Epidemiology of Sports Injuries Among High School Athletes in the United States: Data From 2015 to 2019.

Background: Nearly 8 million high school students in the United States participate in sports each year. With the lack of recent population data, an update to previous studies on US high school athletes is needed. Purpose: To update the epidemiology of sports injuries in high school athletes in the United States. Study Design: Descriptive epidemiology study. Methods: The data from the National Health School Sports-Related Injury Surveillance Study, including 100 nationally representative high schools, were obtained for 9 high school sports (boys' football, soccer, basketball, wrestling, and baseball and girls' soccer, basketball, volleyball, and softball) between the 2015 and 2019 academic years. Injury rates were calculated as the ratio of injuries per 1000 athlete exposures (AEs), defined as 1 athlete participating in 1 practice or competition. Data on injured body area, injury type (sprains/strains, concussions, contusions, and fractures), time loss, and need for surgery were also obtained. Rate ratios (RRs) with 95% CIs and P values were calculated. Results: Athletic trainers reported 15,531 injuries during 6,778,209 AEs, with an overall rate of 2.29 injuries per 1000 AEs. Injury rates were highest in football (3.96), girls' soccer (2.65), and boys' wrestling (2.36). The overall injury rate was lower in girls' sports (1.86) compared with boys' sports (2.52) (RR, 0.74 [95% CI, 0.71-0.76]; P < .001) and was higher in competition compared with practice (RR, 3.39 [95% CI, 3.28-3.49]; P < .001). The most commonly injured body areas were the head/face (24.2%), ankle (17.6%), and knee (14.1%). Sprains/strains (36.8%) and concussions (21.6%) were the most common diagnoses. Overall, 39.2% and 34% of injuries resulted in a time loss of <1 week and 1 to 3 weeks, respectively. Surgery was required in 6.3% of injuries, with wrestling (9.6%), girls' basketball (7.6%), and boys' baseball (7.4%) being the sports with the highest proportion of injuries needing surgery. Conclusion: Study findings demonstrated that boys' football, girls' soccer, and boys' wrestling had the highest injury rates, with boys' sports overall having higher injury rates than girls' sports. Sprains/strains and concussions were the most common diagnoses. Few injuries required surgery.

Alternative and Adjunct Treatments for Scoliosis: A Google Trends Analysis of Public Popularity Compared With Scientific Literature.

Purpose As Google searches have often been found to provide inaccurate information regarding various treatments for orthopedic conditions, it becomes important to analyze search trends to understand what treatments are most popularly considered and the quality of information available. We sought to compare the public interest in popular adjunct/alternative scoliosis treatments to the published literature on these topics and assess any temporal trends in the public interest in these treatments. Methods The study authors compiled the most common adjunct/alternative treatments for scoliosis on PubMed. Chiropractic manipulation, Schroth exercises, physical therapy, pilates, and yoga, along with "scoliosis," were each entered into Google Trends, collected from 2004 to 2021. A linear regression analysis of covariance (ANCOVA) was done to determine whether there was a linear relationship between Google Trends' popularity and PubMed publication data. The seasonal popularity of the terms was assessed using locally estimated scatterplot smoothing (LOESS) regression. Results Google Trends and publication frequency linear regression curves were different for chiropractic manipulation (p < 0.001), Schroth exercises (p < 0.001), physical therapy (p < 0.001), and pilates (p = 0.003). Chiropractic manipulation (p < 0.001), Schroth exercises (p = 0.003), and physical therapy (p < 0.001) had positive trends, and yoga (p < 0.001) had a negative trend. Chiropractic manipulation and yoga were more popular in the summer and winter months. Conclusion Google Trends can provide orthopedic surgeons and other healthcare professionals with valuable information on which treatments are gaining popularity with the public, so physicians may specifically inform themselves prior to patient encounters, leading to more productive shared decision-making.

Socioeconomic Factors Correlation With Idiopathic Scoliosis Curve Type and Cobb Angle Severity.

INTRODUCTION: Race and socioeconomic status correlate with disease outcomes and treatment in patients with idiopathic scoliosis (IS) to varying degrees, although there is no clear association with Cobb angle and curve type. The purpose of this study was to assess socioeconomic factors and their association with Cobb angles in patients with IS. METHODS: A retrospective chart review was completed with the radiographic analysis of 89 patients diagnosed with IS and spinal curves >10° between the ages of six and 18. Associations between the Cobb angles and socioeconomic categorical variables were analyzed using a nonparametric Kruskal-Wallis test and continuous variables using a Spearman Rank correlation.  Results: There were no significant associations between proximal thoracic, main thoracic, or thoracolumbar/lumbar Cobb angles and sex, insurance type, race, access to healthy food, financial difficulty, or income. BMI and proximal thoracic Cobb angle (ρ = 0.2375, p=0.0268) had a significant positive correlation, and BMI and income (ρ = -0.2468, p=0.0228) shared a significant negative correlation. CONCLUSIONS: The severity of IS proximal thoracic Cobb angles was positively associated with BMI and income. Other socioeconomic factors such as age, race, sex, access to food, insurance, and financial difficulties related to scoliosis treatment were not correlated with Cobb angle severity. The data presented suggest that patients with IS have varying degrees of curve type and severity that overall do not correlate with various socioeconomic factors. Validating which factors are predictive of curve severity could lead to early intervention preventing further morbidity of IS.

The Role of Music-Based Interventions in Orthopaedic Surgery.

Music-based interventions (MBIs), such as music therapy, are interventions in which music is used to address the physical, emotional, and social needs of individuals. The origin of music-based therapy can be traced to ancient Egypt and expanded into the United States during the mid-1900s. These interventions have shown efficacy in reducing anxiety and pain in both nonsurgical and surgical settings across various medical specialities, one of which is orthopaedic surgery. Prior studies have investigated the use of MBI in adult and paediatric patients and have shown an improvement in patient well-being following medical care and a reduction in healthcare costs across both patient populations. This standard review covers the current utility of MBI in the field of orthopaedic surgery and explores the current literature on the application and limitations of MBI in both the operative and nonoperative aspects of orthopaedic care.

The Utility of Social Media on Urology Residency Doximity Rankings.

Background Social media has been more widely used by urology residency programs since the COVID-19 pandemic. There are no studies on the relationship between Doximity residency ranking and social media usage in urology. Objectives In this study, we aim to investigate the relationship between social media usage and the academic prestige of urology residency programs. Methods Residency reputation data was acquired from the Doximity Residency Navigator website. Twitter and Instagram activity in 2019 and 2021 was analyzed by collecting data on the total number of posts and followers. Data on residency virtual recruitment was obtained from Twitter and UroResidency website. Results By the end of 2021, 122/139 (87.8%) urology residency programs had a Twitter account and 61/139 (43.9%) had an Instagram account. A significant linear regression was found between Doximity ranking and the number of Twitter followers (p<0.001), Twitter posts (p=0.005), and Instagram followers (p=0.026). Virtual recruitment events were held by 107/139 (77%) programs in 2021. There was a significant linear regression between Doximity rankings and the number of virtual events (p<0.006). Conclusions Social media use by urology residency programs has increased since the COVID-19 pandemic. A program's higher Doximity ranking was correlated with the presence of Twitter and Instagram accounts as well as the number of Twitter followers, Twitter posts, and Instagram followers. There was a significant relationship between Doximity rankings and the number of hosted virtual events. Programs should consider increasing social media visibility to potentially improve their Doximity rankings.

Optimizing Total Joint Arthroplasty for Patients Living With Human Immunodeficiency Virus.

Introduction Significant advancements in human immunodeficiency virus (HIV) treatment have led to an increasing life expectancy among patients living with HIV (PLWH). Given this rise in life expectancy, as well as the ability to lead a more active lifestyle, the rate of total joint arthroplasty (TJA) in this population is increasing. Unfortunately, the current medical literature surrounding the safety and efficacy of TJA in this patient population is indeterminant. Therefore, the purpose of this study was to determine if optimization of PLWH prior to TJA would result in any changes in the incidence of postoperative complications and hospital length of stay (LOS) when compared to historically reported data.  Materials and methods A retrospective study was performed of all PLWH 18 years and older who underwent either a primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) between 2009 and 2019 at our academic institution. Medical records were reviewed for each patient to assess demographics, comorbidities, preoperative laboratory studies, operative details, length of hospital stay, complications, and follow-up time. Patients were optimized using our institution's current optimization guidelines: body mass index (BMI) less than 40 kg/m2, hemoglobin >12 g/dL, no tobacco use within 30 days of surgery, albumin >3.5 g/dL. Independent-sample t-tests and Pearson's chi-square tests were used to evaluate the continuous and categorical variables, respectively. Results This study included 47 TJA in PLWH, including 14 TKA and 33 THA. Out of the 47 patients, 13 (27.7%) were fully optimized for all four variables: BMI, hemoglobin, non-smoking status, and albumin. There was no significant difference between the group of PLWH that was completely optimized and the group that was not in any patient characteristics, preoperative labs, intraoperative variables, or postoperative variables, including length of hospital stay and complications. A larger proportion of patients not completely optimized was found to be active smokers (p=0.0003). All complications occurred in cases in which the patients were not fully optimized. Subgroup analysis of PLWH, who were completely optimized, showed an average LOS of 4.3+/-1.5 days following TKA and 2.9+/-1.1 days following THA. Subgroup analysis of PLWH not completely optimized showed that each case was optimized for at least one variable and that those optimized for albumin had the largest (12.2%) number of complications. Conclusion PLWH can achieve a low rate of complications and LOS similar to that of the general population if medically and nutritionally optimized. Additional research is necessary to reveal well-defined parameters for achieving a higher rate of optimization prior to surgery in this important patient population.

Differences of Search Engine Digital Footprints Between Podiatrists and Foot and Ankle Orthopaedic Surgeons: A Need to Join the Digital Era.

BACKGROUND: Search engines generate lists of the most relevant websites using a keyword or phrase query and are integral in guiding consumer preferences. Digital information is important in the field of medicine, influencing what patients learn about their conditions and who they choose as providers. When two types of healthcare providers, such as podiatry and foot and ankle orthopaedic surgeons (FAOSs), share an overlapping consumer market, whichever group has a larger digital footprint receives increased digital engagement. METHODS: The Google search engine was used to query nine common foot and ankle-associated terms using a "search term + zip code" format for 150 zip codes divided into urban, suburban, and rural population densities. The first 10 results of each search were classified into one of five categories. Site content was classified as podiatry-oriented, other MD/DO-oriented, or FAOS-oriented. Separately, a ratio between podiatrists and FAOSs was calculated for each population density group. Data were then normalized using this ratio and reanalyzed with the Wilcoxon signed-rank test with significance at P < 0.05. RESULTS: Of 13,500 total search results, 4,992 (36.9%) were podiatry-oriented, 2,109 (15.6%) were other MD/DO-oriented, and 436 (3.2%) were FAOS-oriented. All geographic areas featured a higher number of podiatry than FAOS-oriented sites. FAOSs have more results per provider in urban areas (P < 0.001), although podiatrists had more in suburban and rural areas (P < 0.001, P < 0.001). Podiatrists have greater digital engagement in descriptive search terms. "Ankle replacement" has greater FAOS engagement in all three geographic areas. DISCUSSION: Foot and ankle-related Internet search terms results are overwhelmingly composed of podiatry-oriented sites. Per provider, regional differences are demonstrated, with FAOS having more sites in urban areas only. FAOS scope-of-practice terms such as "ankle replacement" still retain greater engagement by FAOSs. Search engine optimization and saturation strategies should be considered. LEVEL OF EVIDENCE: Level 3 (observational study).

Total Knee Arthroplasty Complicated by Posterior Dislocation of a Polyethylene Insert and Neurovascular Compromise.

Dislocation of the polyethylene insert is a rare complication of total knee arthroplasty (TKA), which has only been described in a handful of case reports. Here, we describe a report of a 55-year-old woman presenting 13 months after the primary TKA with signs of neurovascular compromise. A magnetic resonance image showed posterior extrusion of her polyethylene insert causing a mass effect on the gastrocnemius muscle and the popliteal neurovascular bundle. A multidisciplinary team including a joint reconstruction surgeon, vascular surgeon, and nerve specialist performed a revision TKA with peroneal nerve decompression. The polyethylene insert was noted to be dislocated, rotated 90 degrees, and incarcerated in the posterior knee.

The Evolving Role of Social Media in Pediatric Orthopaedics.

BACKGROUND: Social media has grown significantly and its application in health care has been dramatically accentuated by the COVID-19 pandemic. It is often considered as a "new dimension" of health care, particularly in its ability to provide health information. In 2017, the top social media sites utilized by pediatric orthopaedic surgeons included Facebook, LinkedIn, and Twitter. In our study, we analyze the current social media usage, trends in Instagram and TikTok content, and the perceptions on social media usage among pediatric orthopaedic surgeons. METHODS: The Pediatric Orthopaedic Society of North America (POSNA) membership directory was searched for the presence of social media. A review of all Instagram and TikTok posts made by the POSNA members were reviewed. A survey regarding the perception of social media networks and content was distributed to all POSNA members. RESULTS: A total of 1231 POSNA members actively practicing in the United States were included in our study. In all, 327 (26.6%) had a LinkedIn profile, 34 (2.8%) had a professional Facebook profile, 15 (1.2%) had a public Instagram account, 0 (0%) had TikTok, and 72 (5.8%) had a professional Twitter account. Fifteen POSNA members with public Instagram accounts had 10,878 followers. A total of 907 Instagram posts were made, 134 (14.8%) of which were education and 462 (50.9%) of which were personal or political. The perception of various social media networks such as Instagram (3.02), Facebook (3.16), and LinkedIn (3.51) were positive on a 5-point Likert scale, while perceptions of TikTok (2.36) and Twitter (2.99) were negative. Educational posts on Instagram (3.19) and Facebook (3.37) were positive. CONCLUSIONS: We provide an update to the utilization of social media by pediatric orthopaedists. Use of Instagram and TikTok accounts remain rare. Educational posts, when hosted on an appropriate social media platform, are perceived positively among pediatric orthopaedists. LEVEL OF EVIDENCE: Level IV.

Enhanced mitochondrial fission suppresses signaling and metastasis in triple-negative breast cancer.

BACKGROUND: Mitochondrial dynamics underlies malignant transformation, cancer progression, and response to treatment. Current research presents conflicting evidence for functions of mitochondrial fission and fusion in tumor progression. Here, we investigated how mitochondrial fission and fusion states regulate underlying processes of cancer progression and metastasis in triple-negative breast cancer (TNBC). METHODS: We enforced mitochondrial fission and fusion states through chemical or genetic approaches and measured migration and invasion of TNBC cells in 2D and 3D in vitro models. We also utilized kinase translocation reporters (KTRs) to identify single cell effects of mitochondrial state on signaling cascades, PI3K/Akt/mTOR and Ras/Raf/MEK/ERK, commonly activated in TNBC. Furthermore, we determined effects of fission and fusion states on metastasis, bone destruction, and signaling in mouse models of breast cancer. RESULTS: Enforcing mitochondrial fission through chemical or genetic approaches inhibited migration, invasion, and metastasis in TNBC. Breast cancer cells with predominantly fissioned mitochondria exhibited reduced activation of Akt and ERK both in vitro and in mouse models of breast cancer. Treatment with leflunomide, a potent activator of mitochondrial fusion proteins, overcame inhibitory effects of fission on migration, signaling, and metastasis. Mining existing datasets for breast cancer revealed that increased expression of genes associated with mitochondrial fission correlated with improved survival in human breast cancer. CONCLUSIONS: In TNBC, mitochondrial fission inhibits cellular processes and signaling pathways associated with cancer progression and metastasis. These data suggest that therapies driving mitochondrial fission may benefit patients with breast cancer.

The role of preoperative vascular imaging and embolisation for the surgical resection of bilateral hip heterotopic ossification.

The surgical excision of heterotopic ossification can provide improved function for patients; however, complications can include damage to nearby vessels and nerves, blood loss and recurrence. In the preoperative planning for excision, our case report describes the combination of CT angiography, preoperative embolisation of involved vascular structures and the use of intraoperative vascular surgery for dissection around key structures to aid in the reduction of morbidity in these patients.

Plasminogen Activator Inhibitor 1 (PAI1) Promotes Actin Cytoskeleton Reorganization and Glycolytic Metabolism in Triple-Negative Breast Cancer.

Migration and invasion of cancer cells constitute fundamental processes in tumor progression and metastasis. Migratory cancer cells commonly upregulate expression of plasminogen activator inhibitor 1 (PAI1), and PAI1 correlates with poor prognosis in breast cancer. However, mechanisms by which PAI1 promotes migration of cancer cells remain incompletely defined. Here we show that increased PAI1 drives rearrangement of the actin cytoskeleton, mitochondrial fragmentation, and glycolytic metabolism in triple-negative breast cancer (TNBC) cells. In two-dimensional environments, both stable expression of PAI1 and treatment with recombinant PAI1 increased migration, which could be blocked with the specific inhibitor tiplaxtinin. PAI1 also promoted invasion into the extracellular matrix from coculture spheroids with human mammary fibroblasts in fibrin gels. Elevated cellular PAI1 enhanced cytoskeletal features associated with migration, actin-rich migratory structures, and reduced actin stress fibers. In orthotopic tumor xenografts, we discovered that TNBC cells with elevated PAI1 show collagen fibers aligned perpendicular to the tumor margin, an established marker of invasive breast tumors. Further studies revealed that PAI1 activates ERK signaling, a central regulator of motility, and promotes mitochondrial fragmentation. Consistent with known effects of mitochondrial fragmentation on metabolism, fluorescence lifetime imaging microscopy of endogenous NADH showed that PAI1 promotes glycolysis in cell-based assays, orthotopic tumor xenografts, and lung metastases. Together, these data demonstrate for the first time that PAI1 regulates cancer cell metabolism and suggest targeting metabolism to block motility and tumor progression. IMPLICATIONS: We identified a novel mechanism through which cancer cells alter their metabolism to promote tumor progression.

Mammary fibroblasts remodel fibrillar collagen microstructure in a biomimetic nanocomposite hydrogel.

Architecture and microstructure of type I collagen fibers constitute central regulators of tumor invasion with aligned fibers providing a route for migration of stromal and cancer cells. Several different aspects of fibrillar collagen, such as stiffness, density, thickness, and pore size, may regulate migration of cancer cells, but determining effects of any one parameter requires clear decoupling of physical properties of collagen networks. The objective of this work is to develop and apply an in vitro three-dimensional (3D) tumor-extra cellular matrix (ECM) model with tunable physical parameters to define how stromal fibroblasts modulate collagen microstructure to control migration of breast cancer cells. We incorporated two different types of polyhedral oligomeric silsesquioxane (POSS) nano-molecules into a collagen/alginate matrix to induce different mechanisms of gelling. The resultant biomimetic, nanocomposite hydrogels show different collagen fibrillar microstructures while maintaining constant overall matrix stiffness, density, and porosimetry. Spheroids of human mammary fibroblasts embedded in these 3D matrices remodel the collagen network to varying extents based on differences in underlying matrix microstructures. The remodeled collagen matrix shows oriented, thicker fibrillar tracks, facilitating invasion of tumor cells. By decoupling effects of matrix stiffness and architecture, our nanocomposite hydrogels serve as robust platforms to investigate how biophysical properties of tumor environments control key processes regulating tumor progression in breast cancer and other malignancies. STATEMENT OF SIGNIFICANCE: Our manuscript demonstrates a new type of nanocomposite hydrogel with two different gelling mechanisms, produced by incorporating two types of polyhedral oligomeric silsesquioxane (POSS) nano-molecules into a collagen/alginate matrix. The resultant biomimetic hydrogels show different fibrillar collagen microstructures while maintaining constant overall matrix stiffness, density, and porosimetry. These gels allow us to uncouple effects of matrix stiffness versus architecture on migration and invasion of breast cancer cells and stromal fibroblasts. Upon embedding spheroids of human mammary fibroblasts (HMFs) and dissociated 231 breast cancer cells, we showed that HMFs remodeled the collagen network to differing extents dependent on starting matrix microstructures in each hydrogel. The remodeled collagen matrix showed aligned collagen fibers perpendicular to the surface of a spheroid with migrating HMFs following these fibers as occurs in tumors in vivo. To our knowledge, this is the first study showing significant different fibrillar collagen microstructures with constant collagen density and gel stiffness. This study establishes a new type of nanocomposite 3D hydrogels for studies of biophysical and cellular interactions in engineered tumor environments.

Obesity Updates: Understanding Obesity as a Disease and Intermittent Fasting

@#Obesity is now recognised as a chronic disease which needs chronic treatment to treat or prevent obesity related complications. This article discusses the biology of weight regulation as a basis to understanding obesity as a disease, and to appreciate the complex and multifactorial nature of the obesity problem. Finally, the article highlights the dietary approaches as part of the multi-pronged approach to treating obesity and gives a brief update on intermittent fasting.

Hybrid collagen alginate hydrogel as a platform for 3D tumor spheroid invasion.

Extracellular matrix regulates hallmark features of cancer through biochemical and mechanical signals, although mechanistic understanding of these processes remains limited by lack of models that recreate physiology of tumors. To tissue-engineer models that recapitulate three-dimensional architecture and signaling in tumors, there is a pressing need for new materials permitting flexible control of mechanical and biophysical features. We developed a hybrid hydrogel system composed of collagen and alginate to model tumor environments in breast cancer and other malignancies. Material properties of the hydrogel, including stiffness, microstructure and porosimetry, encompass parameters present in normal organs and tumors. The hydrogel possesses a well-organized, homogenous microstructure with adjustable mechanical stiffness and excellent permeability. Upon embedding multicellular tumor spheroids, we constructed a 3D tumor invasion model showing follow-the-leader migration with fibroblasts leading invasion of cancer cells similar to in vivo. We also demonstrated effects of CXCL12-CXCR4 signaling, a pathway implicated in tumor progression and metastasis, in a dual-tumor spheroid invasion model in 3D hydrogels. These studies establish a new hydrogel platform with material properties that can be tuned to investigate effects of environmental conditions on tumor progression, which will advance future studies of cancer cell invasion and response to therapy. STATEMENT OF SIGNIFICANCE: Our manuscript describes a novel design of hybrid hydrogel system composed of collagen and alginate modeling 3D tumor environments in breast cancer. The hydrogel possesses a well-organized, homogenous microstructure with adjustable mechanical stiffness. Upon embedding tumor spheroids, we successfully showed a 3D tumor invasion model showing follow-the-leader migration with fibroblasts leading invasion of cancer cells similar to in vivo. To the best of our knowledge, this is the first study showing two spheroids invade simultaneously and forming bridge-like connection and effects of chemical gradients in 3D hydrogel environment. This research provides a new model for tumor-stromal interactions in cancer cell migration and establishes a novel hydrogel system for analyzing physical and biochemical signals regulating cancer progression and response to therapy.

Functional Isolation of Tumor-Initiating Cells using Microfluidic-Based Migration Identifies Phosphatidylserine Decarboxylase as a Key Regulator.

Isolation of tumor-initiating cells currently relies on markers that do not reflect essential biologic functions of these cells. We proposed to overcome this limitation by isolating tumor-initiating cells based on enhanced migration, a function tightly linked to tumor-initiating potential through epithelial-to-mesenchymal transition (EMT). We developed a high-throughput microfluidic migration platform with automated cell tracking software and facile recovery of cells for downstream functional and genetic analyses. Using this device, we isolated a small subpopulation of migratory cells with significantly greater tumor formation and metastasis in mouse models. Whole transcriptome sequencing of migratory versus non-migratory cells from two metastatic breast cancer cell lines revealed a unique set of genes as key regulators of tumor-initiating cells. We focused on phosphatidylserine decarboxylase (PISD), a gene downregulated by 8-fold in migratory cells. Breast cancer cells overexpressing PISD exhibited reduced tumor-initiating potential in a high-throughput microfluidic mammosphere device and mouse xenograft model. PISD regulated multiple aspects of mitochondria, highlighting mitochondrial functions as therapeutic targets against cancer stem cells. This research establishes not only a novel microfluidic technology for functional isolation of tumor-initiating cells regardless of cancer type, but also a new approach to identify essential regulators of these cells as targets for drug development.

Intrathecal infusion of BMAA induces selective motor neuron damage and astrogliosis in the ventral horn of the spinal cord.

The neurotoxin beta-N-methylamino-l-alanine (BMAA) was first identified as a "toxin of interest" in regard to the amyotrophic lateral sclerosis-Parkinsonism Dementia Complex of Guam (ALS/PDC); studies in recent years highlighting widespread environmental sources of BMAA exposure and providing new clues to toxic mechanisms have suggested possible relevance to sporadic ALS as well. However, despite clear evidence of uptake into tissues and a range of toxic effects in cells and animals, an animal model in which BMAA induces a neurodegenerative picture resembling ALS is lacking, possibly in part reflecting limited understanding of critical factors pertaining to its absorption, biodistribution and metabolism. To bypass some of these issues and ensure delivery to a key site of disease pathology, we examined effects of prolonged (30day) intrathecal infusion in wild type (WT) rats, and rats harboring the familial ALS associated G93A SOD1 mutation, over an age range (80±2 to 110±2days) during which the G93A rats are developing disease pathology yet remain asymptomatic. The BMAA exposures induced changes that in many ways resemble those seen in the G93A rats, with degenerative changes in ventral horn motor neurons (MNs) with relatively little dorsal horn pathology, marked ventral horn astrogliosis and increased 3-nitrotyrosine labeling in and surrounding MNs, a loss of labeling for the astrocytic glutamate transporter, GLT-1, surrounding MNs, and mild accumulation and aggregation of TDP-43 in the cytosol of some injured and degenerating MNs. Thus, prolonged intrathecal infusion of BMAA can reproduce a picture in spinal cord incorporating many of the pathological hallmarks of diverse forms of human ALS, including substantial restriction of overt pathological changes to the ventral horn, consistent with the possibility that environmental BMAA exposure could be a risk factor and/or contributor to some human disease.

Enhancing skin wound healing by direct delivery of intracellular adenosine triphosphate.

BACKGROUND: A new intracellular adenosine triphosphate (ATP) delivery technique has been developed and was tested for skin wound care. METHODS: Eleven pairs of adult nude mice were used. ATP-vesicles were applied in 11 mice, and another 11 mice were treated with lipid vesicles only. RESULTS: The group treated with ATP-encapsulated fusogenic small, unilamellar lipid vesicles healed faster than the group treated with only lipid vesicles. Histologic study indicated better developed granular tissue and re-epithelialization in the study group, and wound tissue vascular endothelial growth factor expressions were also higher in ATP-vesicles treated mice. CONCLUSIONS: This intracellular ATP delivery system may provide a new hope for wound healing as well as the treatment of medical conditions in which ischemia is involved.