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One of the most sensitive areas to climate change impacts are coastal-near and low-relief areas. While these coastal zones often are places of high population density and important infrastructure, they are also particularly exposed to multiple future climate change hazards such as sea level rise, intensified storm surges, rising groundwater and high-intense precipitation events. Thus, elevated risks of overbank spilling, dam breaks and flooding events are expected in a future climate in temperate wet regions such as Denmark. To mitigate and adapt to such elevated risks, prediction of future flooding events is vital, and here hydrological modelling is an essential tool. However, such impact evaluations are subject to a range of uncertainties such as emission, climate and sea level prediction uncertainties as well as impact model uncertainty.In this study, we investigate the uncertainties of predicted flooding from a river course and the groundwater system using a hydrodynamic model coupled with a 3D groundwater model. The model is forced with different climate scenarios and inputs from two different approaches of downscaled global sea level rise implemented using an indirect and direct bias correction procedure. The indirect procedure uses a simple delta change approach perturbing future climate and sea level change on observations, while the direct method uses bias-corrected climate model data, corresponding ocean model run data (for internal oceanic response to climate change), combined with global sea level change. This approach makes it possible to investigate the relative importance (sensitivity) of the flood prediction of sea level projection and bias correction procedure as well as the identification of past and future origin (surface or groundwater) of flooding events.

INTRODUCTION: Both educational attainment and genetic propensity to education (PGS Edu) have been associated with geographic mobility. Socioeconomic conditions are, in turn, associated with individuals' health. Geographic mobility could therefore lead to better health for some since it could provide better opportunities, like education. Our aim was to study how attained education and genetic predisposition for higher education are related to geographic mobility, and how they affect the association between geographic mobility and mortality. METHODS: We used data from the Swedish Twin Registry (twins born 1926-1955; n = 14,211) in logistic regression models to test if attained education and PGS Edu predicted geographic mobility. Cox regression models were then performed to test if geographic mobility, attained education, and PGS Edu were associated with mortality. RESULTS: The results show that both attained education and PGS Edu predicted geographic mobility, in both independent and joint effect models, with higher education associated with higher mobility. Geographic mobility was associated with lower mortality in the independent effect model, but joint effect models showed that this association was completely explained by attained education. CONCLUSIONS: To conclude, both attained education and PGS Edu were associated with geographic mobility. Moreover, attained education explained the relationship between geographic mobility and mortality.

Context Repetitive joint use is a risk factor for osteoarthritis, which is a leading cause of disability. Sports requiring a racket or bat to perform repetitive high-velocity impacts may increase the risk of thumb-base osteoarthritis. However, this hypothesis remains untested. Objective To determine if a history of participation in racket or bat sports was associated with the prevalence of thumb-base osteoarthritis. Design Descriptive epidemiologic study. Setting Four US clinical sites associated with the Osteoarthritis Initiative. Patients or Other Participants We recruited 2309 men and women from the community. Eligible participants had dominant-hand radiographic readings, hand symptom assessments, and historical physical activity survey data. Main Outcome Measure(s) A history of exposure to racket or bat sports (badminton, baseball or softball, racketball or squash, table tennis [or ping pong], tennis [doubles], or tennis [singles]) was based on self-reported recall data covering 3 age ranges (12–18, 19–34, and 35–49 years). Prevalent radiographic thumb-base osteoarthritis was defined as Kellgren-Lawrence grade >2 in the first carpometacarpal joint or scaphotrapezoidal joint at the Osteoarthritis Initiative baseline visit. Symptomatic thumb-base osteoarthritis was defined as radiographic osteoarthritis and hand or finger symptoms. Results Radiographic or symptomatic thumb-base osteoarthritis was present in 355 (34%) and 56 (5%), respectively, of men (total = 1049) and 535 (42%) and 170 (13%), respectively, of women (total = 1260). After adjusting for age, race, and education level, we found no significant associations between a history of any racket or bat sport participation and thumb-base osteoarthritis (radiographic or symptomatic; odds ratios ranged from 0.82 to 1.34). Conclusions In a community-based cohort, a self-reported history of participation in racket or bat sports was not associated with increased odds of having radiographic or symptomatic thumb-base osteoarthritis in the dominant hand.

Discharge data used to calibrate and evaluate hydrological models can be highly uncertain and this uncertainty affects the conclusions that we can draw from modelling results. We investigated the role of discharge data uncertainty and its representation in hydrological model calibration to give recommendations on methods to account for data uncertainty. We tested five different representations of discharge data uncertainty in calibrating the HBV-model for three Swiss catchments, ranging from using no information to using full empirical probability distributions for each time step. We developed a new objective function to include discharge data uncertainty, as quantified by these distributions directly in calibration to hydrological time series. This new objective function provided more reliable results than using no data uncertainty or multiple realizations of discharge time series. We recommend using the new objective function in combination with empirical or triangular distributions of the discharge data uncertainty.

To describe the prevalence, incidence, and progression of radiographic and symptomatic hand osteoarthritis (OA), and to evaluate differences according to age, sex, race, and other risk factors.Participants were assessed for radiographic and symptomatic hand OA at baseline and year 4 to determine incident disease. A modified Poisson regression with a robust variance estimator was used to account for clustering of joints within fingers within persons to estimate the prevalence ratios and relative risk estimates associated with participant characteristics.Among 3,588 participants, the prevalence of radiographic hand OA was 41.4%, and the prevalence of symptomatic hand OA was 12.4%. The incidence over 48 months was 5.6% for radiographic hand OA and 16.9% for symptomatic hand OA. Over 48 months, 27.3% of the participants exhibited OA progression. We found complex differences by age, sex, and race, with increasing rates of prevalent hand OA with older age in both men and women, but with rates of incident disease peaking at ages 55-64 years in women. Women had higher rates of symptomatic hand OA, but only nonsignificantly higher rates of incident radiographic hand OA, than men. Women more frequently had distal interphalangeal joint disease, while men more frequently had metacarpophalangeal joint OA. Black men and women had lower rates of hand OA than White participants, but Black men had higher rates of prevalent hand OA than Black women at younger ages.Hand OA is a heterogeneous disease with complex differences by age, sex, race, hand symptoms, and patterns of specific joints affected. Further research investigating the mechanisms behind these differences, whether mechanical, metabolic, hormonal, or constitutional, is warranted.

Loss of body armour, sometimes including a reduction in or loss of pelvic spines, is an adaptation observed in many isolated freshwater populations. Pelvic reduction in sticklebacks has previously been associated with recurrent, but variant, deletions within pelvic enhancer regions PelA and PelB, which regulate expression of the homeodomain transcription factor gene Pitx1. We investigated variation in nucleotide sequences of pelvic enhancers in sticklebacks collected from two small freshwater lakes in the same watercourse and a nearby marine site in subarctic Norway. Spineless, as well as asymmetrically spined and completely spined sticklebacks are present in the upper lake, while only specimens with complete spines are found at the other lake and the marine site. Observed variation at PelA between the three sites was mainly due to variable numbers of repeats at three fragile TG-repeat loci. The length of PelA, mainly at one of the TG-repeat loci, was consistently shorter among individuals in the upper lake compared with specimens from the two other sites. However, no obvious association was revealed between enhancer variants and pelvic status. No polymorphism was found at PelB. Thus, additional genetic factors and/or environmental cues need to be identified to fully explain the occurrence of pelvic reduction in sticklebacks in this lake.

The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article. CA extern

Objective: Osteoarthritis (OA) is a highly prevalent chronic condition. The subchondral bone plays an important role in onset and progression of OA making it a potential treatment target for disease-modifying therapeutic approaches. However, little is known about changes of periarticular bone mineral density (BMD) in OA and its relation to meniscal coverage and meniscal extrusion at the knee. Thus, the aim of this study was to describe periarticular BMD in the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort at the knee and to analyze the association with structural disease severity, meniscal coverage and meniscal extrusion. Design: Quantitative CT (QCT), MRI and radiographic examinations were acquired in 275 patients with knee osteoarthritis (OA). QCT was used to assess BMD at the femur and tibia, at the cortical bone plate (Cort) and at the epiphysis at three locations: subchondral (Sub), mid-epiphysis (Mid) and adjacent to the physis (Juxta). BMD was evaluated for the medial and lateral compartment separately and for subregions covered and not covered by the meniscus. Radiographs were used to determine the femorotibial angle and were evaluated according to the Kellgren and Lawrence (KL) system. Meniscal extrusion was assessed from 0 to 3. Results: Mean BMD differed significantly between each anatomic location at both the femur and tibia (p < 0.001) in patients with KL0. Tibial regions assumed to be covered with meniscus in patients with KL0 showed lower BMD at Sub (p < 0.001), equivalent BMD at Mid (p = 0.07) and higher BMD at Juxta (p < 0.001) subregions compared to regions not covered with meniscus. Knees with KL2-4 showed lower Sub (p = 0.03), Mid (p = 0.01) and Juxta (p < 0.05) BMD at the medial femur compared to KL0/1. Meniscal extrusion grade 2 and 3 was associated with greater BMD at the tibial Cort (p < 0.001, p = 0.007). Varus malalignment is associated with significant greater BMD at the medial femur and at the medial tibia at all anatomic locations. Conclusion: BMD within the epiphyses of the tibia and femur decreases with increasing distance from the articular surface. Knees with structural OA (KL2-4) exhibit greater cortical BMD values at the tibia and lower BMD at the femur at the subchondral level and levels beneath compared to KL0/1. BMD at the tibial cortical bone plate is greater in patients with meniscal extrusion grade 2/3.

Objective: Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to investigate these correlations, and to explore the influence of different factors that could contribute to longitudinal differences between the two methods. Methods: The current study included 178 participants with medial osteoarthritis (OA) out of the 297 knee OA participants enrolled in the IMI-APPROACH cohort. Changes over 2 years in medial JSW (delta JSWmed), minimum JSW (delta JSWmin), and medial femorotibial cartilage thickness (delta MFTC) were assessed using linear regression, using measurements from radiographs and MRI acquired at baseline, 6 months, and 1 and 2 years. Pearson R correlations were calculated. The influence of cartilage quality (T2 mapping), meniscal extrusion (MOAKS scoring), potential pain-induced unloading (difference in knee specific pain scores), and increased loading (BMI) on the correlations was analyzed by dividing participants in groups based on each factor separately, and comparing correlations (slope and strength) between groups using linear regression models. Result: Correlations between delta MFTC and delta JSWmed and delta JSWmin were statistically significant (p < 0.004) but weak (R < 0.35). Correlations were significantly different between groups based on cartilage quality and on meniscal extrusion: only patients with the lowest T2 values and with meniscal extrusion showed significant moderate correlations. Pain-induced unloading or BMI-induced loading did not influence correlations.Conclusions: While the amount of loading does not seem to make a difference, weight-bearing radiographic JSW changes are a better reflection of non-weight-bearing MRI cartilage thickness changes in knees with higher quality cartilage and with meniscal extrusion.

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40–64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI. Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGSBMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGSBMI, respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGSBMI. Results were similar when obesity was measured in late-life, but suffered from low power. Interpretation: Obesity was associated with CVD regardless of PGSBMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGSBMI, still influence the associations. Funding: The Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman's Foundation; Foundation for Geriatric Diseases at Karolinska Institutet; the Swedish Research Council for Health, Working Life and Welfare; the Swedish Research Council; and the National Institutes of Health. CC BY 4.0© 2023 The Author(s)Corresponding author: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-1177 Stockholm, Sweden.E-mail address: ida.karlsson@ki.se (I.K. Karlsson).This work was supported by the Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman’s Foundation (2022-01222); Foundation for Geriatric Diseases at Karolinska Institutet (2022-01296); the Swedish Research Council for Health, Working Life and Welfare (2018-01201 and 2022-00672); the Swedish Research Council (2016-03081); and the National Institutes of Health (R01 AG060470). We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641. The STR sub-studies were supported by the National Institutes of Health (grants R01 AG10175, R01 AG08724, R01 AG08861, R01 AG028555, and U01 DK066134), the MacArthur Foundation Research Network on Successful Aging, the Axel and Margaret Ax:son Johnsons Foundation, the Swedish Research Council, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Council for Working Lifeand Social Research (2013-2292).

In this study, we propose a novel framework that utilizes deep learning (DL) and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of seven years. This study included subjects (1832 subjects, 3276 knees) from the baseline of the MOST study. PF joint regions-of-interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end DL method was developed for predicting PFOA progression based on imaging data in a 5-fold cross-validation setting. A set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, BMI and WOMAC score, and the radiographic osteoarthritis stage of the tibiofemoral joint (KL score). Finally, we trained an ensemble model using both imaging and clinical data. Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an AUC of 0.856 and AP of 0.431; slightly outperforming the deep learning approach without attention (AUC=0.832, AP= 0.4) and the best performing reference GBM model (AUC=0.767, AP= 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP=0.447), although the clinical significance of this minor performance gain remains unknown. This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

The mass transfer of gas–liquid systems is commonly reported through the volumetric mass transfer coefficient, , which is a function of several complex phenomena. To optimize the rate of mass transfer, increased knowledge about the individual effects of the interfacial area, a, and the liquid-side mass transfer coefficient, , on is necessary. In this study, was measured by monitoring the dissolved oxygen concentration in a bubble column. The bubble flows were recorded by a photographic method and the images were analyzed by means of artificial neural network to determine the bubble size. The effects of rheology, superficial gas velocity, and gas sparger design were analyzed. decreased with an increase in the superficial gas velocity and with an increase in the viscosity. The relative change in a was much larger compared to the relative change in , and hence, for the investigated operational conditions and liquid solutions, the change in was mainly attributed to the change in a. Bubble clusters were formed in the non-Newtonian solutions but for the given operating conditions and liquid solutions, the bubble cluster formation did not have a prominent effect on the mass transfer.

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/., Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories.

To determine the associations between Black race and the presence of radiographic, symptomatic, and clinical hand osteoarthritis (OA).Using available hand radiographs from the Osteoarthritis Initiative cohort (total 4,699; n = 849 Black subjects [18.1%], n = 3,850 non-Black subjects [81.9%]), a propensity score-matching method was used to match Black subjects with non-Black subjects for known potential risk factors of hand OA (age, sex, body mass index, smoking status, cardiovascular disease, osteoporosis, excessive occupation- or recreation-related hand use, and knee OA). Posteroanterior radiographs of subjects' dominant hands were reviewed by a musculoskeletal radiologist in a blinded manner. To assess the severity of hand OA, the modified Kellgren/Lawrence (K/L) radiographic OA scoring scale (grades 0-4) was used, and the presence of erosive OA in the hand joints was recorded. Associations between race and the severity of hand OA (measured as the summed modified K/L grade), presence of radiographic hand OA (modified K/L grade ≥2), presence of erosive hand OA, presence of symptomatic hand OA (radiographic OA with hand pain), and presence of clinical hand OA (indicated by clinical findings of Heberden's nodes in the hands) were studied using regression models. In these models, beta coefficients or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated for the associations between Black race and any of these radiographic and symptomatic hand OA phenotypes.Black subjects had less severe hand OA (β = -1.93 [95% CI -2.53, -1.34]), as well as a lower risk of developing radiographic hand OA (OR 0.79 [95% CI 0.66, 0.94]), erosive hand OA (OR 0.23 [95% CI 0.11, 0.47]), symptomatic hand OA (OR 0.63 [95% CI 0.49, 0.82]), and clinical hand OA (OR 0.49 [95% CI 0.41, 0.60]), as compared to non-Black subjects.In contrast to the well-established association between Black race and knee or hip OA, the findings of this study suggest that the risk of hand OA is lower in Black subjects compared to non-Black subjects, which is not mediated by known hand OA risk factors. Future studies are warranted to determine the mediating protective factors for hand OA among Black subjects.

This study explores the subjective experiences of dyspareunia among queer women in Sweden. Ten semi-structured, in-depth interviews were conducted with five participants who were all interviewed on two separate occasions. Interviews were analyzed using thematic analysis (Braun & Clarke, 2006). Dyspareunia was described as affecting the participants’ sexual activities, intimate relationships, and identity constructs. Reported struggles involved feelings of sadness, guilt, frustration, and fear of pain. Dyspareunia was described as threatening the participants’ queer identities through its effect on their ability to be sexual in idealized ways. However, queer experiences and communities were also found to be associated with advantages in pain management, such as well-developed sexual communication skills, anatomic similarity to their partner, access to non-heteronormative sexual scripts and a focus on nurturing desire. Queer related advantages in pain management are proposed to buffer to some extent against pain interference with sexual function and desire. Findings indicate that it is important to consider the unique relational and social context of queer women to understand their experiences of dyspareunia. More research is needed on the role of differences of normativities, context and communication in dyspareunia.

Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated.

The paper analyses the national DK-model Hydrological Information and Prediction (HIP) system and HIP portal viewed as a ‘Digital Twin’ and how the introduction of real-time dynamic updating of the DK-model HIP simulations can give room for plug-in sub-models with real-time boundary conditions made available from a HIP portal. The possible feedback to a national real-time risk knowledge base during extreme events (flooding and drought) is also discussed. Under climate change conditions, Denmark is likely to experience more rain in winter, more evapotranspiration in summer, intensified cloudbursts, drought, and sea level rise. These challenges have been addressed as part of the Joint Governmental Digitalization Strategy 2016-2020 for better use and sharing of public data about the terrain, water, and climate to support climate adaptation, water management, and disaster risk reduction. This initiative included the development of a new web-based data portal (HIP portal) developed by the Danish Agency for Data Supply and Infrastructure (SDFI). GEUS delivered 5 terra-byte of hydrological model data to the portal with robust calibration methods and hybrid Machine Learning (ML) being key parts of the deliverables. The paper discusses the challenges and potentials of further developing the HIP Digital Twin with ‘plug-in Digital Twins’ for local river basins including feedback to the national level.

Background The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period. Methods MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition. Results Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee). Conclusions A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. Trial Registration Clinicaltrials.gov identification: NCT03883568.

Phages Cassita and Fransoyer were isolated from soil in northwestern Wisconsin using Microbacterium paraoxydans as the host. The genomes of Cassita and Fransoyer are 61,868 bp and 62,277 bp, respectively, with direct terminal repeats. Both phages exhibit siphoviral morphology and are predicted to have lytic life cycles.

Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated.

Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to investigate these correlations, and to explore the influence of different factors that could contribute to longitudinal differences between the two methods.The current study included 178 participants with medial osteoarthritis (OA) out of the 297 knee OA participants enrolled in the IMI-APPROACH cohort. Changes over 2 years in medial JSW (ΔJSWmed), minimum JSW (ΔJSWmin), and medial femorotibial cartilage thickness (ΔMFTC) were assessed using linear regression, using measurements from radiographs and MRI acquired at baseline, 6 months, and 1 and 2 years. Pearson R correlations were calculated. The influence of cartilage quality (T2 mapping), meniscal extrusion (MOAKS scoring), potential pain-induced unloading (difference in knee-specific pain scores), and increased loading (BMI) on the correlations was analyzed by dividing participants in groups based on each factor separately, and comparing correlations (slope and strength) between groups using linear regression models.Correlations between ΔMFTC and ΔJSWmed and ΔJSWmin were statistically significant (p 0.004) but weak (R 0.35). Correlations were significantly different between groups based on cartilage quality and on meniscal extrusion: only patients with the lowest T2 values and with meniscal extrusion showed significant moderate correlations. Pain-induced unloading or BMI-induced loading did not influence correlations.While the amount of loading does not seem to make a difference, weight-bearing radiographic JSW changes are a better reflection of non-weight-bearing MRI cartilage thickness changes in knees with higher quality cartilage and with meniscal extrusion.

Funding Information: Open access funding provided by Università degli Studi di Palermo within the Nicola Veronese reports personal fees from IBSA, Mylan, and Fidia outside of the submitted work. Cyrus Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB outside of the submitted work. Jean-Yves Reginster reports CRUI-CARE Agreement. Funding Information:grants from IBSA-Genevrier, Mylan, CNIEL, and Radius Health (through his institution); consulting fees from IBSA-Genevrier, Mylan, CNIEL, Radius Health, and Pierre Fabre; fees for participation in review activities from IBSA-Genevrier, Mylan, CNIEL, Radius Health, and Teva; and payment for lectures from Ag-Novos, CERIN, CNIEL, Dairy Research Council (DRC), Echolight, IBSA-Genevrier, Mylan, Pfizer Consumer Health, Teva, and Theramex outside of the submitted work. Olivier Bruyère reports grants or lecture fees from Amgen, Aptissen, Biophytis, IBSA, MEDA, Mylan, Novartis, Sanofi, Servier, SMB, TRB Chemedica, UCB, and Viatris outside of the submitted work. Ali Mobasheri declares personal fees from Abbott, Abbvie, Achē Laboratórios Farmacêuticos, Galapagos, GSK Consumer Healthcare, Kolon TissueGene, Laboratoires Expansciences, Merck, Pacira Biosciences, Pfizer, Sanofi, and Servier. François Rannou reports grants or lecture fees from Pierre Fabre, Mylan, MSD, Thuasne, IBSA, Pfizer, Genévrier, Expanscience, Scarcell, Skindermic, and Peptinov. Ida K. Haugen reports grants from Pfizer and is a consultant for Novartis outside of the submitted work. Elaine M. Dennison declares grants/fees from Pfizer, Lilly, UCB, and Viatris. Philip G. Conaghan is supported in part by the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (the views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health), and reports consultancies or lecture fees from AbbVie, Amgen, AstraZeneca, Eli Lilly, Galapagos, GSK, Grunenthal, Pfizer, Novartis, and UCB. Nasser M. Al-Daaghri, Antonella Fioravanti, Sara Cheleschi, Jean-Pierre Pelletier, Maarten de Wit, Etienne Cavalier, Radmila Matijevic, Germain Honvo, Régis Pierre Radermecker, René Rizzoli, Jaime Branco, Andrea Laslop, María Concepción Prieto Yerro, Alberto Migliore, Gabriel Herrero-Beaumont, and Nicholas R. Fuggle declare that they have no conflicts of interest. Publisher Copyright: © 2022, The Author(s). Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories. publishersversion published

In this review, we highlight the important role of the clinical electrodiagnostic (EDX) evaluation after cervical spinal cord injury (SCI). Our discussion focuses on the need for timely, frequent, and accurate EDX evaluations in the context of nerve transfer surgery to restore critical upper limb functions, including elbow extension, hand opening, and hand closing. The EDX evaluation is crucial to define the extent of lower motor neuron lesions and determine candidacy for surgery. We also discuss the important role of the postoperative EDX evaluation in determining prognosis and supporting rehabilitation. We propose a practical framework for EDX evaluation in this clinical setting.

Objective To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA). Methods The Outcome Measures in Rheumatology Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with 6 sonographers testing inflammatory and structural features in 12 hand OA patients. We used Cohen's kappa for intrareader and Light's kappa for interreader reliability for all features except PD, in which prevalence-adjusted bias-adjusted kappa (PABAK) was applied. Percentage agreement was also assessed. Results The web-based reliability exercise demonstrated substantial intra- and interreader reliability for all inflammatory features (kappa > 0.64). In the patient-based exercise, intra- and interreader reliability, respectively, varied: SH kappa = 0.73 and 0.45; JE kappa = 0.70 and 0.55; PD PABAK = 0.90 and 0.88; PIP joint cartilage kappa = 0.56 and 0.45; and STT osteophytes kappa = 0.62 and 0.36. Percentage close agreement was high for all features (>85%). Conclusion With ultrasound, substantial to excellent intrareader reliability was found for inflammatory features of hand OA. Interreader reliability was moderate, but overall high close agreement between readers suggests that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less reliability and the latter is not endorsed.

Vulvodynia is common and has an immense impact on affected women and their partners. Psychological factors have been found to contribute to pain maintenance and exacerbation, and treatments addressing psychological factors have yielded positive results. This study employed a replicated single-case experimental design to examine a cognitive behavioral therapy (CBT) group treatment with partner involvement in vulvodynia. Repeated measures of pain intensity related to pain-inflicting behaviors were collected weekly throughout baseline and treatment phases. Associated outcomes were measured pre-, post- and at two follow-up assessments. Participants were 18-45-year-old women, in a stable sexual relationship with a man, experiencing vulvodynia. Five women completed the treatment consisting of 10 group sessions and 3 couple sessions. Data were analyzed through visual inspection and supplementary nonparametric calculations. The study showed promising results of the CBT treatment in alleviating pain intensity in connection to specific pain-inflicting behavior since three out of five participants showed improvements. For the participants who improved, sexual function, pain catastrophizing, avoidance, and endurance behavior changed during treatment and were maintained at follow-ups. These results warrant further study of the CBT treatment, in larger, and controlled formats.

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer's disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast "resilient" unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.

OBJECTIVE To compare levels of grip strength in individuals with hand osteoarthritis (OA) with normative values, and to examine how hand OA severity and other biopsychosocial factors are associated with grip strength. METHODS Levels of grip strength across age groups were compared with normative values from the general population in sex-stratified analyses using 2-sample t-tests. Associations between radiographic hand OA severity (Kellgren/Lawrence sum score) in different joint groups and grip strength of the same hand were examined in 300 individuals from the Nor-Hand study using linear regression. Analyses were repeated using markers of pain, demographic factors, comorbidities, and psychological and social factors as independent variables. We adjusted for age, sex, and body mass index. RESULTS Individuals with hand OA had lower grip strength than the general population, especially in individuals age

Systematic scoping review The purpose of this study was to understand the barriers to accessing upper extremity (UE) reconstructive surgery among those living with tetraplegia, and to identify gaps in knowledge. Using standardized scoping review methods, a literature search was conducted using four databases and 1069 articles were procured. Two independent reviewers systematically screened the articles in two phases. Retrieved articles underwent thematic analysis using a constructivist grounded theory methodology. The reviewed articles (n = 25) were published between 2002 and 2019, and study designs included: cross-sectional (64%), retrospective (16%), and review articles (8%). Common barriers to UE reconstruction were categorized into factors related to patients, providers, and systems. These general domains included lack of awareness of UE reconstruction and its benefits among people with tetraplegia and providers, poor interdisciplinary working relationships, and a lack of specialized centers that provide these reconstructive surgeries. Specific patient-related barriers related to intrinsic (coping skills, trust, fear) and extrinsic (support network, finances, postoperative course) factors that influenced decision-making. There are many barriers that prevent individuals with tetraplegia from accessing surgery at different levels of the healthcare system. Establishing specialized centers with strong interdisciplinary working relationships and raising awareness about the advantages and disadvantages of UE reconstruction through peer networks may help to improve accessibility. Using a value-based, patient-centered approach by exploring how individuals with SCI weigh each decision factor when considering surgery may help providers develop treatment options that better align with their goals.

Objectives The IMI-APPROACH knee osteoarthritis study used machine learning (ML) to predict structural and/or pain progression, expressed by a structural (S) and pain (P) predicted-progression score, to select patients from existing cohorts. This study evaluates the actual 2-year progression within the IMI-APPROACH, in relation to the predicted-progression scores. Methods Actual structural progression was measured using minimum joint space width (minJSW). Actual pain (progression) was evaluated using the Knee injury and Osteoarthritis Outcomes Score (KOOS) pain questionnaire. Progression was presented as actual change (Δ) after 2 years, and as progression over 2 years based on a per patient fitted regression line using 0, 0.5, 1 and 2-year values. Differences in predicted-progression scores between actual progressors and non-progressors were evaluated. Receiver operating characteristic (ROC) curves were constructed and corresponding area under the curve (AUC) reported. Using Youden’s index, optimal cut-offs were chosen to enable evaluation of both predicted-progression scores to identify actual progressors. Results Actual structural progressors were initially assigned higher S predicted-progression scores compared with structural non-progressors. Likewise, actual pain progressors were assigned higher P predicted-progression scores compared with pain non-progressors. The AUC-ROC for the S predicted-progression score to identify actual structural progressors was poor (0.612 and 0.599 for Δ and regression minJSW, respectively). The AUC-ROC for the P predicted-progression score to identify actual pain progressors were good (0.817 and 0.830 for Δ and regression KOOS pain, respectively). Conclusion The S and P predicted-progression scores as provided by the ML models developed and used for the selection of IMI-APPROACH patients were to some degree able to distinguish between actual progressors and non-progressors. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03883568.

Mortality increases nearly 5-fold in the approximately 5% of patients who develop sternal wound complications after cardiothoracic surgery. Flap-based reconstruction can improve outcomes by providing well-vascularized soft tissue for potential space obliteration, antibiotic delivery, and wound coverage; however, reoperation and readmission rates remain high. This study used the high case volume at a tertiary referral center and a diverse range of reconstructive approaches to compare various types of flap reconstruction. Combined (pectoralis and rectus abdominis) flap reconstruction is hypothesized to decrease sternal wound complication-related adverse outcomes.A retrospective cohort study of consecutive adult patients treated for cardiothoracic surgery sternal wound complications between 2008 and 2018 was performed. Patient demographics, comorbidities, wound characteristics, surgical parameters, and perioperative data were collected. Multivariable regression modeling with stepwise forward selection was used to characterize predictive factors for sternal wound-related readmissions and reoperations.In total, 215 patients were assessed for sternal wound reconstruction. Patient mortality at 1 year was 12.4%. Flap selection was significantly associated with sternal wound-related readmissions (P = .017) and reoperations (P = .014). Multivariate regression demonstrated rectus abdominis flap reconstruction independently predicted increased readmissions (odds ratio 3.4, P = .008) and reoperations (odds ratio 2.9, P = .038). Combined pectoralis and rectus abdominis flap reconstruction independently predicted decreased readmissions overall (odds ratio 0.4, P = .031) and in the deep sternal wound subgroup (odds ratio 0.1, P = .033).Although few factors can be modified in this complex highly comorbid population with a challenging and rare surgical problem, consideration of a more surgically aggressive multiflap reconstructive approach may be justified to improve outcomes.

STUDY DESIGN: Case Series. OBJECTIVES: To describe the donor activation focused rehabilitation approach (DAFRA) in the setting of the hand closing nerve transfers in cervical spinal cord injury (SCI) so that therapists may apply it to treatment of individuals undergoing this procedure. SETTING: United States of America—Academic Level 1 Trauma Center. METHODS: We reviewed the records of individuals with cervical SCI who underwent nerve transfer to restore hand closing and post-surgery DAFRA therapy at our institution. The three post-surgery phases of DAFRA included (1) early phase (0–12 months) education, limb preparation, and donor activation exercises, (2) middle phase (12–24 months) volitional recipient muscle activation and (3) late phase (18 + months) strengthening and incorporation of motion in activities of daily living. RESULTS: Subtle gains in hand closing were first observed at a mean of 8.4 months after hand closing nerve transfer surgery. Remarkable improvements including discontinuation of assistive devices, independence with feeding and urinary function, and measurable grip were observed. Function continued to improve slowly for one to two more years. CONCLUSIONS: A deliberate, slow-paced (monthly for >2 years post-surgery) and incremental therapy program—DAFRA—can be used to improve outcomes after nerve transfer to restore hand closing in cervical SCI. SPONSORSHIP: This work was made possible by funding from the Craig H. Neilsen Foundation Spinal Cord Injury Research on the Translation Spectrum (SCIRTS) Grant: Nerve Transfers to Restore Hand Function in Cervical Spinal Cord Injury (PI: Ida Fox).

Body mass index (BMI) is associated with cognitive abilities, but the nature of the relationship remains largely unexplored. We aimed to investigate the bidirectional relationship from midlife through late-life, while considering sex differences and genetic predisposition to higher BMI. We used data from 23,892 individuals of European ancestry from the Health and Retirement Study, with longitudinal data on BMI and three established cognitive indices: mental status, episodic memory, and their sum, called total cognition. To investigate the dynamic relationship between BMI and cognitive abilities, we applied dual change score models of change from age 50 through 89, with a breakpoint at age 65 or 70. Models were further stratified by sex and genetic predisposition to higher BMI using tertiles of a polygenic score for BMI (PGSBMI). We demonstrated bidirectional effects between BMI and all three cognitive indices, with higher BMI contributing to steeper decline in cognitive abilities in both midlife and late-life, and higher cognitive abilities contributing to less decline in BMI in late-life. The effects of BMI on change in cognitive abilities were more evident in men compared to women, and among those in the lowest tertile of the PGSBMI compared to those in the highest tertile, while the effects of cognition on BMI were similar across groups. In conclusion, these findings highlight a reciprocal relationship between BMI and cognitive abilities, indicating that the negative effects of a higher BMI persist from midlife through late-life, and that weight-loss in late-life may be driven by cognitive decline. CC BY 4.0Correspondence and requests for materials should be addressed to I.K.K. ida.karlsson@ki.se

Objectives To investigate whether Fluorescence Optical Imaging (FOI) enhancement and MRI-defined synovitis are associated with pain and physical function in hand OA patients. Methods Bilateral FOI scans and MRI of the dominant hand were available for 221 patients. Finger joints were examined for tenderness on palpation. Pain in individual finger joints during the last 24 h and last 6 weeks and hand pain intensity by the Australian/Canadian hand index and Numeric Rating Scale were self-reported. On joint level, we applied logistic regression with generalized estimating equations to examine whether FOI enhancement and MRI-defined synovitis were associated with pain in the same joint. On subject level, we applied linear regression to assess whether FOI and MRI sum scores were associated with pain intensity and physical function. Results Metacarpophalangeal and thumb base joints were excluded from analyses due to little/no FOI enhancement. Finger joints with FOI enhancement on the composite image had higher odds (95% CI) of pain during the last 6 weeks [grade 1: 1.4 (1.2–1.6); grade 2–3: 2.1 (1.7–2.6)]. Similar results were found for joint pain during the last 24 h and joint tenderness in fingers. Numerically stronger associations were found between MRI-defined synovitis and finger joint pain/tenderness. FOI and MRI sum scores demonstrated no/weak associations with hand pain and physical function. Conclusion FOI enhancement and MRI-defined synovitis were associated with pain in the same finger joint. None of the imaging modalities demonstrated consistent associations with pain, stiffness and physical function on subject level.

This study contributes to the conceptualization of a sustainable circular business model (CBM), the application of the circular economy (CE) by companies. The study utilized a three‐level framework adapted from the CE literature with company (micro), supply chain (meso) and society (macro) levels. This multiple‐case study in the textile industry included two types of companies operating in the CE: companies founded on the sustainable principles of a CE (natives) and companies transitioning to a CE from the linear economy (adopters). The findings show that the adopters emphasized long‐term economic sustainability on a company level and implemented CE elements to varying degrees on all three levels. The natives pursued business decisions from environmental and social sustainability standpoints, and the three levels were integral in their systemic approach to a CE. The study highlights two key claims: established operational structures and economic volition hindered adopters in their systemic CE implementation, and an integral part of the CBM for natives was a proactive approach towards the society level.

OBJECTIVE To explore whether ultrasound-detected gray-scale synovitis and power Doppler activity in the interphalangeal and first carpometacarpal (CMC1) joints are associated with pain and physical function in patients with hand osteoarthritis (OA). METHODS A total of 290 patients with hand OA underwent an ultrasound examination of the bilateral interphalangeal and CMC1 joints. Using logistic regression analyses with generalized estimating equations, we examined whether grade 0-3 gray-scale synovitis and power Doppler activity were associated with pain in the same joint. Using linear regression analyses, we examined whether the degree of inflammation was associated with numeric rating scale and Australian/Canadian (AUSCAN) Osteoarthritis Hand Index hand pain, AUSCAN physical function, and grip strength scores. Analyses were made separately for interphalangeal and CMC1 joints, and adjusted for age, sex, body mass index, psychosocial factors, use of analgesics, and presence of osteophytes. RESULTS At joint level, increasing gray-scale synovitis severity was associated with higher odds of pain upon palpation in both the interphalangeal (grade 2-3; odds ratio [OR] 3.17 [95% confidence interval (95% CI) 2.35, 4.28]) and CMC1 joints (grade 2-3; OR 4.40 [95% CI 2.10, 9.24]). Similar associations were found for power Doppler activity and joint pain in the previous 24 hours and 6 weeks. Power Doppler activity in CMC1 was also related to overall hand pain/physical function and lower grip strength. CONCLUSION Inflammation in both the interphalangeal and CMC1 joints was associated with pain in the same joint. However, associations with hand pain, reduced physical function, and lower grip strength were only present for inflammation in the CMC1 joints, suggesting that lowering CMC1 inflammation is an important treatment target.

Background We evaluated the effectiveness of a simple, low-cost educational brochure in improving disposal rates of unused opioids after outpatient upper extremity surgery. Methods This cross-sectional study enrolled eligible adult patients from a peripheral nerve clinic between November 2017 and September 2018. Patients either received or did not receive the educational brochure, which outlined a simple method to dispose of unused opioids and completed a survey at 2 weeks after surgery. We compared the proportion of patients who disposed of unused opioids after surgery between the group that had received the brochure and the group that had not. Categorical data were analyzed with χ2 test, proportions data with binomial tests, and numerical data with Mann-Whitney U test, all with a significance level of P < .05. Results There were 339 survey respondents. Nineteen patients who did not meet inclusion criteria were excluded. Of the 320 remaining patients, 139 received the brochure and 181 did not. An additional 55 patients were excluded due to preoperative opioid use. Overall, 35.3% of recipients and 38.3% of those who did not receive the brochure used all of their prescribed opioid medication ( P = .625; confidence interval = −14.6%-8.8%). Among patients with unused opioid medication, a significantly higher proportion of brochure recipients disposed of the medicine compared with those who did not receive the brochure (46.7% vs 19.6%, P < .001). Conclusions Distribution of an educational brochure significantly improved disposal of unused opioids after surgery. This easily implemented intervention can improve disposal of unused opioids and ultimately decrease excess opioids available for diverted use in the community.

Differences in gene-wide DNA methylation of the Alzheimer’s disease (AD) associated genes BIN1, HLA-DRB5, SORL1, SLC24A4, and ABCA7 are reported to be associated with AD in post-mortem brain samples. We investigated whether the same associations could be found in leukocytes collected pre-mortem. Using cohort data of 544 Swedish twins (204 dementia diagnoses), we replicated the findings in HLA-DRB5 and SLC24A4 at p HLA-DRB5 and SLC24A4 are present in both neuronal cells and leukocytes, but may be influenced by familial factors.

Objective To examine the association of body mass index (BMI) with pain in people with hand osteoarthritis (OA), and explore whether this association, if causal, is mediated by systemic inflammatory biomarkers. Methods In 281 Nor-Hand study participants, we estimated associations between BMI and hand pain, as measured by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN; range 0–20) and Numerical Rating Scale (NRS; range 0–10); foot pain, as measured by NRS (range 0–10); knee/hip pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; range 0–20); painful total body joint count; and pain sensitization. We fit natural-effects models to estimate natural direct and natural indirect effects of BMI on pain through inflammatory biomarkers. Results Each 5-unit increase in BMI was associated with more severe hand pain (on average increased AUSCAN by 0.64 [95% confidence interval (95% CI) 0.23, 1.08]), foot pain (on average increased NRS by 0.65 [95% CI 0.36, 0.92]), knee/hip pain (on average increased WOMAC by 1.31 [95% CI 0.87, 1.73]), generalized pain, and pain sensitization. Mediation analyses suggested that the effects of BMI on hand pain and painful total body joint count were partially mediated by leptin and high-sensitivity C-reactive protein (hsCRP), respectively. Effect sizes for mediation by leptin were larger for the hands than for the lower extremities, and were statistically significant for the hands only. Conclusion In people with hand OA, higher BMI is associated with greater pain severity in the hands, feet, and knees/hips. Systemic effects of obesity, measured by leptin, may play a larger mediating role for pain in the hands than in the lower extremities. Low-grade inflammation, measured by hsCRP, may contribute to generalized pain in overweight/obese individuals.

[Abstract] Background: There are multiple measures for assessment of physical function in knee osteoarthritis (OA), but each has its strengths and limitations. The GaitSmart® system, which uses inertial measurement units (IMUs), might be a user-friendly and objective method to assess function. This study evaluates the validity and responsiveness of GaitSmart® motion analysis as a function measurement in knee OA and compares this to Knee Injury and Osteoarthritis Outcome Score (KOOS), Short Form 36 Health Survey (SF-36), 30s chair stand test, and 40m self-paced walk test. Methods: The 2-year Innovative Medicines Initiative-Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee OA cohort was conducted between January 2018 and April 2021. For this study, available baseline and 6 months follow-up data (n = 262) was used. Principal component analysis was used to investigate whether above mentioned function instruments could represent one or more function domains. Subsequently, linear regression was used to explore the association between GaitSmart® parameters and those function domains. In addition, standardized response means, effect sizes and t-tests were calculated to evaluate the ability of GaitSmart® to differentiate between good and poor general health (based on SF-36). Lastly, the responsiveness of GaitSmart® to detect changes in function was determined. Results: KOOS, SF-36, 30s chair test and 40m self-paced walk test were first combined into one function domain (total function). Thereafter, two function domains were substracted related to either performance based (objective function) or self-reported (subjective function) function. Linear regression resulted in the highest R2 for the total function domain: 0.314 (R2 for objective and subjective function were 0.252 and 0.142, respectively.). Furthermore, GaitSmart® was able to distinguish a difference in general health status, and is responsive to changes in the different aspects of objective function (Standardized response mean (SRMs) up to 0.74). Conclusion: GaitSmart® analysis can reflect performance based and self-reported function and may be of value in the evaluation of function in knee OA. Future studies are warranted to validate whether GaitSmart® can be used as clinical outcome measure in OA research and clinical practice. The research leading to these results have received support from the Innovative Medicines Initiative Joint Undertaking under Grant Agreement n° 115770, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. See www.imi.europa.eu and www.approachproject.eu. SM and FL are supported by the Dutch Arthritis Society This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.

Background: Diabetes is a well-established risk factor for severe digital infection, and patients are more likely to require digital amputation for adequate source control. This study aims to identify factors predictive of digital amputation compared with preservation in patients with diabetes who present with surgically treated finger infections. Methods: Current Procedural Terminology (CPT) and International Classification of Diseases Versions 9 and 10 (ICD-9/10) databases from a single academic medical center were queried to identify patients with type 1 or type 2 diabetes mellitus who underwent surgical treatment in the operating room for treatment of a digital infection from 2010 to 2020. Electronic medical records were reviewed to obtain historical and acute clinical variables at the time of hospital presentation. Bivariate and multivariable regression were used to identify factors associated with amputation. Results: In total, 145 patients (61 digital amputation, 84 digital preservation) met inclusion criteria for this retrospective cohort study. Mean hospital stay was 6 days, and the average patient underwent 2 operations. Multivariable analysis revealed that the presence of osteomyelitis, ipsilateral upper extremity dialysis fistula, end-stage renal disease, and vascular disease each had significant independent predictive value for amputation rather than digital preservation. Conclusions: Digital amputation is common in the setting of diabetic finger infection. The 4 variables found to independently predict the outcome of amputation can be understood as factors which decrease the likelihood of successful digital salvage and increase the potential consequence of ongoing uncontrolled infection. Further study should focus on clinical factors affecting surgical decision making and how the treatment rendered affects patient outcomes.

People with cervical spinal cord injury (SCI) identify improving upper extremity (UE) function as a top priority. In addition to comprehensive rehabilitation, UE surgeries, including nerve and tendon transfers, enhance function. However, barriers exist to disseminating information about surgical options to enhance UE function.To assess the experiences and preferences of people with cervical SCI and their caregivers in accessing information about surgery to enhance UE function.Prospective cohort study. Participants were followed up for 24 months and completed up to three interviews.Tertiary care at academic and affiliated Veterans Administration Health Care Centers.Adults with cervical SCI (n = 35) ages 18 to 80 years with mid-cervical SCI American Spinal Injury Association Impairment Scale A, B, or C (at least 6 months post-injury) and their caregivers (n = 23) were eligible to participate. Participants were enrolled in three groups: nerve transfer, tendon transfer, or no UE reconstructive surgery.Not applicable.Semi-structured interviews about surgical knowledge and experiences.Data were analyzed and three themes were identified. First, providing information about UE surgical options early post-injury was recommended. The acute or inpatient rehabilitation phases of recovery were the preferred times to receive surgical information. Second, challenges with information dissemination were identified. Participants learned about UE surgery through independent research, medical provider interactions, or peers. Third, peers were identified as valuable resources for SCI needs and surgical information.Following cervical SCI, information about UE reconstructive surgeries should be a standard component of education during rehabilitation. An increased understanding of the reconstructive options available to improve UE function is necessary to educate stakeholders. Future research is needed to support the development of strategies to effectively present surgical information to individuals with SCI and health care providers.