Bioprocessing considerations for generation of iPSCs intended for clinical application: perspectives from the ISCT Emerging Regenerative Medicine Technology working group.

Approval of induced pluripotent stem cells (iPSCs) for the manufacture of cell therapies to support clinical trials is now becoming realized after 20 years of research and development. In 2022 the International Society for Cell and Gene Therapy (ISCT) established a Working Group on Emerging Regenerative Medicine Technologies, an area in which iPSCs-derived technologies are expected to play a key role. In this article, the Working Group surveys the steps that an end user should consider when generating iPSCs that are stable, well-characterised, pluripotent, and suitable for making differentiated cell types for allogeneic or autologous cell therapies. The objective is to provide the reader with a holistic view of how to achieve high-quality iPSCs from selection of the starting material through to cell banking. Key considerations include: (i) intellectual property licenses; (ii) selection of the raw materials and cell sources for creating iPSC intermediates and master cell banks; (iii) regulatory considerations for reprogramming methods; (iv) options for expansion in 2D vs. 3D cultures; and (v) available technologies and equipment for harvesting, washing, concentration, filling, cryopreservation, and storage. Some key process limitations are highlighted to help drive further improvement and innovation, and includes recommendations to close and automate current open and manual processes.

Using standardized mental health patient simulations to increase critical thinking and confidence in undergraduate nursing students.

PURPOSE: The purpose of the activity described in this article is to engage undergraduate nursing students undertaking a mental health course in active learning that allows them to practice clinical decision-making and higher-order learning. A secondary goal is to increase students' comfort level with interviewing and interacting with mental health patients. METHODS: Simulated interviews were performed with two standardized patients (SPs), one presenting with depression with suicidal tendencies and the other with generalized anxiety disorder. Students were given reflections to assess the effectiveness of the simulations as a learning technique. These essays were evaluated using five-step thematic data analysis. RESULTS: Students demonstrated a high level of engagement with the SPs which lead to a deeper level of understanding and learning demonstrated in their reflections. All participating students felt more confident and better prepared for real-world encounters with mental health patients. CONCLUSIONS: Students want exposure and practice in mental health as there is widespread under confidence in performing patient interviews and assessments. The use of simulations involving standardized mental health patients have proven to increase confidence and better prepare students for future experience while also circumventing any ethical issues which would be presented having non-licensed students assess actual mental health patients.

A global community-sourced assessment of the state of conservation technology.

Conservation technology holds the potential to vastly increase conservationists' ability to understand and address critical environmental challenges, but systemic constraints appear to hamper its development and adoption. Understanding of these constraints and opportunities for advancement remains limited. We conducted a global online survey of 248 conservation technology users and developers to identify perceptions of existing tools' current performance and potential impact, user and developer constraints, and key opportunities for growth. We also conducted focus groups with 45 leading experts to triangulate findings. The technologies with the highest perceived potential were machine learning and computer vision, eDNA and genomics, and networked sensors. A total of 95%, 94%, and 92% respondents, respectively, rated them as very helpful or game changers. The most pressing challenges affecting the field as a whole were competition for limited funding, duplication of efforts, and inadequate capacity building. A total of 76%, 67%, and 55% respondents, respectively, identified these as primary concerns. The key opportunities for growth identified in focus groups were increasing collaboration and information sharing, improving the interoperability of tools, and enhancing capacity for data analyses at scale. Some constraints appeared to disproportionately affect marginalized groups. Respondents in countries with developing economies were more likely to report being constrained by upfront costs, maintenance costs, and development funding (p = 0.048, odds ratio [OR] = 2.78; p = 0.005, OR = 4.23; p = 0.024, OR = 4.26), and female respondents were more likely to report being constrained by development funding and perceived technical skills (p = 0.027, OR = 3.98; p = 0.048, OR = 2.33). To our knowledge, this is the first attempt to formally capture the perspectives and needs of the global conservation technology community, providing foundational data that can serve as a benchmark to measure progress. We see tremendous potential for this community to further the vision they define, in which collaboration trumps competition; solutions are open, accessible, and interoperable; and user-friendly processing tools empower the rapid translation of data into conservation action. Article impact statement: Addressing financing, coordination, and capacity-building constraints is critical to the development and adoption of conservation technology.

La tecnología de conservación tiene el potencial para incrementar considerablemente la habilidad de los conservacionistas para entender y lidiar con los retos ambientales más importantes, pero las restricciones sistémicas parecen dificultar su desarrollo y adopción. La comprensión de estas restricciones y las oportunidades para el avance todavía son limitadas. Encuestamos en línea a 248 usuarios y programadores mundiales de tecnología de conservación para identificar las percepciones existentes del desempeño e impacto potencial de las herramientas actuales, restricciones para los usuarios y programadores y oportunidades clave para el crecimiento. También realizamos grupos de discusión con 45 expertos destacados para triangular los hallazgos. Las tecnologías con el potencial percibido más alto fueron el aprendizaje mecánico y la visión por computadora, la genómica y el eADN y los sensores en red. El 95%, 94% y 92% de los respondientes, respectivamente, clasificó estas tecnologías como muy útiles o como puntos de inflexión. Los retos más apremiantes que afectaron al área como conjunto fueron la competencia por el financiamiento limitado, la duplicación de esfuerzos y el desarrollo inadecuado de capacidades. El 76%, 67% y 55% de los respondientes, respectivamente, identificaron estos retos como de interés primario. Las oportunidades clave para el crecimiento que se identificaron en los grupos de diálogo fueron el incremento de la colaboración y la distribución de información, la mejoría de la operatividad entre herramientas y la potenciación de la capacidad de análisis de datos a escala. Algunas restricciones parecieron afectar desproporcionadamente a grupos marginalizados. Los respondientes de países con economías en desarrollo tuvieron mayor probabilidad de reportar la restricción por los costos iniciales, costos de mantenimiento y la financiación del desarrollo (p = 0.048, tasa de probabilidad [OR] = 2.78; p = 0.005, OR = 4.23; p = 0.024, OR = 4.26), y las mujeres respondientes tuvieron una mayor probabilidad de reportar restricciones por la financiación del desarrollo y habilidades técnicas percibidas (p = 0.027, OR = 3.98; p = 0.048, OR = 2.33). A nuestro entendimiento, este es el primero intento por capturar formalmente las perspectivas y necesidades de la comunidad mundial de la tecnología de conservación, proporcionando datos fundamentales que pueden servir como referencia para medir el progreso. Vemos un potencial tremendo para que esta comunidad amplíe la visión que definen, en la cual la colaboración se sobrepone a la competencia; las soluciones son abierta, accesibles e interoperativas; y las herramientas intuitivas de procesamiento capacitan la traducción veloz de datos a acciones de conservación.

Going above and beyond: using nursing theories to explore volunteerism during the COVID-19 pandemic.

Historically, nurses have volunteered to serve in wars and natural catastrophes. However, instead of a distant disaster, many nurses in the UK volunteered, working above and beyond, to assist their colleagues, local communities and health systems in the NHS during the peaks of the COVID-19 pandemic. Although the motivations and benefits to the community or self of volunteerism have been discussed in the literature, there is a paucity of literature and theoretical understanding from the field of nursing. Using a reflective and personal account of volunteering, this article aims to provide a better understanding of the concept of volunteerism in nursing. By exploring associated nursing theories from Jean Watson and Kristen Swanson, this article aims to illuminate and expand the knowledge base about nursing volunteerism. These nursing theories can frame the act of volunteerism and nursing and illustrate the interrelations of nursing theory and the practice of nursing volunteerism.

Global citizens.

Nurses and nursing students from the UK and overseas are learning in each other's countries.

Current perspectives on the use of ancillary materials for the manufacture of cellular therapies.

Continued growth in the cell therapy industry and commercialization of cell therapies that successfully advance through clinical trials has led to increased awareness around the need for specialized and complex materials utilized in their manufacture. Ancillary materials (AMs) are components or reagents used during the manufacture of cell therapy products but are not intended to be part of the final products. Commonly, there are limitations in the availability of clinical-grade reagents used as AMs. Furthermore, AMs may affect the efficacy of the cell product and subsequent safety of the cell therapy for the patient. As such, AMs must be carefully selected and appropriately qualified during the cell therapy development process. However, the ongoing evolution of cell therapy research, limited number of clinical trials and registered cell therapy products results in the current absence of specific regulations governing the composition, compliance, and qualification of AMs often leads to confusion by suppliers and users in this field. Here we provide an overview and interpretation of the existing global framework surrounding AM use and investigate some common misunderstandings within the industry, with the aim of facilitating the appropriate selection and qualification of AMs. The key message we wish to emphasize is that in order to most effectively mitigate risk around cell therapy development and patient safety, users must work with their suppliers and regulators to qualify each AM to assess source, purity, identity, safety, and suitability in a given application.

Measuring and monitoring illegal use of natural resources.

Illegal use of natural resources is a threat to biodiversity globally, but research on illegal activities has methodological challenges. We examined 100 studies that empirically identify targeted resources, techniques used to procure resources illegally, locations of illegal activities, characteristics of typical violators, incentives driving illegal use of resources, magnitude of the problem of illegal use (e.g., quantities used), or frequency of illegal activity. We based our evaluation of the methods used in these studies on their ability to provide these empirical data, relative labor demands, training and technology requirements, and levels of uncontrollable bias. We evaluated eight different methods: law-enforcement records, indirect observation, self-reporting, direct observation, direct questioning, randomized response technique (a survey method designed to improve accuracy of responses to sensitive questions), forensics, and modeling. Different situations favored different methods, each with distinct advantages and limitations. Six context-specific factors-location of resource use (in situ vs. ex situ), budget, technology and training capacity, ease of detection of illegal activity, scope of illegal activity (limited vs. widespread), and researchers' willingness to accept bias in results-help narrow the choice of methods. Several methodological concerns applied to any study of illegal resource use: regular monitoring can detect trends; modeling can incorporate sampling error and data uncertainties; researchers must manage levels of bias that vary between methods; triangulation of results from multiple methods can improve accuracy. No method is a panacea, but a combination of techniques can help address the lack of data on illegal activity. Researchers empirically compared results from different methods in only four studies, and no one has compared more than two methods simultaneously. Conservation would benefit from more research focused on: methods comparisons that include cost effectiveness, time efficiency, and statistical rigor; unique applications of the eight techniques currently in use; and testing of new methods.

Bone marrow-derived cells in the central nervous system of a mouse model of amyotrophic lateral sclerosis are associated with blood vessels and express CX(3)CR1.

Amyotrophic lateral sclerosis (ALS) is associated with increased numbers of microglia within the CNS. However, it is unclear to what extent bone marrow (BM)-derived cells contribute to this microgliosis. We have studied the adoptive transfer of green fluorescent protein (GFP)-labeled whole BM cells and BM from mice that express GFP only in CX(3)CR1+ cells (CX(3)CR1(+/GFP)) into the CNS of a murine model of ALS having over-expression of mutant superoxide dismutase (mSOD), and wt littermates. We find that most GFP+ and CX(3)CR1(+/GFP) cells are found adjacent to the microvasculature within the CNS, both in mSOD and wt mice. GFP+ and CX(3)CR1(+/GFP) cells within the CNS have a variety of morphologies, including cells with an elongated appearance, weak Iba-1 immunoreactivity, and often mannose receptor immunoreactivity, indicating that these cells are perivascular microglia. Typically, less than 10% of BM-derived cells had a stellate-shape and expressed strong Iba-1 immunoreactivity, as expected for parenchymal microglia, indicating that BM-derived cells uncommonly generate parenchymal microglia. Adoptive transfer of BM-derived cells from CX(3)CR1(+/GFP) mice revealed that many elongated cells are GFP+, demonstrating that some perivascular cells are derived from BM cells of the CX(3)CR1+ lineage. The significantly greater numbers of BM cells in mSOD than in control mice indicate that the presence of these BM cells in the spinal cord is regulated by conditioning stimuli that may include irradiation and inflammatory factors within the CNS.

Safe transport from a specialist paediatric intensive care unit to a referral hospital.

There are 23 paediatric intensive care units (PICU) in the UK and 19 of these have a retrieval team responsible for the safe and uneventful transfer of critically ill children from referring hospitals. There are two established PICUs in University Hospitals of Leicester (UHL) NHS Trust that work as a team. In 2001, a transfer service was introduced to support the UHL PICU retrieval service and the referring district general hospitals. At the time of writing this article there was no other PICU in the UK providing a dedicated paediatric clinical transport nurse service, whose main responsibility is the safe transfer of infants and children back to their local hospitals. This article will discuss the development of this service and the benefits to PICU and referral hospitals.

Treatment of symptomatic degenerative intervertebral discs with autologous platelet-rich plasma: follow-up at 5-9 years.

Aim: This study assessed pain and function at 5-9 years postinjection in a subset of patients who received intradiscal platelet-rich plasma (PRP) injections for moderate-to-severe lumbar discogenic pain. Patients & methods: All patients received injections of intradiscal PRP in a previous randomized controlled trial. Data on pain, function, satisfaction, and need for surgery were collected at one time point of 5-9 years postinjection and compiled with existing data. Results: In comparison to baseline, there were statistically significant improvements in pain and function (p < 0.001). All improvements were clinically significant. Six patients had undergone surgery during the follow-up period. Conclusion: This subset of patients demonstrated statistically and clinically significant improvements in pain and function at 5-9 years postinjection.

Understanding the drivers of sensitive behavior using Poisson regression from quantitative randomized response technique data.

Understanding sensitive behaviors-those that are socially unacceptable or non-compliant with rules or regulations-is essential for creating effective interventions. Sensitive behaviors are challenging to study, because participants are unlikely to disclose sensitive behaviors for fear of retribution or due to social undesirability. Methods for studying sensitive behavior include randomized response techniques, which provide anonymity to interviewees who answer sensitive questions. A variation on this approach, the quantitative randomized response technique (QRRT), allows researchers to estimate the frequency or quantity of sensitive behaviors. However, to date no studies have used QRRT to identify potential drivers of non-compliant behavior because regression methodology has not been developed for the nonnegative count data produced by QRRT. We develop a Poisson regression methodology for QRRT data, based on maximum likelihood estimation computed via the expectation-maximization (EM) algorithm. The methodology can be implemented with relatively minor modification of existing software for generalized linear models. We derive the Fisher information matrix in this setting and use it to obtain the asymptotic variance-covariance matrix of the regression parameter estimates. Simulation results demonstrate the quality of the asymptotic approximations. The method is illustrated with a case study examining potential drivers of non-compliance with hunting regulations in Sierra Leone. The new methodology allows assessment of the importance of potential drivers of different quantities of non-compliant behavior, using a likelihood-based, information-theoretic approach. Free, open-source software is provided to support QRRT regression.

Percutaneous Rupture of Zygapophyseal Joint Synovial Cysts: A Prospective Assessment of Nonsurgical Management.

BACKGROUND: Although lumbar zygapophyseal joint synovial cysts are fairly well recognized, they are an uncommon cause of lumbosacral radicular pain. Nonoperative treatments include percutaneous aspiration of the cysts under computed tomography or fluoroscopic guidance with a subsequent corticosteroid injection. However, there are mixed results in terms of long-term outcomes and cyst reoccurrence. This study prospectively evaluates percutaneous ruptures of zygapophyseal joint (Z-joint) synovial cysts for the treatment of lumbosacral radicular pain. OBJECTIVES: Primary: To determine whether percutaneous rupture of symptomatic Z-joint synovial cysts leads to sustained improvements in radicular pain and function. Secondary: To assess the rates of cyst recurrence and progression to surgical intervention following percutaneous rupture of symptomatic Z-joint synovial cysts. DESIGN: Prospective cohort study. SETTING: Outpatient academic spine practice. PARTICIPANTS: Adults with primary radicular pain due to a facet synovial cyst. METHODS: Participants underwent fluoroscopically guided percutaneous Z-joint synovial cyst ruptures under standard-of-care practice. Data on pain, physical function, satisfaction, and progression to surgery were collected at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year after rupture. An intention-to-treat analysis was used for assessment of patient-reported outcome measures. MAIN OUTCOME MEASURES: The Numerical Rating Scale, Oswestry Disability Index, and modified North American Spine Society questionnaires were used to measure pain, function, and satisfaction with the procedure, respectively. RESULTS: Thirty-five participants were included in the study, and data were analyzed by an independent researcher. Statistically significant changes in Oswestry Disability Index were reported at 2 weeks, 3 months, and 1 year postintervention (P = .034, .040, and .039, respectively). A statistically and clinically significant relief of current pain was reported at 2 weeks (P = .025) and 6 weeks (P = .014) with respect to baseline. Patients showed significant improvements for best pain at 6 weeks with respect to baseline (P = .031). Patients' worst pain showed the greatest amount of improvement with clinically meaningful changes at all time points compared with baseline. Patient-reported satisfaction was found nearly 70% of the time at all time points. Forty percent (14/35) of participants required repeat cyst rupture, and 31% (11/35) required surgical interventions. CONCLUSIONS: There were statistically and clinically significant improvements in pain and function after percutaneous rupture of Z-joint synovial cysts. In addition, the outcomes support previous retrospective studies indicating that approximately 40% of patients will need surgery. This study provides further research to determine the utility of this procedure and to precisely define a subset of ideal candidates. LEVEL OF EVIDENCE: Level II.

ACL tears in female athletes.

With the growing number of female athletes, an increase is occurring in the number of sports-related injuries, which can cause physical, psychological, academic, and financial suffering. Female athletes are reported to be two to eight times more likely to sustain an anterior cruciate ligament (ACL) injury than male athletes. Further research on risk factors and preventative strategies for the female ACL is needed, because the cause of the disparity in injury rates remains equivocal and controversial. Individualized treatment for the injured knee is necessary and can include either conservative treatment or reconstructive surgery.

Identification and characterization of survival-related gene, a novel cell survival gene controlling apoptosis and tumorigenesis.

Apoptosis plays a critical role in cellular homeostasis during development, immune responses, and tumorigenesis. Recent studies have identified a number of genes that control this process. We report here our identification of a novel cell survival-related gene (SRG) from a human expression cDNA library by functional cloning. SRG shows no significant nucleotide sequence homology to any known genes in the Genbank. Our fluorescence in situ hybridization analysis has estimated that SRG is located at 1p36, agreeing with the location at 1p36.22 in the human genome sequence. SRG encodes a putative protein of 172 amino acids, which is mainly located in the perinuclear region. Northern blotting analysis indicates that SRG is highly expressed in many human cancer cell lines although it is low in most tissues except liver and placenta. To investigate the function of SRG in apoptosis, we transfected SRG cDNA into BAF/BO3 and B16/F0 cells and induced apoptosis by cytokine/serum deprivation. We found that SRG-transfected cells are resistant to apoptosis induced by cytokine/serum deprivation. In addition, mice bearing SRG-transfected melanoma had more tumor formation and larger tumor growth. Melanoma transfected with antisense SRG showed significantly less tumor formation and smaller tumor growth. Interestingly, mouse SRG gene was also identified on chromosome 4 and blocking SRG expression with small interfering RNA promoted serum deprivation-induced apoptosis of NIH3T3 cells. Our results show that SRG is a novel cell survival gene that critically controls apoptosis and tumor formation.

Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.

OBJECTIVE: To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. DESIGN: Prospective, double-blind, randomized controlled study. SETTING: Outpatient physiatric spine practice. PARTICIPANTS: Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. METHODS: Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. MAIN OUTCOME MEASURES: Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. RESULTS: Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome Questionnaire) (P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. CONCLUSION: Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal treatment and the ideal cellular characteristics of the intradiskal PRP injectate.

The role of activation-induced cell death in the differentiation of T-helper-cell subsets.

Activation-induced cell death (AICD) has been demonstrated in T-cell hybridomas, immature thymocytes, and activated mature T cells. However, the molecular mechanisms of AICD and its physiological role in T-helper-cell differentiation remain uncertain. Recently, we have shown that Th1 and Th2 cells have distinct mechanisms of AICD. Our findings suggest that signaling from cytokines initiates the differentiation program, but that the selective action of death effectors determines the fate of differentiating T-helper cells, and thus, the ultimate balance between T-helper subpopulations. Among T cells, activation- induced expression of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is observed exclusively in Th2 clones and primary T-helper cells differentiated under Th2 conditions, while the expression of CD95L (Fas ligand) occurs mainly in Th1 cells. Furthermore, Th1 cells are more susceptible than Th2 cells to apoptosis induced through either TRAIL or CD95L, and radiolabeled Th1 cells can be induced into apoptosis via fratricide by both Th1 and Th2 cells, while Th2 cells are spared. The pan-caspase inhibitor, z-VAD, prevents AICD in Th1 cells, but not Th2 cells, indicating different mechanisms of AICD in each T-helper subtype. Antibody blockade of TRAIL and CD95L significantly boosts interferon-gamma (IFN-gamma) production in vitro. Also, young mice with mutant CD95 (MRL/MpJ-lpr/lpr) have a stronger Th1 response to ovalbumin immunization than do controls. We conclude that apoptosis mediated by CD95L and TRAIL is critical in the selective removal of differentiating T helper cells.

Gift wrapping ourselves: the final gift exchange.

OBJECTIVE: This qualitative study examines the "final gift exchange" process by which older adults give cherished possessions in return for lasting appreciation. METHODS: We interviewed 54 middle- and upper-middle-class people (39 women) aged 50-90 who had to dispose of personal objects when moving to smaller residences. RESULT: We used Goffman's spiraling strategy in our analysis of people's reports of disposing of personal possessions. We identified three salient dimensions (family, economy, and self) of this process and created a heuristic describing eight ideal-type gift exchange scenarios by categorizing objects as valued or not valued by family and the economy as well as being an important aspect of the gift giver's material self. DISCUSSION: By applying the heuristic, we observed that a lack of shared definitions of the meaning and value of objects created dilemmas in disposing of personal objects, particularly those connected to a person's material self. We also offer suggestions for making the process go more smoothly, such as inquiring about the preferences of others and telling stories associated with objects to create shared definitions of the objects' significance to the giver and/or to family history.

The relationship between lower extremity injury and the hip abductor to extensor strength ratio in collegiate athletes.

OBJECTIVE: To determine the relationship of previous lower extremity injury and the measured ratio of hip abduction to extension strength in collegiate athletes. DESIGN: Cohort study of college athletes at time of pre-participation screening physical. SETTING: An NCAA Division I college. PARTICIPANTS: Two hundred and thirty-six college athletes from a NCAA Division I school (162) males and (74) females. MAIN OUTCOME MEASURES: The ratio of maximal hip abduction to extension strength was calculated, following raw data collection with a specially designed dynamometer anchoring station. Injury to the lower extremities, in the past year, was recorded via personal interview at the time of screening and verified by review of previous injury records. RESULTS: A significant difference in the ratio of hip abduction to extension strength was noted on the left lower extremity of athletes with reported lower extremity (LE) injury compared to those without injury. Upon further review of data, hip extension weakness appears to be the likely cause of this difference. CONCLUSION: Athletes with reported lower extremity injury demonstrated a significant residual difference in the ratio of hip abduction to extension strength. This may be the result of injury related muscle weakness, altered muscle firing patterns, central inhibition or unknown compensatory strategies which all may be risk factors for recurrent injury. Further research is underway to identify the cause/effect relationship of this finding. CLINICAL RELEVANCE: This study may advance our understanding of potential compensatory strategies about the hip which theoretically may result from previous lower extremity injury or injuries which are incompletely rehabilitated. Additionally, this study provides some reasoning to support the screening of hip strength during the pre-participation physical, as it may be an important factor to prevent recurrent injury.

Origin and distribution of bone marrow-derived cells in the central nervous system in a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is associated with increased numbers of microglia within the central nervous system (CNS). However, it is unknown whether the microgliosis results from proliferation of CNS resident microglia, or recruitment of bone marrow (BM)-derived microglial precursors. Here we assess the distribution and number of BM-derived cells in spinal cord using transplantation of green fluorescent protein (GFP)-labeled BM cells into myelo-ablated mice over-expressing human mutant superoxide dismutase 1 (mSOD), a murine model of ALS. Transplantation of GFP+ BM did not affect the rate of disease progression in mSOD mice. Mean numbers of microglia and GFP+ cells in spinal cords of control mice were not significantly different from those in asymptomatic mSOD mice and showed no change with animal age. The number of GFP+ cells and microglia (F4/80+ and CD11b+ cells) within the spinal cord of mSOD mice increased compared to age-matched controls at a time when mSOD mice exhibited disease symptoms, continuing up to disease end-stage. Although we observed an increase in the number of GFP+ cells in spinal cords of mSOD mice with disease symptoms, mean numbers of GFP+ F4/80+ cells comprised less than 20% of all F4/80+ cells and did not increase with disease progression. Furthermore, the relative rates of proliferation in CD45+GFP- and CD45+GFP+ cells were comparable. Thus, we demonstrate that the microgliosis present in spinal cord tissue of mSOD mice is primarily due to an expansion of resident microglia and not to the recruitment of microglial precursors from the circulation.