Proximal Femur Guided Growth: A Systematic Review.

Children with cerebral palsy (CP) and those with avascular necosis (AVN) after treatment of developmental hip dysplasia (DDH) are at risk of developing coxa valga. Proximal femur guided growth is a minimally invasive option to correct this deformity. A systematic review of articles that described treatment of coxa valga with proximal femur guided growth (PFGG) and reporting on primary radiographic outcomes, demographic variables, surgical variables and complications. One hundred and seventy-nine hips underwent PFGG (117 with CP and 62 with lateral overgrowth). Average age at surgery was 8.1 years; average follow-up was 52.5 months. Migration percentage improved from 11.2% (p < 0.0001). Neck-shaft angle improved by 11.9° (p < 0.0001). The most common complication was screw growth out of the physis (30% of cases). PFGG can correct coxa valga, improve radiographic parameters, and in children with CP prevent further subluxation. This technique modulates proximal femur growth, induces changes to the acetabulum and can correct valgus deformity. Evidence Level III. (Journal of Surgical Orthopaedic Advances 32(4):049-052, 2024).

A roadmap for implanting microelectrode arrays to evoke tactile sensations through intracortical microstimulation.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.

Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.

Glutamine synthetase (GS), encoded by GLUL, catalyzes the conversion of glutamate to glutamine. GS is pivotal for the generation of the neurotransmitters glutamate and gamma-aminobutyric acid and is the primary mechanism of ammonia detoxification in the brain. GS levels are regulated post-translationally by an N-terminal degron that enables the ubiquitin-mediated degradation of GS in a glutamine-induced manner. GS deficiency in humans is known to lead to neurological defects and death in infancy, yet how dysregulation of the degron-mediated control of GS levels might affect neurodevelopment is unknown. We ascertained nine individuals with severe developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry with de novo variants in GLUL. Seven out of nine were start-loss variants and two out of nine disrupted 5' UTR splicing resulting in splice exclusion of the initiation codon. Using transfection-based expression systems and mass spectrometry, these variants were shown to lead to translation initiation of GS from methionine 18, downstream of the N-terminal degron motif, resulting in a protein that is stable and enzymatically competent but insensitive to negative feedback by glutamine. Analysis of human single-cell transcriptomes demonstrated that GLUL is widely expressed in neuro- and glial-progenitor cells and mature astrocytes but not in post-mitotic neurons. One individual with a start-loss GLUL variant demonstrated periventricular nodular heterotopia, a neuronal migration disorder, yet overexpression of stabilized GS in mice using in utero electroporation demonstrated no migratory deficits. These findings underline the importance of tight regulation of glutamine metabolism during neurodevelopment in humans.

The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells.

Changes during the production cycle of dairy cattle can leave these animals susceptible to oxidative stress and reduced antioxidant health. In particular, the periparturient period, when dairy cows must rapidly adapt to the sudden metabolic demands of lactation, is a period when the production of damaging free radicals can overwhelm the natural antioxidant systems, potentially leading to tissue damage and reduced milk production. Central to the protection against free radical damage and antioxidant defense is the transcription factor NRF2, which activates an array of genes associated with antioxidant functions and cell survival. The objective of this study was to evaluate the effect that two natural NRF2 modulators, the NRF2 agonist sulforaphane (SFN) and the antagonist brusatol (BRU), have on the transcriptome of immortalized bovine mammary alveolar cells (MACT) using both the RT-qPCR of putative NRF2 target genes, as well as RNA sequencing approaches. The treatment of cells with SFN resulted in the activation of many putative NRF2 target genes and the upregulation of genes associated with pathways involved in cell survival, metabolism, and antioxidant function while suppressing the expression of genes related to cellular senescence and DNA repair. In contrast, the treatment of cells with BRU resulted in the upregulation of genes associated with inflammation, cellular stress, and apoptosis while suppressing the transcription of genes involved in various metabolic processes. The analysis also revealed several novel putative NRF2 target genes in bovine. In conclusion, these data indicate that the treatment of cells with SFN and BRU may be effective at modulating the NRF2 transcriptional network, but additional effects associated with cellular stress and metabolism may complicate the effectiveness of these compounds to improve antioxidant health in dairy cattle via nutrigenomic approaches.

Indole-3-acetic acid promotes growth in bloom-forming Microcystis via an antioxidant response.

Interactions between bacteria and phytoplankton in the phycosphere facilitate and constrain biogeochemical cycling in aquatic ecosystems. Indole-3-acetic acid (IAA) is a bacterially produced chemical signal that promotes growth of phytoplankton and plants. Here, we explored the impact of IAA on bloom-forming cyanobacteria and their associated bacteria. Exposure to IAA and its precursor, tryptophan, resulted in a strong growth response in a bloom of the freshwater cyanobacterium, Microcystis. Metatranscriptome analysis revealed the induction of an antioxidant response in Microcystis upon exposure to IAA, potentially allowing populations to increase photosynthetic rate and overcome internally generated reactive oxygen. Our data reveal that co-occurring bacteria within the phycosphere microbiome exhibit a division of labor for supportive functions, such as nutrient mineralization and transport, vitamin synthesis, and reactive oxygen neutralization. These complex dynamics within the Microcystis phycosphere microbiome are an example of interactions within a microenvironment that can have ecosystem-scale consequences.

Biomimetic versus arbitrary motor control strategies for bionic hand skill learning.

A long-standing engineering ambition has been to design anthropomorphic bionic limbs: devices that look like and are controlled in the same way as the biological body (biomimetic). The untested assumption is that biomimetic motor control enhances device embodiment, learning, generalization and automaticity. To test this, we compared biomimetic and non-biomimetic control strategies for non-disabled participants when learning to control a wearable myoelectric bionic hand operated by an eight-channel electromyography pattern-recognition system. We compared motor learning across days and behavioural tasks for two training groups: biomimetic (mimicking the desired bionic hand gesture with biological hand) and arbitrary control (mapping an unrelated biological hand gesture with the desired bionic gesture). For both trained groups, training improved bionic limb control, reduced cognitive reliance and increased embodiment over the bionic hand. Biomimetic users had more intuitive and faster control early in training. Arbitrary users matched biomimetic performance later in training. Furthermore, arbitrary users showed increased generalization to a new control strategy. Collectively, our findings suggest that biomimetic and arbitrary control strategies provide different benefits. The optimal strategy is probably not strictly biomimetic, but rather a flexible strategy within the biomimetic-to-arbitrary spectrum, depending on the user, available training opportunities and user requirements.

Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas.

Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to <1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy. SIGNIFICANCE: True2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.

The FOXP3+ Pro-Inflammatory T Cell: A Potential Therapeutic Target in Crohn's Disease.

BACKGROUND & AIMS: The incidence of Crohn's disease (CD) continues to increase worldwide. The contribution of CD4+ cell populations remains to be elucidated. We aimed to provide an in-depth transcriptional assessment of CD4+ T cells driving chronic inflammation in CD. METHODS: We performed single-cell RNA-sequencing in CD4+ T cells isolated from ileal biopsies of patients with CD compared with healthy individuals. Cells underwent clustering analysis, followed by analysis of gene signaling networks. We overlapped our differentially expressed genes with publicly available microarray data sets and performed functional in vitro studies, including an in vitro suppression assay and organoid systems, to model gene expression changes observed in CD regulatory T (Treg) cells and to test predicted therapeutics. RESULTS: We identified 5 distinct FOXP3+ regulatory Treg subpopulations. Tregs isolated from healthy controls represent the origin of pseudotemporal development into inflammation-associated subtypes. These proinflammatory Tregs displayed a unique responsiveness to tumor necrosis factor-α signaling with impaired suppressive activity in vitro and an elevated cytokine response in an organoid coculture system. As predicted in silico, the histone deacetylase inhibitor vorinostat normalized gene expression patterns, rescuing the suppressive function of FOXP3+ cells in vitro. CONCLUSIONS: We identified a novel, proinflammatory FOXP3+ T cell subpopulation in patients with CD and developed a pipeline to specifically target these cells using the US Food and Drug Administration-approved drug vorinostat.

The Effect of Early Cultures and Dual-port Expanders on Two-stage, Prepectoral Breast Reconstruction: The 25/25 Study.

Background: Two-stage tissue expander to implant surgery remains the predominant technique for breast reconstruction. Unfortunately, there is a high incidence of reconstruction failure which portends a financial and emotional burden. Most failures are related to postmastectomy skin flap necrosis and infection. Recently, a dual-port tissue expander was introduced to the market, and the authors hypothesize that early cultures from the peri-implant fluid will guide antibiotic treatment and decrease reconstruction failure. Methods: This is a cohort study of 50 consecutive patients treated for breast cancer or genetic susceptibility via a two-stage, prepectoral technique. The first 25 patients (46 breasts) were treated with a variety of tissue expanders, and the subsequent 25 patients (47 breasts) received a dual-port expander. Routine cultures from the drain port were taken from the dual-port group at the second postoperative visit, and cultures were taken in the control group only when signs of infection were present. All other procedures and interventions were similar. Results: Fifty patients, totaling 93 breasts, completed the study with a mean follow-up of 145 days. There were no statistically significant demographic or pathologic differences between groups. Fifteen tissue expanders were explanted in the control group and five in the dual-port cohort (32.6% versus 10.6%, P = 0.012). All bacteria in the control group failures were either methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis, whereas failures in the dual-port group varied. Conclusion: Treatment of routine, early cultures from a dual-port expander led to a statistically significant decrease in tissue expander explantation.

Premature Deaths Due To Heat Exposure: The Potential Effects of Neighborhood-Level Versus City-Level Acclimatization Within US Cities.

For the population of a given US city, the risk of premature death associated with heat exposure increases as temperatures rise, but risks in hotter cities are generally lower than in cooler cities at equivalent temperatures due to factors such as acclimatization. Those living in especially hot neighborhoods within cities might therefore suffer much more than average if such adaptation is only at the city-wide level, whereas they might not experience greatly increased risk if adjustment is at the neighborhood level. To compare these possibilities, we use high spatial resolution temperature data to evaluated heat-related deaths assuming either adjustment at the city-wide or at the neighborhood scale in 10 large US cities. On average, we find that if inhabitants are adjusted to their local conditions, a neighborhood that was 10°C hotter than a cooler one would experience only about 1.0-1.5 excess heat deaths per year per 100,000 persons. By contrast, if inhabitants are acclimatized to city-wide temperatures, the hotter neighborhood would experience about 15 excess deaths per year per 100,000 persons. Using idealized analyses, we demonstrate that current city-wide epidemiological data do not differentiate between these differing adjustments. Given the very large effects of assumptions about neighborhood-level acclimatization found here, as well as the fact that current literature is conflicting on the spatial scale of acclimatization, more neighborhood-level epidemiological data are urgently needed to determine the health impacts of variations in heat exposure within urban areas, better constrain projected changes, and inform mitigation efforts.

Feeding Ractopamine Improves the Growth Performance and Carcass Characteristics of the Lard-Type Mangalica Pig.

Mangalica pigs are gaining popularity within the U.S. as a niche breed, given their reputation for superior-quality pork. However, slow growth rates, a poor lean yield, and excessive adiposity limit the widespread adoption of Mangalica. To determine if feeding the metabolic modifier, ractopamine hydrochloride (RAC), would improve growth performance without impairing pork quality in the Mangalica, pigs were fed either 0 or 20 mg per kg RAC for 21 days. At 24 h postharvest, pork quality and carcass composition measurements were recorded; then, primal cuts were fabricated and assessed. RAC increased ADG (p < 0.04) and gain efficiency (p < 0.03) by 24% and 21%, respectively. RAC increased Loin Eye Area (p < 0.0001) by 21% but did not impact the 10th rib fat depth (p > 0.90) or marbling score (p > 0.77). RAC failed to alter any primal cut weights. Feeding RAC lowered b* values (p < 0.04) and tended to lower L* values (p < 0.08) while not affecting a* values (p > 0.30), suggesting RAC darkened loin color. Finally, RAC decreased cook yield percentage (p < 0.02) by 11% without impacting Warner-Bratzler Shear Force (p > 0.31). These data support the hypothesis that feeding RAC to Mangalica improves growth performance without impairing pork quality in this breed.

Methylxanthine Derivatives in the Treatment of Sinus Node Dysfunction: A Systematic Review.

While the chronotropic effects of theophylline and aminophylline are well-known, their clinical application in the treatment of sinus node dysfunction has not been established in a review. The purpose of this systematic review is to evaluate the efficacy and safety of methylxanthines in the treatment of bradyarrhythmias associated with sinus node dysfunction. A systematic review was conducted in accordance with PRISMA guidelines on Embase, PubMed, MEDLINE, Cochrane Central, Web of Science, SciELO, Korean Citation Index, Global Index Medicus, and CINAHL through June 2023. A total of 607 studies were identified through the literature search. After applying the inclusion and exclusion criteria, 14 studies were included in this review. The causes of bradyarrhythmias involving the sinoatrial node included acute cervical spinal cord injury, coronavirus disease of 2019, carotid sinus syncope, chronotropic incompetence, heart transplant, and chronic sinus node dysfunction. Theophylline and aminophylline were shown to be effective for increasing heart rate and reducing the reoccurrence of bradyarrhythmias. The data on symptom resolution was conflicting. While many case studies reported a resolution of symptoms, a randomized controlled trial reported no significant difference in symptom scores between the control, theophylline, and pacemaker groups in the treatment of sick sinus syndrome. The incidence of adverse effects was low across all study designs. The data suggests methylxanthines may be useful as an alternative or bridge to nonpharmacologic pacing; however, dosing has yet to be established for various indications. Overall, methylxanthines proved safe and effective as a pharmacologic therapy for bradyarrhythmic manifestations of sinus node dysfunction.

Human microglia maturation is underpinned by specific gene regulatory networks.

Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.

Hypomethylation and Overexpression of Th17-Associated Genes is a Hallmark of Intestinal CD4+ Lymphocytes in Crohn's Disease.

BACKGROUND: The development of Crohn's disease [CD] involves immune cell signalling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4+ lymphocytes has not been evaluated. MATERIALS AND METHODS: Genome-wide DNA methylation sequencing was performed from terminal ileum CD4+ cells from 21 CD patients and 12 age- and sex-matched controls. Data were analysed for differentially methylated CpGs [DMCs] and methylated regions [DMRs]. Integration was performed with RNA-sequencing data to evaluate the functional impact of DNA methylation changes on gene expression. DMRs were overlapped with regions of differentially open chromatin [by ATAC-seq] and CCCTC-binding factor [CTCF] binding sites [by ChIP-seq] between peripherally derived Th17 and Treg cells. RESULTS: CD4+ cells in CD patients had significantly increased DNA methylation compared to those from the controls. A total of 119 051 DMCs and 8113 DMRs were detected. While hypermethylated genes were mostly related to cell metabolism and homeostasis, hypomethylated genes were significantly enriched within the Th17 signalling pathway. The differentially enriched ATAC regions in Th17 cells [compared to Tregs] were hypomethylated in CD patients, suggesting heightened Th17 activity. There was significant overlap between hypomethylated DNA regions and CTCF-associated binding sites. CONCLUSIONS: The methylome of CD patients shows an overall dominant hypermethylation yet hypomethylation is more concentrated in proinflammatory pathways, including Th17 differentiation. Hypomethylation of Th17-related genes associated with areas of open chromatin and CTCF binding sites constitutes a hallmark of CD-associated intestinal CD4+ cells.

Geography Influences Susceptibility to SARS-CoV-2 Serological Response in Patients With Inflammatory Bowel Disease: Multinational Analysis From the ICARUS-IBD Consortium.

BACKGROUND: Beyond systematic reviews and meta-analyses, there have been no direct studies of serological response to COVID-19 in patients with inflammatory bowel disease (IBD) across continents. In particular, there has been limited data from Asia, with no data reported from India. The ICARUS-IBD (International study of COVID-19 Antibody Response Under Sustained immunosuppression in IBD) consortium assessed serological response to SARS-CoV-2 in patients with IBD in North America, Europe, and Asia. METHODS: The ICARUS-IBD study is a multicenter observational cohort study spanning sites in 7 countries. We report seroprevalence data from 2303 patients with IBD before COVID-19 vaccination between May 2020 and November 2021. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies were analyzed. RESULTS: The highest and lowest SARS-CoV-2 anti-spike seropositivity rates were found in Asia (81.2% in Chandigarh and 57.9% in Delhi, India; and 0% in Hong Kong). By multivariable analysis, country (India: odds ratio [OR], 18.01; 95% confidence interval [CI], 12.03-26.95; P < .0001; United Kingdom: OR, 2.43; 95% CI, 1.58-3.72; P < .0001; United States: OR, 2.21; 95% CI, 1.27-3.85; P = .005), male sex (OR, 1.46; 95% CI, 1.07-1.99; P = .016), and diabetes (OR, 2.37; 95% CI, 1.04-5.46; P = .039) conferred higher seropositivity rates. Biological therapies associated with lower seroprevalence (OR, 0.22; 95% CI, 0.15-0.33; P < .0001). Multiple linear regression showed associations between anti-spike and anti-nucleocapsid titers with medications (P < .0001) but not with country (P = .3841). CONCLUSIONS: While the effects of medications on anti-SARS-CoV-2 antibody titers in patients with IBD were consistent across sites, geographical location conferred the highest risk of susceptibility to serologically detectable SARS-CoV-2 infection. Over half of IBD patients in India were seropositive prior to vaccination. These insights can help to inform shielding advice, therapeutic choices, and vaccine strategies in IBD patients for COVID-19 and future viral challenges.

In this multinational study of SARS-CoV-2 seroprevalence prior to vaccination, including the first data from India, where over half of patients seroconverted, geographical location conferred the highest risk of susceptibility to serologically detectable infection.

Operative Versus Non-operative Treatment of Medial Epicondyle Fractures in Pediatric Athletes: A Systematic Review.

Treatment of medial epicondyle fractures is controversial in pediatric orthopaedics with a recent trend towards operative fixation in overhead athletes. We performed a systematic review to compare outcomes in operative and non-operatively overhead athletes. A systematic review of the literature was performed. Articles investing pediatric athletes with medial epicondyle fractures treated operatively and non-operatively that reported functional and radiographic outcomes were compiled. We identified 6 studies with a total of 99 patients (52 treated operatively and 47 treated non-operatively). We found a significantly higher union rate with operative treatment (100%) compared to non-operative treatment (76%, p = 0.0025), with equivalent return to sport time and rate. Non-operative treatment had a lower complication and repeat surgery rates (p = 0.009). This study demonstrates lower complication rates and equivalent functional outcomes between operative and non-operatively treated medial epicondyle fractures in athletes. Non-operative treatment is a valid option in these patients. (Journal of Surgical Orthopaedic Advances 32(1):009-013, 2023).

Digital Antimicrobial Stewardship Decision Support to Improve Antimicrobial Management.

OBJECTIVES: We sought to create a digital application to support clinicians in empiric and pathogen-directed antibiotic ordering based on local susceptibility patterns and evidence-based treatment durations, thereby promoting antimicrobial stewardship. METHODS: We formed a multidisciplinary team that met bimonthly from 2017 to 2018 to design and construct a web-based antimicrobial stewardship platform called Antibiogram + . We used an iterative and agile technical development process with frequent feedback from clinicians. RESULTS: Antibiogram+ is an online tool, accessible via the electronic health record and hospital intranet, which offers institutional antibiotic susceptibilities for major pathogens, recommendations for empiric antibiotic selection and treatment durations for common pediatric conditions, antimicrobial dosing and monitoring guidance, and links to other internal clinical decision support resources. The tool was accessed 11,823 times with 492 average monthly views during the first 2 years after release. Compared with use of a preexisting print antibiogram and dosing card, pediatric residents more frequently reported "often" being sure of antibiotic dosing with Antibiogram+ (58 vs. 15%, p < 0.01). Respondents also reported improved confidence in choice of antibiotic, but this finding did not reach statistical significance (55 vs. 35%, p = 0.26). CONCLUSION: We report the successful development of a digital antimicrobial stewardship platform with consistent rates of access during the first 2 years following release and improved provider comfort with antibiotic management.

Should bionic limb control mimic the human body? Impact of control strategy on bionic hand skill learning.

A longstanding engineering ambition has been to design anthropomorphic bionic limbs: devices that look like and are controlled in the same way as the biological body (biomimetic). The untested assumption is that biomimetic motor control enhances device embodiment, learning, generalization, and automaticity. To test this, we compared biomimetic and non-biomimetic control strategies for able-bodied participants when learning to operate a wearable myoelectric bionic hand. We compared motor learning across days and behavioural tasks for two training groups: Biomimetic (mimicking the desired bionic hand gesture with biological hand) and Arbitrary control (mapping an unrelated biological hand gesture with the desired bionic gesture). For both trained groups, training improved bionic limb control, reduced cognitive reliance, and increased embodiment over the bionic hand. Biomimetic users had more intuitive and faster control early in training. Arbitrary users matched biomimetic performance later in training. Further, arbitrary users showed increased generalization to a novel control strategy. Collectively, our findings suggest that biomimetic and arbitrary control strategies provide different benefits. The optimal strategy is likely not strictly biomimetic, but rather a flexible strategy within the biomimetic to arbitrary spectrum, depending on the user, available training opportunities and user requirements.

A Randomized, Self-Controlled Case Series Evaluating Core Osteostixis of Osseous Cyst-Like Lesions of the Navicular Bone to Improve Lameness in Horses with Podotrochlear Syndrome.

Introduction: Podotrochlear syndrome is a common cause of lameness in Quarter Horses involving both soft tissue and bony structures within the heel region. Current surgical treatment of podotrochlear syndrome addresses pathological changes affecting the soft tissue structures of the navicular region but does not address either edema or cyst-like lesions of the navicular bone. Objective: The objective of this randomized, self-controlled case series was to determine whether core osteostixis improved lameness in Quarter Horses with podotrochlear syndrome characterized by bilateral magnetic resonance imaging (MRI) findings of osseous cyst-like lesions of the navicular bone. Methods: Seven Quarter Horses that had not responded to standard medical management were included. Each horse had an affected forefoot randomly assigned to surgical treatment with navicular bursoscopy and core osteostixis; the contralateral limb was assigned to navicular bursoscopy only. Video recordings were used to assign lameness scores and make comparisons of each limb at baseline and 24 weeks post-operatively by an observer blinded to the surgical treatment. A second MRI was performed 24 weeks after surgery to reevaluate navicular bone edema, osseous cyst-like lesions of the navicular bone, and tears of the deep digital flexor tendon (DDFT). Results: Reduction of lameness score from baseline was significantly (P = 0.0254) greater for the limbs treated with core osteostixis than limbs treated with bursoscopy. New DDFT tears were noted in 3 of 7 limbs treated with core osteostixis and in 1 of 7 bursoscopy limbs. Conclusion: Results of this study suggest that core osteostixis of the navicular bone combined with navicular bursoscopy can improve lameness in horses with osseous cyst-like lesions. Further evaluation of this technique is warranted.