Comparison Between Movement Pattern Training and Strengthening on Kinematics and Kinetics in Patients With Chronic Hip-Related Groin Pain.

The purpose of this study was to compare the preliminary effects of movement pattern training (MoveTrain) versus strengthening/flexibility (standard) treatment on hip and pelvic biomechanics in patients with chronic hip-related groin pain. This is a secondary analysis of data collected during a pilot randomized clinical trial. Thirty patients with hip pain, between the ages of 15 and 40 years, were randomized to MoveTrain or standard. Both groups completed 10 treatment sessions over 12 weeks along with a daily home exercise program. Three-dimensional motion analysis was used to collect kinematic and kinetic data of the pelvis and hip during a single-leg squat task at pretreatment and immediately posttreatment. Compared with the standard group, the MoveTrain group demonstrated smaller hip adduction angles (P = .006) and smaller hip external adduction moments (P = .008) at posttreatment. The desired changes to hip joint biomechanics, as found in this study, may require specificity in training that could allow health care professionals to better customize the rehabilitation of patients with hip pain. These findings can also be applied to the design and implementation of future clinical trials to strengthen our understanding of the long-term implications of different rehabilitation techniques for patients with hip pain.

Increased hemoglobin affinity for oxygen with GBT1118 improves hypoxia tolerance in sickle cell mice.

Therapeutic agents that increase the Hb affinity for oxygen (O2) could, in theory, lead to decreased O2 release from Hb and impose a hypoxic risk to tissues. In this study, GBT1118, an allosteric modifier of Hb affinity for O2, was used to assess the impact of increasing Hb affinity for O2 on brain tissue oxygenation, blood pressure, heart rate, O2 delivery, and tolerance to hypoxia in Townes transgenic sickle cell disease (SCD) mice. Brain oxygenation and O2 delivery were studied during normoxia and severe hypoxic challenges. Chronic treatment with GBT1118 increased Hb affinity for O2, reducing the Po2 for 50% HbO2 saturation (P50) in SCD mice from 31 mmHg to 18 mmHg. This treatment significantly reduced anemia, increasing hematocrit by 33%, improved cardiac output (CO), and O2 delivery and extraction. Chronically increasing Hb affinity for O2 with GBT1118 preserved cortical O2 tension during normoxia, improved cortical O2 tension during hypoxia, and increased tolerance to severe hypoxia in SCD mice. Independent of hematological changes induced by chronic treatment, a single dose of GBT1118 significantly improved tolerance to hypoxia, highlighting the benefits of increasing Hb affinity for O2 and consequently reducing sickling of RBCs in blood during hypoxia in SCD.NEW & NOTEWORTHY Chronic pharmacologically increased hemoglobin affinity for oxygen in sickle cell disease mice alleviated hematological consequences of sickle cell disease, increasing RBC half-life, hematocrit, and hemoglobin concentration, while also decreasing reticulocyte count. Additionally, chronically increased hemoglobin affinity for oxygen significantly improved survival as well as cortical tissue oxygenation in sickle cell disease mice during hypoxia, suggesting that oxygen delivery and utilization is improved by increased hemoglobin affinity for oxygen.

Safety profile of high molecular weight polymerized hemoglobins.

BACKGROUND: Hemoglobin (Hb)-based oxygen (O2 ) carriers (HBOCs) are being developed as alternatives to red blood cells and blood when these products are unavailable. Clinical trials of previous HBOC generations revealed side effects, including hypertension and vasoconstriction, that were not observed in preclinical studies. Large molecular weight (MW) polymerized bovine Hb (PolybHb) represents a new class of HBOC with promising results. We evaluated the safety profile of PolybHb after an exchange transfusion (ET) in guinea pigs (GPs). This study compares changes in indices of cardiac, inflammatory, and organ function after ET with high (R-state) and low (T-state) O2 affinity PolybHb with high MW. STUDY DESIGN AND METHODS: Guinea pigs underwent a 20% ET with PolybHb. To assess the implication of PolybHb ET on the microcirculation, hamsters instrumented with a dorsal window chamber were subjected to a similar volume ET. RESULTS: T and R-state PolybHb did not induce significant alterations in cardiac function. T-state PolybHb induced mild vasoconstriction shortly after transfusion, while R-state did not have acute effects on microvascular tone. CONCLUSION: Large MW PolybHbs were found to be safe and efficacious in increasing O2 carrying capacity and the O2 affinity of the PolybHb did not affect O2 delivery or extraction by tissues in relevant preclinical models. In conclusion, these results suggest that both T-state and R-state PolybHb are safe and do not impair O2 delivery. The results are encouraging and support further evaluation of high MW PolybHbs and their future feasibility compared to allogenic blood in a trauma model.

A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease.

Ataxia telangiectasia (AT) is a progressive multisystem disorder caused by mutations in the AT-mutated (ATM) gene. AT is a neurodegenerative disease primarily characterized by cerebellar degeneration in children leading to motor impairment. The disease progresses with other clinical manifestations including oculocutaneous telangiectasia, immune disorders, increased susceptibly to cancer and respiratory infections. Although genetic investigations and physiological models have established the linkage of ATM with AT onset, the mechanisms linking ATM to neurodegeneration remain undetermined, hindering therapeutic development. Several murine models of AT have been successfully generated showing some of the clinical manifestations of the disease, however they do not fully recapitulate the hallmark neurological phenotype, thus highlighting the need for a more suitable animal model. We engineered a novel porcine model of AT to better phenocopy the disease and bridge the gap between human and current animal models. The initial characterization of AT pigs revealed early cerebellar lesions including loss of Purkinje cells (PCs) and altered cytoarchitecture suggesting a developmental etiology for AT and could advocate for early therapies for AT patients. In addition, similar to patients, AT pigs show growth retardation and develop motor deficit phenotypes. By using the porcine system to model human AT, we established the first animal model showing PC loss and motor features of the human disease. The novel AT pig provides new opportunities to unmask functions and roles of ATM in AT disease and in physiological conditions.

Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome.

Dipeptidyl peptidase 4 (DPP4, CD26), a type II transmembrane ectopeptidase, is the receptor for the Middle Eastern respiratory syndrome coronavirus (MERS-CoV). MERS emerged in 2012 and has a high mortality associated with severe lung disease. A lack of autopsy studies from MERS fatalities has hindered understanding of MERS-CoV pathogenesis. We investigated the spatial and cellular localization of DPP4 to evaluate an association MERS clinical disease. DPP4 was rarely detected in the surface epithelium from nasal cavity to conducting airways with a slightly increased incidence in distal airways. DPP4 was also found in a subset of mononuclear leukocytes and in serous cells of submucosal glands. In the parenchyma, DPP4 was found principally in type I and II cells and alveolar macrophages and was also detected in vascular endothelium (eg, lymphatics) and pleural mesothelia. Patients with chronic lung disease, such as chronic obstructive pulmonary disease and cystic fibrosis, exhibited increased DPP4 immunostaining in alveolar epithelia (type I and II cells) and alveolar macrophages with similar trends in reactive mesothelia. This finding suggests that preexisting pulmonary disease could increase MERS-CoV receptor abundance and predispose individuals to MERS morbidity and mortality, which is consistent with current clinical observations. We speculate that the preferential spatial localization of DPP4 in alveolar regions may explain why MERS is characterized by lower respiratory tract disease.

Immunohistochemical Detection of Markers for Translational Studies of Lung Disease in Pigs and Humans.

Genetically engineered pigs are increasingly recognized as valuable models for the study of human disease. Immunohistochemical study of cellular markers of disease is an important tool for the investigation of these novel models so as to evaluate genotype and treatment differences. Even so, there remains a lack of validated markers for pig tissues that can serve as a translational link to human disease in organs such as the lung. Herein, we evaluate markers of cellular inflammation (cluster of differentiation [CD]3, CD79a, B cell lymphoma [BCL] 6, ionized calcium-binding adapter molecule [IBA]1, and myeloperoxidase) and those that may be involved with tissue remodeling (alpha-smooth muscle actin, beta-tubulin-III, lactoferrin, mucin [MUC]5AC, MUC5B, and cystic fibrosis transmembrane conductance regulator [CFTR]) for study of lung tissues. We compare the utility of these markers between pig and human lungs to validate translational relevance of each marker. Our results suggest these markers can be a useful addition in the pathological evaluation of porcine models of human disease.

Uncovering Distinct Peptide Charging Behaviors in Electrospray Ionization Mass Spectrometry Using a Large-Scale Dataset.

Electrospray ionization is a powerful and prevalent technique used to ionize analytes in mass spectrometry. The distribution of charges that an analyte receives (charge state distribution, CSD) is an important consideration for interpreting mass spectra. However, due to an incomplete understanding of the ionization mechanism, the analyte properties that influence CSDs are not fully understood. Here, we employ a machine learning-based approach and analyze CSDs of hundreds of thousands of peptides. Interestingly, half of the peptides exhibit charges that differ from what one would naively expect (the number of basic sites). We find that these peptides can be classified into two regimes (undercharging and overcharging) and that these two regimes display markedly different charging characteristics. Notably, peptides in the overcharging regime show minimal dependence on basic site count, and more generally, the two regimes exhibit distinct sequence determinants. These findings highlight the rich ionization behavior of peptides and the potential of CSDs for enhancing peptide identification.

Novel high molecular weight polymerized hemoglobin in a non-obese model of cardiovascular and metabolic dysfunction.

The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20 % blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.

AP-1 elements and TCL1 protein regulate expression of the gene encoding protein tyrosine phosphatase PTPROt in leukemia.

We previously demonstrated that the gene encoding PTPROt, the truncated form of protein tyrosine phosphatase receptor type O expressed predominantly in hematopoietic cells, is a candidate tumor suppressor and is down-regulated in chronic lymphocytic leukemia (CLL). Here, we show that PTPROt expression is significantly reduced in CD19(+) spleen B cells from Eµ-T cell leukemia 1 (TCL1) transgenic mice relative to the wild-type mice. Strikingly, as much as a 60% decrease in PTPROt expression occurs at 7 weeks independently of promoter methylation. To elucidate the potential mechanism for this early suppression of PTPROt in these mice, we explored the role of activating protein-1 (AP-1) in its expression. We first demonstrate that AP-1 activation by 12-O-tetradecanoylphorbol-13-acetate induces PTPROt expression with concurrent recruitment of c-fos and c-jun to its promoter. The PTPROt promoter is also responsive to over- and underexpression of AP-1, confirming the role of AP-1 in PTPROt expression. Next, we demonstrate that TCL1 can repress the PTPROt promoter by altering c-fos expression and c-jun activation state. Finally, using primary CLL cells we have shown an inverse relationship between TCL1 and PTPROt expression. These findings further substantiate the role of TCL1 in PTPROt suppression and its importance in the pathogenesis of CLL.

A high-throughput approach reveals distinct peptide charging behaviors in electrospray ionization mass spectrometry.

Electrospray ionization is a powerful and prevalent technique used to ionize analytes in mass spectrometry. The distribution of charges that an analyte receives (charge state distribution, CSD) is an important consideration for interpreting mass spectra. However, due to an incomplete understanding of the ionization mechanism, the analyte properties that influence CSDs are not fully understood. Here, we employ a machine learning-based high-throughput approach and analyze CSDs of hundreds of thousands of peptides. Interestingly, half of the peptides exhibit charges that differ from what one would naively expect (number of basic sites). We find that these peptides can be classified into two regimes-undercharging and overcharging-and that these two regimes display markedly different charging characteristics. Strikingly, peptides in the overcharging regime show minimal dependence on basic site count, and more generally, the two regimes exhibit distinct sequence determinants. These findings highlight the rich ionization behavior of peptides and the potential of CSDs for enhancing peptide identification.

Exploring Race Differences in Satisfaction With Rehabilitation Following Total Knee Arthroplasty: A Qualitative Study.

BACKGROUND: The purpose of this qualitative focus group study was to explore race differences in the rehabilitation experience and satisfaction with rehabilitation following total knee arthroplasty (TKA). METHOD: We conducted a series of qualitative focus group discussions with groups of non-Hispanic White and non-Hispanic Black older adults who recently underwent TKA. We used grounded theory approach, which asks the researcher to develop theory from the data that are collected. Participants discussed barriers and facilitators to accessing rehabilitation after surgery, opinions regarding their physical therapists, the amount of postoperative physical therapy received, and overall satisfaction with the postoperative rehabilitation process. RESULTS: Thirty-six individuals participated in focus groups. Three major themes emerged: (i) Participants reported overall positive views of their post-TKA rehabilitation experience. They particularly enjoyed one-on-one care, the ability to participate in "prehabilitation," and often mentioned specific interventions they felt were most helpful in their recovery. (ii) Despite this, substantial barriers to accessing physical therapy exist. These include suboptimal pain management, copayments and other out-of-pocket costs, and transportation to visits. (iii) There were minor differences in the rehabilitation experiences between Black and White participants. Black participants reported longer paths toward surgery and occasional difficulty interacting with rehabilitation providers. CONCLUSIONS: Individuals undergoing TKA can largely expect positive rehabilitation experiences postoperatively. However, some barriers to postoperative physical therapy exist and may differ between Black and White patients. Physical therapists should increase their awareness of these barriers and work to minimize them whenever possible.

Race Differences in Postacute Physical Therapy Utilization and Patient-Reported Function After Total Knee Arthroplasty.

OBJECTIVE: This observational cohort study included patients of Black and White race and non-Hispanic ethnicity with end-stage knee osteoarthritis who were scheduled to receive total knee arthroplasty (TKA) surgery. Our objective was to examine whether race differences exist in the use of physical therapy (PT) across all postacute settings and to examine patient-reported physical function following TKA. METHODS: We collected pre- and postoperative physical function data and postoperative rehabilitation data on 104 Black and White individuals undergoing TKA. Regression analyses and independent samples t-tests were used to explore the predictive value of race on postoperative functional outcome and to compare PT utilization within each postacute setting and across all postacute rehabilitation settings. RESULTS: Total PT received was similar between White and Black participants, but significant race differences in PT utilization existed within specific settings. Race did not significantly predict function after TKA, but Black participants had slightly lower self-reported function both before and after surgery than White participants. CONCLUSION: This is the first study to examine both PT utilization and functional outcomes in a sample of individuals undergoing TKA, and results indicate differences in where postoperative PT is received between Black and White patients.

Safety and efficacy of human polymerized hemoglobin on guinea pig resuscitation from hemorrhagic shock.

For the past thirty years, hemoglobin-based oxygen carriers (HBOCs) have been under development as a red blood cell substitute. Side-effects such as vasoconstriction, oxidative injury, and cardiac toxicity have prevented clinical approval of HBOCs. Recently, high molecular weight (MW) polymerized human hemoglobin (PolyhHb) has shown positive results in rats. Studies have demonstrated that high MW PolyhHb increased O2 delivery, with minimal effects on blood pressure, without vasoconstriction, and devoid of toxicity. In this study, we used guinea pigs to evaluate the efficacy and safety of high MW PolyhHb, since like humans guinea pigs cannot produce endogenous ascorbic acid, which limits the capacity of both species to deal with oxidative stress. Hence, this study evaluated the efficacy and safety of resuscitation from severe hemorrhagic shock with high MW PolyhHb, fresh blood, and blood stored for 2 weeks. Animals were randomly assigned to each experimental group, and hemorrhage was induced by the withdrawal of 40% of the blood volume (BV, estimated as 7.5% of body weight) from the carotid artery catheter. Hypovolemic shock was maintained for 50 min. Resuscitation was implemented by infusing 25% of the animal's BV with the different treatments. Hemodynamics, blood gases, total hemoglobin, and lactate were not different before hemorrhage and during shock between groups. The hematocrit was lower for the PolyhHb group compared to the fresh and stored blood groups after resuscitation. Resuscitation with stored blood had lower blood pressure compared to fresh blood at 2 h. There was no difference in mean arterial pressure between groups at 24 h. Resuscitation with PolyhHb was not different from fresh blood for most parameters. Resuscitation with PolyhHb did not show any remarkable change in liver injury, inflammation, or cardiac damage. Resuscitation with stored blood showed changes in liver function and inflammation, but no kidney injury or systemic inflammation. Resuscitation with stored blood after 24 h displayed sympathetic hyper-activation and signs of cardiac injury. These results suggest that PolyhHb is an effective resuscitation alternative to blood. The decreased toxicities in terms of cardiac injury markers, vital organ function, and inflammation following PolyhHb resuscitation in guinea pigs indicate a favorable safety profile. These results are promising and support future studies with this new generation of PolyhHb as alternative to blood when blood is unavailable.

High fat high sucrose diet-induced dyslipidemia in guinea pigs.

Easy access to high-calorie and fat-dense fast food has resulted in unhealthy dietary and lifestyle changes worldwide, which affects both developed and developing economies. This predisposes populations to a considerable number of metabolic and inflammatory conditions, such as diabetes, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Guinea pigs have been proposed as a model to study high-fat diet-induced metabolic disease due to their similar antioxidant metabolism and lipid profile to humans, and their susceptibility to atherosclerosis and endothelial disease. This study aims to evaluate cardiovascular and metabolic disorders induced by high-fat high-sucrose diet (HFHSD) in guinea pigs. Two to three-week-old male guinea pigs were fed a normal diet (ND) or HFHSD for 12 wk. Guinea pigs fed a HFHSD developed glucose intolerance, dyslipidemia, and liver, cardiac, and kidney damage. However, hypertension, dysautonomia, endothelial disease, and obesity were absent in these HFHSD guinea pigs. Taken together, these results show that guinea pigs fed a HFHSD are a nonobese model of metabolic disorders, resulting in important cardiac damage. Moreover, our findings suggest that NAFLD may be an important risk factor for diet-induced CVD.NEW & NOTEWORTHY In this study, we show a new animal model for diet-induced disease metabolic disorders without obesity in guinea pigs. Moreover, results suggest a strong relation between liver disease and increased cardiovascular risks.

A Qualitative Study of Preparation for Lumbar Spinal Stenosis Surgery: Perceptions of Patients and Physical Therapists.

OBJECTIVES: To gain the perspectives of patients who underwent lumbar spinal stenosis (LSS) surgery and physical therapists who treat spine-related disorders regarding rehabilitation and other care prior to LSS surgery. DESIGN: Qualitative focus group study. METHODS: Sixteen patients (4 female; average ± SD age, 64.3 ± 8.8 years; time since surgery, 9.9 ± 4.4 months) and 10 physical therapists (2 female; average ± SD age, 40.9 ± 6.6 years; time in practice, 17.2 ± 7.7 years) participated. Four groups were conducted: 2 with patients post LSS surgery and 2 with physical therapists who treat spine-related disorders. Participants were asked open-ended questions by a trained facilitator regarding their perceptions of preoperative LSS education and rehabilitation. Transcripts were coded and themes were identified. RESULTS: Analyses revealed 4 themes within the discussions: (1) desire for helpful information, (2) benefits of preoperative rehabilitation, (3) downfalls of preoperative rehabilitation, and (4) desire for coordinated care. Varying opinions on preoperative physical therapy between patients and physical therapists were discussed, revealing that similar numbers of participants held positive and negative perceptions of preoperative physical therapy. A desire for more thorough preoperative education and care was expressed by both groups. CONCLUSION: There is a clear need for standardized preoperative LSS care and education. This may decrease misunderstandings about LSS surgery and its treatments in the future as well as improve coordinated care between surgeons and physical therapists. J Orthop Sports Phys Ther 2020;50(4):198-205. Epub 30 Oct 2019. doi:10.2519/jospt.2020.8887.

Polymerized Hemoglobin With Increased Molecular Size Reduces Toxicity in Healthy Guinea Pigs.

Hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) have been developed as an alternative to red blood cells (RBCs) for use in transfusion medicine. HBOCs have many benefits over RBCs; however, previous generations of HBOCs failed in clinical trials due to unanticipated cardiotoxicity. These problems likely originated from vasoconstriction, hypertension, oxidative stress, and the presence of low-molecular-weight (MW) Hb species in the HBOC formulation. Therefore, the objective of this study is to compare the toxicity of small-MW Polymerized bovine Hb (SPolyHb) to large-MW Polymerized bovine Hb (LPolyHb) in guinea pigs, since they lack the ability to synthesize vitamin C and are more sensitive to oxidative stress than other preclinical animal models. The two PolyHbs used in this study have similar molecular diameters (72 and 69 nm, respectively), but the SPolyHb included approximately 15% Hb polymers with MW below 256 kDa, which were significantly removed from LPolyHb. Solutions were injected as a hypervolemic (topload) infusion of 10% of the blood volume into animals. SPolyHb caused a 50% elevation in mean arterial pressure (MAP) from the baseline, while LPolyHb caused only a small increase in MAP. Both PolyHbs also increased markers of organ damage and tissue and systemic inflammation compared to controls. SPolyHb caused significant changes in tissue function and vital organ toxicity markers compared to LPolyHb, specifically markers related to kidney, liver, and lung injury and systemic inflammation and iron transport by the reticuloendothelial system. LPolyHb had a longer half-life than SPolyHb, which correlates with observations made in the reticuloendothelial and iron transport systems. These studies indicate that the molecular size of PolyHb determines vasoactivity, circulation time, mechanism of elimination, toxicity, and inflammation induced by its infusion.

Movement pattern training compared with standard strengthening and flexibility among patients with hip-related groin pain: results of a pilot multicentre randomised clinical trial.

STUDY DESIGN: Pilot, multicentre randomised clinical trial (RCT). OBJECTIVES: Assess viability of performing a definitive RCT and compare preliminary effects of movement pattern training (MoveTrain) and strengthening/flexibility (Standard) to improve function in people with chronic hip-related groin pain (HRGP). BACKGROUND: To determine the best physical therapist-led intervention for patients with HRGP, we must understand treatment effects of different treatment modes. METHODS: Forty-six patients (17M:29F; 29±5.3 years; body mass index 25.6±6.3 kg/m2) with HRGP were randomised. MoveTrain included task-specific training to optimise biomechanics during daily tasks. Standard included strengthening/flexibility. Treatment included 10 visits/12 weeks and home exercise programme (HEP). Primary outcomes for feasibility were recruitment, retention, treatment adherence and treatment fidelity. Secondary outcomes were patient-reported function (Hip disability and Osteoarthritis Outcome Score (HOOS)), lower extremity kinematics and hip muscle strength. RESULTS: We achieved target recruitment, and retention was excellent (91%). Patient session attendance was high (93%); however, reported HEP adherence (62%) was lower than expected. Physical therapists' adherence to treatment protocols was high (90%). Patients demonstrated high treatment receipt; 91% of exercises performed were rated independent. Both groups demonstrated clinically important improvements in function (HOOS) and muscle strength; however, there were no between-group differences (HOOS subscales, p≥0.13, strength, p≥0.34). Compared with Standard, MoveTrain demonstrated greater reductions in hip adduction (p=0.016) and pelvic drop (p=0.026) during a single leg squat. No adverse events were noted. CONCLUSION: Our experience in completing this RCT confirmed that a larger, multicentre RCT is feasible and highlighted modifications we will implement to optimise the future RCT. TRIAL REGISTRATION NUMBER: NCT02913222.

Providing no-cost transport to patients in an underserved area: Impact on access to physical therapy.

Background: Barriers to accessing outpatient health care services are common and contribute to poor health outcomes. We describe the efforts of a private practice physical therapy (PT) clinic to reduce these barriers by offering a door-to-door van service at no cost to patients. Methods: Clinic records and national census databases were retrospectively reviewed to explore the impact of offering no-cost van rides to patients attending outpatient PT appointments. We used descriptive statistics and linear regression to describe volume of utilization of the van service over a 40-month period. Paired t-tests compared PT clinic attendance rates (percentage of scheduled visits that were attended) before and after implementation of the van service. Results: Use of the van service increased significantly over time, from a mean of 83 riders per month in 2010 to 205 riders per month in 2013 (p < 0.001). Overall clinic attendance rate increased from 80.1% to 84.1% after implementation of the service (p = 0.002). Following introduction of the van service, 48% of patients using the van, compared to 25% of clinic patients overall, were uninsured or insured by Medicaid. Conclusion: Use of the van service increased over time, and availability of no-cost van transportation was associated with increased visit attendance for patients at an outpatient PT clinic.

Echinacea-induced macrophage activation.

Public interest in Echinacea is growing rapidly. Unfortunately, there is little scientific evidence to support claims of efficacy of this widely used botanical, and little information about potential mechanism of action. This study examines the ability of Echinacea to upregulate macrophage function and begins to elucidate the mechanism of Echinacea-induced macrophage activation. Murine peritoneal macrophages were cultured with E. purpurea extracts enriched for plant polysaccharide (EP). ELISA was used to measure cytokine production. MAPKs were blocked using specific inhibitors, and Western blotting used to identify phosphorylated proteins involved in signal transduction. To examine in vivo efficacy, EP was administered orally and Listeria monocytogenes given i.v. Mice were sacrificed three days post-infection to determine bacterial load in the spleen. We demonstrate that an endotoxin-free EP extract activates the innate immune response, stimulating production of IL-6, TNF, IL-12, and NO from macrophages in vitro. Along with evidence of enhanced macrophage function, we found that oral EP reduces bacterial burden during infection by Listeria monocytogenes, demonstrating its efficacy in vivo. EP initiates a signaling cascade within macrophages through both TLR4-dependent and -independent mechanisms, involving ERK, p38 and JNK, and ultimately the activation of NF-kappaB.