Comparison of Pain Characteristics, Strength, and Movement Patterns in Adolescents with Juvenile Fibromyalgia and High versus Low Fear of Movement.

Physical activity avoidance and fear of movement (FOM) is often observed in individuals with chronic musculoskeletal pain, along with difficulties coping with pain. There is little research regarding how FOM may also relate to reduced physical strength and altered movement patterns that may perpetuate a cycle of pain, FOM, and disability. The objective of this observational study was to compare how adolescents with juvenile fibromyalgia (JFM) exhibiting high versus low FOM (Tampa Scale of Kinesiophobia [TSK-11]) differed on patient-reported measures of pain, fatigue, catastrophizing and pain interference, and performance-based measures of strength, postural control and biomechanical function. Participants were youth with JFM (N=135, Meanage = 15.6 years, 88.9% female) enrolled in an ongoing clinical trial who completed self-report questionnaires and standardized tests including knee and hip strength, the Star Excursion Balance Test and the Drop Vertical Jump (with 3-D motion capture). Participants were categorized into Low, Medium and High FOM groups based on TSK-11 tertile scores. Relative to the Low FOM group, the High FOM group reported significantly greater fatigue, pain interference and catastrophizing, as well as reduced dominant leg knee strength. Additionally, those with High FOM showed altered lower extremity movement patterns. This preliminary study highlights the importance of combining self-reported measures of symptoms and functioning with physical assessments to gain a more comprehensive view of the impact of FOM in patients with chronic musculoskeletal pain. Results could inform the development of more precise interventions to reduce FOM using a combination of behavioral and exercise-based interventions. PERSPECTIVE: Results of this study demonstrate the association between fear of movement, fatigue and pain interference in adolescents with juvenile fibromyalgia as well as preliminary evidence for altered movement patterns in that may predispose them to further pain/injury and activity avoidance. GOV REGISTRATION: NCT03268421.

Understanding social determinants of health and physical therapy outcomes in patients with low back pain: A scoping review.

BACKGROUND: Low back pain (LBP) is the number one cause of disability worldwide; however, it is not clear how social determinants of health (SDOH) impact care management and outcomes related to physical therapy (PT) services for patients with LBP. OBJECTIVE: The purposes of this scoping review are to examine and assimilate the literature on how SDOH and PT care relate to non-specific LBP outcomes and identify gaps in the literature to target for future research. METHODS: Data were extracted from eight electronic databases from January 2011 to February 2022. Reviewers independently screened all studies using the PRISMA extension for scoping review guidelines. Data related to study design, type of PT, type of non-specific LBP, patient demographics, PT intervention, SDOH, and PT outcomes were extracted from the articles. RESULTS: A total of 30,523 studies were screened, with 1961 articles undergoing full text review. Ultimately, 76 articles were identified for inclusion. Sex and age were the most frequent SDOH examined (88% and 78% respectively) followed by education level (18%). Approximately half of the studies that examined age, sex, and education level identified no effect on outcomes. The number of studies examining other factors was small and the types of outcomes evaluated were variable, which limited the ability to pool results. CONCLUSIONS: Sex and age were the most frequent SDOH examined followed by education level. Other factors were evaluated less frequently, making it difficult to draw conclusions. Study design and heterogeneity of determinants and outcomes were barriers to examining the potential impact on patients with LBP.

Mass spectrometry imaging protocol for spatial mapping of lipids, N-glycans and peptides in murine lung tissue.

RATIONALE: The application of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to murine lungs is challenging due to the spongy nature of the tissue. Lungs consist of interconnected air sacs (alveoli) lined by a single layer of flattened epithelial cells, which requires inflation to maintain its natural structure. Therefore, a protocol that is compatible with both lung instillation and high spatial resolution is essential to enable multi-omic studies on murine lung disease models using MALDI-MSI. METHODS AND RESULTS: To maintain the structural integrity of the tissue, murine lungs were inflated with 8% (w/v) gelatin for lipid MSI of fresh frozen tissues or 4% (v/v) paraformaldehyde neutral buffer for N-glycan and peptide MSI of FFPE tissues. Tissues were sectioned and prepared for enzymatic digestion and/or matrix deposition. Glycerol-free PNGase F was applied for N-glycan MSI, while Trypsin Gold was applied for peptide MSI using the iMatrixSpray and ImagePrep Station, respectively. For lipid, N-glycan and peptide MSI, α-cyano-4-hydroxycinnamic acid matrix was deposited using the iMatrixSpray. MS data were acquired with 20 µm spatial resolution using a timsTOF fleX MS instrument followed by MS fragmentation of lipids, N-glycans and peptides. For lipid MSI, trapped ion mobility spectrometry was used to separate isomeric/isobaric lipid species. SCiLS™ Lab was used to visualize all MSI data. For analyte identification, MetaboScape®, GlycoMod and Mascot were used to annotate MS fragmentation spectra of lipids, N-glycans and tryptic peptides, respectively. CONCLUSIONS: Our protocol provides instructions on sample preparation for high spatial resolution MALDI-MSI, MS/MS data acquisition and lipid, N-glycan and peptide annotation and identification from murine lungs. This protocol will allow non-biased analyses of diseased lungs from preclinical murine models and provide further insight into disease models.

Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.

Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Associations between patient-reported functional disability and measures of physical ability in juvenile fibromyalgia.

ABSTRACT: Juvenile fibromyalgia (JFM) is a chronic condition characterized by symptoms of pain and fatigue and is associated with sedentary behavior and functional disability. Adults with fibromyalgia exhibit deficits in physical fitness as evidenced by lower aerobic capacity and physical endurance, but it is unknown whether these impairments are apparent in adolescents with JFM. Furthermore, the extent to which functional disability and pain interference relate to measures of physical fitness has not been investigated in a pediatric pain population. During a baseline assessment for a clinical trial, 321 adolescents with juvenile fibromyalgia (M age = 15.14, 85.2% female) completed measures of pain intensity, fatigue, JFM symptom severity, functional disability, and pain interference. They also completed 2 validated fitness tasks: (1) the Harvard step test, which assesses aerobic fitness, and (2) the 6-minute walk test, a simple submaximal test of endurance. We examined associations among self-report measures and fitness assessments using bivariate correlations. We then employed hierarchical regression analyses to determine the unique contributions of physical fitness assessments to self-reported functional disability and pain interference. Results indicated that youth with JFM exhibited deficits in aerobic capacity and physical endurance. However, physical fitness explained negligible variance in functional disability and pain interference beyond that accounted for by pain, fatigue, and JFM symptom severity. Scores on available functional disability measures may reflect perceived difficulties in coping with symptoms during physical tasks rather than actual physical capability. Rigorous and sensitive assessments of physical fitness and endurance are needed to determine whether rehabilitation interventions for pediatric pain improve physical functioning.

High-Resolution N-Glycan MALDI Mass Spectrometry Imaging of Subchondral Bone Tissue Microarrays in Patients with Knee Osteoarthritis.

N-glycan alterations contribute to the progression of several joint diseases, including knee osteoarthritis (KOA). However, molecular changes in KOA subchondral trabecular bone, when exposed to different joint loading forces, are still unknown. The aim of this study was, therefore, to demonstrate the feasibility to differentiate N-glycan changes in subchondral trabecular bone from four different joint loading forces of the tibial plateau regions (i.e., Lateral Anterior (L-A), Lateral Posterior (L-P), Medial Anterior (M-A), and Medial Posterior (M-P)) in KOA patients (n = 10) using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) at 20 µm spatial resolution. The degree of cartilage degeneration was evaluated histologically, and the subchondral bone tissue microarrays (TMAs) were subsequently manually constructed from formalin-fixed paraffin-embedded (FFPE) KOA osteochondral (i.e., cartilage-subchondral bone) tissues. Overall, the Osteoarthritis Research Society International (OARSI) histological grade was significantly higher and the size of chondrocytes in the superficial zone was much larger for both M-A and M-P compared to L-A and L-P of cartilage (p = 0.006, p = 0.030, p = 0.028, and p = 0.010; respectively). Among the 65 putative N-glycans observed by MALDI-MSI, 2 core fucosylated bi-antennary N-glycans, m/z 1809.64; (Hex)5(HexNAc)4(Fuc)1 and 2100.73; (NeuAc)1(Hex)5(HexNAc)4(Fuc)1, were significantly higher in intensity in M-A compared to L-A of the trabecular bone (p = 0.027, and p = 0.038, respectively). These N-glycans were then further structurally characterized by in situ MS/MS fragmentation post-MALDI-MSI. Our results demonstrate, for the first time, N-glycan alterations can occur at different joint loading forces in the KOA tibial plateau and the feasibility of subchondral bone TMA construction for N-glycan MALDI-MSI.

Complex-Type N-Glycans Are Associated with Cartilage Degeneration within Different Loading Sites of the Tibial Plateau for Knee Osteoarthritis Patients.

Abnormal N-glycosylation has been shown to play an important role in the pathogenesis of multiple diseases. However, little is known about the relationship between N-glycosylation and knee osteoarthritis (KOA) progression at the tissue level. Thus, the aim of this study was to quantify the cartilage histomorphometric changes in formalin-fixed paraffin-embedded (FFPE) tissue collected from the lateral and medial compartments of the tibial plateau KOA patients (n = 8). Subsequently, N-glycans were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) followed by in situ MS/MS fragmentation. Overall, the Osteoarthritis Research Society International (OARSI) histological grade and cartilage surface fibrillation index were significantly higher, and chondrocyte size in the superficial zone was much larger, for the medial high-loaded cartilage compared to the lateral less-loaded cartilage. Among 92 putative N-glycans observed by MALDI-MSI, 3 complex-type N-glycans, (Hex)4(HexNAc)3, (Hex)4(HexNAc)4, and (Hex)5(HexNAc)4, and 1 oligomannose-type N-glycan, (Hex)9(HexNAc)2, were significantly higher in intensity in the medial cartilage compared to the lateral cartilage, whereas 2 tetra-antennary fucosylated-type N-glycans, (Hex)3(HexNAc)6(Fuc)2 and (Hex)3(HexNAc)6(Fuc)3, were significantly higher in intensity in the lateral cartilage than the medial cartilage. Our findings indicate that complex-type N-glycans are associated with higher severity of cartilage degeneration and may influence the cellular processes of KOA.

Does graded motor imagery benefit individuals with knee pain: A systematic review and meta-analysis.

OBJECTIVE: Evaluate how Graded Motor Imagery (GMI) may be used in those with knee pain, if individuals with knee pain present with a central nervous system (CNS) processing deficit, and if GMI is associated with improved outcomes. METHODS: An electronic database search was conducted of PubMed, SPORTDiscus, CINHAL, MEDLINE, Google Scholar, and Sports Medicine Education Index using keywords related to GMI and knee pain. This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Out of the 13,224 studies reviewed, 14 studies were included that used GMI for knee pain. Effect sizes were reported with standardized mean differences (SMD). RESULTS: Individuals with knee osteoarthritis demonstrated poor performance with correctly identifying images of left or right knees, and GMI improved performance. In contrast, individuals with an anterior cruciate ligament injury demonstrated no evidence of CNS processing deficit and mixed outcomes with GMI. Meta-analysis was limited to individuals post total knee arthroplasty showing low certainty that GMI can improve quadriceps force production [SMD 0.64 (0.07,1.22)], but evidence of no effect to reduce pain or improve Timed up and Go performance and self-reported function. CONCLUSIONS: Graded motor imagery may be an effective intervention for individuals with knee osteoarthritis. However, there was limited evidence that GMI was effective for an anterior cruciate ligament injury.

Kinesiophobia Is Associated With Poor Function and Modifiable Through Interventions in People With Patellofemoral Pain: A Systematic Review With Individual Participant Data Correlation Meta-Analysis.

OBJECTIVE: The aim of this systematic review and correlation meta-analysis was to identify factors associated with kinesiophobia in individuals with patellofemoral pain (PFP) and to identify interventions that may reduce kinesiophobia in individuals with PFP. METHODS: Seven databases were searched for articles including clinical factors associated with kinesiophobia or interventions that may reduce kinesiophobia in individuals with PFP. Two reviewers screened articles for inclusion, assessed risk of bias and quality, and extracted data from each study. A mixed-effects model was used to calculate correlations of function and pain with kinesiophobia using individual participant data. Meta-analyses were performed on interventional articles; Grading of Recommendations, Assessment, Development, and Evaluation was used to evaluate certainty of evidence. Results were reported narratively when pooling was not possible. RESULTS: Forty-one articles involving 2712 individuals were included. Correlation meta-analyses using individual participant data indicated a moderate association between self-reported function and kinesiophobia (n = 499; r = -0.440) and a weak association between pain and kinesiophobia (n = 644; r = 0.162). Low-certainty evidence from 2 articles indicated that passive treatment techniques were more effective than minimal intervention in reducing kinesiophobia (standardized mean difference = 1.11; 95% CI = 0.72 to 1.49). Very low-certainty evidence from 5 articles indicated that interventions to target kinesiophobia (psychobehavioral interventions, education, and self-managed exercise) were better in reducing kinesiophobia than physical therapist treatment approaches not specifically targeting kinesiophobia (standardized mean difference = 1.64; 95% CI = 0.14 to 3.15). CONCLUSION: Higher levels of kinesiophobia were moderately associated with poorer function and weakly associated with higher pain in individuals with PFP. Taping and bracing may reduce kinesiophobia immediately after use, and specific kinesiophobia-targeted interventions may reduce kinesiophobia following the full intervention; however, the certainty of evidence is very low. IMPACT: Assessment of kinesiophobia in clinical practice is recommended, on the basis of the relationships identified between kinesiophobia and other important factors that predict outcomes in individuals with PFP.

Role of Oral Intake, Mobility, and Activity Measures in Informing Discharge Recommendations for Hospitalized Inmate and Noninmate Patients With COVID-19: Retrospective Analysis.

BACKGROUND: Patients who were incarcerated were disproportionately affected by COVID-19 compared with the general public. Furthermore, the impact of multidisciplinary rehabilitation assessments and interventions on the outcomes of patients admitted to the hospital with COVID-19 is limited. OBJECTIVE: We aimed to compare the functional outcomes of oral intake, mobility, and activity between inmates and noninmates diagnosed with COVID-19 and examine the relationships among these functional measures and discharge destination. METHODS: A retrospective analysis was performed on patients admitted to the hospital for COVID-19 at a large academic medical center. Scores on functional measures including the Functional Oral Intake Scale and Activity Measure for Postacute Care (AM-PAC) were collected and compared between inmates and noninmates. Binary logistic regression models were used to evaluate the odds of whether patients were discharged to the same place they were admitted from and whether patients were being discharged with a total oral diet with no restrictions. Independent variables were considered significant if the 95% CIs of the odds ratios (ORs) did not include 1.0. RESULTS: A total of 83 patients (inmates: n=38; noninmates: n=45) were included in the final analysis. There were no differences between inmates and noninmates in the initial (P=.39) and final Functional Oral Intake Scale scores (P=.35) or in the initial (P=.06 and P=.46), final (P=.43 and P=.79), or change scores (P=.97 and P=.45) on the AM-PAC mobility and activity subscales, respectively. When examining separate regression models using AM-PAC mobility or AM-PAC activity scores as independent variables, greater age upon admission decreased the odds (OR 0.922, 95% CI 0.875-0.972 and OR 0.918, 95% CI 0.871-0.968) of patients being discharged with a total oral diet with no restrictions. The following factors increased the odds of patients being discharged to the same place they were admitted from: being an inmate (OR 5.285, 95% CI 1.334-20.931 and OR 6.083, 95% CI 1.548-23.912), "Other" race (OR 7.596, 95% CI 1.203-47.968 and OR 8.515, 95% CI 1.311-55.291), and female sex (OR 4.671, 95% CI 1.086-20.092 and OR 4.977, 95% CI 1.146-21.615). CONCLUSIONS: The results of this study provide an opportunity to learn how functional measures may be used to better understand discharge outcomes in both inmate and noninmate patients admitted to the hospital with COVID-19 during the initial period of the pandemic.

Comparisons of Clinical Competency and Job Responsibilities of Physical Therapists With and Without Postprofessional Training.

INTRODUCTION: Understanding how educational pathways may influence clinical competence and work responsibilities is important in providing guidance to academic and clinic stakeholders and physical therapists (PTs) on PT career development. The purpose of this paper was to compare perceived clinical competency and job duties between PTs with formal mentored postprofessional clinical education with PTs without formal postprofessional clinical education. REVIEW OF LITERATURE: The understanding of self-perceived clinical competence of PTs overall in the United States is limited, especially as related to the impact of postprofessional education. Furthermore, there is limited understanding of the career pathways and development of job duties of PTs in the United States. SUBJECTS: Two thousand three hundred thirty-four PTs in the United States. METHODS: An online survey was sent to licensed PTs. This survey included items measuring self-perceived clinical competency and questions related to weekly job responsibilities. Participants were categorized as residency trained, fellowship trained, or non-residency/fellowship trained. Frequency analyses and Kruskal-Wallis tests with pairwise post hoc tests were performed comparing the 3 groups. RESULTS: Residency-trained (P < .007) and fellowship-trained (P < .001) groups demonstrated elements of higher self-perceived clinical competency compared with the non-residency-/fellowship-trained group. Both the residency- and fellowship-trained groups spent less time with patient care and more time with other responsibilities (e.g., teaching, mentoring, and research) (P < .02) during an average workweek. Fellowship-trained PTs (P < .001) spent more time with administrative duties compared with the non-residency-/fellowship-trained group. DISCUSSION AND CONCLUSION: Results from this paper demonstrate that residency- and fellowship-trained PTs have elements of higher self-perceived clinical competency and spend more of their job duties outside of direct patient care compared with PTs who were not residency or fellowship trained. These results may help guide PTs, academic institutions, and employers in planning and achieving specific career paths.

Functional connectivity patterns are altered by low back pain and cause different responses to sham and real dry needling therapies: a systematic review of fMRI studies.

BACKGROUND: There is a relationship between low back pain (LBP) and central nervous system dysfunction. Needling therapies (e.g. acupuncture, dry needling) are proposed to impact the nervous system, however their specific influence is unclear. PURPOSE: Determine how needling therapies alter functional connectivity and LBP as measured by functional magnetic resonance imaging (fMRI). METHODS: Databases were searched following PRISMA guidelines. Studies using fMRI on individuals with LBP receiving dry needling or acupuncture compared to control or sham treatments were included. RESULTS: Eight studies were included, all of which used acupuncture. The quality of studies ranged from good (n = 6) to excellent (n = 2). After acupuncture, individuals with LBP demonstrated significant functional connectivity changes across several networks, notably the salience, somatomotor, default mode network (DMN) and limbic networks. A meta-analysis demonstrated evidence of no effect to potential small effect of acupuncture in reducing LBP (SMD -0.28; 95% CI: -0.70, 0.13). CONCLUSION: Needling therapies, like acupuncture, may have a central effect on patients beyond the local tissue effects, reducing patients' pain and disability due to alterations in neural processing, including the DMN, and potentially other central nervous system effects. The meta-analysis should be interpreted with caution due to the narrow focus and confined sample used.

Financial impact associated with implementation of the low back pain clinical practice guideline in outpatient physical therapist practice at a large academic medical center.

INTRODUCTION: Low back pain (LBP) is the top health condition requiring rehabilitation in the United States. The financial burden of managing LBP is also amongst the highest in the United States. Clinical practice guidelines (CPGs) provide management recommendations and have the potential to lower health costs. Limited evidence exists on the impact of CPG implementation on downstream medical costs. OBJECTIVE: To examine the impact of CPG implementation in physical therapist (PT) practice on direct and downstream costs for patients with LBP. METHODS: A retrospective observational study examined billing data from 270 patients with LBP who were treated at multiple sites within one large academic medical center by PTs who participated in a multifaceted CPG implementation program. Costs were analyzed for direct PT services, downstream medical services, and PT utilization from September 2017 to March 2018 (pre-implementation group) and compared with costs from June 2018 to December 2018 (post-implementation group). RESULTS: Direct PT costs were significantly lower post-implementation than pre-implementation mean: $2,863 USD (SD: $1,968) vs. $3,459 USD (SD: $2,838), p = .05, 95% CI [11, 1182]. All downstream costs were lower post-implementation with statistically significant lower costs found in downstream imaging: p = .04, 95% CI [32, 1,905]; pharmacy: p = .03, 95% CI [70, 1,217]; surgery: p = .03, 95% CI [446, 9,152], and "other": p = .02, 95% CI [627, 7,920]. CONCLUSION: Implementing the LBP CPG in outpatient PT practice can have a positive impact on lowering downstream costs and the potential to increase the value of PT services.

Structural Characterization and Spatial Mapping of Tetrodotoxins in Australian Polyclads.

Tetrodotoxin (TTX) is a potent marine neurotoxin that occurs in several Australian phyla, including pufferfish, toadfish, gobies, and the blue-ringed octopus. These animals are partially immune, and TTX is known to bioaccumulate and subject to trophic transfer. As such, it could be more ubiquitously distributed in animals than is currently known. Flatworms of the order Polycladida are commonly occurring invertebrates in intertidal ecosystems and are especially diverse in Australian waters. While TTX has been identified in polyclads from Japan and New Zealand, Australian species have yet to be tested. In this study, several eastern Australian polyclad flatworm species from the suborders Cotylea and Acotylea were tested for TTX and analogs by HILIC-HRMS to understand the distribution of this toxin within these suborders. Herein, we report the detection of TTX and some known analogs in polyclad species, one of which is a pest to shellfish aquaculture. We also report, for the first time, the application of MALDI mass spectrometry imaging utilized to map TTX spatially within the intestinal system of polyclads. The identification of TTX and its analogs in Australian flatworms illustrates a broader range of toxic flatworms and highlights that analogs are important to consider when studying the distributions of toxins in animals.

Mass spectrometry imaging spatially identifies complex-type N-glycans as putative cartilage degradation markers in human knee osteoarthritis tissue.

N-Glycan alterations contribute to the pathophysiology and progression of various diseases. However, the involvement of N-glycans in knee osteoarthritis (KOA) progression at the tissue level, especially within articular cartilage, is still poorly understood. Thus, the aim of this study was to spatially map and identify KOA-specific N-glycans from formalin-fixed paraffin-embedded (FFPE) osteochondral tissue of the tibial plateau relative to cadaveric control (CTL) tissues. Human FFPE osteochondral tissues from end-stage KOA patients (n=3) and CTL individuals (n=3), aged >55 years old, were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Overall, it was revealed that 22 N-glycans were found in the cartilage region of KOA and CTL tissue. Of those, 15 N-glycans were more prominent in KOA cartilage than CTL cartilage. We then compared sub-regions of KOA and CTL tissues based on the Osteoarthritis Research Society International (OARSI) histopathological grade (1 to 6), where 1 is an intact cartilage surface and 6 is cartilage surface deformation. Interestingly, three specific complex-type N-glycans, (Hex)4(HexNAc)3, (Hex)4(HexNAc)4, and (Hex)5(HexNAc)4, were found to be localized to the superficial fibrillated zone of degraded cartilage (KOA OARSI 2.5-4), compared to adjacent cartilage with less degradation (KOA OARSI 1-2) or relatively healthy cartilage (CTL OARSI 1-2). Our results demonstrate that N-glycans specific to degraded cartilage in KOA patients have been identified at the tissue level for the first time. The presence of these N-glycans could further be evaluated as potential diagnostic and prognostic biomarkers.

The effects of knee osteoarthritis on neural activity during a motor task: A scoping systematic review.

OBJECTIVE: To examine the evidence of neural activation with functional magnetic resonance imaging (fMRI), corticospinal excitability, and other central nervous system measurement differences during motor tasks between those with and without knee osteoarthritis (KOA). METHODS: A scoping review strategy was systematically performed. We searched PubMed, CINAHL, Embase, PsychInfo, SportDiscus, SCOPUS and Web of Science from database inception to April 2021. Any study investigating central nervous system measures during a motor task for individuals with KOA with or without a healthy control group for comparison was included. Two reviewers independently screened all studies in accordance with the Preferred Reported Items for Systematic Reviews and Meta-analyses extension for scoping reviews. RESULTS: Thirteen studies met the inclusion criteria. KOA had reduced activation of the premotor cortex during a gait imagery task when examining the brain using fMRI. This hypoactivation was not significant when the task was combined with ankle movement. Individuals with KOA had decreased motor cortex activation during a force matching motor task. KOA was associated with gamma loop dysfunction of the quadriceps and increased responsiveness of the triceps surae muscles. Also, there was an increased soleus Hoffmann reflex during heel strike of gait cycle. The flexor withdrawal reflex was heighted for individuals with KOA with a lower threshold of the reflex occurring with increased joint compression, but this reflex was modulated with joint mobilizations. CONCLUSION: Individuals with KOA have motor deficits associated with decreased neural activation, central nervous system sensitization, decreased quadriceps muscle spindle responsiveness, and increased triceps surae muscle activity.

Biomechanical variations in children who are overweight and obese during high-impact activities: A systematic review and meta-analysis.

Youth who are obese or overweight demonstrate evidence of poor lower extremity joint health and alterations in gait characteristics compared with youth who are healthy weight. However, there is no consensus if altered movement patterns are still present during high-impact activities. The purpose of this review was to determine if spatiotemporal and kinematic and kinetic variables during high-impact activities were significantly different between youth who are overweight and obese compared with youth who are healthy weight. An electronic search of five databases was conducted, and a meta-analysis and qualitative evidence synthesis was performed to determine the level of evidence, analyzing three tasks: running, jumping, and hopping. The findings of this review include the following: (1) overweight/obese (OW/OB) had higher stance phase time during running, (2) OW/OB had decreased hip flexion angles during running and stationary running, (3) OW/OB had decreased knee flexion angles during landing phase of jumping and hopping, and (4) OW/OB had increased hip abduction moments during running and jumping. These altered kinematic and kinetic variables at the hip and knee may result in mechanical inefficiency with high-impact activities, as well as potentially increased risk of joint degradation and poor joint health into adulthood.

Moderate reliability of the lateral step down test amongst experienced and novice physical therapists.

BACKGROUND/INTRODUCTION: The lateral step-down test is used to appraise movement quality in patients with patellofemoral pain (PFP), however, it is unclear if reliability of the test is affected by physical therapist experience. OBJECTIVE: Determine if there is a difference in reliability between 'experienced' and 'novice' physical therapists appraising movement quality of patients with PFP during the lateral step-down test. METHODS: Three 'experienced' and 3 'novice' physical therapists analyzed movement quality of 22 participants [mean age (SD) 28.25 (6.5) years] with PFP. Physical therapists viewed two-dimensional videos of participants performing the lateral step-down test and appraised the quality with a score (0-1 = 'good'; 2-3 = 'fair', and 4-5 = 'poor') at baseline and 1 week. Inter- and intra-rater reliability were calculated with kappa and percent agreement. Differences between the groups were assessed with the chi-square test with an a priori alpha level of < 0.05. RESULTS: Inter- and intra-rater reliability ranged from fair to moderate (ĸ = 0.40-0.65). There was no difference in reliability between 'experienced' and 'novice' physical therapists at baseline (p = .13) or 1 week post testing (p = .94). CONCLUSIONS: There was no difference in reliability between 'experienced' and 'novice' physical therapists using categories to appraise movement quality during the lateral step-down test for patients with chronic PFP.

A preliminary analysis of physical therapist agreement regarding the perceived impairments in cases of runners with knee pain.

BACKGROUND: There is a scarcity of evidence describing how physical therapists use data from clinical examinations to inform the treatment of runners with knee pain. OBJECTIVE: Our purpose was to examine the between physical therapist agreement on the selection of perceived impairments in runners with knee pain. METHODS: Twelve physical therapists reviewed two cases of runners with knee pain. The cases included clinical subjective information, objective data, and review of videos of each participant running. Each rater selected up to three perceived impairments (from a list of eight) that each physical therapist would address at the next physical therapy session. Percent agreement was calculated to determine the between rater agreement on each individual perceived impairment selection and Fleiss Kappa was calculated for each unique combination of three perceived impairments per case. RESULTS: Twelve raters with 51 (18-156) months of clinical experience participated. Percent agreement ranged from 8%-100% for both cases for individual impairments. When assessing the unique combination of three impairments selected, inter-rater agreement was less than what is expected due to chance alone (κ = -0.09, p = .92; κ = -0.09, p = .98) for both cases. CONCLUSION: The 12 physical therapists demonstrated poor to excellent levels of agreement when selecting an individual perceived impairment. Agreement was worse than chance when selecting a combination of three unique impairments.