Short-term dietary changes are reflected in the cerebral content of adult ring-billed gulls.

Omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) are produced primarily in aquatic ecosystems and are considered essential nutrients for predators given their structural role in vertebrates' cerebral tissues. Alarmingly, with urbanization, many aquatic animals now rely on anthropogenic foods lacking n3-LCPUFAs. In this study undertaken in Newfoundland (Canada), we tested whether recent or longer term diet explains the cerebral fatty acid composition of ring-billed gulls (Larus delawarensis), a seabird that now thrives in cities. During the breeding season, cerebral levels of n3-LCPUFAs were significantly higher for gulls nesting in a natural habitat and foraging on marine food (mean ± s.d.: 32 ± 1% of total identified fatty acids) than for urban nesters exploiting rubbish (27 ± 1%). Stable isotope analysis of blood and feathers showed that urban and natural nesters shared similar diets in autumn and winter, suggesting that the difference in cerebral n3-LCPUFAs during the breeding season was owing to concomitant and transient differences in diet. We also experimentally manipulated gulls' diets throughout incubation by supplementing them with fish oil rich in n3-LCPUFAs, a caloric control lacking n3-LCPUFAs, or nothing, and found evidence that fish oil increased urban nesters' cerebral n3-LCPUFAs. These complementary analyses provide evidence that the brain of this seabird remains plastic during adulthood and responds to short-term dietary changes.

Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice.

INTRODUCTION: We developed a multimarker blood test result interpretation tool for the clinical dementia practice, including phosphorylated (P-)tau181, amyloid-beta (Abeta)42/40, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). METHODS: We measured the plasma biomarkers with Simoa (n = 1199), applied LASSO regression for biomarker selection and receiver operating characteristics (ROC) analyses to determine diagnostic accuracy. We validated our findings in two independent cohorts and constructed a visualization approach. RESULTS: P-tau181, GFAP, and NfL were selected. This combination had area under the curve (AUC) = 83% to identify amyloid positivity in pre-dementia stages, AUC = 87%-89% to differentiate Alzheimer's or controls from frontotemporal dementia, AUC = 74%-76% to differentiate Alzheimer's or controls from dementia with Lewy bodies. Highly reproducible AUCs were obtained in independent cohorts. The resulting visualization tool includes UpSet plots to visualize the stand-alone biomarker results and density plots to visualize the biomarker results combined. DISCUSSION: Our multimarker blood test interpretation tool is ready for testing in real-world clinical dementia settings. HIGHLIGHTS: We developed a multimarker blood test interpretation tool for clinical dementia practice. Our interpretation tool includes plasma biomarkers P-tau, GFAP, and NfL. Our tool is particularly useful for Alzheimer's and frontotemporal dementia diagnosis.

Implementation of a Hand Training Curriculum in Junior Resident Education: Experience at a Military Orthopedic Residency Program.

Purpose: The American Society for Surgery of the Hand developed the Surgery Training and Educational Platform (STEP) in order to assess essential skills in hand surgery. The American Society for Surgery of the Hand designed modules spanning both osseous and soft tissue skills aimed to be cost effective for the purpose of orthopedic surgical education. The STEP curriculum was adapted and implemented at a single military orthopedic residency program. Methods: The following six modules were implemented: (1) depth of plunge, (2) scaphoid pinning, (3) phalangeal fracture pinning, (4) microsurgery, (5) full-thickness skin graft harvest, and (6) wrist arthroscopy. Both first- (PGY1) and second-year (PGY2) residents participated. Scores were calculated according to the original STEP curriculum criteria and were compared with historic data from the previous year. All residents responded to an evaluation questionnaire following the performance of the tasks. Results: The PGY2 cohort outperformed PGY1 cohorts across all modules except for the depth of plunge and scaphoid fixation modules. In the phalangeal pinning module, PGY2s did significantly better when compared with pooled PGY1 performance and their own PGY1 performance (P < .05). In the microsurgery module, PGY2s scored better than pooled PGY1s. In the full-thickness skin grafting module, PGY2s outperformed PGY1s (P < .05). On the post-task evaluation, residents unanimously responded that this was a valuable exercise, but the time required to complete all the modules was significant, similar to that of the previous year survey. Conclusions: The STEP simulation is a cost effective and reliable program to engage residents in hand surgery-related skills. However, adaptations should be encouraged according to institutional resources to provide the most inclusive training platform possible per institutional constraints. The STEP simulation is interpreted by residents as a valuable exercise but requires a significant time commitment that could be a barrier to implementation and regular use. Type of study/level of evidence: Therapeutic IV.

Pentacyclic fused diborepinium ions with carbene- and carbone-mediated deep-blue to red emission.

Designing molecules that can undergo late-stage modifications resulting in specific optical properties is useful for developing structure-function trends in materials, which ultimately advance optoelectronic applications. Herein, we report a series of fused diborepinium ions stabilized by carbene and carbone ligands (diamino-N-heterocyclic carbenes, cyclic(alkyl)(amino) carbenes, carbodicarbenes, and carbodiphosphoranes), including a detailed bonding analysis. These are the first structurally confirmed examples of diborepin dications and we detail how distortions in the core of the pentacyclic fused system impact aromaticity, stability, and their light-emitting properties. Using the same fused diborepin scaffold, coordinating ligands were used to dramatically shift the emission profile, which exhibit colors ranging from blue to red (358-643 nm). Notably, these diborepinium ions access expanded regions of the visible spectrum compared to known examples of borepins, with quantum yields up to 60%. Carbones were determined to be superior stabilizing ligands, resulting in improved stability in the solution and solid states. Density functional theory was used to provide insight into the bonding as well as the specific transitions that result in the observed photophysical properties.

Emerging Strategies to Prevent Bacterial Infections on Titanium-Based Implants.

Titanium and titanium alloys remain the gold standard for dental and orthopedic implants. These materials are heavily used because of their bioinert nature, robust mechanical properties, and seamless integration with bone. However, implant-associated infections (IAIs) remain one of the leading causes of implant failure. Eradicating an IAI can be difficult since bacteria can form biofilms on the medical implant, protecting the bacterial cells against systemic antibiotics and the host's immune system. If the infection is not treated promptly and aggressively, device failure is inevitable, leading to costly multi-step revision surgeries. To circumvent this dire situation, scientists and engineers continue to develop novel strategies to protect the surface of medical implants from bacteria. In this review, details on emerging strategies to prevent infection in titanium implants are reported. These strategies include anti-adhesion properties provided by polymers, superhydrophobic, superhydrophilic, and liquid-infused surface coatings, as well as strategies and coatings employed to lyse the bacteria. Additionally, commercially available technologies and those under preclinical trials are examined while discussing current and future trends.

Complex Fractures of the Radial and Ulnar Shaft.

SUMMARY: Successful management of radial and ulnar shaft fractures is an essential skill for all orthopaedic surgeons. The frequent presentation of these injuries coupled with the nuanced anatomic considerations that must be observed for successful outcomes dictate that these injuries require a thorough understanding by the treating surgeon. Intraoperative care to restore the anatomic radial bow and rotation is essential for the resumption of functional forearm rotation postinjury. Often, problems arising during the operative treatment of radial and ulnar shaft fractures come in predictable patterns that can be mitigated with preoperative planning and sound technique. Cases of increased complexity with segmental bone defects and soft tissue defects require a variety of advanced reconstructive techniques.

Discovery and In Vivo Efficacy of AZ-PRMT5i-1, a Novel PRMT5 Inhibitor with High MTA Cooperativity.

PRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative PRMT5 inhibitors suitable for MTAP-deficient cancers, herein we report our efforts to develop novel "MTA-cooperative" compounds identified through a high-throughput biochemical screening approach. Optimization of hits was achieved through structure-based design with a focus on improvement of oral drug-like properties. Bioisosteric replacement of the original thiazole guanidine headgroup, spirocyclization of the isoindolinone amide scaffold to both configurationally and conformationally lock the bioactive form, and fine-tuning of the potency, MTA cooperativity, and DMPK properties through specific substitutions of the azaindole headgroup were conducted. We have identified an orally available in vivo lead compound, 28 ("AZ-PRMT5i-1"), which shows sub-10 nM PRMT5 cell potency, >50-fold MTA cooperativity, suitable DMPK properties for oral dosing, and significant PRMT5-driven in vivo efficacy in several MTAP-deficient preclinical cancer models.

Unlocking the significant worldwide potential of better waste and resource management for climate mitigation: with particular focus on the Global South.

Numbers do matter; the Intergovernmental Panel on Climate Change (IPCC)'s 2010 data that the waste sector is responsible for just 3% of global greenhouse gas (GHG) emissions has led to the misperception that solid waste management (SWM) has little to contribute to climate mitigation. Global efforts to control methane emissions and divert organic waste from landfills had already reduced direct emissions. But end-of-pipe SWM has also been evolving into more circular waste and resource management, with indirect GHG savings from the 3Rs (reduce, reuse, recycle) which IPCC accounts for elsewhere in the economy. The evidence compiled here on both direct emissions and indirect savings demonstrates with high confidence that better waste and resource management can make a significant contribution to climate mitigation, and must form a core part of every country's nationally determined contribution. Even the most advanced countries can still achieve much from the 3Rs. In the Global South, the challenge of extending waste collection to all and stopping open dumping and burning (sustainable development goal 11.6.1), essential to improve public health, can be turned into a huge opportunity. Moving early to divert waste from landfill by separation at source and collecting clean organic and dry recycling fractions, will mitigate global GHG emissions, slash ocean plastics and create decent livelihoods. But this can only happen with targeted climate, plastics and extended producer responsibility finance; and help to local communities to help themselves.

Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders.

Decades of research have identified genetic and environmental factors involved in age-related neurodegenerative diseases and, to a lesser extent, neuropsychiatric disorders. Genomic instability, i.e., the loss of genome integrity, is a common feature among both neurodegenerative (mayo-trophic lateral sclerosis, Parkinson's disease, Alzheimer's disease) and psychiatric (schizophrenia, autism, bipolar depression) disorders. Genomic instability is associated with the accumulation of persistent DNA damage and the activation of DNA damage response (DDR) pathways, as well as pathologic neuronal cell loss or senescence. Typically, DDR signaling ensures that genomic and proteomic homeostasis are maintained in both dividing cells, including neural progenitors, and post-mitotic neurons. However, dysregulation of these protective responses, in part due to aging or environmental insults, contributes to the progressive development of neurodegenerative and/or psychiatric disorders. In this Special Issue, we introduce and highlight the overlap between neurodegenerative diseases and neuropsychiatric disorders, as well as the emerging clinical, genomic, and molecular evidence for the contributions of DNA damage and aberrant DNA repair. Our goal is to illuminate the importance of this subject to uncover possible treatment and prevention strategies for relevant devastating brain diseases.

Genomic stress in diseases stemming from defects in the second brain.

This review discusses the less-explored realm of DNA damage and repair within the enteric nervous system (ENS), often referred to as the "second brain." While the central nervous system has been extensively studied for its DNA repair mechanisms and associated neuropathologies, the ENS, which can autonomously coordinate gastrointestinal function, experiences unique challenges and vulnerabilities related to its genome integrity. The susceptibility of the ENS to DNA damage is exacerbated by its limited protective barriers, resulting in not only endogenous genotoxic exposures, such as oxidative stress, but also exogenous threats, such as ingested environmental contaminants, local inflammatory responses, and gut dysbiosis. Here, we discuss the evidence for DNA repair defects in enteric neuropathies, most notably, the reported relationship between inherited mutations in RAD21 and LIG3 with chronic intestinal pseudo-obstruction and mitochondrial gastrointestinal encephalomyopathy disorders, respectively. We also introduce the lesser-recognized gastrointestinal complications in DNA repair syndromes, including conditions like Cockayne syndrome. The review concludes by pointing out the potential role of DNA repair defects in not only congenital disorders but also aging-related gut dysfunction, as well as the crucial need for further research to establish direct causal links between DNA damage accumulation and ENS-specific pathologic phenotypes.

Synthesis and Structure Optimization of Star Copolymers as Tunable Macromolecular Carriers for Minimal Immunogen Vaccine Delivery.

Minimal immunogen vaccines are being developed to focus antibody responses against otherwise challenging targets, including human immunodeficiency virus (HIV), but multimerization of the minimal peptide immunogen on a carrier platform is required for activity. Star copolymers comprising multiple hydrophilic polymer chains ("arms") radiating from a central dendrimer unit ("core") were recently reported to be an effective platform for arraying minimal immunogens for inducing antibody responses in mice and primates. However, the impact of different parameters of the star copolymer (e.g., minimal immunogen density and hydrodynamic size) on antibody responses and the optimal synthetic route for controlling those parameters remains to be fully explored. We synthesized a library of star copolymers composed of poly[N-(2-hydroxypropyl)methacrylamide] hydrophilic arms extending from poly(amidoamine) dendrimer cores with the aim of identifying the optimal composition for use as minimal immunogen vaccines. Our results show that the length of the polymer arms has a crucial impact on the star copolymer hydrodynamic size and is precisely tunable over a range of 20-50 nm diameter, while the dendrimer generation affects the maximum number of arms (and therefore minimal immunogens) that can be attached to the surface of the dendrimer. In addition, high-resolution images of selected star copolymer taken by a custom-modified environmental scanning electron microscope enabled the acquisition of high-resolution images, providing new insights into the star copolymer structure. Finally, in vivo studies assessing a star copolymer vaccine comprising an HIV minimal immunogen showed the criticality of polymer arm length in promoting antibody responses and highlighting the importance of composition tunability to yield the desired biological effect.

Structural and Physicochemical Features of Oral PROTACs.

Achieving oral bioavailability with Proteolysis Targeting Chimeras (PROTACs) is a key challenge. Here, we report the in vivo pharmacokinetic properties in mouse, rat, and dog of four clinical oral PROTACs and compare with an internally derived data set. We use NMR to determine 3D molecular conformations and structural preorganization free in solution, and we introduce the new experimental descriptors, solvent-exposed H-bond donors (eHBD), and acceptors (eHBA). We derive an upper limit of eHBD ≤ 2 for oral PROTACs in apolar environments and show a greater tolerance for other properties (eHBA, polarity, lipophilicity, and molecular weight) than for Rule-of-5 compliant oral drugs. Within a set of structurally related PROTACs, we show that examples with eHBD > 2 have much lower oral bioavailability than those that have eHBD ≤ 2. We summarize our findings as an experimental "Rule-of-oral-PROTACs" in order to assist medicinal chemists to achieve oral bioavailability in this challenging space.

Scalar and Tensor Charmonium Resonances in Coupled-Channel Scattering from Lattice QCD.

We determine J^{PC}=0^{++} and 2^{++} hadron-hadron scattering amplitudes in the charmonium energy region up to 4100 MeV using lattice QCD, a first-principles approach to QCD. Working at m_{π}≈391 MeV, more than 200 finite-volume energy levels are computed and these are used in extensions of the Lüscher formalism to determine infinite-volume coupled-channel scattering amplitudes. We find that this energy region contains a single χ_{c0} and a single χ_{c2} resonance. Both are found as pole singularities on the closest unphysical Riemann sheet, just below 4000 MeV with widths around 70 MeV. The largest couplings are to kinematically closed D^{*}D[over ¯]^{*} channels in S-wave, and couplings to several decay channels consisting of pairs of open-charm mesons are found to be large and significant in both cases. Above the ground state χ_{c0}, no other scalar bound states or near-DD[over ¯] threshold resonances are found, in contrast to several theoretical and experimental studies.

Protocol for producing hyperpolarized 13C-bicarbonate for clinical MRI of extracellular pH in aggressive tumors.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) 13C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule 13C-glycerol carbonate (13C-GLC), the post-dissolution reaction, and converting HP 13C-GLC to an injectable HP 13C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al.1.

Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease.

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need for biomarker confirmation of amyloid pathology. Blood biomarker (BBM) tests for amyloid pathology are more acceptable, accessible and scalable than amyloid PET or cerebrospinal fluid (CSF) tests, but have highly variable levels of performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider the minimum acceptable performance of BBM tests for clinical use. Amyloid PET status was identified as the reference standard. For use as a triaging test before subsequent confirmatory tests such as amyloid PET or CSF tests, the BBM Workgroup recommends that a BBM test has a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75-85% in secondary care depending on the availability of follow-up testing. For use as a confirmatory test without follow-up tests, a BBM test should have performance equivalent to that of CSF tests - a sensitivity and specificity of ~90%. Importantly, the predictive values of all biomarker tests vary according to the pre-test probability of amyloid pathology and must be interpreted in the complete clinical context. Use of BBM tests that meet these performance standards could enable more people to receive an accurate and timely Alzheimer disease diagnosis and potentially benefit from new treatments.

Prediction of Covalent Metal-Metal Bonding in Cp-M-M'-Nacnac Complexes of Group 2 and 12 Metals (Be, Mg, Ca, Zn, Cd, Hg).

Bimetallic CpMM'Nacnac molecules with group 2 and 12 metals (M=Be, Mg, Ca, Zn, Cd, Hg) that contain novel metal-metal bonding have been investigated in a theoretical study of their molecular and electronic structure, thermodynamic stability, and metal-metal bonding. In all cases the metal-metal bonds are characterized as electron-sharing covalent single bonds from natural bond orbital (NBO) and energy-decomposition analysis with natural orbitals of chemical valence (EDA-NOCV) analysis. The sum of [MM'] charges is relatively constant, with all complexes exhibiting a [MM']2+ core. Quantum theory of atoms in molecules (QTAIM) analysis indicates the presence of non-nuclear attractors (NNA) in the metal-metal bonds of the BeBe, MgMg, and CaCa complexes. There is substantial electron density (0.75-1.33 e) associated with the NNAs, which indicates that these metal-metal bonds, while classified as covalent electron-sharing bonds, retain significant metallic character that can be associated with reducing reactivity of the complex. The predicted stability of these complexes, combined with their novel covalent metal-metal bonding and potential as reducing agents, make them appealing targets for the synthesis of new metal-metal bonds.

Preclinical efficacy of potent and selective menin-KMT2A inhibitor JNJ-75276617 in KMT2A- and NPM1-altered leukemias.

The interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)-altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) AML cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3. JNJ-75276617 displayed potent anti-proliferative activity across several AML and ALL cell lines and patient samples harboring KMT2A- or NPM1-alterations in vitro. In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied by expression changes of menin-KMT2A target genes. JNJ-75276617 demonstrated synergistic effects with gilteritinib in vitro in AML cells harboring KMT2A-r. JNJ-75276617 further exhibited synergistic effects with venetoclax and azacitidine in AML cells bearing KMT2A-r in vitro, and significantly increased survival in mice. Interestingly, JNJ-75276617 showed potent anti-proliferative activity in cell lines engineered with recently discovered mutations (MEN1M327I or MEN1T349M) that developed in patients refractory to the menin-KMT2A inhibitor revumenib. A co-crystal structure of menin in complex with JNJ-75276617 indicates a unique binding mode distinct from other menin-KMT2A inhibitors, including revumenib. JNJ-75276617 is being clinically investigated for acute leukemias harboring KMT2A or NPM1 alterations, as a monotherapy for relapsed/refractory (R/R) acute leukemia (NCT04811560), or in combination with AML-directed therapies (NCT05453903).

NerveTracker: a Python-based software toolkit for visualizing and tracking groups of nerve fibers in serial block-face microscopy with ultraviolet surface excitation images.

Significance: Information about the spatial organization of fibers within a nerve is crucial to our understanding of nerve anatomy and its response to neuromodulation therapies. A serial block-face microscopy method [three-dimensional microscopy with ultraviolet surface excitation (3D-MUSE)] has been developed to image nerves over extended depths ex vivo. To routinely visualize and track nerve fibers in these datasets, a dedicated and customizable software tool is required. Aim: Our objective was to develop custom software that includes image processing and visualization methods to perform microscopic tractography along the length of a peripheral nerve sample. Approach: We modified common computer vision algorithms (optic flow and structure tensor) to track groups of peripheral nerve fibers along the length of the nerve. Interactive streamline visualization and manual editing tools are provided. Optionally, deep learning segmentation of fascicles (fiber bundles) can be applied to constrain the tracts from inadvertently crossing into the epineurium. As an example, we performed tractography on vagus and tibial nerve datasets and assessed accuracy by comparing the resulting nerve tracts with segmentations of fascicles as they split and merge with each other in the nerve sample stack. Results: We found that a normalized Dice overlap ( Dice norm ) metric had a mean value above 0.75 across several millimeters along the nerve. We also found that the tractograms were robust to changes in certain image properties (e.g., downsampling in-plane and out-of-plane), which resulted in only a 2% to 9% change to the mean Dice norm values. In a vagus nerve sample, tractography allowed us to readily identify that subsets of fibers from four distinct fascicles merge into a single fascicle as we move ∼ 5 mm along the nerve's length. Conclusions: Overall, we demonstrated the feasibility of performing automated microscopic tractography on 3D-MUSE datasets of peripheral nerves. The software should be applicable to other imaging approaches. The code is available at https://github.com/ckolluru/NerveTracker.

Vertical pelvic movement asymmetry and lameness location in ipsilateral combined forelimb and hindlimb lameness cases.

BACKGROUND: Compensatory vertical head and pelvis movement asymmetry may occur in trotting horses with a primary cause of lameness in one end of the body due to the weight shifting between limbs, leading to apparent combined forelimb and hindlimb lameness (CFHL). Little is known about CFHL patterns observed with body-mounted inertial sensors (BMIS) and regardless of their underlying mechanisms, compensatory and secondary lameness may complicate the definitive identification of the primary causes of lameness. OBJECTIVE: Determine associations between vertical pelvic movement asymmetry and location of primary lameness in ipsilateral CFHL cases where hindlimb lameness is solely impact or push-off type. STUDY DESIGN: Retrospective cohort. METHODS: From a body-mounted inertial sensor (BMIS) evaluated equine lameness database, we identified cases with a consistent, low-variability ipsilateral impact (IpI) or ipsilateral pushoff (IpP) hindlimb lameness in a straight-line trot and that had definitive diagnoses. Cases were categorised by lameness location to the limb(s), diagnosis, and ratio of the amplitude of forelimb to hindlimb lameness (Forea/Hinda). Differences in the numbers of IpI and IpP cases in these categories were analysed with chi-square tests, effect sizes, and odds ratios. RESULTS: Among the 2375 total lameness cases screened, 49 IpI and 36 IpP cases met the criteria for consistency, low variability, and definitive diagnosis. IpI cases were more likely than IpP cases to have forelimb-only lameness causes when Forea/Hinda >1 (OR = 43, 95% CI = 2.3-798). IpP cases were more likely than IpI cases to have hindlimb-only causes at both Forea/Hinda >1.0 (OR = 20, 95% CI = 2.2-200) and <1.0 (OR = 14, 95% CI = 2.9-66.7). Compared with IpI, IpP cases were more frequently diagnosed with tendon, suspensory ligament, or high-motion joint disorders in hindlimbs (OR = 3.6, 95% CI = 1.1-12.3) and less with unknown causes (OR = 13.2, 95% CI = 3.2-75.2). In IpI cases, positive forelimb regional anaesthesia often reduced hindlimb lameness, whereas in IpP cases, positive hindlimb regional anaesthesia typically lessened forelimb lameness. MAIN LIMITATIONS: Most cases were Quarter Horses. The likelihood of location and cause of lameness may be different for other breeds. CONCLUSIONS: The type of pelvic movement asymmetry observed in IpI and IpP cases is linked to the location and underlying cause of the primary lameness.