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Introduction: The Constant-Murley Score (CMS) uses universal goniometry (UG), and the Shoulder Functional Reach Score (SFRS) uses visual estimation (VE). The CMS has validity challenges, and the SFRS has been critiqued for using VE. This study sought to determine the reliability and concurrent validity of VE when compared to the UG for shoulder flexion and abduction. Differences between symptomatic and asymptomatic shoulder and expert and novice raters were also explored., Methods: Participants were included if they were at least 18 years old with unilateral, symptomatic shoulder pain, with no post-surgical contraindications. All conditions were randomized, and raters were blinded., Results: The intertester reliability for UG had Intraclass Correlation Coefficient (ICC) values of 0.76-0.91 at visit one. VE had ICC values that ranged from 0.87 to 0.92 at visit one. VE test-retest reliability had ICC values from 0.81 to 0.94. At visit one, concurrent validity was demonstrated by rho values from 0.84 to 0.89. There were statistically significant differences between the shoulders (P ≤ 0.0448), and there were no differences between the raters (P ≥ 0.0960)., Discussion: UG and VE of active shoulder flexion and abduction are reliable and concurrently valid. Additionally, there were differences between symptomatic and asymptomatic shoulders, and there were no differences between novice and expert raters., Conclusion: The SFRS may be reliable and valid for measuring shoulder motion using VE within and between treatment sessions. Future research should examine this in larger, more diverse participant populations., Competing Interests: Declaration of competing interest Conflict of interest disclosure: Sean Riley was the primary author of the publication on the Shoulder Functional Reach Score, which may be a conflict when establishing the preliminary reliability and validity of the shoulder flexion and abduction measures used in this study., (Copyright © 2024. Published by Elsevier Ltd.)

Streptococcus pneumoniae ( Spn ), a Gram-positive bacterium, is responsible for causing a wide variety of invasive infections. The emergence of multi-drug antibiotic resistance has prompted the search for antimicrobial alternatives. Phage-derived peptidoglycan hydrolases, known as endolysins, are an attractive alternative. In this study, an endolysin active against Spn , designated SP-CHAP, was cloned, produced, purified, biochemically characterized, and evaluated for its antimicrobial properties. Cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domains are widely represented in bacteriophage endolysins but have never previously been reported for pneumococcal endolysins. Here, we characterize the first pneumococcal endolysin with a CHAP catalytic domain. SP-CHAP was antimicrobial against all Spn serovars tested, including capsular and capsule-free pneumococci, and it was found to be more active than the most widely studied pneumococcal endolysin, Cpl-1, while not affecting various oral or nasal commensal organisms tested. SP-CHAP was also effective in eradicating Spn biofilms at concentrations as low as 1.56 µg/mL. In addition, a Spn mouse nasopharyngeal colonization model was employed, which showed that SP-CHAP caused a significant reduction in Spn colony-forming units, even more than Cpl-1. These results indicate that SP-CHAP may represent a promising alternative to combating Spn infections., Importance: Considering the high rates of pneumococcal resistance reported for several antibiotics, alternatives are urgently needed. In the present study, we report a Streptococcus pneumoniae -targeting endolysin with even greater activity than Cpl-1, the most characterized pneumococcal endolysin to date. We have employed a combination of biochemical and microbiological assays to assess the stability and lytic potential of SP-CHAP and demonstrate its efficacy on pneumococcal biofilms in vitro and in an in vivo mouse model of colonization. Our findings highlight the therapeutic potential of SP-CHAP as an antibiotic alternative to treat Streptococcus pneumoniae infections., Competing Interests: The authors declare no conflict of interest.

Background: Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP., Methods/design: This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2-125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05., Discussion: This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants., Trial Registration: ClinicalTrials.gov NCT05812885. Registered on 24th May 2023., (© 2024. The Author(s).)

Objectives: To perform a 'trustworthy' systematic review (SR) with meta-analysis on the potential mechanisms of manual therapy used to treat spinal impairments., Design: SR with meta-analysis., Literature Search: Articles published between January 2010 and October 2022 from CENTRAL, CINAHL, MEDLINE, PubMed, ProQuest, and PEDro., Methods: This SR included English-language randomized clinical trials (RCTs) involving manual therapy to treat spinal impairments in adults. The primary outcome was pressure pain thresholds (PPTs). To synthesize RCTs with high confidence in estimated effects using the GRADE, RCTs with questionable prospective, external, and internal validity, and high risk of bias (RoB) were excluded., Results: Following title and abstract screening, 89 full-text RCTs were reviewed. Twenty-two studies included the criteria of interest. Sixteen were not prospectively registered, two contained discussion/conclusions judged to be inconsistent with the registry, and one was rated as having a high RoB. Three studies met the inclusion criteria; heterogeneous interventions and locations for PPT testing prevented synthesis into practice recommendations. The two studies with high confidence in estimated effects had small effect sizes, and one study had confidence intervals that crossed zero for the outcome measures of interest., Discussion: Standardized PPT testing, as a potential measure of centrally mediated pain, could provide clues regarding the mechanisms of manual therapy or help identify/refine research questions., Conclusion: High-quality RCTs could not be synthesized into strong conclusions secondary to the dissimilarity in research designs. Future research regarding quantitative sensory testing should develop RCTs with high confidence in estimated effects that can be translated into strong recommendations.

The primary objective of this review was to create a 'trustworthy,' living systematic review and meta-analysis for the application of manual therapy interventions in treating patients with shoulder dysfunction. Included studies were English-language randomized controlled trials published between 1/1/2010 and 8/3/2023, with searches performed in: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINHAL, ProQuest Nursing & Allied Health, EBSCO Medline, and PEDro. The population of focus included adults 18 years and older with musculoskeletal impairments related to shoulder dysfunction. Our primary outcomes included pain and region-specific outcome measures. We excluded trials, including participants having shoulder dysfunction resulting from surgery, radicular pain, instability/dislocation, fracture, lymphedema, and radiation. Our screening methodology was based upon a previously published 'trustworthy' systematic review protocol. This included the application of our PICOTS criteria in addition to screening for prospective clinical trial registration and following of prospective intent, as well as assessment of PEDro scores, risk-of-bias ratings, GRADE scoring, and examination of confidence in estimated effects. Twenty-six randomized controlled trials met our PICOTS criteria; however, only 15 of these were registered. Only three were registered prospectively. Two of these did not have discussions and conclusions that aligned with their primary outcome. The remaining single study was found to have a high risk-of-bias, meaning the remainder of the protocol could not be employed and that no randomized controlled trials could undergo further assessment or meta-analysis. The results of this systematic review indicate there are no 'trustworthy' randomized controlled trials examining the effectiveness of manual therapy interventions for the treatment of patients with shoulder dysfunction, as defined by the prospectively established methodology. Therefore, these findings signal that creating a 'trustworthy,' living systematic review on this clinically relevant topic is not yet possible due to a lack of 'trustworthy' randomized controlled trials., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Brian Swanson and Sean Riley were authors on one of the papers identified in this review. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Flowers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can "win" by taking over the host, or the bacteria can "lose" if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that "activate" innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections., Competing Interests: The authors declare no conflict of interest.

Objectives: To establish a 'trustworthy' living systematic review (SR) with a meta-analysis of manual therapy for treating non-radicular cervical impairments., Design: SR with meta-analysis., Literature Search: Articles published between January 2010 and September 2022 were included from: Cochrane Central Register of Controlled Trials (CENTRAL); CINAHL; MEDLINE; PubMed; PEDro, and ProQuest Nursing and Allied Health., Methods: This SR included English-language randomized clinical trials (RCTs) of manual therapy involving adults used to treat non-radicular cervical impairments. The primary outcomes were pain and region-specific outcome measures. Cervicogenic headaches and whiplash were excluded to improve homogeneity. Two reviewers independently assessed RCTs. The prospective plan was to synthesize results with high confidence in estimated effects using GRADE., Results: Thirty-five RCTs were screened for registration status. Twenty-eight were not registered or registered prospectively. In 5 studies, the discussion and conclusion did not match the registry, or this could not be determined. One study did not meet the external validity criterion, and another was rated as having a high risk of bias. One study met the inclusion and exclusion criteria, so practice recommendations could not be made. The remaining study did not identify any clinically meaningful group differences., Discussion: Only one prospectively registered RCT met this SR's strict, high-quality standards. The single identified paper provides initial high-quality evidence on this topic., Conclusion: This SR establishes a foundation of trustworthiness and can be used to generate research agendas to determine the potential clinical utility of manual therapy directed at the cervical spine for non-radicular cervical complaints.

Background: Preprocessed research resources are believed to be highly 'trustworthy' when translating research to clinical practice. However, the overall 'trustworthiness' is unknown if this evidence contains randomized clinical trials (RCTs) where prospective has not been/cannot be verified, has low confidence in estimated effects, and if they are not up to date., Objectives: This protocol will be used to create a baseline benchmark for a series of trustworthy living systematic reviews (SRs) regarding manual therapy interventions., Methods: Data will originate from RCTs related to manual therapy neuromusculoskeletal interventions, indexed in 6 search engines in English from 1 January 2010, to the present. Two blinded reviewers will identify the RCTs and extract data using Covidence. The data will be synthesized based on consensus and analyzed using the Cochrane collaboration's Review Manager., Expected Outcomes: It is expected that there will be a shortage of RCTs with at least a moderate confidence in estimated effects that will allow for strong practice recommendations., Discussion: Identifying evidence that can be translated into strong practice recommendations is essential to identify beneficial and harmful interventions, decrease practice variability, and identify neuromusculoskeletal manual therapy interventions that require further disciplined methodological focus.

Introduction: It is unknown if verified prospective registration of systematic reviews (SRs) and the randomized clinical trials (RCTs) that they use affect an SR's methodological quality on A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2)., Methods: Data originated from interventional SRs published in International Society of Physiotherapy Journals Editors (ISPJE) member journals, indexed in MEDLINE, between 1 January 2018 and 18 August 2021. Blinded reviewers identified the SRs and extracted the data for the variables of interest for the SRs and the RCTs., Results: Two of 14 ISPJE member journals required prospective SR registration. Twenty SRs were identified, and 169 unique, retrievable RCTs were included within those SRs. One (5.0%) of the 20 SRs and 15 of the 169 (8.9%) RCTs were prospectively registered and published consistent with this intent. Nineteen (95.0%) of the 20 identified SRs was categorized as 'critically low' on the AMSTAR 2., Discussion: SRs and the RCTs identified within them were infrequently prospectively registered, prospectively verifiable, or prospectively verified based on the established research record., Conclusions: Ensuring that SRs and RCTs have fidelity with the research record from conception to publication may help rule out low-value interventions, decrease variability in physical therapy practice, and solidify evidence-based physical therapy practice.

Trustworthy, preprocessed sources of evidence, such as systematic reviews and clinical practice guidelines, are crucial for practicing clinicians. Confidence in estimated effects is related to how different the outcome data were between the two groups. Factors including the effect size, variability of the effect, research integrity, research methods, and selected outcome measures impact confidence in the estimated effect. The current evidence suggests that post-randomization biases cannot be ruled out with a high degree of certainty in published research, limiting the utility of preprocessed sources for clinicians. Research should be prospectively registered to improve this situation, and fidelity with prospective intent should be verified to minimize biases and strengthen confidence in estimated effects. Otherwise, discussions related to preprocessed literature, including P-values, point estimates of effect, confidence intervals, post-randomization biases, external and internal validity measures, and the confidence in estimated effects required to translate research into practice confidently, are all moot points., (© 2023. The Author(s).)

Objectives: Examine: (1) whether variability in dry needling (DN) dosage affects pain outcomes, (2) if effect sizes are clinically important, and (3) how adverse events (AE) were documented and whether DN safety was determined., Methods: Nine databases were searched for randomized controlled trials (RCTs) investigating DN in symptomatic musculoskeletal disorders. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Included RCTs met PEDro criteria #1 and scored > 7/10. Data extraction included DN dosage, pain outcome measures, dichotomous AE reporting (yes/no), and AE categorization. Clinically meaningful differences were determined using the minimum clinically important difference (MCID) for pain outcomes ., Results: Out of 22 identified RCTs, 11 demonstrated significant between-group differences exceeding the MCID, suggesting a clinically meaningful change in pain outcomes. Nine documented whether AE occurred. Only five provided AEs details and four cited a standard means to report AE., Discussion: There was inconsistency in reporting DN dosing parameters and AE. We could not determine if DN dosing affects outcomes, whether DN consistently produces clinically meaningful changes, or establish optimal dosage. Without more detailed reporting, replication of methods in future investigations is severely limited. A standardized method is lacking to report, classify, and provide context to AE from DN. Without more detailed AE reporting in clinical trials investigating DN efficacy, a more thorough appraisal of relative risk, severity, and frequency was not possible. Based on these inconsistencies, adopting a standardized checklist for reporting DN dosage and AE may improve internal and external validity and the generalizability of results.

Objectives: To determine if there are any statistically significant associations between: 1) randomized clinical trials (RCTs) investigating physical therapy musculoskeletal interventions, 2) journal impact factor (JIF), 3) frequency of RCT citation, 4) whether prospective intent was identifiable, and 5) the Physiotherapy Evidence Database (PEDro) scores., Methods: MEDLINE indexed RCTs addressing musculoskeletal interventions published between January 2016 and July 2020 in physical therapy journals were included. Two blinded reviewers identified the RCTs and extracted the variables of interest., Results: With a familywise alpha adjustment, there was no statistically significant correlation between JIF and number of citations ( rho  = 0.187; p = 0.0280). Statistically significant weak positive correlations were identified between the JIF and prospectively registered RCTs ( rho  = 0.240; p = 0.0046), JIF and PEDro scores ( rho  = 0.250; p = 0.0031), and PEDro scores and prospectively registered RCTs ( rho  = 0.335; p < 0.0001)., Conclusion: The findings of this study suggest that JIF and PEDro scores may not be accurate measures of RCT quality. Failing to ensure that published RCTs followed their prospective intent and using bibliometrics that fail to accurately measure what they propose appears to create untrustworthy preprocessed resources for practicing physical therapists during the evidence-based practice process., Level of Evidence: 1a.

Background: Physical therapists obtain information from a variety of sources. The sources may influence their believability and use in clinical practice., Objectives: In this hypothesis-based study, we queried physical therapists (PTs) on the believability of evidence across six musculoskeletal treatment domains and analyzed variables that predicted the strength of beliefs., Methods: This international survey included six different language portals and used a snowball dispensation strategy. PTs who were credentialed, licensed, or who practiced in the field, were queried on the believability of six treatment domains (i.e., exercise, manual therapy, psychologically-informed practice, sports/occupational performance, thermal/electrical agents, and pain science/patient education) and potential predictors of believability (i.e., social media use, years of practice, time and access to literature, specialization, confidence in reviewing literature and attributions of the researcher)., Results: In total, 1098 PTs from 36 countries completed the survey. PTs had strong beliefs in what they read or hear about exercise, sports/occupational performance, pain science/patient education, and psychologically-informed interventions. There was only moderate believability regarding manual therapy treatment and weak believability associated with thermal/electrical agents. Multiple linear regression analyses revealed that the most robust predictor to outcome relationships included time and access to literature and believability of pain science/patient education, years of clinical practice and believability of psychologically informed practice, and believability of thermal/electrical agents., Conclusion: An important takeaway from this study is that believability was influenced by several factors (primarily by years of practice, attributions of the researcher, and time and access to literature) and appeared to vary across treatment domains., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2022 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Fast growth rate in broiler chickens comes with welfare concerns and the contribution of growth rate to pathogen resistance and sickness behavior is relatively unknown. The objective of this study was to evaluate physiological and behavioral responses of conventional (CONV) and slow-growing (SG) male broilers challenged with Salmonella Typhimurium. CONV ( n = 156) and SG ( n = 156) chicks were raised in a pen with wood litter shavings until day 7 of age, when birds were transferred to 24 isolators ( n = 11 chicks/isolator). On day 14 of age, half of the birds ( n = 12 isolators) were challenged with S. Typhimurium (ST) and the other half ( n = 12 isolators) received a control (C). On days 7, 13, 17, 21, and 24, body weight was recorded, and blood, jejunum and ileum sections were collected from 2 birds/isolator ( n = 48 birds/sampling) to measure plasma IgA and IgG and intestinal histomorphology, respectively. On days 12, 16, 21, and 23, video was recorded to evaluate bird postures (sitting, standing, or locomoting) and behaviors (eating, drinking, preening, stretching, sham foraging, allopreening, and aggression). CONV birds were 70 g heavier ( p = 0.03) on day 21 and 140 g heavier ( p = 0.007) on day 24 than SG. On day 7, CONV jejunum villus height and crypt depth were 22 and 7 μm greater ( p ≤ 0.001), respectively, than SG. On day 24, ST ileum villus height was 95 μm shorter ( p = 0.009) than C. IgA increased after day 17 for all birds and at day 21, CONV IgA was greater ( p = 0.01) than SG. Although SG IgG was 344 μg/ml greater ( p = 0.05) than CONV on day 7, CONV IgG increased with age ( p < 0.0001) to greater ( p ≤ 0.03) concentrations than SG on day 21 and day 24 by 689 μg/ml and 1,474 μg/ml, respectively, while SG IgG remained at similar concentrations after day 13. Generally, a greater proportion of birds sham foraged as they aged ( p < 0.0001). A greater proportion of CONV tended to sit ( p = 0.09) and fewer locomoted ( p < 0.0001) than SG as they aged. The results illustrate conventional and slow-growing broilers differ in their behavior, immunity, and response to Salmonella ., 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 Snyder, Riley, Robison, Karcher, Wickware, Johnson and Weimer.)

Functional resonance magnetic imaging (fMRI) allows for identification of eloquent cortex in pre-treatment planning. Previous studies have shown a correlation among lesion to activation distance (LAD) measures and morbidity and mortality. This study investigates the relationship between LAD, well-established language centers (Wernicke's and Broca's), and language performance measures. We included a sample population of brain tumor patients that received language fMRI (verbal fluency and sentence verification) for pre-treatment assessment (n = 51). LAD to the nearest language area was measured and divided into groups ≤ 10 mm and > 10 mm. Verbal fluency scores were compared between these groups. Additionally, patients were divided into similar groups based on LAD to either Broca's or Wernicke's areas, and the verbal fluency scores and sentence verification accuracy (n = 29) were subsequently compared between groups. Brain tumor patients with LAD ≤ 10 mm to either language area had significantly lower verbal fluency scores (p = 0.028). The difference in verbal fluency scores between groups with LAD ≤ 10 mm and > 10 mm to Wernicke's area trends toward significance (p = 0.067). The sentence verification accuracy was significantly lower in patients with LAD ≤ 10 mm to either language area (p = 0.039). These findings suggest that there exists a significant relationship between LAD to language centers and measures; greater language deficits are seen when LAD ≤ 10 mm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Pathogenic Rickettsia are obligate intracellular bacteria and the etiologic agents of many life-threatening infectious diseases. Due to the serious nature of these infections, it is imperative to both identify the responsive immune sensory pathways and understand the associated immune mechanisms that restrict Rickettsia proliferation. Previous studies have demonstrated that the mammalian complement system is both activated during Rickettsia infection and contributes to the immune response to infection. To further define this component of the mammalian anti-Rickettsia immune response, we sought to identify the mechanism(s) of complement activation during Rickettsia infection. We have employed a series of in vitro and in vivo models of infection to investigate the role of the classical complement activation pathway during Rickettsia infection. Depletion or elimination of complement activity demonstrates that both C1q and pre-existing IgM contribute to complement activation; thus implicating the classical complement system in Rickettsia-mediated complement activation. Elimination of the classical complement pathway from mice increases susceptibility to R. australis infection with both increased bacterial loads in multiple tissues and decreased immune activation markers. This study highlights the role of the classical complement pathway in immunity against Rickettsia and implicates resident Rickettsia-responsive IgM in the response to infection., (© 2021 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Objectives: To determine the prevalence of prospective clinical trial registration and postrandomization bias in published musculoskeletal physical therapy randomized clinical trials (RCTs)., Design: A methods review., Literature Search: Articles indexed in MEDLINE and published between January 2016 and July 2020 were included., Study Selection Criteria: Two independent blinded reviewers identified the RCTs using Covidence. We included RCTs related to musculoskeletal interventions that were published in International Society of Physiotherapy Journal Editors member journals., Data Synthesis: Data were extracted independently for the variables of interest from the identified RCTs by 2 blinded reviewers. The data were presented descriptively or in frequency tables., Results: One hundred thirty-eight RCTs were identified. One third of RCTs were consistent with their prospectively registered intent (49/138); consistency with prospectively registered intent could not be determined for two thirds (89/138) of the RCTs. Four RCTs (8%)reported inconsistent results with the primary aims and 7 (14%) with the outcomes from the prospective clinical trial registry, despite high methodological quality (Physiotherapy Evidence Database [PEDro] scale score). Differences between prospectively registered and non-prospectively registered RCTs for PEDro scale scores had a medium effect size ( r = 0.30). Two of 15 journals followed their clinical trial registration policy 100% of the time; in 1 journal, the published RCTs were consistent with the clinical trial registration., Conclusion: Postrandomization bias in musculoskeletal physical therapy RCTs could not be ruled out, due to the lack of prospective clinical trial registration and detailed data analysis plans. J Orthop Sports Phys Ther 2021;51(11):542-550. Epub 21 Sep 2021. doi:10.2519/jospt.2021.10491 .

Anellovirus infections are highly prevalent in mammals, however, prior to this study only a handful of anellovirus genomes had been identified in members of the Felidae family. Here we characterise anelloviruses in pumas (Puma concolor), bobcats (Lynx rufus), Canada lynx (Lynx canadensis), caracals (Caracal caracal) and domestic cats (Felis catus). The complete anellovirus genomes (n = 220) recovered from 149 individuals were diverse. ORF1 protein sequence similarity network analysis coupled with phylogenetic analysis, revealed two distinct clusters that are populated by felid-derived anellovirus sequences, a pattern mirroring that observed for the porcine anelloviruses. Of the two-felid dominant anellovirus groups, one includes sequences from bobcats, pumas, domestic cats and an ocelot, and the other includes sequences from caracals, Canada lynx, domestic cats and pumas. Coinfections of diverse anelloviruses appear to be common among the felids. Evidence of recombination, both within and between felid-specific anellovirus groups, supports a long coevolution history between host and virus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The objectives of this study were the following: (1) to determine if there was a difference in outcomes between immediate responders to glenohumeral mobilizations at the initial evaluation, 2-week, 4-week, and 6-month follow-up as compared to those that do not respond in participants with subacromial pain syndrome; (2) to see if there were statistically significant differences in outcomes within these groups between these time frames of interest, and (3) to see if symptom response at the initial evaluation was predictive of a favorable recovery., Methods: This was a prospective, single-group observational design. Clinicians pragmatically identified positive responders as improving at least two points on the Numeric Pain Rating Scale and/or a 20° improvement in shoulder active range of motion (AROM) following shoulder mobilization at the initial evaluation. Data were collected for the subjective and objective variables of interest at the initial evaluation, 2-week, 4-week, and 6-month follow-up., Results: The prevalence of responders at the initial evaluation was 99 (81.8%). There were no statistically significant between-group differences for the variables of interest except for the Global Rating of Change (GRoC; f = 2.79, p = 0.006). The shoulder abduction AROM between-group difference exceeded the minimal detectable change at 4 weeks. The pair-wise comparison showed statistically significant differences for the outcomes of interest at each time point except for the GRoC between 4 weeks and 6 months. There was a statistically significant correlation between responders at the initial evaluation and shoulder abduction AROM at the 4-week follow-up (r pb (112) = 0.27, p = 0.004)., Conclusion: Individuals with SAPS may benefit from shoulder mobilization independent of their within-session response to shoulder mobilization at the initial evaluation. Future research should seek to differentiate if these improvements are related to the within-session positive treatment response at the initial evaluation in individuals who are randomized to receive shoulder mobilization or not., (© 2021 John Wiley & Sons Ltd.)

Background: There is considerable overlap between pain referral patterns from the lumbar disc, lumbar facets, the sacroiliac joint (SIJ), and the hip. Additionally, sciatic like symptoms may originate from the lumbar spine or secondary to extra-spinal sources such as deep gluteal syndrome (GPS). Given that there are several overlapping potential anatomic sources of symptoms that may be synchronous in patients who have low back pain (LBP), it may not be realistic that a linear deductive approach can be used to establish a diagnosis and direct treatment in this group of patients., Objective: The objective of this theoretical clinical reasoning model is to provide a framework to help clinicians integrate linear and non-linear clinical reasoning approaches to minimize clinical reasoning errors related to logically fallacious thinking and cognitive biases., Methods: This masterclass proposes a hypothesis-driven and probabilistic approach that uses clinical reasoning for managing LBP that seeks to eliminate the challenges related to using any single diagnostic paradigm., Conclusions: This model integrates the why (mechanism of primary symptoms), where (location of the primary driver of symptoms), and how (impact of mechanical input and how it may or may not modulate the patient's primary complaint). The integration of these components individually, in serial, or simultaneously may help to develop clinical reasoning through reflection on and in action. A better understanding of what these concepts are and how they are related through the proposed model may help to improve the clinical conversation, academic application of clinical reasoning, and clinical outcomes., (Copyright © 2020 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: The purposes of this study were to determine whether there are differences between the dominant and nondominant arms for the Median Neurodynamic Test 1 (MNT 1); whether there are differences between men and women on the MNT 1; the reliability of an assessment of resting scapular position; the reliability of the MNT 1; and the frequency and percentage of sensory responses that are present during the MNT 1 in the asymptomatic population., Methods: This was a reliability and agreement study. It included asymptomatic students enrolled in the college of health professions and the college of nursing at a university. The Mann-Whitney U was used to determine whether there were any differences between the dominant and nondominant sides and between sexes for elbow extension range of motion and for sensory responses on the numeric pain rating scale when performing the MNT 1. A χ 2 analysis was used to determine whether there were any differences between sexes and between dominant and nondominant upper extremities for sensory-response location, sensory-response type, and structural differentiation for raters 1 and 2. The intraclass correlation coefficient (ICC 2,3 ) was used to determine the intertester and intratester reliability for the degrees of elbow extension attained during testing., Results: Reliability for degrees of elbow extension and strength of the sensory response was excellent (ICC 2,3 ˃ 0.75) and substantial (κ ≥ 0.68), respectively. Resting scapular position and all other components of the MNT 1 demonstrated statistically significant side-to-side differences and κ values ranging from 0.23 to 0.88., Conclusion: Elbow extension and magnitude of sensory response are reliable components of the MNT 1 that are not different between the dominant and nondominant sides in the asymptomatic population., (© 2020 by National University of Health Sciences.)

The World Health Organization has designated Zika virus (ZIKV) as a dangerous, mosquito-borne pathogen that can cause severe developmental defects. The primary goal of this work was identification of small molecules as potential ZIKV inhibitors that target the viral envelope glycoprotein (ZIKV E) involved in membrane fusion and viral entry. A homology model of ZIKV E containing the small molecule β-octyl glucoside (BOG) was constructed, on the basis of an analogous X-ray structure from dengue virus, and >4 million commercially available compounds were computationally screened using the program DOCK6. A key feature of the screen involved the use of similarity-based scoring to identify inhibitor candidates that make similar interaction energy patterns (molecular footprints) as the BOG reference. Fifty-three prioritized compounds underwent experimental testing using cytotoxicity, cell viability, and tissue culture infectious dose 50% (TCID50) assays. Encouragingly, relative to a known control (NITD008), six compounds were active in both the cell viability assay and the TCID50 infectivity assay, and they showed activity in a third caspase activity assay. In particular, compounds 8 and 15 (tested at 25 μM) and compound 43 (tested at 10 μM) appeared to provide significant protection to infected cells, indicative of anti-ZIKV activity. Overall, the study highlights how similarity-based scoring can be leveraged to computationally identify potential ZIKV E inhibitors that mimic a known reference (in this case BOG), and the experimentally verified hits provide a strong starting point for further refinement and optimization efforts.

Introduction: There is a lack of understanding of the impact of generalized joint mobility, joint hypermobility, and resting scapular position on neurodynamic testing of the median nerve. The objectives of the study were to determine: 1) the reliability of the Beighton score (BS) with and without the cutoff score for general joint hypermobility (GJH); 2) if there are differences in the Median Neurodynamic Test 1 (MNT 1) based on the Beighton cutoff score for GJH; 3) if there are differences in the MNT 1 based on an assessment of resting scapular position; 4) if there are relationships between the BS with and without the cutoff score for GJH, resting scapular position, and MNT 1., Methods: Testing was performed by two testers at two-time intervals at least 1 week apart. The population of interest was healthy asymptomatic adults. The outcome measures included the BS, resting scapular position, and MNT 1., Results: Intraclass correlation coefficients (ICC 2,1 ) were 0.52 for intertester reliability at visit 1 and 0.86 at visit 2, with intratester reliability of 0.88 for Tester 1 and 0.71 for Tester 2 for the BS. Intertester prevalence-adjusted bias-adjusted kappa (PABAK) values for the Beighton GJH cutoff scores were 0.80-0.84 and 0.80 to 0.92 for intratester reliability. There were no statistically significant differences or relationships for any of the other variables of interest., Conclusion: Joint mobility and resting scapular position are not confounding variables when performing MNT 1 in an asymptomatic population., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease caused by Rickettsia rickettsii , which is widely distributed throughout the Americas. Over 4000 cases of RMSF are recorded annually in the United States, while only around 100 cases are reported in Brazil. Conversely, while case fatality rates in the United States oscillate around 5%, in Brazil they can surpass 70%, suggesting that differences in tick vectoring capacity, population sensitivity, and/or variability in virulence of the rickettsial strains may exist. In this study, we compared the susceptibility of C3H/HeN mice to two highly virulent strains of R. rickettsii , one from the United States (Sheila Smith) and the other from Brazil (Taiaçu). Animals inoculated with the Taiaçu strain succumbed to infection earlier and exhibited severe histological lesions in both liver and spleen sooner than mice infected with the Sheila Smith strain. These differences in survival and signs of the disease are not related to a greater proliferation of the Taiaçu strain, as there were no significant differences in the rickettsial load in mice tissues inoculated with either strain. The present study is the first step to experimentally assess differences in fatality rates of RMSF in two different regions of the American continent.

Objectives: To identify if a plausible theoretical construct exists for a test cluster in a group of patients with subacromial pain syndrome presenting with glenohumeral internal rotation deficit (GIRD); determine the intertester agreement and reliability of the proposed test cluster; determine if there are any meaningful relationships between the test cluster and the component tests for the entire sample; and determine if there are any differences in disability on the Dutch version of the shoulder pain and disability index between participants with a positive and negative test cluster., Methods: This study is a retrospective secondary analysis of data that were collected to determine the interrater agreement and reliability of clinical tests for assessment of patients with shoulder pain in primary care., Results: The test cluster total agreement and negative specific agreement was 87.8 and 90.4%, respectively. The prevalence-adjusted bias-adjusted kappa for the test cluster was substantial at 0.76. There were statistically significant meaningful relationships (≥0.50) between GIRD and the test cluster for Tester A (Phi = 0.71, p < .01) and Tester B (Phi = 0.82, p < .01). No differences in disability were identified between those with a positive and negative test cluster., Conclusion: The test cluster described in this study may be a reliable means of identifying a subgroup of patients with subacromial pain syndrome related to GIRD. Future research should look to validate this test cluster prospectively., (© 2020 John Wiley & Sons, Ltd.)

Objective: To examine the mediating role of changes in fear-avoidance beliefs and self-efficacy on pain and physical functioning at discharge in patients with acute and chronic low back pain (LBP)., Design: Retrospective study., Methods: Baseline and discharge data from 418 participants with acute and chronic LBP were analyzed. At discharge, functional status and pain intensity were analyzed to assess their role as a predictor of acute and chronic LBP status and as a mediator of fear-avoidance beliefs and self-efficacy from baseline to discharge., Results: In multivariable analyses, patients with chronic LBP had lower discharge functional status ( β = -7.4; 95% confidence interval [CI]: -10.5, -4.3), lower self-efficacy for physical function ( β = -5.3; 95% CI: -10.2, -0.4), higher pain intensity ( β = 0.9; 95% CI: 0.3, 1.5), and no difference in discharge fear-avoidance beliefs compared to patients with acute LBP. Change in self-efficacy for physical function had a small indirect association ( β = -1.1; 95% bias-corrected CI: -2.5, -0.004), mediating the relationship between chronic LBP and discharge functional status., Conclusion: Fear-avoidance beliefs were not a mediator of pain or function at discharge in patients with chronic LBP. Self-efficacy may be an important mediating factor for function at discharge in patients with chronic LBP who receive physical therapy. J Orthop Sports Phys Ther 2020;50(6):301-308. Epub 6 Jan 2020. doi:10.2519/jospt.2020.8982 .

Objectives : The reporting of sampling methods in Randomized Clinical Trials (RCTs) allows for research quality assessment, determination of sampling bias, and assures the presence of details necessary for reproducibility in future trials. The purpose of this study was to: (1) determine if sampling methodology was reproducible in RCTs related to musculoskeletal physical therapy (MSKPT) interventions to treat non-specific low back pain (NSLBP) and (2) establish if there was a relationship between sample reproducibility and established measures of research quality. Methods : Data were collected through a systematic review by a professional librarian. The identified RCTs were assessed for methodological quality by two blinded individual reviewers. Data analysis was performed by a third, blinded researcher; additional comparisons were made based on Journal Impact Factor and PEDro score. Results : Ninety-nine published peer-reviewed RCTs were identified that met inclusion criteria. Only 29% of the articles were judged to be reproducible based on the reported sampling methodology. There were meaningful correlations between two out of ten of the sampling reporting criteria and the judgement made if the sample was reported in significant detail to allow for replication. There was no relationship between sampling reporting criteria, Journal Impact Factors (JIFs), and Physiotherapy Evidence Database (PEDro) scores. Discussion : The reporting of sampling methodology needs to be considered to ensure reproducibility and avoid sampling bias. Despite the proliferation of measures of research quality, the overall reporting quality of RCTs continues to be inadequate to allow widespread reproducibility of trials. Level of Evidence : 1a.

Purpose: The purpose of this study was to determine: 1) the test-retest reliability of Fear-Avoidance Beliefs Questionnaire (FABQ) Work (FABQW) subscale, FABQ Physical Activity (FABQPA) subscale, Shoulder Pain and Disability Index (SPADI) Pain subscale, SPADI Disability subscale, and Numeric Pain Rating scale (NPRS); and 2) the relationship between the FABQPA, FABQW, SPADI pain, SPADI disability, and NPRS after 4 weeks of pragmatically applied physical therapy (PT) in patients with shoulder pain., Design: Prospective, single-group observational design., Methods: Data were collected at initial evaluation, the first follow-up visit prior to the initiation of treatment, and after 4 weeks of treatment., Results: Statistically significant Intraclass Correlation Coefficient (ICC 2,1 ) values were reported for the FABQPA, FABQW, SPADI Pain, SPADI Disability, and NPRS. A statistically significant moderate relationship between the FABQPA subscale, SPADI subscale, and NPRS could not be established prior to and after 4 weeks of pragmatically applied PT. Statistically significant differences were observed between the initial evaluation and four-week follow-up for the FABQPA, SPADI Pain, SPADI Disability, and NPRS (p < 0.01)., Discussion: Since a meaningful relationship between the FABQ, SPADI, and NPRS did not exist, it suggests that the FABQPA may be measuring a metric other than pain., Conclusions: This study suggests that the FABQW may not be sensitive to change over time.

Despite their high degree of genomic similarity, different spotted fever group (SFG) Rickettsia are often associated with very different clinical presentations. For example, Rickettsia conorii causes Mediterranean spotted fever, a life-threatening disease for humans, whereas Rickettsia montanensis is associated with limited or no pathogenicity to humans. However, the molecular basis responsible for the different pathogenicity attributes are still not understood. Although killing microbes is a critical function of macrophages, the ability to survive and/or proliferate within phagocytic cells seems to be a phenotypic feature of several intracellular pathogens. We have previously shown that R. conorii and R. montanensis exhibit different intracellular fates within macrophage-like cells. By evaluating early macrophage responses upon insult with each of these rickettsial species, herein we demonstrate that infection with R. conorii results in a profound reprogramming of host gene expression profiles. Transcriptional programs generated upon infection with this pathogenic bacteria point toward a sophisticated ability to evade innate immune signals, by modulating the expression of several anti-inflammatory molecules. Moreover, R. conorii induce the expression of several pro-survival genes, which may result in the ability to prolong host cell survival, thus protecting its replicative niche. Remarkably, R. conorii -infection promoted a robust modulation of different transcription factors, suggesting that an early manipulation of the host gene expression machinery may be key to R. conorii proliferation in THP-1 macrophages. This work provides new insights into the early molecular processes hijacked by a pathogenic SFG Rickettsia to establish a replicative niche in macrophages, opening several avenues of research in host-rickettsiae interactions.

Objectives : The purpose of this systematic review was to determine if movement-based classification (MBC) systems are more effective than therapeutic exercise or guideline-based care (GBC) in improving outcomes in patients with low back pain (LBP) based upon randomized clinical trials (RCT) with moderate to high methodological quality and low to moderate risk of bias. Methods : The search strategy was developed by a librarian experienced in systematic review methodology and peer reviewed by a second research librarian. The following databases were searched from their inception to May 17, 2018: PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. The identified RCTs with a PEDro score of ≥6 were screened and assessed for risk of bias by two blinded individual reviewers using Covidence. Results : Seven studies were identified that had moderate-to-high methodological quality. One of the studies was identified as having a high risk of bias. Of the six studies that remained, only one study reported finding a statistically significant difference at the immediate follow-up that was not clinically significant. There was no significance at 6 and 12 months. Discussion : There is a paucity of moderate to high methodological quality RCTs with similar methodology that compare MBC to standard of care treatments for patients with LBP. Studies with moderate to high methodological quality that have a low risk of bias do not support MBCs as being superior to general exercise or GBC in the treatment of nonradicular LBP. Level of Evidence : 1a.

Objective: The purpose of this study was to determine (a) if the newly developed shoulder functional reach score (SFRS) is reliable; (b) if the SFRS demonstrates construct validity by being able to differentiate between patients' symptomatic and asymptomatic shoulders; (c) if the SFRS is able to detect changes over time; and (d) if the potential changes in the SFRS demonstrated criterion validity at three different time intervals by being associated the Numeric Pain Rating Scale (NPRS) and Shoulder Pain and Disability Index (SPADI)., Methods: Patients were consecutively screened for consultation related to complaints of shoulder pain. Thirty-eight subjects agreed to participate and signed informed consent. Twenty-nine subjects fulfilled the study after the 4 weeks of follow-up. Outcome measures were collected at the initial evaluation and at the first follow-up visit prior to the initiation of treatment. Data were then collected after 2 and 4 weeks of treatment., Results: There were statistically significant differences between symptomatic and asymptomatic shoulders on the SFRS. Intratester reliability of the SFRS was intraclass correlation coefficient (ICC 2,1 ) = 0.94. Intertester reliability of the SFRS was ICC 2,1  = 0.92. Statistically significant differences were observed between the initial evaluation, 2 and 4 weeks for the SFRS, SPADI, and NPRS. Moderate (r s  = 0.62) to strong (r s  = 0.87) positive correlations were observed between the NPRS and SPADI. Moderate negative (r s  = -0.50-0.51) correlations were found between the SFRS and the SPADI. Moderate negative (r s  = -0.36-0.54) statistically significant (p < 0.05) correlations were found between the SFRS and the NPRS., Conclusion: In this small sample, the SFRS was an objective, reliable, and valid tool for assessing shoulder active range of motion in a clinical setting., (© 2018 John Wiley & Sons, Ltd.)

The complement system has a well-defined role in deterring blood-borne infections. However, complement is not entirely efficacious, as several bacterial pathogens, including some obligate intracellular pathogens, have evolved mechanisms for resistance. It is presumed that obligate intracellular bacteria evade complement attack by residing within a host cell; however, recent studies have challenged this presumption. Here, we demonstrate that the complement system is activated during infection with the obligate intracellular bacterium Rickettsia australis and that genetic ablation of complement increases susceptibility to infection. Interaction of Rickettsia australis with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence R. australis. The C9-dependent membrane attack complex can lead to deposition of a bacteriolytic membrane pore on the bacteria, but this system does not contribute to control of rickettsial infection. Similarly, complement receptor (CR1/2)-dependent opsonophagocytosis may lead to engulfment and killing of the bacteria, but this system is also dispensable for immunity. Nevertheless, intact complement is essential for naturally acquired and antibody-mediated immunity to Rickettsia infection. Comparison of infection in mice lacking the central complement protein C3 with infection in their wild-type counterparts demonstrated decreases in gamma interferon (IFN-γ) production, IgG secretion, and spleen hyperplasia in animals lacking complement. The correlation between loss of secondary immune functions and loss of complement indicates that the proinflammatory signaling components of the complement system, and not membrane attack complex or opsonophagocytosis, contribute to the immune response to this pathogen., (Copyright © 2018 Riley et al.)

Background: The evolution of three-dimensional printing into prosthetics has opened conversations about the availability and cost of prostheses. This report will discuss how a prosthetic team incorporated additive manufacture techniques into the treatment of a patient with a partial hand amputation to create and test a unique assistive device which he could use to hold his French horn. Case description and methods: Using a process of shape capture, photogrammetry, computer-aided design and finite element analysis, a suitable assistive device was designed and tested. The design was fabricated using three-dimensional printing. Patient satisfaction was measured using a Pugh's Matrix™, and a cost comparison was made between the process used and traditional manufacturing. Findings and outcomes: Patient satisfaction was high. The three-dimensional printed devices were 56% cheaper to fabricate than a similar laminated device., Conclusion: Computer-aided design and three-dimensional printing proved to be an effective method for designing, testing and fabricating a unique assistive device. Clinical relevance CAD and 3D printing techniques can enable devices to be designed, tested and fabricated cheaper than when using traditional techniques. This may lead to improvements in quality and accessibility.

Competing Interests: Competing interests: Pramod Puligandla received a one-time honorarium, outside the submitted work, for participation in a meeting regarding the use of inhaled nitric oxide in adults and children hosted by Ikaria Canada Inc. Ian Adatia reports a forthcoming grant award from Malinkcrodt. No other competing interests were declared.

The lifecycle of Rickettsia rickettsii includes infection of both mammalian and arthropod hosts, with each environment presenting distinct challenges to survival. As such, these pathogens likely have distinctive transcriptional strategies for infection of each host. Herein, we report the utilization of next generation sequencing (RNAseq) and bioinformatic analysis techniques to examine the global transcriptional profile of R. rickettsii within an infected animal, and to compare that data to transcription in tissue culture. The results demonstrate substantial R. rickettsii transcriptional alteration in vivo, such that the bacteria are considerably altered from cell culture. Identification of significant transcriptional changes and validation of RNAseq by quantitative PCR are described with particular emphasis on known antigens and suspected virulence factors. Together, these results suggest that transcriptional regulation of a distinct cohort of genes may contribute to successful mammalian infection.

Bacteria exposed to host serum are subject to the antibacterial effects to the complement system. However, pathogenic microorganisms have evolved mechanisms of evading this immune attack. We have previously demonstrated that at least two R. conorii antigens, RC1281/Adr1 and OmpB β-peptide, contribute to the evasion of complement-mediated killing by binding the complement regulatory proteins vitronectin and factor H. RC1282/Adr2, a protein related to Adr1, is predicted to share similar structural features, suggesting that this protein may also contribute to evasion of complement-mediated killing. Interestingly, the R. prowazekii Adr1 and Adr2(RP828) proteins were originally found to interact with host cell surface proteins, suggesting their putative roles as adhesins in this pathogenic rickettsial species. In this study, we expressed both R. conorii and R. prowazekii Adr2 on the surface of a non-adherent, serum-sensitive strain of E. coli to examine the potential role of this protein to mediate evasion of complement-mediated killing and adherence to host cells. We demonstrate that, similar to R. conorii Adr1, R. conorii and R. prowazekii Adr2 are sufficient to mediate serum resistance and to promote interaction with the host complement regulator vitronectin. Furthermore, we demonstrate that expression of Adr2 in a non-adherent strain of E. coli is insufficient to mediate adherence to cultured mammalian endothelial cells. Together, our data demonstrate that the R. conorii and R. prowazekii Adr2 protein does not participate in the interactions with mammalian cells, but rather, participates in the evasion of killing by complement.

Spotted fever group (SFG) Rickettsia species are inoculated into the mammalian bloodstream by hematophagous arthropods. Once in the bloodstream and during dissemination, the survival of these pathogens is dependent upon the ability of these bacteria to evade serum-borne host defenses until a proper cellular host is reached. Rickettsia conorii expresses an outer membrane protein, Adr1, which binds the complement inhibitory protein vitronectin to promote resistance to the anti-bacterial effects of the terminal complement complex. Adr1 is predicted to consist of 8 transmembrane beta sheets that form a membrane-spanning barrel with 4 peptide loops exposed to the extracellular environment. We previously demonstrated that Adr1 derivatives containing either loop 3 or 4 are sufficient to bind Vn and mediate resistance to serum killing when expressed at the outer-membrane of E. coli . By expressing R. conorii Adr1 on the surface of non-pathogenic E. coli , we demonstrate that the interaction between Adr1 and vitronectin is salt-sensitive and cannot be interrupted by addition of heparin. Additionally, we utilized vitroenctin-derived peptides to map the minimal Adr1/vitronectin interaction to the C-terminal region of vitronectin. Furthermore, we demonstrate that specific charged amino acid residues located within loops 3 and 4 of Adr1 are critical for mediating resistance to complement-mediated killing. Interestingly, Adr1 mutants that were no longer sufficient to mediate resistance to serum killing still retained the ability to bind to Vn, suggesting that Adr1-Vn interactions responsible for resistance to serum killing are more complex than originally hypothesized. In summary, elucidation of the mechanisms governing Adr1-Vn binding will be useful to specifically target this protein-protein interaction for therapeutic intervention.

Study Design : Systematic review and meta-analysis. Objectives : To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) in the orthopaedic manual therapy (OMT) literature from January 2010 to June 2014 in order to determine if the CONSORT checklist and Cochrane Risk of Bias (RoB) assessment tools: (1) are reliable; (2) have improved the reporting and decreased the risk of bias in RCTs in the OMT literature; (3) differ based on journal impact factor (JIF); and (4) scores are associated with each other. Background : The CONSORT statement is used to improve the accuracy of reporting within RCTs. The Cochrane RoB tool was designed to assess the risk of bias within RCTs. To date, no evaluation of the quality of reporting and risk of bias in OMT RCTs has been published. Methods : Relevant RCTs were identified by a literature review from January 2010 to June 2014. The identified RCTs were assessed by two individual reviewers utilizing the 2010 CONSORT checklist and the RoB tool. Agreement and a mean composite total score for each tool were attained in order to determine if the CONSORT and RoB tools were reliable and varied by year and impact factor. Results : A total of 72 RCTs in the OMT literature were identified. A number of categories within the CONSORT and RoB tools demonstrated prevalence-adjusted bias-adjusted kappa (PABAK) scores of less than 0.20 and from 0.20 to 0.40. The total CONSORT and RoB scores were correlated to each other ( r  = 0.73; 95% CI 0.60 to 0.82; p  < 0.0001). There were no statistically significant differences in CONSORT or RoB scores by year. There was a statistically significant correlation between both CONSORT scores and JIF ( r  = 0.64, 95% CI 0.47 to 0.76; p  < 0.0001), and between RoB scores and JIF ( r  = 0.42, 95% confidence interval 0.21-0.60; p  < 0.001). There was not a statistically significant correlation between JIF and year of publication. Conclusion : Our findings suggest that the CONSORT and RoB have a number of items that are unclear and unreliable, and that the quality of reporting in OMT trials has not improved in recent years. Improvements in reporting are necessary to allow advances in OMT practice. Level of Evidence : 1A.

The extinction vortex is a theoretical model describing the process by which extinction risk is elevated in small, isolated populations owing to interactions between environmental, demographic, and genetic factors. However, empirical demonstrations of these interactions have been elusive. We modelled the dynamics of a small mountain lion population isolated by anthropogenic barriers in greater Los Angeles, California, to evaluate the influence of demographic, genetic, and landscape factors on extinction probability. The population exhibited strong survival and reproduction, and the model predicted stable median population growth and a 15% probability of extinction over 50 years in the absence of inbreeding depression. However, our model also predicted the population will lose 40-57% of its heterozygosity in 50 years. When we reduced demographic parameters proportional to reductions documented in another wild population of mountain lions that experienced inbreeding depression, extinction probability rose to 99.7%. Simulating greater landscape connectivity by increasing immigration to greater than or equal to one migrant per generation appears sufficient to largely maintain genetic diversity and reduce extinction probability. We provide empirical support for the central tenet of the extinction vortex as interactions between genetics and demography greatly increased extinction probability relative to the risk from demographic and environmental stochasticity alone. Our modelling approach realistically integrates demographic and genetic data to provide a comprehensive assessment of factors threatening small populations., (© 2016 The Author(s).)

Background: Arguments against reimbursement for direct access to physical therapy (PT) are that a physician examination is necessary to diagnose and that there is a potential for increased cost., Objective: To determine what percentage of PT referrals had a specific diagnosis and treatment orders. Additionally, specific and non-specific diagnoses and treatment orders were compared in regards to PT units billed, average visits per referral, and average cost per referral., Methods: The charts of 1,000 patients treated in outpatient PT underwent a retrospective chart review. Interferential statistics were used to determine if there was a statistically significant difference between specific and non-specific diagnoses and treatment orders in regard to PT units billed, average visits per referral, and average cost per referral., Results: Twenty-nine percent of all referring diagnoses were non-specific in nature and 58% contained treatment orders that were non-specific. Charts with a specific diagnosis had a statistically significant higher utilization as compared to non-specific diagnoses (p ≤ 0.001). Patients with a specific treatment order also displayed a statistically significant larger average in billed units, average visits per referral, and average reimbursement per referral than those without a specific treatment order (p ≤ 0.0001)., Conclusion: Our findings suggest that a physician diagnosis and referral may not be required to direct care for patients seeking PT services. Third-party payers that require a physician referral for PT services may be delaying access to healthcare and increasing costs.

Spotted fever group (SFG) rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (Rickettsia conorii) and Rocky Mountain spotted fever (Rickettsia rickettsii). Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Herein, we evaluated the ability of two SFG rickettsial species, R. conorii (a recognized human pathogen) and Rickettsia montanensis (a non-virulent member of SFG) to proliferate in THP-1 macrophage-like cells, or within non-phagocytic cell lines. Our results demonstrate that R. conorii was able to survive and proliferate in both phagocytic and epithelial cells in vitro. In contrast, R. montanensis was able to grow in non-phagocytic cells, but was drastically compromised in the ability to proliferate within both undifferentiated and PMA-differentiated THP-1 cells. Interestingly, association assays revealed that R. montanensis was defective in binding to THP-1-derived macrophages; however, the invasion of the bacteria that are able to adhere did not appear to be affected. We have also demonstrated that R. montanensis which entered into THP-1-derived macrophages were rapidly destroyed and partially co-localized with LAMP-2 and cathepsin D, two markers of lysosomal compartments. In contrast, R. conorii was present as intact bacteria and free in the cytoplasm in both cell types. These findings suggest that a phenotypic difference between a non-pathogenic and a pathogenic SFG member lies in their respective ability to proliferate in macrophage-like cells, and may provide an explanation as to why certain SFG rickettsial species are not associated with disease in mammals.

Understanding population and individual-level behavioral responses of large carnivores to human disturbance is important for conserving top predators in fragmented landscapes. However, previous research has not investigated resource selection at predation sites of mountain lions in highly urbanized areas. We quantified selection of natural and anthropogenic landscape features by mountain lions at sites where they consumed their primary prey, mule deer (Odocoileus hemionus), in and adjacent to urban, suburban, and rural areas in greater Los Angeles. We documented intersexual and individual-level variation in the environmental conditions present at mule deer feeding sites relative to their availability across home ranges. Males selected riparian woodlands and areas closer to water more than females, whereas females selected developed areas marginally more than males. Females fed on mule deer closer to developed areas and farther from riparian woodlands than expected based on the availability of these features across their home ranges. We suggest that mortality risk for females and their offspring associated with encounters with males may have influenced the different resource selection patterns between sexes. Males appeared to select mule deer feeding sites mainly in response to natural landscape features, while females may have made kills closer to developed areas in part because these are alternative sites where deer are abundant. Individual mountain lions of both sexes selected developed areas more strongly within home ranges where development occurred less frequently. Thus, areas near development may represent a trade-off for mountain lions such that they may benefit from foraging near development because of abundant prey, but as the landscape becomes highly urbanized these benefits may be outweighed by human disturbance.

Background: To date, no research has examined the reliability or predictive validity of manual unloading tests of the lumbar spine to identify potential responders to lumbar mechanical traction., Purpose: To determine: (1) the intra and inter-rater reliability of a manual unloading test of the lumbar spine and (2) the criterion referenced predictive validity for the manual unloading test., Methods: Ten volunteers with low back pain (LBP) underwent a manual unloading test to establish reliability. In a separate procedure, 30 consecutive patients with LBP (age 50·86±11·51) were assessed for pain in their most provocative standing position (visual analog scale (VAS) 49·53±25·52 mm). Patients were assessed with a manual unloading test in their most provocative position followed by a single application of intermittent mechanical traction. Post traction, pain in the provocative position was reassessed and utilized as the outcome criterion., Results: The test of unloading demonstrated substantial intra and inter-rater reliability K = 1·00, P = 0·002, K = 0·737, P = 0·001, respectively. There were statistically significant within group differences for pain response following traction for patients with a positive manual unloading test (P<0·001), while patients with a negative manual unloading test did not demonstrate a statistically significant change (P>0·05). There were significant between group differences for proportion of responders to traction based on manual unloading response (P = 0·031), and manual unloading response demonstrated a moderate to strong relationship with traction response Phi = 0·443, P = 0·015., Discussion and Conclusion: The manual unloading test appears to be a reliable test and has a moderate to strong correlation with pain relief that exceeds minimal clinically important difference (MCID) following traction supporting the validity of this test.

Purpose: This study aimed to compare selectivity characteristics among institution characteristics to determine differences by institutional funding source (public vs. private) or research activity level (research vs. non-research)., Methods: This study included information provided by the Commission on Accreditation in Physical Therapy Education (CAPTE) and the Federation of State Boards of Physical Therapy. Data were extracted from all students who graduated in 2011 from accredited physical therapy programs in the United States. The public and private designations of the institutions were extracted directly from the classifications from the 'CAPTE annual accreditation report,' and high and low research activity was determined based on Carnegie classifications. The institutions were classified into four groups: public/research intensive, public/non-research intensive, private/research intensive, and private/non-research intensive. Descriptive and comparison analyses with post hoc testing were performed to determine whether there were statistically significant differences among the four groups., Results: Although there were statistically significant baseline grade point average differences among the four categorized groups, there were no significant differences in licensure pass rates or for any of the selectivity variables of interest., Conclusion: Selectivity characteristics did not differ by institutional funding source (public vs. private) or research activity level (research vs. non-research). This suggests that the concerns about reduced selectivity among physiotherapy programs, specifically the types that are experiencing the largest proliferation, appear less warranted.

Understanding how landscape, host, and pathogen traits contribute to disease exposure requires systematic evaluations of pathogens within and among host species and geographic regions. The relative importance of these attributes is critical for management of wildlife and mitigating domestic animal and human disease, particularly given rapid ecological changes, such as urbanization. We screened > 1000 samples from sympatric populations of puma (Puma concolor), bobcat (Lynx rufus), and domestic cat (Felis catus) across urban gradients in six sites, representing three regions, in North America for exposure to a representative suite of bacterial, protozoal, and viral pathogens (Bartonella sp., Toxoplasma gondii, feline herpesvirus-1, feline panleukopenea virus, feline calicivirus, and feline immunodeficiency virus). We evaluated prevalence within each species, and examined host trait and land cover determinants of exposure; providing an unprecedented analysis of factors relating to potential for infections in domesticated and wild felids. Prevalence differed among host species (highest for puma and lowest for domestic cat) and was greater for indirectly transmitted pathogens. Sex was inconsistently predictive of exposure to directly transmitted pathogens only, and age infrequently predictive of both direct and indirectly transmitted pathogens. Determinants of pathogen exposure were widely divergent between the wild felid species. For puma, suburban land use predicted increased exposure to Bartonella sp. in southern California, and FHV-1 exposure increased near urban edges in Florida. This may suggest interspecific transmission with domestic cats via flea vectors (California) and direct contact (Florida) around urban boundaries. Bobcats captured near urban areas had increased exposure to T. gondii in Florida, suggesting an urban source of prey Bobcats captured near urban areas in Colorado and Florida had higher FIV exposure, possibly suggesting increased intraspecific interactions through pile-up of home ranges. Beyond these regional and pathogen specific relationships, proximity to the wildland-urban interface did not generally increase the probability of disease exposure in wild or domestic felids, empha- sizing the importance of local ecological determinants. Indeed, pathogen exposure was often negatively associated with the wildland-urban interface for all felids. Our analyses suggest cross-species pathogen transmission events around this interface may be infrequent, but followed by self-sustaining propagation within the new host species. virus; puma (Puma concolor); Toxoplasma gondii; urbanization.