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SPECIFIC AIM: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research. METHODS: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research. RESULTS: While transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain. CONCLUSIONS: While significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

Abstract Background Individuals with Parkinson’s disease (PD) report a diminished perceived functional autonomy as their condition progresses. For those seeking emergency care, it is unknown whether the patient-physician relationship is instrumental in respecting patient autonomy. This study evaluated patient autonomy ideals in individuals with PD requiring emergency care and the perceived support for autonomy from emergency department physicians. Method Individuals with PD (n = 36, average age 78.1 years) were surveyed using the Ideal Patient Autonomy questionnaire (IPA) and the Health Care Climate Questionnaire (HCCQ). A multivariable regression analysis assessed whether patients’ Hoehn and Yahr stage and IPA questionnaire results predicted HCCQ items. Results The IPA questionnaire revealed that individuals with PD in need of emergency care emphasize the significance of medical expertise (IPA ‘doctor should decide’ theme 0.71) in decision-making and their desire to be fully informed about all potential risks (IPA ‘obligatory risk information’ theme 0.71). The average HCCQ values showed a decreasing trend across Hoehn and Yahr stages 1 to 5: 6.19, 6.03, 5.83, 5.80, and 5.23, respectively. HY scale values also influenced HCCQ items related to the physician’s role. Conclusion In our cohort, individuals with Parkinson’s disease tend to rely on medical expertise for decision-making and prioritize complete risk information during emergency care. However, this autonomy support diminishes as functional disability levels increase.

Abstract Dengue fever represents a significant medical and socio-economic burden in (sub)tropical regions, yet antivirals for treatment or prophylaxis are lacking. JNJ-A07 was described as highly active against the different genotypes within each serotype of the disease-causing dengue virus (DENV). Based on clustering of resistance mutations it has been assumed to target DENV non-structural protein 4B (NS4B). Using a photoaffinity labeling compound with high structural similarity to JNJ-A07, here we demonstrate binding to NS4B and its precursor NS4A-2K-NS4B. Consistently, we report recruitment of the compound to intracellular sites enriched for these proteins. We further specify the mechanism-of-action of JNJ-A07, which has virtually no effect on viral polyprotein cleavage, but targets the interaction between the NS2B/NS3 protease/helicase complex and the NS4A-2K-NS4B cleavage intermediate. This interaction is functionally linked to de novo formation of vesicle packets (VPs), the sites of DENV RNA replication. JNJ-A07 blocks VPs biogenesis with little effect on established ones. A similar mechanism-of-action was found for another NS4B inhibitor, NITD-688. In summary, we unravel the antiviral mechanism of these NS4B-targeting molecules and show how DENV employs a short-lived cleavage intermediate to carry out an early step of the viral life cycle.

Background and purpose: The low-dose EOS Imaging System is an emerging tool for 3-dimensional measurements in orthopedics. The clinical feasibility for measuring total hip arthroplasty (THA) liner wear has not yet been investigated. We aimed to evaluate the feasibility of using EOS to measure THA liner wear by examining the experimental accuracy using a THA phantom and clinical precision of patients with THA, considering a clinically relevant precision at the 95% repeatability limit to be 0.2 mm. Methods: An experimental THA phantom with movable stem and a fixed cup with a plastic liner was constructed to simulate progressive 3D liner wear. Series of 11 pairs of radiographs with 50 μm femoral movement in between were obtained for each 3D axis in EOS. 30 patients with a THA were scanned twice using EOS to assess precision. Model-based radiostereometric analysis (RSA) was used for wear measurement. Results: The mean difference (true minus simulated wear) with standard deviation (SD) and 95% limits of agreement for experimental THA wear were 0.005 (0.037) and [–0.069 to 0.079] mm for the vertical (y) axis. The mean (SD) and 95% repeatability limit for precision for clinical measurement were –0.029 (0.105) and 0.218 mm. Conclusion: Experimental THA liner wear using EOS was within clinically relevant tolerances and without bias. The clinical precision was just outside our defined clinically relevant precision. Compared with conventional RSA, EOS is less accurate and precise but may still be of value for certain clinical applications, provided larger sample size or longer follow-up are available.

Aims: Custom triflange acetabular components (CTACs) play an important role in reconstructive orthopaedic surgery, particularly in revision total hip arthroplasty (rTHA) and pelvic tumour resection procedures. Accurate CTAC positioning is essential to successful surgical outcomes. While prior studies have explored CTAC positioning in rTHA, research focusing on tumour cases and implant flange positioning precision remains limited. Additionally, the impact of intraoperative navigation on positioning accuracy warrants further investigation. This study assesses CTAC positioning accuracy in tumour resection and rTHA cases, focusing on the differences between preoperative planning and postoperative implant positions. Methods: A multicentre observational cohort study in Australia between February 2017 and March 2021 included consecutive patients undergoing acetabular reconstruction with CTACs in rTHA (Paprosky 3A/3B defects) or tumour resection (including Enneking P2 peri-acetabular area). Of 103 eligible patients (104 hips), 34 patients (35 hips) were analyzed. Results: CTAC positioning was generally accurate, with minor deviations in cup inclination (mean 2.7°; SD 2.84°), anteversion (mean 3.6°; SD 5.04°), and rotation (mean 2.1°; SD 2.47°). Deviation of the hip centre of rotation (COR) showed a mean vector length of 5.9 mm (SD 7.24). Flange positions showed small deviations, with the ischial flange exhibiting the largest deviation (mean vector length of 7.0 mm; SD 8.65). Overall, 83% of the implants were accurately positioned, with 17% exceeding malpositioning thresholds. CTACs used in tumour resections exhibited higher positioning accuracy than rTHA cases, with significant differences in inclination (1.5° for tumour vs 3.4° for rTHA) and rotation (1.3° for tumour vs 2.4° for rTHA). The use of intraoperative navigation appeared to enhance positioning accuracy, but this did not reach statistical significance. Conclusion: This study demonstrates favourable CTAC positioning accuracy, with potential for improved accuracy through intraoperative navigation. Further research is needed to understand the implications of positioning accuracy on implant performance and long-term survival. Cite this article: Bone Jt Open 2024;5(4):260–268.

Acacia mearnsii and Eucalyptus dunnii plantations play an important role in the South African economy as a source for a variety of wood products. However, these species are commonly associated with high evapotranspiration (ET) which may cause streamflow reduction, affecting downstream water users who are reliant on the stream for survival. The potential future increase in exotic plantations worldwide necessitates understanding the impact of these different species on the water balance, hence the streamflow. At the Two Streams research catchment in South Africa, intense hydrological observations (streamflow, ET and weather) have been conducted on A. mearnsii for almost two decades. In 2018, the catchment was clear-felled with subsequent replanting of E. dunnii and hydrological measurements continued. This provided an opportunity to present observations of the surface water balance of the catchment. However, gaps in the data at various times prevented a compilation of a continuous hydrological record. Therefore, three window periods, with complete records of streamflow, ET and precipitation, and with similar weather conditions, were compared. Only the interception loss (Il) was estimated using the Von Hoyningen-Huene method. First window, A. mearnsii trees were three years old (Amear3), second window, A. mearnsii trees were seven years old (Amear7) and the third window, E. dunnii trees were three years old (Edun3). Results indicated a negative catchment surface water balance for all window periods. During the Amear7 window period, the Il was highest compared to the young crops, which reduced effective precipitation, in turn contributing to the lowest measured streamflow. The negative surface water balance and high ET, suggests that trees were accessing water not quantified in the surface water balance. Crops of all three window periods were found to have the potential to significantly reduce the streamflow, which may in turn affect downstream water users. Further research using isotopes to trace the sources of water used by trees in the system is suggested.

Aseptic loosening is the leading cause for revision of total hip and total knee arthroplasties (THAs/TKAs) reported in national arthroplasty registries (1, 2). Aseptic loosening may have a multitude of causes including factors related to implant design, surgical technique, and genetic predisposition (3, 4, 5, 6, 7, 8, 9). For the implant-related causes, polymer, bone cement, and metal wear particles released due to repetitive motion of the joint can induce inflammation and osteolysis (10, 11, 12). The latter may differ between individuals due to reaction of the foreign body inflammatory response (4, 13). Other mechanisms influencing aseptic loosening such as stress shielding, micromotion, high fluid pressure, and endotoxins have been proposed as well (14, 15, 16, 17).

Pine plantations are the dominant species currently planted within the South African commercial forestry industry. Improvements in bio-economy markets for dissolving wood pulp products have seen an expansion in fast-growing Eucalyptus plantations due to their higher productivity rates and better pulping properties than pine. This has raised concerns regarding the expansion of Eucalyptus plantations and how they will affect water resources as they have been reported to have higher water use (quantified using transpiration rates) than pine. We measured transpiration rates (mm yr−1), diameter at breast height (quantified as quadratic mean diameter, Dq, m) and leaf area index of an 8-year-old Eucalyptus grandis × Eucalyptus nitens clonal hybrid (GN) and a 20-year-old Pinus elliottii. Transpiration rates were measured for two consecutive hydrological years (2019/20 and 2020/21) using a heat ratio sap-flow method, calibrated against a lysimeter. In the 2019/20 year, annual transpiration for P. elliottii exceeded GN by 28 %, while for the 2020/21 hydrological year, there was no significant difference between the transpiration of the two species, despite a 17 % and 21 % greater leaf area index for P. elliottii than GN in 2019/20 and 2020/21 measurement years respectively. Quadratic mean diameter increments were statistically similar (p > 0.05) in 2019/20, whereas the 2020/21 year produced significant differences (p). Tree transpiration is known to be influenced by climatic variables; therefore, a random forest regression model was used to test the level of influence between tree transpiration and climatic parameters. The soil water content, solar radiation and vapour pressure deficit were found to highly influence transpiration, suggesting these variables can be used in future water-use modelling studies. The profile water content recharge was influenced by rainfall events. After rainfall and soil profile water recharge, there was a rapid depletion of soil water by the GN trees, while the soil profile was depleted more gradually at the P. elliottii site. As a result, trees at the GN site appeared to be water stressed (reduced stem diameters and transpiration), suggesting that there was limited access to alternative water source (such as groundwater). The study concluded that previous long-term paired catchment studies indicate that eucalypts use more water than pine; however, periods of soil water stress and reduced transpiration observed in this study must be accommodated in hydrological models. Long-term total soil water balance studies are recommended in the same region to understand the long-term impact of commercial plantations on water resources.

Opening remarks: These guidelines are the result of discussions within a diverse group of RSA researchers. They were approved in December 2023 by the board and selected members of the International Radiostereometry Society to update the guidelines by Valstar et al. [1]. By adhering to these guidelines, RSA studies will become more transparent and consistent in execution, presentation, reporting, and interpretation. Both authors and reviewers of scientific papers using RSA may use these guidelines, summarized in the Checklist, as a reference. Deviations from these guidelines should have the underlying rationale stated.

Specific AimProvide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research.MethodsA team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research.ResultsWhile transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain.ConclusionsWhile significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

Background and purpose: Different marker-selection methods are applied to represent implant and tibial segments in radiostereometric analysis (RSA) studies of total knee arthroplasty (TKA). Either a consistent set of markers throughout subsequent RSA examinations (“consistent-marker method”) is used or all available markers at each follow-up (“all-marker method”). The aim of this secondary analysis was to compare marker-selection methods on individual and group level TKA migration results. Methods: Data from a randomized RSA study with 72 patients was included. Tibial baseplate migration was evaluated at 3 months, 1, 2, and 5 years postoperatively with both marker-selection methods. Additionally, migration was calculated using 5 fictive points, either plotted based on the consistent set of markers or all available markers. Results: Migration could be calculated with both marker-selection methods for 248 examinations. The same prosthesis and bone markers (n = 136), different prosthesis markers (n = 71), different bone markers (n = 21), or different prosthesis and bone markers (n = 20) were used. The mean difference in maximum total point motion (MTPM) between all examinations was 0.02 mm, 95% confidence interval –0.26 to 0.31 mm. 5 implants were classified as continuously migrating with the consistent-marker method versus 6 implants (same 5 plus one additional implant) with the all-marker method. Using fictive points, fewer implants were classified as continuously migrating in both marker-selection methods. Differences between TKA groups in mean MTPM were comparable with both marker-selection methods, also when fictive points were used. Conclusion: Estimated group differences in mean MTPM were similar between marker-selection methods, but individual migration results differed. The latter has implications when classifying implants for estimated risk of future loosening.

AbstractHepatorenal syndrome (HRS) is a diagnosis of exclusion defined as acute kidney injury (AKI) with cirrhosis and ascites, with serum creatinine unresponsive to standardized volume administration and diuretic withdrawal. Persistent intravascular hypovolemia or hypervolemia may contribute to AKI and be revealed by inferior vena cava ultrasound (IVC US), which may guide additional volume management. Twenty hospitalized adult patients meeting HRS-AKI criteria had IVC US to assess intravascular volume after receiving standardized albumin administration and diuretic withdrawal. Six had IVC collapsibility index (IVC-CI) ≥50% and IVCmax ≤0.7 cm suggesting intravascular hypovolemia, 9 had IVC-CI 0.7 cm suggesting intravascular hypervolemia, and 5 had IVC-CI ≥20% to 0.7 cm. Additional volume management was prescribed in the 15 patients with either hypovolemia or hypervolemia. After 4–5 days, serum creatinine levels decreased ≥20% without hemodialysis in 6 of 20 patients – 3 with hypovolemia received additional volume, and 2 with hypervolemia plus one with ‘euvolemia’ and dyspnea were volume restricted and received diuretics. In the other 14 patients, serum creatinine failed to persistently decrease ≥20% or hemodialysis was required indicating that AKI did not improve. In summary, fifteen of 20 patients (75%) were presumed to have intravascular hypovolemia or hypervolemia by IVC ultrasound. Six of the 20 patients (40%) improved AKI by 4-5 days of follow-up with additional IVC US-guided volume management, and thus had been misdiagnosed as HRS-AKI. IVC US may more accurately define HRS-AKI as being neither hypovolemic nor hypervolemic, and guide volume management, decreasing the frequency of HRS-AKI misdiagnosis.

Abstract Parkinson’s disease characteristics can create a self-perceived sense of stigmatization and disapproval by others, thereby affecting self-perceived autonomy. This study investigated the metaphors related to the loss of autonomy and stigma in stories and drawings of Parkinson’s disease. We compare a contemporary first-person illness narrative and -drawing from a person with Parkinson’s disease, with two novels (Jonathan Franzen’s The Corrections and Claudia Piñeiro’s Elena Knows), a graphic novel (Peter Dunlap-Shohl’s My Degeneration: A Journey Through Parkinson’s), a non-fiction book (Oliver Sacks’ Awakenings) and a first-person illness narrative (John Palfreman’s The Bright Side of Parkinson’s). Metaphors in the patient narrative, novels, and non-fiction work were reviewed and a list of themes or categorizations common to 2 of the metaphors was generated. Parkinson’s disease metaphors indicate a ‘Parkinson’s prism’ thereby depicting extreme experiences (24.4%) like a ‘fall by mischance’, a ‘tantrum of selfish misery’ or a ‘bottomless darkness and unreality’ (Table 1). Both novels signify a sense of ‘betrayal and disconnection’ in the Parkinson’s disease experience while non-fiction of Parkinsonism depicts a space in which one feels ‘caged and deprived’. This makes the Parkinson’s disease narrative a chaos story that could influence the decision to initiate treatment and treatment adherence. We conclude that narrative medicine can help to focus the medical consultations with affected individuals on issues that matter most to them, thereby improving self-perceived autonomy and stigma. As such, it is a critical component of the much-needed move towards personalized medicine in Parkinson’s disease, achieved through the reciprocity of thinking with stories.

Abstract Background In medical, social, and behavioral research we often encounter datasets with a multilevel structure and multiple correlated dependent variables. These data are frequently collected from a study population that distinguishes several subpopulations with different (i.e., heterogeneous) effects of an intervention. Despite the frequent occurrence of such data, methods to analyze them are less common and researchers often resort to either ignoring the multilevel and/or heterogeneous structure, analyzing only a single dependent variable, or a combination of these. These analysis strategies are suboptimal: Ignoring multilevel structures inflates Type I error rates, while neglecting the multivariate or heterogeneous structure masks detailed insights. Methods To analyze such data comprehensively, the current paper presents a novel Bayesian multilevel multivariate logistic regression model. The clustered structure of multilevel data is taken into account, such that posterior inferences can be made with accurate error rates. Further, the model shares information between different subpopulations in the estimation of average and conditional average multivariate treatment effects. To facilitate interpretation, multivariate logistic regression parameters are transformed to posterior success probabilities and differences between them. Results A numerical evaluation compared our framework to less comprehensive alternatives and highlighted the need to model the multilevel structure: Treatment comparisons based on the multilevel model had targeted Type I error rates, while single-level alternatives resulted in inflated Type I errors. Further, the multilevel model was more powerful than a single-level model when the number of clusters was higher. A re-analysis of the Third International Stroke Trial data illustrated how incorporating a multilevel structure, assessing treatment heterogeneity, and combining dependent variables contributed to an in-depth understanding of treatment effects. Further, we demonstrated how Bayes factors can aid in the selection of a suitable model. Conclusion The method is useful in prediction of treatment effects and decision-making within subpopulations from multiple clusters, while taking advantage of the size of the entire study sample and while properly incorporating the uncertainty in a principled probabilistic manner using the full posterior distribution.