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Multisensory sensitivity (MSS), observed in some chronic pain patients, may reflect a generalized central nervous system sensitivity. While several surveys measure aspects of MSS, there remains no gold standard. We explored the underlying constructs of four MSS-related surveys (80 items in total) using factor analyses using REDCap surveys (N = 614, 58.7% with pain). Four core- and six associated-MSS factors were identified from the items assessed. None of these surveys addressed all major sensory systems and most included additional related constructs. A revised version of the Somatosensory Amplification Scale was developed, encompassing five core MSS systems: vision, hearing, smell, tactile, and internal bodily sensations: the 12-item Multisensory Amplification Scale (MSAS). The MSAS demonstrated good internal consistency (alpha = 0.82), test-retest reliability (ICC3,1 = 0.90), and construct validity in the original and in a new, separate cohort (R = 0.54 - 0.79, p < 0.0001). Further, the odds of having pain were 2 - 3.5 times higher in the highest sex-specific MSAS quartile relative to the lowest MSAS quartile, after adjusting for age, sex, BMI, and pain schema (p < 0.03). The MSAS provides a psychometrically comprehensive, brief, and promising tool for measuring the core-dimensions of MSS. PERSPECTIVE: Multiple multisensory sensitivity (MSS) tools are used, but without exploration of their underlying domains. We found several measures lacking core MSS domains, thus we modified an existing scale to encompass five core MSS domains: light, smell, sound, tactile, and internal bodily sensations using only 12 items, with good psychometric properties.

Post-synthetic modification strategy is presented to extend the π-system of covalent organic framework (COF) backbone giving access to boronic ester based pyrene-fused azaacene COFs. Optimized catalyst-free reaction conditions yield COFs post-synthetically modified with up to 33% conversion and corresponding intriguing optical properties. The presented chemistry is expected to find application in post-synthetic tailoring of the optical properties of COFs., S.P.S.F. acknowledges the FCT − Fundação para a Ciência e Tecnologia for the Ph.D. scholarship SFRH/BD/131791/2017. This work received funding from the COFforH2 project (UTA-EXPL/NPN/0055/2019) through the Portuguese Foundation for Science and Technology funds under UT Austin Portugal, Charm project (PTDC/QUI-OUT/2095/2021) through the Portuguese Foundation for Science and Technology funds, The Excellence Clusters ‘Nanosystems Initiative Munich (NIM)’, and from the Free State of Bavaria through the Research Network ‘Solar Technologies go Hybrid’.

Vacuolar protein sorting 45 homolog (VPS45), a member of the Sec1/Munc18 (SM) family, has been implicated in the regulation of endosomal trafficking. VPS45 deficiency in human patients results in congenital neutropenia, bone marrow fibrosis, and extramedullary renal hematopoiesis. Detailed mechanisms of the VPS45 function are unknown. Here, we show an essential role of mammalian VPS45 in maintaining the intracellular organization of endolysosomal vesicles and promoting recycling of cell-surface receptors. Loss of VPS45 causes defective Rab5-to-Rab7 conversion resulting in trapping of cargos in early endosomes and impaired delivery to lysosomes. In this context, we demonstrate aberrant trafficking of the granulocyte colony-stimulating factor receptor in the absence of VPS45. Furthermore, we find that lack of VPS45 in mice is not compatible with embryonic development. Thus, we identify mammalian VPS45 as a critical regulator of trafficking through the endosomal system and early embryogenesis of mice.

Under the Treaty of Versailles the German colonial empire was placed under the mandate system of the League of Nations. France, Britain and South Africa took over legal responsibility for the administration of Germany’s former African territories, whose populations were, in theory, placed under the ‘diplomatic protection’ of the same states. What this amounted to was unspecified, but as this article shows, the willingness of the mandate states to take responsibility for their new charges would be particularly tested in Germany itself. There, to the concern of the German colonial authorities, a small population of African colonial subjects, willingly or otherwise, had set up home and formed families. This article examines the legal and real-life consequences the shift from German colony to Mandate state had during the interwar period for these men, their white, European wives and their German-born children who remained in Germany. At the same time, it highlights public and private initiatives undertaken by German-based Black people to raise attention to their plight and to improve their legal status.

OBJECTIVE: Adults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA. METHODS: Participants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over nine years, hazard ratios (aHR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders., A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality. RESULTS: Deaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI+MOST. Walking 0.2 meters/second slower during short- and standard-distance walk tests was associated with 23% (aHR[95%CI]; 1.23[1.10, 1.39]) and 25% (1.25[1.09, 1.43]) higher mortality risk, respectively. Walking

Purpose Some individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS preferentially relates to pain measures which reflect central influences (eg, dynamic quantitative sensory testing (QST) or referred pain), or whether the MSS-pain relationship requires priming from chronic pain, is unknown. Thus, this cross-sectional study investigated the relationships between MSS assessed in a pain-free state and evoked pain sensitivity. Methods Experimental intramuscular infusion pain and multiple static and dynamic QST were assessed in 465 healthy, pain-free adults: pain thresholds using pressure (PPTs) and heat (HPTs), temporal summation of pain (TSP) using pressure, heat or punctate stimuli, and conditioned pain modulation (CPM) using pressure or heat test stimuli. MSS was assessed using 7 items from Barsky's Somatosensory Amplification Scale. Differences in pain and QST between sex-specific MSS quartiles were assessed, adjusting for multiple comparisons. All participants completed at least one intramuscular infusion condition, but not all were asked to complete each QST (n=166-465). Results Both static and dynamic QST differed between highest and lowest MSS quartiles using pressure stimuli: lower PPTs (adjusted-p 0.05). Odds of experiencing TSP or referred pain was not greater, whereas CPM was 8-fold less likely, in those with highest MSS. Conclusion Normal variation in non-noxious MSS is related to both static and dynamic pain sensitivity, without sensitization associated with chronic pain, but is dependent on the QST stimulus. Thus, common influences on MSS and pain sensitivity may involve central mechanisms but are likely more complex than previously recognized.

Study Design Clinical commentary. Introduction/Purpose Pain and movement are universally relevant phenomena that influence human experiences in readily observable ways. Improved understanding of pain-movement relationships can guide medical and rehabilitative approaches to recovery and decrease risk of dysfunctional long-term consequences of otherwise normal neuromuscular responses. Therefore, the overall intent of this article is to elucidate the relationships between pain and movement as they relate to clinical decision making. Conclusions Motor output is highly adaptable, can be influenced by multiple mechanisms at various levels along the nervous system, and may vary between individuals despite similar diagnoses. Therefore, interventions need to be individualized and consider both the types of motor response observed (ie, whether the response is protective or maladaptive), and the patient's acute physical activity tolerance when prescribing exercise/movement.

Wrist-worn accelerometers are increasingly used to assess free-living physical activity (PA), but the implications of different processing methods are not well characterized. To advance research in this area it is important to better understand how choice of processing method influences estimates of free-living PA behavior. This study compared PA profiles resulting from processing wrist-worn data collected under free-living conditions using four different methods in a clinical sample of 160 women with chronic pain, a condition for which PA serves as a treatment. Participants wore monitors on their non-dominant wrist for 7 days and completed a self-report PA measure. Processing methods were Hildebrand linear, a modified nonlinear Hildebrand, Staudenmayer linear, and Staudenmayer random forest. Using each method, minutes per day in sedentary, light, and moderate-to-vigorous PA (MVPA) were estimated and individuals were classified as meeting PA guidelines based on their accumulated MVPA. Comparisons of outcomes among processing methods and with self-reported PA were made using repeated measures ANOVA, correlations, and kappa statistics. With few exceptions, estimated time at each intensity differed significantly across processing methods and with self-report (p range = 0.09 to 1.00) and showed inconsistent agreement for classifying individuals as meeting PA guidelines (κrange: −0.02 to 0.90). Thus, choice of processing method significantly influenced conclusions regarding free-living PA. Researchers and clinicians should exercise caution when interpreting accelerometer activity data and comparing across existing studies using different processing methods when examining how PA influences clinical conditions.

INTRODUCTION: We have a limited understanding of how antagonist muscle coactivation relates to measurement of strength in both individuals with and without knee osteoarthritis (KOA). OBJECTIVE: We sought to determine if hamstring coactivation during a maximal quadriceps activation task attenuates net quadriceps strength. DESIGN: Cross-sectional cohort analysis was conducted using data from the 60-month visit of the Multicenter Osteoarthritis Study (MOST). SETTING: Laboratory PARTICIPANTS: A sample of 2328 community-dwelling MOST participants between the ages of 55 and 84 years, with or at elevated risk for KOA, completed the 60-month MOST follow-up visit. Of these, 1666 met inclusion criteria for the current study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Quadriceps strength; percent combined hamstring coactivation (HC), medial HC, and lateral HC. Quadriceps and hamstring strength were assessed using an isokinetic dynamometer. Surface electromyography was used to assess muscle activation patterns. General linear models, adjusted for age, BMI, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Kellgren-Lawrence (KL) grade and study site, modeled the relationship between antagonist hamstring coactivation and quadriceps strength. RESULTS: Men had significantly greater quadriceps strength (p

Objective: The objective of the review is to determine whether conditioned pain modulation (CPM) is impaired in adults with chronic low back pain (CLBP) when compared with pain-free individuals. Methods: A a systematic search of the literature was undertaken using the databases: MEDLINE, Scopus, CINAHL and Web of Science. The citations of included studies were reviewed for additional studies. Observational, cross-sectional, case-control studies published in English between January 1990 and August 2019 were considered. Studies that investigated the efficiency of standardized CPM regimens among defined cases of CLBP and in comparison, with pain-free controls were included. After initial title and abstract screening, 2 authors reviewed the full texts of the eligible articles independently. Risk of bias was carried out using assessment of 4 categories: blinding of the outcome assessors, representativeness of cases to the specified population, comparability of cases and controls, and control of confounding variables. Results: In total, 643 records were identified, of which 7 studies were included. Overall, the results of the studies reported mixed conclusions on the efficiency of CPM in CLBP. Three studies identified significant differences for CPM between CLBP and pain-free controls and the other 4 studies reported no significant differences. The common methodological limitations were unclear reporting about blinding of the outcome assessors and inadequate control of confounding factors. Conclusions: High-quality research is strongly recommended to determine the function of endogenous pain modulatory mechanisms in CLBP.

Historically, the global mental health system has pathologized transgender and gender diverse (TGD) identities, imposing spurious diagnoses and nocuous "cures." Recently, the World Health Organization declassified "transgender" as a mental health disorder, and psychological organizations have acknowledged the harmful practice of conversion therapy and other culturally inept interventions. Some practitioners have begun to advertise their therapeutic services as "trans-affirming" or "trans-competent," but to date, there are no published studies delineating their efficacy. The following content analysis addresses this gap by considering the open-ended responses of 1,567 participants in the Trans Mental Health Survey. While inclusive mental health care is clearly needed, this study suggests that affirming providers are not axiomatically adroit: some providers inflate their expertise, conflate TGD experiences with sexual minority experiences, and manipulate their clients. Conversely, competent providers are identified by their helpfulness, trustworthiness, and understanding of TGD issues. In addition to promulgating best practices, this content analysis also acknowledges systemic barriers to quality care. The solutions to these macroissues include free or affordable mental health care and increased access to services. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pain is prevalent in older adults of both genders but more so in women. The extent to which this is impacted by opioids is not well established. We sought to evaluate common pain diagnoses among older adults noting whether the pattern of female preponderance holds across all conditions and whether opioids might impact this. Utilizing the 2017 Medicare 5% standard analytical claim sample we examined the rate of pain condition diagnoses in older females and males with or without opioid-related diagnoses. We have previously reported that low back pain and opioid diagnosis coding rates interact in older adults, we here expand this finding. We established a condition definition file for opioid use, not including overdose-related codes. We segmented the older adult Medicare part B claims file into those with and those without opioid diagnoses, separated by CMS-coded gender. Diagnostic rates of the 100 most common pain diagnoses in each of the subpopulations showed low back pain was the most prevalent pain diagnosis regardless of gender or opioid diagnosis status. Chest pain unspecified, neck pain, and abdominal pain unspecified, were also highly prevalent. All pain conditions were diagnosed at higher rates in the opioid subpopulation. Few diagnoses were more common in males, these included sex-specific conditions, diabetic neuropathy, and vascular claudication. Although pain conditions are common in older adults, diagnosis rates are elevated in those with opioid diagnoses. This impacts the educational needs of geriatricians, and other healthcare providers, and may indicate needs for more research in pain and aging.

Modular, well-defined, and robust hierarchical functional materials are targets of numerous synthesis endeavors. Covalent organic frameworks (COFs) are crystalline and porous materials with a vast chemical and structural diversity, and they are synthesized in a bottom-up approach from molecular building blocks by condensation polymerization reactions to form layered or spatial complex structures. Boronic-acid-containing building blocks were the first to be employed as monomers in the synthesis of COFs, setting the foundations for an exceedingly growing, exciting field of research. Here, an overview is provided on boronic-acid-derived COFs, including synthesis, building block design and mechanism of COF formation, structures and properties, processing and implementation into functional devices, as well as examples of application for which these materials have been studied.

Objectives: To examine whether physical activity (PA) was associated with fatigue, and quantify the extent of potential mediation through depressive symptoms or physical function (PF) on the relationship between PA and fatigue in symptomatic knee osteoarthritis (KOA).Method: This longitudinal study used data from the Multicenter Osteoarthritis Study (n=484), comprising subjects aged ≥50years. Baseline PA was quantified via an ankle-worn accelerometer. The outcome was fatigue, measured using a 0-10 rating scale at 2 year follow-up. Mediators included gait speed as a measure of PF and depressive symptoms at 2 year follow-up. Mediation analysis was carried out after adjustment for baseline confounders. Stratified analysis by baseline fatigue status [no/low (

We report the development of a microfluidic system capable of repeated infusions of anti-inflammatory factors post-implantation for use as a coating for neural probes. This system consists of a microchannel in a thin gelatin methacryloyl (GelMA)-polyethylene glycol (PEG) composite hydrogel surrounded by a porous polydimethylsiloxane (PDMS) membrane, where the hydrogel can be dried to increase the stiffness for easy insertion. Reswelling allowed us to perfuse interleukin (IL)-4 and dexamethasone (DEX) as anti-inflammatory factors through the channel with minimal burst release and significant amounts of IL-4 were observed to release for up to 96 hr post-infusion. Repeated injections of IL-4 increased the ratio of prohealing M2 versus proinflammatory M1 phenotypes of macrophages encapsulated in the hydrogel by six fold compared with a single injection, over a 2-week period. These repeated infusions also significantly downregulated the expression of inflammatory markers tumor necrosis factor (TNF)-α and IL-6 in astrocytes encapsulated in hydrogel. To demonstrate the system as a coating of neural probe for in vivo applications, we further fabricated a prototype device, where a thin dual-layered microfluidic system was integrated onto a metal probe. Such a drug delivery system could help reduce the formation of a glial scar around neural probes.

Summary Objective To examine the relation of pain sensitization to altered motor activity in knee OA as assessed by hamstrings muscle co-contraction during maximal effort knee extension. Design Medial, lateral, and overall hamstring co-contraction was assessed in the Multicenter Osteoarthritis (MOST) Study cohort using electromyography during isokinetic knee extension at 60°/second. Mechanical temporal summation of pain (TS) was assessed at the right wrist and pressure pain thresholds (PPT) were assessed at the patellae; PPTs were categorized into sex-specific tertiles. Muscle co-contraction was categorized into age- and sex-specific tertiles. We evaluated the relation of measures of sensitization to muscle co-contraction using a generalized logistic regression model. Results 1633 participants were included: mean age and BMI was 67.3 ± 7.7 years and 30.3 ± 5.6 kg/m2, respectively; 58% were female. Presence of TS was associated with higher overall (OR 1.3, 95% confidence interval (CI) (1.0–1.8)), medial (1.4 (1.0–1.9), and lateral (1.3 (1.0, 1.9)) hamstring co-contraction. The lowest PPT tertile (greater sensitivity) was associated with higher overall (1.5 (1.0, 2.3)) and medial (1.5 (1.0, 2.3)) hamstring co-contraction compared with those in the highest PPT tertile. Conclusion Greater pain sensitization, as assessed by presence of TS at the wrist and low patellar PPT, was associated with greater overall and medial hamstring co-contraction during knee extension. This provides support to the possibility that peripheral and/or central nervous system alterations may not only affect pain sensitivity, but also motor function.

A common problem of mid-air interaction is excessive arm fatigue, known as the "Gorilla arm" effect. To predict and prevent such problems at a low cost, we investigate user testing of mid-air interaction without real users, utilizing biomechanically simulated AI agents trained using deep Reinforcement Learning (RL). We implement this in a pointing task and four experimental conditions, demonstrating that the simulated fatigue data matches human fatigue data. We also compare two effort models: 1) instantaneous joint torques commonly used in computer animation and robotics, and 2) the recent Three Compartment Controller (3CC-) model from biomechanical literature. 3CC- yields movements that are both more efficient and relaxed, whereas with instantaneous joint torques, the RL agent can easily generate movements that are quickly tiring or only reach the targets slowly and inaccurately. Our work demonstrates that deep RL combined with the 3CC- provides a viable tool for predicting both interaction movements and user experiencein silico, without users.

An acute bout of physical activity and exercise can increase pain in individuals with chronic pain, but regular exercise is an effective treatment. This review will discuss these two dichotomous findings by summarizing studies in human and animal subjects. We will provide the data that supports the role of physical activity in modulating central nervous system excitability and inhibition, immune system function, and psychological constructs associated with pain. We show evidence that the sedentary condition is associated with greater excitability and less inhibition in both the central nervous system (brainstem inhibitory/facilitatory sites) and the immune system. We further show that exercise and regular physical activity decreases excitability and improves inhibition in both the central nervous system (brainstem inhibitory/facilitatory sites) and the immune system. We will then discuss the clinical implications of these findings, make recommendations for clinical application of exercise, and suggest future research directions.

This study aimed to test whether adding a rest recovery parameter, r, to the analytical three-compartment controller (3CC) fatigue model (Xia and Frey Law, 2008) will improve fatigue estimates during intermittent contractions. The 3CC muscle fatigue model uses differential equations to predict the flow of muscle between three muscle states: Resting (M(R)), Active (M(A)), and Fatigued (M(F)). This model uses a feedback controller to match the active state to target loads and two joint-specific parameters: F, fatigue rate controlling flow from active to fatigued compartments) and R, the recovery rate controlling flow from the fatigued to the resting compartments. This model does well to predict intensity-endurance time curves for sustained isometric tasks. However, previous studies find when rest intervals are present that the model over predicts fatigue. Intermittent rest periods would allow for the occurrence of subsequent reactive vasodilation and post-contraction hyperemia. We hypothesize a modified 3CC-r fatigue model will improve predictions of force decay during intermittent contractions with the addition of a rest recovery parameter, r, to augment recovery during rest intervals, representing muscle re-perfusion. A meta-analysis compiling intermittent fatigue data from 63 publications reporting decline in peak torque (% torque decline) were used for comparison. The original model over-predicted fatigue development from 19 – 29% torque decline; the addition of a rest multiplier significantly improved fatigue estimates to 6 – 10% torque decline. We conclude the addition of a rest multiplier to the three-compartment controller fatigue model provides a physiologically consistent modification for tasks involving rest intervals, resulting in improved estimates of muscle fatigue.

Quantifying pain intensity using a numerical rating scale is a well validated means for assessing the subjective perception of pain. A cognitive framework to interpret and characterize a concept is referred to as a schema. The schema used to conceptualize pain rating can vary, potentially through assimilation of new experiences and information. Thus, whether pain-rating schema differ systematically between those with chronic pain and pain-free individuals is unknown. Secondary analysis of a survey dataset were used to compare pain rating schema across individuals with various forms of chronic pain (n= 785) and pain-free adults (n=451). Schema were assessed using 6 items from the Pain Severity Questionnaire (Frey Law, et al 2014), as part of a larger study. Mean ratings (0 – 10 scale, allowing 0.5 intervals) for 2 common hypothetical pain conditions: mild, moderate, and severe headache and joint pain. Differences and percent reduction between severities were assessed between subgroups, based on type nad number of pain co-morbidities. Patients with FM, with or without multiple pain co-morbidities reported higher pain ratings than pain-free individuals across mild, moderate and severe conditions by approximately 1 out of 10 (p

We have shown people with fibromyalgia experience exacerbated pain in the exercising limb up to three days following submaximal isometric and concentric exercise however, the pain response following eccentric exercise has not been investigated. This study investigated the change in experimental pain up to two days following submaximal eccentric exercise while clinical pain was assessed through the 7-day recovery period in women with and without FM. Eighteen women with fibromyalgia (49.1±11.8yr, BMI: 31.4±7.6) and 18 controls (49.5±10.1yr, BMI: 27.1±4.8) completed session 1 (exercise) and session 2 (recovery assessment) separated by 2 days; session 1 included a 10-minute bout of submaximal (20% of maximal voluntary contraction) eccentric exercise with the right elbow flexors. Pressure pain thresholds (PPTs), mechanical pain summation, and punctate pain summation were assessed before, immediately after exercise, and in session 2. Clinical pain (0-10 NRS) in the exercising arm and whole-body was assessed before, during, immediately after, and up to seven days following the exercise bout. PPTs and mechanical pain summation did not change immediately following exercise or session 2 (Time, p>0.05). Punctate pain summation changed following exercise (Time x Summation, p=0.003) however, post hoc analysis did not reveal a significant difference immediately after exercise (p=0.296) or at session two (p=0.03). The fibromyalgia group reported greater increases in exercising arm pain during (Time x Group, p

Background The ankle is an important component of the human kinetic chain, and deficits in ankle strength can negatively impact functional tasks such as balance and gait. While peak torque is influenced by joint angle and movement velocity, ankle strength is typically reported for a single angle or movement speed. To better identify deficits and track recovery of ankle strength after injury or surgical intervention, ankle strength across a range of movement velocities and joint angles in healthy adults is needed. Thus, the primary goals of this study were to generate a database of strength values and 3-dimensional strength surface models for plantarflexion (PF) and dorsiflexion (DF) ankle strength in healthy men and women. Secondary goals were to develop a means to estimate ankle strength percentiles as well as examine predictors of maximal ankle strength in healthy adults. Methods Using an isokinetic dynamometer, we tested PF and DF peak torques at five joint angles (−10° [DF], 0° [neutral], 10° [PF], 20° [PF] and 30° [PF]) and six velocities (0°/s, 30°/s, 60°/s, 90°/s, 120°/s and 180°/s) in 53 healthy adults. These data were used to generate 3D plots, or “strength surfaces”, for males and females for each direction; surfaces were fit using a logistic equation. We also tested predictors of ankle strength, including height, weight, sex, and self-reported physical activity levels. Results Torque-velocity and torque-angle relationships at the ankle interact, indicating that these relationships are interdependent and best modeled using 3D surfaces. Sex was the strongest predictor of ankle strength over height, weight, and self-reported physical activity levels. 79 to 97 % of the variance in mean peak torque was explained by joint angle and movement velocity using logistic equations, for men and women and PF and DF directions separately. Conclusions The 3D strength data and surface models provide a more comprehensive dataset of ankle strength in healthy adults than previously reported. These models may allow researchers and clinicians to quantify ankle strength deficits and track recovery in patient populations, using angle- and velocity-specific ankle strength values and/or strength percentiles from healthy adults. Electronic supplementary material The online version of this article (doi:10.1186/s13047-016-0174-1) contains supplementary material, which is available to authorized users.

Objective It is not clear why some individuals develop pain with knee osteoarthritis (OA). We undertook this study to identify pain susceptibility phenotypes (PSPs) and their relationship to incident persistent knee pain (PKP) 2 years later. Methods We identified individuals free of PKP from the Multicenter Osteoarthritis Study, a longitudinal cohort of older adults with or at risk of knee OA. Latent class analysis was used to determine PSPs that may contribute to development of PKP apart from structural pathology. These included widespread pain, poor sleep, and psychological factors as well as pressure pain threshold and temporal summation (TS) as determined by quantitative sensory testing (QST). We used logistic regression to evaluate the association of sociodemographic factors with PSPs and the relationship of PSPs to the development of PKP over 2 years. Results A total of 852 participants were included (mean age 67 years, body mass index 29.5 kg/m2 , 55% women). Four PSPs were identified, primarily characterized by varying proportions (low/absent, moderate, or high) of the presence of pressure pain sensitivity and of facilitated TS, reflecting different measures of sensitization. Subjects in the PSP with a high proportion of pressure pain sensitivity and a moderate proportion of facilitated TS were twice as likely to develop incident PKP over 2 years (odds ratio 1.98 [95% confidence interval 1.07-3.68]) compared with subjects in the PSP having a low proportion of sensitization by both measures. Conclusion Four PSPs were identified, 3 of which were predominated by QST evidence of sensitization and 1 of which was associated with developing PKP 2 years later. Prevention or amelioration of sensitization may be a novel approach to preventing onset of PKP in OA.

A three-compartment controller model (3CC) predicts muscle fatigue development. Determination of fatigue (F) and recovery (R) model parameters is critical for model accuracy. Numerical methods can be used to determine parameter values using maximum voluntary contractions (MVCs) as input. We tested the effects of using reduced MVC data on parameter solutions using twenty published datasets of intermittent, isometric contractions. The work here examines three sampling variations using approximately half of the MVCs: MVC measurements distributed equally (dMVC), split between the initial and final times (sMVC), and only during the first half (fMVC). Furthermore, solved F and R parameters were used to model fatigue development for three hypothetical task scenarios. Both model parameters and predictions were statistically insensitive to measured data reduction using dMVC, followed closely by sMVC. However, using the fMVC reduction frequently resulted in overestimated parameter values and produced significantly larger prediction errors. We conclude that parameter solutions are robust when using fewer MVCs as long as they are sampled in a manner that captures later fatigue behavior.