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Stretching before performance is a common practice among athletes in hopes of increasing performance and reducing the risk of injury. However, cumulative results indicate a negative impact of static stretching and proprioceptive neuromuscular facilitation (PNF) on performance; thus, there is a need for evaluating other stretching strategies for effective warm-up. The purpose of this study was to compare the differences between two sets of ballistic stretching and two sets of a dynamic stretching routine on vertical jump performance. Twenty healthy male and female college students between the ages of 22 and 34 (24.8 +/- 3 years) volunteered to participate in this study. All subjects completed three individual testing sessions on three nonconsecutive days. On each day, the subjects completed one of three treatments (no stretch, ballistic stretch, and dynamic stretch). Intraclass reliability was determined using the data obtained from each subject. A paired samples t-test revealed no significant difference in jump height, force, or power when comparing no stretch with ballistic stretch. A significant difference was found on jump power when comparing no stretch with dynamic stretch, but no significant difference was found for jump height or force. Statistics showed a very high reliability when measuring jump height, force, and power using the Kistler Quattro Jump force plate. It seems that neither dynamic stretching nor ballistic stretching will result in an increase in vertical jump height or force. However, dynamic stretching elicited gains in jump power poststretch. [ABSTRACT FROM AUTHOR]

We compared differences in isometric strength between older adults who have undergone elective unilateral total hip arthroplasty (THA) and completed rehabilitation with a population of community-dwelling older adults who have not had THA. The study was a cross-sectional design, and 22 unilateral THA subjects and 38 community-dwelling older adults participated. THA subjects received on average 13 outpatient or home-based physical therapy sessions before evaluation. THA subjects were evaluated 4 to 5 months postsurgery. We assessed isometric muscle strength by measuring peak hip torque per body weight with a robotic dynamometer during abduction, flexion, and extension. No significant performance differences were observed between operated and nonoperated hips of THA subjects. THA subject operated and nonoperated hips generated significantly less peak torque per body weight during flexion (p = 0.03) compared with community-dwelling older adult hips (THA subject operated hips = 6.96 ft-lb/lb, THA subject nonoperated hips = 8.26 ft-lb/lb, community-dwelling older adult hips = 11.56 ft-lb/lb). No significant differences were observed between THA subjects and community- dwelling older adults during hip extension (p = 0.55) or abduction (p = 0.17). At 4 to 5 months postsurgery, THA subjects were not at the same level of biomechanical performance as community-dwelling older adults. Significant strength deficits were found in THA subject operated versus nonoperated hips during isometric flexion. Additional or modified physical therapy that targets the hip flexors is recommended after THA. [ABSTRACT FROM AUTHOR]

Understanding why certain neurons are more sensitive to dysfunction and death caused by misfolded proteins could provide therapeutically relevant insights into neurodegenerative disorders. Here, we harnessed single-cell transcriptomics to examine live neurons isolated from prion-infected female mice, aiming to identify and characterize prion-vulnerable neuronal subsets. Our analysis revealed distinct transcriptional responses across neuronal subsets, with a consistent pathway-level depletion of synaptic gene expression in damage-vulnerable neurons. By scoring neuronal damage based on the magnitude of depleted synaptic gene expression, we identified a diverse spectrum of prion-vulnerable glutamatergic, GABAergic, and medium spiny neurons. Comparison between prion-vulnerable and resistant neurons highlighted baseline gene expression differences that could influence neuronal vulnerability. For instance, the neuroprotective cold-shock protein Rbm3 exhibited higher baseline gene expression in prion-resistant neurons and was robustly upregulated across diverse neuronal classes upon prion infection. We also identified vulnerability-correlated transcripts that overlapped between prion and Alzheimer's disease. Our findings not only demonstrate the potential of single-cell transcriptomics to identify damage-vulnerable neurons, but also provide molecular insights into neuronal vulnerability and highlight commonalties across neurodegenerative disorders., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. Crown.)

Most cases of human prion disease arise due to spontaneous misfolding of WT or mutant prion protein, yet recapitulating this event in animal models has proven challenging. It remains unclear whether spontaneous prion generation can occur within the mouse lifespan in the absence of protein overexpression and how disease-causing mutations affect prion strain properties. To address these issues, we generated knockin mice that express the misfolding-prone bank vole prion protein (BVPrP). While mice expressing WT BVPrP (I109 variant) remained free from neurological disease, a subset of mice expressing BVPrP with mutations (D178N or E200K) causing genetic prion disease developed progressive neurological illness. Brains from spontaneously ill knockin mice contained prion disease-specific neuropathological changes as well as atypical protease-resistant BVPrP. Moreover, brain extracts from spontaneously ill D178N- or E200K-mutant BVPrP-knockin mice exhibited prion seeding activity and transmitted disease to mice expressing WT BVPrP. Surprisingly, the properties of the D178N- and E200K-mutant prions appeared identical before and after transmission, suggesting that both mutations guide the formation of a similar atypical prion strain. These findings imply that knockin mice expressing mutant BVPrP spontaneously develop a bona fide prion disease and that mutations causing prion diseases may share a uniform initial mechanism of action.

Alterations in renal elimination processes of glomerular filtration and active tubular secretion by renal transporters can result in adverse drug reactions. Nonalcoholic steatohepatitis (NASH) alters hepatic transporter expression and xenobiotic elimination, but until recently, renal transporter alterations in NASH were unknown. This study investigates renal transporter changes in rodent models of NASH to identify a model that recapitulates human alterations. Quantitative protein expression by surrogate peptide liquid chromatography-coupled mass spectrometry (LC-MS/MS) on renal biopsies from NASH patients was used for concordance analysis with rodent models, including methionine/choline deficient (MCD), atherogenic (Athero), or control rats and Lepr db/db MCD ( db/db ), C57BL/6J fast-food thioacetamide (FFDTH), American lifestyle-induced obesity syndrome (ALIOS), or control mice. Demonstrating clinical similarity to NASH patients, db/db, FFDTH, and ALIOS showed decreases in glomerular filtration rate (GFR) by 76%, 28%, and 24%. Organic anion transporter 3 (OAT3) showed an upward trend in all models except the FFDTH (from 3.20 to 2.39 pmol/mg protein), making the latter the only model to represent human OAT3 changes. OAT5, a functional ortholog of human OAT4, significantly decreased in db/db, FFDTH, and ALIOS (from 4.59 to 0.45, 1.59, and 2.83 pmol/mg protein, respectively) but significantly increased for MCD (1.67 to 4.17 pmol/mg protein), suggesting that the mouse models are comparable to human for these specific transport processes. These data suggest that variations in rodent renal transporter expression are elicited by NASH, and the concordance analysis enables appropriate model selection for future pharmacokinetic studies based on transporter specificity. These models provide a valuable resource to extrapolate the consequences of human variability in renal drug elimination. SIGNIFICANCE STATEMENT: Rodent models of nonalcoholic steatohepatitis that recapitulate human renal transporter alterations are identified for future transporter-specific pharmacokinetic studies to facilitate the prevention of adverse drug reactions due to human variability., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Naturally occurring adeno-associated virus (AAV) serotypes that bind to ligands such as AVB sepharose or heparin can be purified by affinity chromatography, which is a more efficient and scalable method than gradient ultracentrifugation. Wild-type AAV8 does not bind effectively to either of these molecules, which constitutes a barrier to using this vector when a high throughput design is required. Previously, AAV8 was engineered to contain a SPAKFA amino acid sequence to facilitate purification using AVB sepharose resin; however, in vivo studies were not conducted to examine whether these capsid mutations altered the transduction profile. To address this gap in knowledge, a mutant AAV8 capsid was engineered to bind to AVB sepharose and heparan sulfate (AAV8-AVB-HS), which efficiently bound to both affinity columns, resulting in elution yields of >80% of the total vector loaded compared to <5% for wild-type AAV8. However, in vivo comparison by intramuscular, intravenous, and intraperitoneal vector administration demonstrated a significant decrease in AAV8-AVB-HS transduction efficiency without alteration of the transduction profile. Therefore, although it is possible to engineer AAV capsids to bind various affinity ligands, the consequences associated with mutating surface exposed residues have the potential to negatively impact other vector characteristics including in vivo potency and production yield. This study demonstrates the importance of evaluating all aspects of vector performance when engineering AAV capsids., (© 2020. Springer Nature Limited.)

Alterations in hepatic transporters have been identified in precirrhotic chronic liver diseases (CLDs) that result in pharmacokinetic variations causing adverse drug reactions (ADRs). However, the effect of CLD on the expression of renal transporters is unknown despite the overwhelming evidence of kidney injury in CLD patients. This study determines the transcriptomic and proteomic expression profiles of renal drug transporters in patients with defined CLD etiology. Renal biopsies were obtained from patients with a history of CLD etiologies, including nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcohol-associated liver disease (ALD), viral hepatitis C (HCV), and combination ALD/HCV. A significant decrease in organic anion transporter (OAT)-3 was identified in NASH, ALD, HCV, and ALD/HCV (1.56 ± 1.10; 1.01 ± 0.46; 1.03 ± 0.43; 0.86 ± 0.57 pmol/mg protein) relative to control (2.77 ± 1.39 pmol/mg protein). Additionally, a decrease was shown for OAT4 in NASH (24.9 ± 5.69 pmol/mg protein) relative to control (43.8 ± 19.9 pmol/mg protein) and in urate transporter 1 (URAT1) for ALD and HCV (1.56 ± 0.15 and 1.65 ± 0.69 pmol/mg protein) relative to control (4.69 ± 4.59 pmol/mg protein). These decreases in organic anion transporter expression could result in increased and prolonged systemic exposure to drugs and possible toxicity. Renal transporter changes, in addition to hepatic transporter alterations, should be considered in dose adjustments for CLD patients for a more accurate disposition profile. It is important to consider a multiorgan approach to altered pharmacokinetics of drugs prescribed to CLD patients to prevent ADRs and improve patient outcomes. SIGNIFICANCE STATEMENT: Chronic liver diseases are known to elicit alterations in hepatic transporters that result in a disrupted pharmacokinetic profile for various drugs. However, it is unknown if there are alterations in renal transporters during chronic liver disease, despite strong indications of renal dysfunction associated with chronic liver disease. Identifying renal transporter expression changes in patients with chronic liver disease facilitates essential investigations on the multifaceted relationship between liver dysfunction and kidney physiology to offer dose adjustments and prevent adverse drug reactions., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters. Non-alcoholic steatohepatitis (NASH) causes disease-specific alterations to the absorption, distribution, metabolism, and excretion (ADME) processes, including a decrease in protein expression of basolateral uptake transporters, an increase in efflux transporters, and modifications to enzyme activity. This can result in increased drug exposure and adverse drug reactions (ADRs). Our goal was to predict drugs that pose increased risks for ADRs in NASH patients. Bibliographic research identified 71 drugs with reported ADRs in patients with liver disease, mainly non-alcoholic fatty liver disease (NAFLD), 54 of which are known substrates of transporters and/or metabolizing enzymes. Since NASH is the progressive form of NAFLD but is most frequently undiagnosed, we identified other drugs at risk based on NASH-specific alterations to ADME processes. Here, we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH, based on their transport and/or metabolism processes. It encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients, especially when eliminated through multiple pathways altered by the disease. Therefore, these results may inform clinicians regarding the selection of drugs for use in NASH patients., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Ochratoxin A (OTA) is an abundant mycotoxin, yet the toxicological impact of its disposition is not well studied. OTA is an organic anion transporter (OAT) substrate primarily excreted in urine despite a long half-life and extensive protein binding. Altered renal transporter expression during disease, including nonalcoholic steatohepatitis (NASH), may influence response to OTA exposure, but the impact of NASH on OTA toxicokinetics, tissue distribution, and associated nephrotoxicity is unknown. By inducing NASH in fast food-dieted/thioacetamide-exposed mice, we evaluated the effect of NASH on a bolus OTA exposure (12.5 mg/kg by mouth) after 3 days. NASH mice presented with less gross toxicity (44% less body weight loss), and kidney and liver weights of NASH mice were 11% and 24% higher, respectively, than healthy mice. Organ and body weight changes coincided with reduced renal proximal tubule cells vacuolation, degeneration, and necrosis, though no OTA-induced hepatic lesions were found. OTA systemic exposure in NASH mice increased modestly from 5.65 ± 1.10 to 7.95 ± 0.61 mg*h/ml per kg BW, and renal excretion increased robustly from 5.55% ± 0.37% to 13.11% ± 3.10%, relative to healthy mice. Total urinary excretion of OTA increased from 24.41 ± 1.74 to 40.07 ± 9.19 µ g in NASH mice, and kidney-bound OTA decreased by ∼30%. Renal OAT isoform expression (OAT1-5) in NASH mice decreased by ∼50% with reduced OTA uptake by proximal convoluted cells. These data suggest that NASH-induced OAT transporter reductions attenuate renal secretion and reabsorption of OTA, increasing OTA urinary excretion and reducing renal exposure, thereby reducing nephrotoxicity in NASH. SIGNIFICANCE STATEMENT: These data suggest a disease-mediated transporter mechanism of altered tissue-specific toxicity after mycotoxin exposure, despite minimal systemic changes to ochratoxin A (OTA) concentrations. Further studies are warranted to evaluate the clinical relevance of this functional model and the potential effect of human nonalcoholic steatohepatitis on OTA and other organic anion substrate toxicity., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

Inflammatory liver diseases, including nonalcoholic steatohepatitis (NASH), alcohol-associated liver disease (ALD), hepatitis C virus (HCV), and ALD/HCV, account for nearly 2 million deaths annually. Despite increasing evidence that liver dysfunction impacts renal physiology, there is limited supportive clinical information, due to limited diagnosis of liver disease, complexity in liver disease etiology, and inadequacy of renal function tests. Human kidney biopsies with liver and renal pathology were obtained from patients with nonalcoholic fatty liver disease (NAFLD), NASH, ALD, HCV, and ALD/HCV (n = 5-7). Each liver disease showed renal pathology with at least 50% interstitial nephritis, 50% interstitial fibrosis, and renal dysfunction by estimated glomerular filtration rate (NAFLD 36.7 ± 21.4; NASH 32.7 ± 15.0; ALD 16.0 ± 11.0; HCV 27.6 ± 11.5; ALD/HCV 21.0 ± 11.2 ml/min/1.73 m2). Transcriptomic analysis identified 55 genes with expression changes in a conserved direction in response to liver disease. Considering association with immune regulation, protein levels of alpha-2-macroglobulin, clusterin, complement C1q C chain (C1QC), CD163, and joining chain of multimeric IgA and IgM (JCHAIN) were further quantified by LC-MS/MS. C1QC demonstrated an increase in NASH, ALD, HCV, and ALD/HCV (42.9 ± 16.6; 38.8 ± 18.4; 39.0 ± 13.5; 40.1 ± 20.1 pmol/mg protein) relative to control (19.2 ± 10.4 pmol/mg protein; p ≤ 0.08). Renal expression changes identified in inflammatory liver diseases with interstitial pathology suggest the pathogenesis of liver associated renal dysfunction. This unique cohort overcomes diagnostic discrepancies and sample availability to provide insight for mechanistic investigations on the impact of liver dysfunction on renal physiology., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The numerous neurological syndromes associated with COVID-19 implicate an effect of viral pathogenesis on neuronal function, yet reports of direct SARS-CoV-2 infection in the brain are conflicting. We used a well-established organotypic brain slice culture to determine the permissivity of hamster brain tissues to SARS-CoV-2 infection. We found levels of live virus waned after inoculation and observed no evidence of cell-to-cell spread, indicating that SARS-CoV-2 infection was non-productive. Nonetheless, we identified a small number of infected cells with glial phenotypes; however, no evidence of viral infection or replication was observed in neurons. Our data corroborate several clinical studies that have assessed patients with COVID-19 and their association with neurological involvement.

Progressive dysfunction and loss of neurons ultimately culminates in the symptoms and eventual fatality of prion disease, yet the pathways and mechanisms that lead to neuronal degeneration remain elusive. Here, we used RNAseq to profile transcriptional changes in microdissected CA1 and thalamus brain tissues from prion infected mice. Numerous transcripts were altered during clinical disease, whereas very few transcripts were reliably altered at pre-clinical time points. Prion altered transcripts were assigned to broadly defined brain cell types and we noted a strong transcriptional signature that was affiliated with reactive microglia and astrocytes. While very few neuronal transcripts were common between the CA1 and thalamus, we described transcriptional changes in both regions that were related to synaptic dysfunction. Using transcriptional profiling to compare how different neuronal populations respond during prion disease may help decipher mechanisms that lead to neuronal demise and should be investigated with greater detail., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Slota, Medina, Frost and Booth.)

Disease-mediated alterations to drug disposition constitute a significant source of adverse drug reactions. Cisplatin (CDDP) elicits nephrotoxicity due to exposure in proximal tubule cells during renal secretion. Alterations to renal drug transporter expression have been discovered during nonalcoholic steatohepatitis (NASH), however, associated changes to substrate toxicity is unknown. To test this, a methionine- and choline-deficient diet-induced rat model was used to evaluate NASH-associated changes to CDDP pharmacokinetics, transporter expression, and toxicity. NASH rats administered CDDP (6 mg/kg, i.p.) displayed 20% less nephrotoxicity than healthy rats. Likewise, CDDP renal clearance decreased in NASH rats from 7.39 to 3.83 mL/min, renal secretion decreased from 6.23 to 2.80 mL/min, and renal CDDP accumulation decreased by 15%, relative to healthy rats. Renal copper transporter-1 expression decreased, and organic cation transporter-2 and ATPase copper transporting protein-7b increased slightly, reducing CDDP secretion. Hepatic CDDP accumulation increased 250% in NASH rats relative to healthy rats. Hepatic organic cation transporter-1 induction and multidrug and toxin extrusion protein-1 and multidrug resistance-associated protein-4 reduction may contribute to hepatic CDDP sequestration in NASH rats, although no drug-related toxicity was observed. These data provide a link between NASH-induced hepatic and renal transporter expression changes and CDDP renal clearance, which may alter nephrotoxicity., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Worldwide efforts are being made to develop vaccines to mitigate this pandemic. We engineered two recombinant Newcastle disease virus (NDV) vectors expressing either the full-length SARS-CoV-2 spike protein (NDV-FLS) or a version with a 19 amino acid deletion at the carboxy terminus (NDV-Δ19S). Hamsters receiving two doses (prime-boost) of NDV-FLS developed a robust SARS-CoV-2-neutralizing antibody response, with elimination of infectious virus in the lungs and minimal lung pathology at five days post-challenge. Single-dose vaccination with NDV-FLS significantly reduced SARS-CoV-2 replication in the lungs but only mildly decreased lung inflammation. NDV-Δ19S-treated hamsters had a moderate decrease in SARS-CoV-2 titers in lungs and presented with severe microscopic lesions, suggesting that truncation of the spike protein was a less effective strategy. In summary, NDV-vectored vaccines represent a viable option for protection against COVID-19., Competing Interests: L.A.S., Y.P., B.W.B., P.P.M., L.S., and S.K.W. are co-inventors on a United States Provisional Application No. 63/196,489 entitled “ENGINEERED NEWCASTLE DISEASE VIRUS VECTOR AND USES THEREOF”, which was filed June 3, 2021., (© 2021 The Author(s).)

More than 100 million people have been infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Common laboratory mice are not susceptible to wild-type SARS-CoV-2 infection, challenging the development and testing of effective interventions. Here, we describe the development and testing of a mouse model for SARS-CoV-2 infection based on transduction of the respiratory tract of laboratory mice with an adeno-associated virus vector ( AAV6 ) expressing human ACE-2 ( AAV6.2FF-hACE2 ). We validated this model using a previously described synthetic DNA vaccine plasmid, INO-4800 ( pS ). Intranasal instillation of AAV6.2FF-hACE2 resulted in robust hACE2 expression in the respiratory tract. pS induced robust cellular and humoral responses. Vaccinated animals were challenged with 10 5 TCID 50 SARS-CoV-2 (hCoV-19/Canada/ON-VIDO-01/2020) and euthanized four days post-challenge to assess viral load. One immunization resulted in 50% protection and two immunizations were completely protective. Overall, the AAV6.2FF-hACE2 mouse transduction model represents an easily accessible, genetically diverse mouse model for wild-type SARS-CoV-2 infection and preclinical evaluation of potential interventions., Competing Interests: D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board series. Remuneration received by D.B.W. includes direct payments, stock or stock options, and in the interest of disclosure D.B.W. discloses the following paid associations with commercial partners: GeneOne (Consultant), Geneos (Advisory Board), Astrazeneca (Advisory Board, Speaker), Inovio (BOD, SRA, Stock), Sanofi (Advisory Board), BBI (Advisory Board)., (© 2021 The Author(s).)

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by orthohantaviruses in the Americas with a fatality rate as high as 35%. In South America, Andes orthohantavirus ( Hantaviridae, Orthohantavirus , ANDV) is a major cause of HCPS, particularly in Chile and Argentina, where thousands of cases have been reported since the virus was discovered. Two strains of ANDV that are classically used for experimental studies of the virus are Chile-9717869, isolated from the natural reservoir, the long-tailed pygmy rice rat, and CHI-7913, an isolate from a lethal human case of HCPS. An important animal model for studying pathogenesis of HCPS is the lethal Syrian golden hamster model of ANDV infection. In this model, ANDV strain Chile-9717869 is uniformly lethal and has been used extensively for pathogenesis, vaccination, and therapeutic studies. Here we show that the CHI-7913 strain, despite having high sequence similarity with Chile-9717869, does not cause lethal disease in Syrian hamsters. CHI-7913, while being able to infect hamsters and replicate to moderate levels, showed a reduced ability to replicate within the tissues compared with Chile-9717869. Hamsters infected with CHI-7913 had reduced expression of cytokines IL-4, IL-6, and IFN-γ compared with Chile-9717869 infected animals, suggesting potentially limited immune-mediated pathology. These results demonstrate that certain ANDV strains may not be lethal in the classical Syrian hamster model of infection, and further exploration into the differences between lethal and non-lethal strains provide important insights into molecular determinants of pathogenic hantavirus infection. Importance: Andes orthohantavirus (ANDV) is a New World hantavirus that is a major cause of hantavirus cardiopulmonary syndrome (HCPS, also referred to as hantavirus pulmonary syndrome) in South America, particularly in Chile and Argentina. ANDV is one of the few hantaviruses for which there is a reliable animal model, the Syrian hamster model, which recapitulates important aspects of human disease. Here we infected hamsters with a human isolate of ANDV, CHI-7913, to assess its pathogenicity compared with the classical lethal Chile-9717869 strain. CHI-7913 had 22 amino acid differences compared with Chile-9717869, did not cause lethal disease in hamsters, and showed reduced ability to replicate in vivo Our data indicate potentially important molecular signatures for pathogenesis of ANDV infection in hamsters and may lead to insights into what drives pathogenesis of certain hantaviruses in humans., (© Crown copyright 2021.)

Background: Wheelchair users (WCUs) often rely on ramps for access to transit buses. Previous studies indicate WCUs have difficulty using ramps for bus ingress/egress and many transportation-related incidents occur on ramps. However, experiences of WCU ramp usage during ingress/egress have not been fully described. Methods: Cross-sectional, internet-based survey of WCUs who ride transit buses was conducted. The participants were queried on frequency of bus usage, difficulty and incidents involving ramps, and factors contributing to difficulty and incidents. Wheelchair characteristics, primary condition, and whether participants received travel training were also captured. Chi-square was used to describe relationships between wheelchair type and frequency of difficulties and incidents, and odd ratios were used to determine likelihood of the incidents. Results: The majority (55.7%) of 384 participants reported using public transportation ≥ 1 per week. Seventy-eight percent of WCUs had ≥ 1 ramp incident over the past 3 years, with an increased likelihood of incidents occurring during ingress (OR = 1.53; CI 1.21-1.86). Of those who had an incident, 22% were injured or had damage to their wheelchair. Over 60% of those who had an incident identified steep ramp slope as being the contributing factor. Steep ramp slope, exterior ramp thresholds and wet surfaces were the most common contributing factors to difficulty using ramps. Conclusion: This is the first large-scale US study enabling WCUs to describe their experiences using transit bus ramps. Despite ADA guidelines, steep ramps remain the primary factor contributing to incidents and difficulty when using ramps to access transit buses.Implications for rehabilitationThe discrepancy between ADA maximum allowable ramp slopes for the built environment and transit buses may require an increased level of effort that is a barrier to transportation accessibility for some wheelchair users.Wheelchair users who access transit buses should be made aware of, and trained, to navigate ramp configurations found in the environment.We suggest rehabilitation therapists provide skills training specific to navigating transit bus ramp slopes that may be steeper and narrower than building ramps.

Nipah virus (NiV) has emerged as a highly lethal zoonotic paramyxovirus that is capable of causing a febrile encephalitis and/or respiratory disease in humans for which no vaccines or licensed treatments are currently available. There are two genetically and geographically distinct lineages of NiV: NiV-Malaysia (NiV-M), the strain that caused the initial outbreak in Malaysia, and NiV-Bangladesh (NiV-B), the strain that has been implicated in subsequent outbreaks in India and Bangladesh. NiV-B appears to be both more lethal and have a greater propensity for person-to-person transmission than NiV-M. Here we describe the generation and characterization of stable RNA polymerase II-driven infectious cDNA clones of NiV-M and NiV-B. In vitro, reverse genetics-derived NiV-M and NiV-B were indistinguishable from a wildtype isolate of NiV-M, and both viruses were pathogenic in the Syrian hamster model of NiV infection. We also describe recombinant NiV-M and NiV-B with enhanced green fluorescent protein (EGFP) inserted between the G and L genes that enable rapid and sensitive detection of NiV infection in vitro. This panel of molecular clones will enable studies to investigate the virologic determinants of henipavirus pathogenesis, including the pathogenic differences between NiV-M and NiV-B, and the high-throughput screening of candidate therapeutics.

Andes virus (ANDV) and Sin Nombre virus (SNV) are the main causative agents responsible for hantavirus cardiopulmonary syndrome (HCPS) in the Americas. HCPS is a severe respiratory disease with a high fatality rate for which there are no approved therapeutics or vaccines available. Some vaccine approaches for HCPS have been tested in preclinical models, but none have been tested in infectious models in regard to their ability to protect against multiple species of HCPS-causing viruses. Here, we utilize recombinant vesicular stomatitis virus-based (VSV) vaccines for Andes virus (ANDV) and Sin Nombre virus (SNV) and assess their ability to provide cross-protection in infectious challenge models. We show that, while both rVSVΔG/ANDVGPC and rVSVΔG/SNVGPC display attenuated growth as compared to wild type VSV, each vaccine is able to induce a cross-reactive antibody response. Both vaccines protected against both homologous and heterologous challenge with ANDV and SNV and prevented HCPS in a lethal ANDV challenge model. This study provides evidence that the development of a single vaccine against HCPS-causing hantaviruses could provide protection against multiple agents.

The World Health Organization has identified Lassa virus (LASV) as one of the top five pathogens to cause a severe outbreak in the near future. This study assesses the ability of a leading vaccine candidate, recombinant Vesicular stomatitis virus expressing LASV glycoprotein (VSVΔG/LASVGPC), and its ability to induce rapid and long-term immunity to lethal guinea pig-adapted LASV (GPA-LASV). Outbred guinea pigs were vaccinated with a single dose of VSVΔG/LASVGPC followed by a lethal challenge of GPA-LASV at 7, 14, 25, 189, and 355 days post-vaccination. Statistically significant rapid and long-term protection was achieved at all time points with 100% protection at days 7 and 14 post-vaccination. While 83 and 87% protection were achieved at 25 days and 6 months post-vaccination, respectively. When guinea pigs were challenged one year after vaccination 71% protection was achieved. Notable infectious virus was isolated from the serum and tissues of some but not all animals. Total LASVGPC-specific IgG titers were also measured on a monthly basis leading up to LASV challenge however, it is unclear if antibody alone correlates with short and long term survival. These studies confirm that a single dose of VSVΔG/LASVGPC can induce rapid and long-term protection from LASV infection in an aggressive outbred model of infection, and supports further development in non-human primates., Competing Interests: The authors declare no competing interests.

Multiple cell types and complex connection networks are an intrinsic feature of brain tissue. In this study we used expression profiling of specific microscopic regions of heterogeneous tissue sections isolated by laser capture microdissection (LCM) to determine insights into the molecular basis of brain pathology in prion disease. Temporal profiles in two mouse models of prion disease, bovine spongiform encephalopathy (BSE) and a mouse-adapted strain of scrapie (RML) were performed in microdissected regions of the CA1 hippocampus and granular layer of the cerebellum which are both enriched in neuronal cell bodies. We noted that during clinical disease the number of activated microglia and astrocytes that occur in these areas are increased, thereby likely diluting the neuronal gene expression signature. We performed a comparative analysis with gene expression profiles determined from isolated populations of neurons, microglia and astrocytes to identify transcripts that are enriched in each of these cell types. Although the incubation periods of these two models are quite different, over 300 days for BSE and ~160 days for RML scrapie, these regional microdissections revealed broadly similar profiles. Microglial and astrocyte-enriched genes contributed a profound inflammatory profile consisting of inflammatory cytokines, genes related to phagocytosis, proteolysis and genes coding for extracellular matrix proteins. CA1 pyramidal neurons displayed a net upregulation of transcription factors and stress induced genes at pre-clinical stages of disease while all tissues showed profound decrease of overlapping genes related to neuronal function, in particular transcripts related to neuronal communication including glutamate receptors, phosphatase subunits and numerous synapse-related markers. Of note, we found a small number of genes expressed in neurons that were upregulated during clinical disease including, COX6A2, FZD9, RXRG and SOX11, that may be biomarkers of neurodegeneration.

Gene therapy for the treatment of genetic disorders has demonstrated considerable therapeutic success in clinical trials. Among the most effective and commonly used gene delivery vectors are those based on adeno-associated virus (AAV). Despite these advances in clinical gene therapy, further improvements in AAV vector properties such as rapid intracellular processing and transgene expression, targeted transduction of therapeutically relevant cell types, and longevity of transgene expression, will render extension of such successes to many other human diseases. Engineering of AAV capsids continues to evolve the specificity and efficiency of AAV-mediated gene transfer. Here, we describe a triple AAV6 mutant, termed AAV6.2FF, containing F129L, Y445F, and Y731F mutations. AAV6.2FF yielded 10-fold greater transgene expression in lung than AAV6 after 21 days. Additionally, this novel capsid demonstrated 101-fold and 49-fold increased transgene expression in the muscle and lungs, respectively, 24 hr post vector delivery when compared with the parental AAV6. Furthermore, AAV6.2FF retains heparin sulfate binding capacity and displays a 10-fold increase in resistance to pooled immunoglobulin neutralization in vitro . The rapid and potent expression mediated by AAV6.2FF is ideally suited to applications such as vectored immunoprophylaxis, in which rapid transgene expression is vital for use during an outbreak response scenario.

The 2013-2016 West Africa outbreak demonstrated the epidemic potential of Ebola virus and highlighted the need for counter strategies. Monoclonal antibody (mAb)-based therapies hold promise as treatment options for Ebola virus infections. However, production of clinical-grade mAbs is labor intensive, and immunity is short lived. Conversely, adeno-associated virus (AAV)-mediated mAb gene transfer provides the host with a genetic blueprint to manufacture mAbs in vivo, leading to steady release of antibody over many months. Here we demonstrate that AAV-mediated expression of nonneutralizing mAb 5D2 or 7C9 confers 100% protection against mouse-adapted Ebola virus infection, while neutralizing mAb 2G4 was 83% protective. A 2-component cocktail, AAV-2G4/AAV-5D2, provided complete protection when administered 7 days prior to challenge and was partially protective with a 3-day lead time. Finally, AAV-mAb therapies provided sustained protection from challenge 5 months following AAV administration. AAV-mAb may be a viable alternative strategy for vaccination against emerging infectious diseases.

Zika virus (ZIKV) is rapidly spreading throughout the Americas and is associated with significant fetal complications, most notably microcephaly. Treatment with polyclonal antibodies for pregnant women at risk of ZIKV-related complications could be a safe alternative to vaccination. We found that large quantities of human polyclonal antibodies could be rapidly produced in transchromosomal bovines (TcB) and successfully used to protect mice from lethal infection. Additionally, antibody treatment eliminated ZIKV induced tissue damage in immunologically privileged sites such as the brain and testes and protected against testicular atrophy. These data indicate that rapid development and deployment of human polyclonal antibodies could be a viable countermeasure against ZIKV., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background: More than twenty-five years after passage of the ADA, little remains known about the experiences of wheelchair users when attempting to access health care and how accessibility may influence health care utilization., Objective/hypothesis: To describe health care utilization among wheelchair users and characterize barriers encountered when attempting to obtain access to health care., Methods: An internet-based survey of wheelchair users was conducted. Measures included demographics, condition, socioeconomic status, health care utilization and receipt of preventive services within the past year, physical barriers encountered at outpatient facilities, and satisfaction with care., Results: Four hundred thirty-two wheelchair users responded to the survey. Nearly all respondents (97.2%) had a primary care appointment within the past year and most reported 3-5 visits to both primary and specialty care providers. Most encountered physical barriers when accessing care (73.8% primary, 68.5% specialty). Participants received most preventive interventions at rates similar to national averages with the exception of Pap tests. Most participants remained clothed for their primary care evaluation (76.1%), and were examined seated in their wheelchair (69.7%). More than half of participants (54.1%) felt they received incomplete care, and 57% believed their physician had no more than a moderate understanding of their disability-specific medical concerns., Conclusions: Wheelchair users face persistent barriers to care, may receive less than thorough physical evaluations, receive fewer screenings for cervical cancer, and largely believe they receive incomplete care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.

Although much research has been done on repetitive transcranial magnetic stimulation (rTMS) in chronic stroke, only sparse research has been done in acute stroke despite the particularly rich potential for neuroplasticity in this stage. We attempted a preliminary clinical trial in one active, high-quality inpatient rehabilitation facility (IRF) in the -United States. But after enrolling only 4 patients in the grant period, the study was stopped because of low enrollment. The purpose of this paper is to offer a perspective describing the important physiologic rationale for including rTMS in the early phase of stroke, the reasons for our poor patient enrollment in our attempted study, and recommendations to help future studies succeed. We conclude that, if scientists and clinicians hope to enhance stroke outcomes, more attention must be directed to leveraging conventional rehabilitation with neuromodulation in the acute phase of stroke when the capacity for neuroplasticity is optimal. Difficulties with patient enrollment must be addressed by reassessing traditional inclusion and exclusion criteria. Factors that shorten patients' length of stay in the IRF must also be reassessed at all policy-making levels to make ethical decisions that promote higher functional outcomes while retaining cost consciousness., (© 2017 American Physical Therapy Association.)

Stroke characteristics vary widely between individuals making it difficult to assess the value of stroke rehabilitation interventions. To eliminate inter-subject variability, this study used an N-of-1 randomized, controlled design to explore the efficacy of repetitive transcranial magnetic stimulation (rTMS) in one unique individual with pontine stroke. We hypothesized that five days of active 6-Hz primed, low-frequency rTMS to the contralesional primary motor area (M1), combined with finger movement tracking training, would accomplish greater gains in hand function than sham rTMS combined with tracking training. We assessed hand function (Box and Block test and finger tracking test), cortical activation (laterality index during functional magnetic resonance imaging), and cortical excitability (interhemispheric inhibition testing (IHI) with transcranial magnetic stimulation (TMS)). Diffusion tensor imaging (DTI) assessed the integrity of his corticospinal tracts at baseline. Results showed no improvement in the Box and Block or finger tracking tests, unreliable IHI findings, and no change in laterality index following active rTMS. DTI suggested truncation of the left corticospinal tract (CST) at the pons. His non-dexterous hand movements combined with no elicitable motor evoked potentials with TMS to ipsilesional M1 and his DTI findings lead us to speculate a reticulospinal mechanism for preserving his rudimentary paretic hand control. We conclude that rTMS combined with tracking training was not effective in the absence of CST pathways and that research is needed to confirm markers of reticulospinal function in humans as an alternative to defective CST function.

Objectives: To estimate the prevalence of wheeled mobility device (WhMD) ramp-related incidents while boarding/alighting a public transit bus and to determine whether the frequency of incidents is less when the ramp slope meets the proposed Americans with Disabilities Act (ADA) maximum allowable limit of ≤9.5°., Design: Observational study., Setting: Community public transportation., Participants: WhMD users (N=414) accessing a public transit bus equipped with an instrumented ramp., Interventions: Not applicable., Main Outcome Measures: Prevalence of boarding/alighting incidents involving WhMD users and associated ramp slopes; factors affecting incidents., Results: A total of 4.6% (n=35) of WhMD users experienced an incident while boarding/alighting a transit bus. Significantly more incidents occurred during boarding (6.3%, n=26) than during alighting (2.2%, n=9) (P<.01), and when the ramp was deployed to street level (mean slope=11.4°) compared with sidewalk level (mean slope=4.2°) (P=.01). The odds ratio for experiencing an incident when the ramp slope exceeded the proposed ADA maximum allowable ramp slope was 5.4 (95% confidence interval, 2.4-12.2; P<.01). The odds ratio for assistance being rendered to board/alight when the ramp slope exceeded the proposed ADA maximum allowable ramp slope was 5.1 (95% confidence interval, 2.9-9.0; P<.01)., Conclusions: The findings of this study support the proposed ADA maximum allowable ramp slope of 9.5°. Ramp slopes >9.5° and ramps deployed to street level are associated with a higher frequency of incidents and provision of assistance. Transit agencies should increase awareness among bus operators of the effect kneeling and deployment location (street/sidewalk) have on the ramp slope. In addition, ramp components and the built environment may contribute to incidents. When prescribing WhMDs, skills training must include ascending/descending ramps at slopes encountered during boarding/alighting to ensure safe and independent access to public transit buses., (Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

The Americans with Disabilities Act (ADA) requires full and equal access to healthcare services and facilities, yet studies indicate individuals with mobility disabilities receive less than thorough care as a result of ADA noncompliance. The objective of our pilot study was to assess ADA compliance within a convenience sample of healthcare clinics affiliated with a statewide healthcare network. Site assessments based on the ADA Accessibility Guidelines for Buildings and Facilities were performed at 30 primary care and specialty care clinics. Clinical managers completed a questionnaire on standard practices for examining and treating patients whose primary means of mobility is a wheelchair. We found a majority of restrooms (83%) and examination rooms (93%) were noncompliant with one or more ADA requirements. Seventy percent of clinical managers reported not owning a height-adjustable examination table or wheelchair accessible weight scale. Furthermore, patients were examined in their wheelchairs (70%-87%), asked to bring someone to assist with transfers (30%), or referred elsewhere due to an inaccessible clinic (6%). These methods of accommodation are not compliant with the ADA. We recommend clinics conduct ADA self-assessments and provide training for clinical staff on the ADA and requirements for accommodating individuals with mobility disabilities.

Background: The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo., Methods: Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155-190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states., Results: Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi., Conclusion: Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times.

Objectives: To identify from whom individuals with spinal cord injury (SCI) seek health care, the percentage who receive preventative care screenings, and the frequency and types of barriers they encounter when accessing primary and specialty care services; and to examine how sociodemographic factors affect access to care and receipt of preventative screenings., Design: Cross-sectional, observational study using an Internet-based survey., Setting: Internet based., Participants: Adults (N=108) with SCI who use a wheelchair as their primary means of mobility in the community., Interventions: Not applicable., Main Outcome Measures: Health care utilization during the past year, barriers encountered when accessing health care facilities, and receipt of routine care and preventative screenings., Results: All but 1 participant had visited a primary care provider within the past 12 months, and 85% had had ≥ 1 visit to specialty care providers. Accessibility barriers were encountered during both primary care (91.1%) and specialty care (80.2%) visits; most barriers were clustered in the examination room. The most prevalent barriers were inaccessible examination tables (primary care=76.9%; specialty care=51.4%) and lack of transfer aids (primary care=69.4%; specialty care=60.8%). Most participants had not been weighed during their visit (89%) and had remained seated in their wheelchair during their examinations (85.2%). Over one third of individuals aged ≥ 50 years had not received a screening colonoscopy, 60% of women aged ≥ 50 years had not had a mammogram within the past year, 39.58% of women had not received a Papanicolaou smear within the previous 3 years, and only 45.37% of respondents had ever received bone density testing., Conclusions: Individuals with SCI face remediable obstacles to care and receive fewer preventative care screenings than their nondisabled counterparts. We recommend that clinics conduct Americans with Disabilities Act self-assessments, ensure that their clinical staff are properly trained in assisting individuals with mobility disabilities, and take a proactive approach in discussing preventative care screenings with their patients who have SCI., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to characterize wheelchair tiedown and occupant restraint system (WTORS) usage in public transit buses based on observations of wheelchair and scooter (wheeled mobility device: WhMD) passenger trips. A retrospective review of on-board video surveillance recordings of WhMD trips on fixed-route, large accessible transit vehicles (LATVs) was performed. Two hundred ninety-five video recordings were collected for review and analysis during the period June 2007-February 2009. Results showed that 73.6% of WhMDs were unsecured during transit. Complete use of all four tiedowns was observed more frequently for manual wheelchairs (14.9%) and power wheelchairs (5.5%), compared to scooters (0.0%), and this difference was significant (p=0.013). Nonuse or misuse (lap belt use only) of the occupant restraint system occurred during 47.5% of WhMD trips. The most frequently observed (52.5%) use of the lap belt consisted of bus operators routing the lap belt around the WhMD seatback in an attempt to secure the WhMD. These findings support the need for development and implementation of WTORS with improved usability and/or WTORS that can be operated independently by WhMD passengers and improved WTORS training for bus operators.

An overview of the current status of wheelchair transportation safety in fixed route and demand-responsive, non-rail, public transportation vehicles within the US is presented. A description of each mode of transportation is provided, followed by a discussion of the primary issues affecting safety, accessibility, and usability. Technologies such as lifts, ramps, securement systems, and occupant restraint systems, along with regulations and voluntary industry standards have been implemented with the intent of improving safety and accessibility for individuals who travel while seated in their wheeled mobility device (e.g., wheelchair or scooter). However, across both fixed route and demand-responsive transit systems a myriad of factors such as nonuse and misuse of safety systems, oversized wheeled mobility devices, vehicle space constraints, and inadequate vehicle operator training may place wheeled mobility device (WhMD) users at risk of injury even under non-impact driving conditions. Since WhMD-related incidents also often occur during the boarding and alighting process, the frequency of these events, along with factors associated with these events are described for each transit mode. Recommendations for improving WhMD transportation are discussed given the current state of

Prion diseases typically have long pre-clinical incubation periods during which time the infectious prion particle and infectivity steadily propagate in the brain. Abnormal neuritic sprouting and synaptic deficits are apparent during pre-clinical disease, however, gross neuronal loss is not detected until the onset of the clinical phase. The molecular events that accompany early neuronal damage and ultimately conclude with neuronal death remain obscure. In this study, we used laser capture microdissection to isolate hippocampal CA1 neurons and determined their pre-clinical transcriptional response during infection. We found that gene expression within these neurons is dynamic and characterized by distinct phases of activity. We found that a major cluster of genes is altered during pre-clinical disease after which expression either returns to basal levels, or alternatively undergoes a direct reversal during clinical disease. Strikingly, we show that this cluster contains a signature highly reminiscent of synaptic N-methyl-D-aspartic acid (NMDA) receptor signaling and the activation of neuroprotective pathways. Additionally, genes involved in neuronal projection and dendrite development were also altered throughout the disease, culminating in a general decline of gene expression for synaptic proteins. Similarly, deregulated miRNAs such as miR-132-3p, miR-124a-3p, miR-16-5p, miR-26a-5p, miR-29a-3p and miR-140-5p follow concomitant patterns of expression. This is the first in depth genomic study describing the pre-clinical response of hippocampal neurons to early prion replication. Our findings suggest that prion replication results in the persistent stimulation of a programmed response that is mediated, at least in part, by synaptic NMDA receptor activity that initially promotes cell survival and neurite remodelling. However, this response is terminated prior to the onset of clinical symptoms in the infected hippocampus, seemingly pointing to a critical juncture in the disease. Manipulation of these early neuroprotective pathways may redress the balance between degeneration and survival, providing a potential inroad for treatment.

Objective: Characterize wheeled mobility device (WhMD) adverse incidents on large accessible transit vehicles (LATVs) based on vehicle motion, WhMD activity during incident, incident scenario and injury., Design: Retrospective records review., Subjects/patients: WhMD passengers traveling on LATVs while remaining seated in their., Methods: Adverse incidents characterized based on vehicle motion, WhMD activity during incident, and incident scenario. Injury characterized based on outcome, medical attention sought, vehicle activity, WhMD activity and incident scenario., Results: 115 WhMD-related incident reports for years 2000-2005 were analyzed. Most incidents occurred when the LATV was stopped (73.9%), during ingress/egress (42.6%), and at the securement station (33.9%) when the LATV was moving. The combination of WhMD tipping and passenger falling (43.4%) occurred most frequently, and was 1.8 times more likely to occur during ingress/egress than at the securement station. One-third (33.6%) of all incidents resulted in injury, and injuries were equally distributed between ingress/egress (43.6%) and at the securement station (43.6%)., Conclusions: WhMD users have a greater chance of incurring injury during ingress/egress than during transit. Research is needed to objectively assess real world transportation experiences of WhMD passengers, and to assess the adequacy of existing federal legislation/guidelines for accessible ramps used in public transportation., (Copyright 2009 IPEM. Published by Elsevier Ltd. All rights reserved.)

Conditioning the body to undergo physical stress such as joint arthroplasty has been termed prehabilitation. This case study examined the effect of a 4-week prehabilitation intervention on functional outcomes after total knee arthroplasty (TKA). Two female subjects completed baseline strength and functional assessments before TKA. Subjects were randomized to either a 4-week prehabilitation intervention (ES) aimed at increasing strength and range of motion or a usual care condition (CS). After 4 weeks of training, subjects were reassessed and underwent TKA. Subjects completed a final assessment 12 weeks after TKA. Functional outcomes included 6-minute walk, number of times up from a chair in 30 seconds, proprioception, and self-reported function and pain using the Western Ontario and McMaster Universities Osteoarthritis Index. The data suggest that 4 weeks of prehabilitation had a positive effect on functional task performance and knee proprioception before surgery. After surgery, the ES continued to exhibit higher levels of functioning and less pain compared with the CS. Prehabilitation before TKA may contribute to improved recovery after surgery.

Sexuality is a complex concept that can be measured based on various aspects. Depending on the variable of interest, investigators may wish to focus on sexual behavior (activity), sexual orientation (attraction to a particular gender), or sexual identity (self-identification with a particular group of people). Further complicating the process is the fact that these aspects of sexuality are not always congruent with one another. Lesbian, gay, and bisexuals (LGB) are sexual minorities that have been identified as one of several groups that experience health disparities. For researchers working with the LGB population, properly identifying and defining which aspect of sexuality is of interest to the investigator is paramount in obtaining accurate outcomes.