoplasmic reticulum calcium handling in unbranched, immediately post-necrotic fast-twitch mdx fibres is similar to wild-type littermates.

NEW FINDINGS: What is the central question of this study? What are the early effects of dystrophin deficiency on sarcoplasmic reticulum Ca2+ handling in the mdx mouse? What is the main finding and its importance? In the mdx mouse, Ca2+ handling by the sarcoplasmic reticulum is little affected by the absence of dystrophin when looking at fibres without branches that have recently regenerated after massive myonecrosis. This has important implications for our understanding of Ca2+ pathology in the mdx mouse. ABSTRACT: There is a variety of results in the literature regarding the effects of dystrophin deficiency on the Ca2+ handling properties of the sarcoplasmic reticulum (SR) in the mdx mouse, an animal model of Duchenne muscular dystrophy. One possible source of variation is the presence of branched fibres. Fibre branching, a consequence of degenerative-regenerative processes such as muscular dystrophy, has in itself a significant influence on the function of the SR. In this study, we attempted to detect early effects of dystrophin deficiency on SR Ca2+ handling by using unbranched fibres from the immediate post-necrotic stage in mdx mice (recently regenerated after massive necrosis). Using kinetically corrected fura-2 fluorescence signals measured during twitch and tetanus, we analysed the amplitude, rise time and decay time of Δ[Ca2+ ]i in unfatigued and fatigued fibres. Decay was also resolved into SR pump and SR leak components. Fibres from mdx mice were similar in all respects to fibres from wild-type littermates apart from: (1) a smaller amplitude of the initial spike of Δ[Ca2+ ]i during a tetanus; and (2) a mitigation of the fall in Δ[Ca2+ ]i amplitude during the course of fatigue. Our findings suggest that the early effects of a loss of dystrophin on SR Ca2+ handling in mdx mice are subtle, and we emphasize the importance of distinguishing between Ca2+ pathology that is attributable to lack of dystrophin and Ca2+ pathology that is attributable to muscle degeneration.

Microdiscectomy Is More Cost-effective Than a 6-Month Nonsurgical Care Regimen for Chronic Radiculopathy.

BACKGROUND: A recent randomized controlled trial (RCT), performed by the authors, comparing early surgical microdiscectomy with 6 months of nonoperative care for chronic lumbar radiculopathy showed that early surgery resulted in improved outcomes. However, estimates of the incremental cost-utility ratio (ICUR), which is often expressed as the cost of gaining one quality-adjusted life year (QALY), of microdiscectomy versus nonsurgical management have varied. Radiculopathy lasting more than 4 months is less likely to improve without surgical intervention and may have a more favorable ICUR than previously reported for acute radiculopathy. QUESTION/PURPOSE: In the setting of chronic radiculopathy caused by lumbar disc herniation, defined as symptoms and/or signs of 4 to 12 months duration, is surgical management more cost-effective than 6 months of nonoperative care from the third-party payer perspective based on a willingness to pay of less than CAD 50,000/QALY? METHODS: A decision analysis model served as the vehicle for the cost-utility analysis. A decision tree was parameterized using data from our single-center RCT that was augmented with institutional microcost data from the Ontario Case Costing Initiative. Bottom-up case costing methodology generates more accurate cost estimates, although institutional costs are known to vary. There were no major surgical cost drivers such as implants or bone graft substitutes, and therefore, the jurisdictional variance would be minimal for tertiary care centers. QALYs derived from the EuroQoL-5D were the health outcome and were derived exclusively from the RCT data, given the paucity of studies evaluating the surgical treatment of lumbar radiculopathy lasting 4 to 12 months. Cost-effectiveness was assessed using the ICUR and a threshold of willingness to pay CAD 50,000 (USD 41,220) per QALY in the base case. Sensitivity analyses were performed to account for the uncertainties within the estimate of cost utility, using both a probabilistic sensitivity analysis and two one-way sensitivity analyses with varying crossover rates after the 6-month nonsurgical treatment had concluded. RESULTS: Early surgical treatment of patients with chronic lumbar radiculopathy (defined as symptoms of 4 to 12 months duration) was cost-effective, in that the cost of one QALY was lower than the CAD 50,000 threshold (note: the purchasing power parity conversion factor between the Canadian dollar (CAD) and the US dollar (USD) for 2019 was 1 USD = 1.213 CAD; therefore, our threshold was USD 41,220). Patients in the early surgical treatment group had higher expected costs (CAD 4118 [95% CI 3429 to 4867]) than those with nonsurgical treatment (CAD 2377 [95% CI 1622 to 3518]), but they had better expected health outcomes (1.48 QALYs [95% CI 1.39 to 1.57] versus 1.30 [95% CI 1.22 to 1.37]). The ICUR was CAD 5822 per QALY gained (95% CI 3029 to 30,461). The 2-year probabilistic sensitivity analysis demonstrated that the likelihood that early surgical treatment was cost-effective was 0.99 at the willingness-to-pay threshold, as did the one-way sensitivity analyses. CONCLUSION: Early surgery is cost-effective compared with nonoperative care in patients who have had chronic sciatica for 4 to 12 months. Decision-makers should ensure adequate funding to allow timely access to surgical care given that it is highly likely that early surgical intervention is potentially cost-effective in single-payer systems. Future work should focus on both the clinical effectiveness of the treatment of chronic radiculopathy and the costs of these treatments from a societal perspective to account for occupational absences and lost patient productivity. Parallel cost-utility analyses are critical so that appropriate decisions about resource allocation can be made. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Loss of α-actinin-3 confers protection from eccentric contraction damage in fast-twitch EDL muscles from aged mdx dystrophic mice by reducing pathological fibre branching.

The common null polymorphism (R577X) in the ACTN3 gene is present in over 1.5 billion people worldwide and results in the absence of the protein α-actinin-3 from the Z-discs of fast-twitch skeletal muscle fibres. We have previously reported that this polymorphism is a modifier of dystrophin-deficient Duchenne Muscular Dystrophy. To investigate the mechanism underlying this, we use a double knockout (dk)Actn3KO/mdx (dKO) mouse model, which lacks both dystrophin and sarcomere α-actinin-3. We used dKO mice and mdx dystrophic mice at 12 months (aged) to investigate the correlation between morphological changes to the fast-twitch dKO EDL and the reduction in force deficit produced by an in vitro eccentric contraction protocol. In the aged dKO mouse, we found a marked reduction in fibre branching complexity that correlated with protection from eccentric contraction induced force deficit. Complex branches in the aged dKO EDL fibres (28%) were substantially reduced compared to aged mdx EDL fibres (68%), and this correlates with a graded force loss over three eccentric contractions for dKO muscles (~36% after first contraction, ~66% overall) compared to an abrupt drop in mdx upon the first eccentric contraction (~75% after first contraction, ~89% after three contractions). In dKO, protection from eccentric contraction damage was linked with a doubling of SERCA1 pump density the EDL. We propose that the increased oxidative metabolism of fast-twitch glycolytic fibres characteristic of the null polymorphism (R577X) and increase in SR Ca2+ pump proteins reduces muscle fibre branching and decreases susceptibility to eccentric injury in the dystrophinopathies.

Using the science of positive psychology in the formative evaluation of social justice interventions: A case example.

The pursuit of culturally responsive approaches for designing and evaluating programs to promote social justice has become of the utmost importance to the evaluation community in the past decade. A strengths-focused evaluation approach has great promise for empowering individuals, groups, communities, and organizations, and identifying program strengths to build upon in addition to illuminating program deficits. However, there is a dearth of literature on using a strengths approach to evaluate interventions and programs to promote social justice. Drawing from the two disciplines of positive psychology and evaluation, this article illustrates a strengths-focused approach to formative evaluation using a case example of a halfway house for previously incarcerated women. The findings exemplify the positive psychological phenomena that emerge as a result of focusing the evaluation on program strengths. The case demonstrates that the application of a strengths-focused approach to evaluating social justice interventions can be empowering for institutions and the communities they serve.

Lifespan Analysis of Dystrophic mdx Fast-Twitch Muscle Morphology and Its Impact on Contractile Function.

Duchenne muscular dystrophy is caused by the absence of the protein dystrophin from skeletal muscle and is characterized by progressive cycles of necrosis/regeneration. Using the dystrophin deficient mdx mouse model, we studied the morphological and contractile chronology of dystrophic skeletal muscle pathology in fast-twitch Extensor Digitorum Longus muscles from animals 4-22 months of age containing 100% regenerated muscle fibers. Catastrophically, the older age groups lost ∼80% of their maximum force after one eccentric contraction (EC) of 20% strain with the greatest loss of ∼92% recorded in senescent 22-month-old mdx mice. In old age groups, there was minimal force recovery ∼24% after 120 min, correlated with a dramatic increase in the number and complexity of branched fibers. This data supports our two-phase model where a "tipping point" is reached when branched fibers rupture irrevocably on EC. These findings have important implications for pre-clinical drug studies and genetic rescue strategies.

Discectomy Compared with Standardized Nonoperative Care for Chronic Sciatica Due to a Lumbar Disc Herniation: A Secondary Analysis of a Randomized Controlled Trial with 2-Year Follow-up.

BACKGROUND: Randomized controlled trials evaluating acute sciatica have not demonstrated prolonged improvements in terms of patient-reported pain and function. For chronic sciatica, however, microdiscectomy has been found to be superior at 1 year. Whether this effect persists during the second year is not known. The purpose of the present study was to report the 2-year outcomes following lumbar microdiscectomy as compared with standardized nonoperative care for the treatment of chronic sciatica resulting from a lumbar disc herniation. METHODS: The present study is a secondary analysis of a previously reported randomized controlled trial with extension to 2 years of follow-up. Patients with radiculopathy for 4 to 12 months resulting from an L4-L5 or L5-S1 disc herniation were randomized to microdiscectomy or 6 months of nonoperative care followed by surgery if needed. Intention-to-treat analysis was performed at 2 years for the primary outcome (the intensity of leg pain) (range of possible scores, 0 [no pain] to 10 [worst pain]) as well as for secondary outcomes (including the Oswestry Disability Index score, the intensity of back pain, and quality of life). RESULTS: One hundred and twenty-eight patients were randomized in the present study. Twenty-four (38%) of the 64 patients who had been randomized to nonoperative care crossed over to surgical treatment by 2 years following enrollment. At the 2-year time point, the follow-up rate was approximately 70%. At 2 years, the operative group had less leg pain than the nonoperative group (mean, 2.8 ± 0.4 compared with 4.2 ± 0.4; treatment effect, 1.3 [95% confidence interval, 0.3 to 2.4]). The treatment effect favored surgery for all secondary outcome measures at 6 months and 1 year and for back pain intensity and physical function at 2 years. CONCLUSIONS: At 2 years, the present study showed that microdiscectomy was superior to nonoperative care for the treatment of chronic sciatica resulting from an L4-L5 or L5-S1 disc herniation. However, the difference between the groups did not surpass the minimal clinically important difference at 2 years as was reached at earlier follow-up points, likely as the result of patients crossing over from nonoperative to operative treatment. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Dystrophin-negative slow-twitch soleus muscles are not susceptible to eccentric contraction induced injury over the lifespan of the mdx mouse.

Duchenne muscular dystrophy (DMD) is the second most common fatal genetic disease in humans and is characterized by the absence of a functional copy of the protein dystrophin from skeletal muscle. In dystrophin-negative humans and rodents, regenerated skeletal muscle fibers show abnormal branching. The number of fibers with branches and the complexity of branching increases with each cycle of degeneration/regeneration. Previously, using the mdx mouse model of DMD, we have proposed that once the number and complexity of branched fibers present in dystrophic fast-twitch EDL muscle surpasses a stable level, we term the "tipping point," the branches, in and of themselves, mechanically weaken the muscle by rupturing when subjected to high forces during eccentric contractions. Here, we use the slow-twitch soleus muscle from the dystrophic mdx mouse to study prediseased "periambulatory" dystrophy at 2-3 wk, the peak regenerative "adult" phase at 6-9 wk, and "old" at 58-112 wk. Using isolated mdx soleus muscles, we examined contractile function and response to eccentric contraction correlated with the amount and complexity of regenerated branched fibers. The intact muscle was enzymatically dispersed into individual fibers in order to count fiber branching and some muscles were optically cleared to allow laser scanning confocal microscopy. We demonstrate throughout the lifespan of the mdx mouse that dystrophic slow-twitch soleus muscle is no more susceptible to eccentric contraction-induced injury than age-matched littermate controls and that this is correlated with a reduction in the number and complexity of branched fibers compared with fast-twitch dystrophic EDL muscles.

Minocycline Treatment Reduces Mass and Force Output From Fast-Twitch Mouse Muscles and Inhibits Myosin Production in C2C12 Myotubes.

Minocycline, a tetracycline-class of antibiotic, has been tested with mixed effectiveness on neuromuscular disorders such as amyotrophic lateral sclerosis, autoimmune neuritis and muscular dystrophy. The independent effect of minocycline on skeletal muscle force production and signalling remain poorly understood. Our aim here is to investigate the effects of minocycline on muscle mass, force production, myosin heavy chain abundance and protein synthesis. Mice were injected with minocycline (40 mg/kg i.p.) daily for 5 days and sacrificed at day six. Fast-twitch EDL, TA muscles and slow-twitch soleus muscles were dissected out, the TA muscle was snap-frozen and the remaining muscles were attached to force transducer whilst maintained in an organ bath. In C2C12 myotubes, minocycline was applied to the media at a final concentration of 10 µg/mL for 48 h. In minocycline treated mice absolute maximal force was lower in fast-twitch EDL while in slow-twitch soleus there was an increase in the time to peak and relaxation of the twitch. There was no effect of minocycline treatment on the other contractile parameters measured in isolated fast- and slow-twitch muscles. In C2C12 cultured cells, minocycline treatment significantly reduced both myosin heavy chain content and protein synthesis without visible changes to myotube morphology. In the TA muscle there was no significant changes in myosin heavy chain content. These results indicate that high dose minocycline treatment can cause a reduction in maximal isometric force production and mass in fast-twitch EDL and impair protein synthesis during myogenesis in C2C12 cultured cells. These findings have important implications for future studies investigating the efficacy of minocycline treatment in neuromuscular or other muscle-atrophy inducing conditions.