Carpal variability and asymmetry in limb reduced Western lesser sirens (Siren nettingi).

Trait functionality can act as a constraint on morphological development. Traits that become vestigialized can exhibit unstable developmental patterns such as fluctuating asymmetry (FA) and variation in populations. We use clearing and staining along with morphometric analyzes to compare FA and allometry of limbs in Western lesser sirens (Siren nettingi) to Ouachita dusky salamanders (Desmognathus brimleyorum). Our results describe new carpal phenotypes and carpal asymmetry in our sample of S. nettingi. However, we found no significant evidence of limb length asymmetry in S. nettingi. The degree of relative limb asymmetry correlates inversely with body size in both of our samples. This work provides strong evidence of increased mesopodal variation within a population of S. nettingi. Our work provides a basis for further study of a broader range of morphological traits across salamanders.

Genicular Artery embolisation in Patients with Osteoarthritis of the Knee (GENESIS) Using Permanent Microspheres: Long-Term Results.

PURPOSE: To report the 2-year follow-up of patients with mild-to-moderate knee osteoarthritis (OA) treated with genicular artery embolisation (GAE) as part of the GENESIS study. MATERIALS AND METHODS: Forty-six patients, median age = 60 (45-83) underwent GAE using permanent microspheres (100-300 µm). Technical success was defined as embolisation of the targeted genicular arteries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) (0-100 mm) were recorded at baseline, 6 weeks, 3 months, 1, 2 years. Contrast-enhanced MRI knee scans were acquired at baseline and 1 year, and evaluated with the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Functional MRI brain imaging and psychometric assessments were undertaken to investigate correlation between neuropsychological phenotypes and clinical outcome. Adverse events were recorded prospectively. RESULTS: Technical success was achieved in forty patients (87%). Mean VAS improved from 58.63 (SD = 20.57, 95% CI 52.7-65.5) at baselines to 37.7 at 2-years (SD = 26.3, 95% CI 27.0-47.5). Whole and subgroup KOOS were significantly improved at each timepoint with associated reductions in analgesia usage. WORMS analysis demonstrated significant reduction in synovitis (p < 0.05) with no cases of osteonecrosis. Self-limiting skin discolouration occurred in four patients. A self-limiting groin haematoma and single case of deep-vein thrombosis due to immobilisation were also recorded. Nine patients subsequently underwent knee arthroplasty with no additional operational complexities identified. Neuropsychometric assessment elucidated a correlation between baseline catastrophising and greater reduction in pain post GAE. CONCLUSION: GAE is a safe intervention for mild-moderate knee osteoarthritis, with sustained efficacy at 2 years. These results are promising and justify ongoing controlled trials.

"We want to change the system": a qualitative study on emergency medicine physician leadership.

OBJECTIVE: The significance of physician leadership to help transform the healthcare system has been increasingly discussed. This study looked at the qualities of emergency medicine (EM) physicians that support or inhibit their work as healthcare leaders. METHODS: Through an iterative process of semi-structured interviews and then focus groups, we examined why EM physicians pursue leadership roles, the strengths they bring and the frustrations they encounter. Thematic analysis identified factors that facilitate and inhibit the work of EM physicians as they enter leadership roles. RESULTS: These findings can be summarized in four key themes. (1) A desire to improve the wider health system was often a prime motivator for entering a leadership role. (2) EM physicians' clinical skills such as confident decision-making, relationship building through communication, and comfort with uncertainty supported their successful transition to leadership. (3) EM physician leaders perceived shiftwork as both a potential benefit and a challenge in their leadership role and felt it needed to be carefully managed to ensure personal wellness and success. And (4) participants were not driven to take on leadership positions by financial remuneration but stated that the discrepancy between EM clinical and leadership compensation was a point of stress. CONCLUSION: As physician leadership is explored as a mechanism to support the healthcare system's success, this project provides insights into the realities experiences by EM physicians and considerations for healthcare professionals as they encourage physicians into leadership positions.

RéSUMé: OBJECTIF: L'importance du leadership des médecins pour aider à transformer le système de santé est de plus en plus discutée. Cette étude s'est penchée sur les qualités des médecins urgentistes (MU) qui soutiennent ou entravent leur travail en tant que leaders dans le domaine des soins de santé. MéTHODES: Grâce à un processus itératif d'entretiens semi-structurés puis de groupes de discussion, nous avons examiné les raisons pour lesquelles les médecins spécialistes en médecine d'urgence assument des fonctions de direction, les forces qu'ils apportent et les frustrations qu'ils rencontrent. L'analyse thématique a permis d'identifier les facteurs qui facilitent et inhibent le travail des médecins en médecine d'urgence lorsqu'ils accèdent à des fonctions de direction. RéSULTATS: Ces résultats peuvent être résumés en quatre thèmes principaux. 1) Le désir d'améliorer le système de santé dans son ensemble était souvent une motivation majeure pour accéder à un rôle de leadership. 2) Les compétences cliniques des médecins en médecine d'urgence, telles que la prise de décision en toute confiance, l'établissement de relations par la communication et l'aisance face à l'incertitude, ont favorisé leur transition réussie vers le leadership. 3) Les médecins leaders en médecine d'urgence percevaient le travail posté comme un avantage potentiel et un défi dans leur rôle de leadership et estimaient qu'il devait être géré avec soin pour assurer le bien-être et la réussite personnels. Et 4) les participants n'ont pas été incités à occuper des postes de direction par la rémunération financière, mais ont déclaré que l'écart entre la rémunération clinique et la rémunération de la direction de MU était un point de stress. CONCLUSIONS: Alors que le leadership des médecins est considéré comme un mécanisme de soutien au succès du système de santé, ce projet donne un aperçu des réalités vécues par les médecins en médecine d'urgence et des considérations pour les professionnels de la santé qui encouragent les médecins à occuper des postes de direction.

Resident Education Curriculum in Pediatric and Adolescent Gynecology: The Short Curriculum 4.0.

Exposure to pediatric and adolescent gynecology (PAG) varies across residency programs in obstetrics and gynecology, family medicine, and pediatrics, as well as both adolescent medicine and PAG fellowship programs. Nevertheless, these programs are responsible for training residents and fellows and providing opportunities to fulfill PAG learning objectives. To that end, the North American Society for Pediatric and Adolescent Gynecology has taken a leadership role in PAG trainee education by creating and maintaining this Short Curriculum. The curriculum outlines specific learning objectives central to PAG education and lists high-yield, concise resources for learners. This updated curriculum replaces the previous 2021 publication with a new focus toward accessible online content and updated resources.

Aboriginal and Torres Strait Islander youth suicide mortality and previous mental health, suicidality and service use in Queensland, Australia, from 2001 to 2021.

BACKGROUND: The current study aimed to compare current suicide rates, trends, previous treatment, suicidality and mental health diagnoses for First Nations and non-Indigenous young people who died by suicide. METHODS: Age-specific suicide rates (ASSRs) were calculated per 100,000 persons/year using suicides aged 10-19 years in the Queensland Suicide Register. Rate Ratios (RRs) and 95 % CIs compared ASSRs for First Nations and non-Indigenous youth dying by suicide in Queensland, Australia, from 2001 to 2018. Risk ratios (RiskR) with 95 % CIs compared characteristics between First Nations and non-Indigenous youth suicides. Joinpoint regression was used to identify any changes in trends and annual percentage change (APC) in suicides with 95 % CIs. RESULTS: The First Nations youth ASSR was 24.71 deaths per 100,000 persons/year, 4.5 times the non-Indigenous ASSR (95 % CI = 3.74-5.38, p < 0.001). Both non-Indigenous and First Nations suicide trends were stable with no joinpoints (APC: 0.3 %, 95 % CI: -1.6-2.2, p = 0.78; APC: 0.9 %, 95 % CI: -0.2-2.1, p = 0.11). Less than a quarter (23.9 %) of First Nations young people had ever received mental health treatment, significantly fewer than non-Indigenous youth (RiskR = 0.80, 95 % CI = 0.71-0.90, p < 0.001). Similarly, in the three months preceding their death, only 14.5 % of First Nations young people had received mental health treatment (RiskR = 0.89, 95 % CI = 0.83-97, p = 0.015). LIMITATIONS: Reported mental illness, suicidality and help-seeking could be underreported due to concealment from family or police. CONCLUSIONS: The current study finds no change in the gap between the First Nations and Non-Indigenous youth suicide rates nor evidence of decrease in the First Nations youth suicide rate. There is a need for alternative approaches to Indigenous youth suicide prevention, such as assertive outreach models outside of traditional triage and mental health systems to proactively build trusting relationships with young people in communities to identify young people needing support.

How neonatal diet affects the long-term development of rumination behavior, rumen fermentation and feed digestion in dairy calves fed a high milk level?

This study was to investigate growth performance, rumination development, rumen fermentation and feed digestion in young calves provided high volumes (about 20% of calf birth weight) of milk with or without forage inclusion and how these parameters correlate with each other. Immediately after birth, 160 newborn Holstein female calves (41.6 ± 4.2 kg of initial BW) were randomly divided into 2 treatments: 1) starter (CON, only starter) and 2) starter and hay (HAY, both starter and hay). The calves were fed their respective experimental diets from d 4 to 84, after which they were all introduced to similar diets until the end of the experiment on d 196. Treatment had no effect on growth and structural measurements throughout the experimental period. However, treatment had an effect on the other parameters, mainly during the post-weaning period. Forage supplementation tended to reduce starter dry matter intake (P = 0.05), while increasing the forage intake (P < 0.01) and the feed-to-gain ratio (P < 0.01). HAY calves had increased neutral detergent fiber (NDF) and physically effective NDF (peNDF) intakes (P < 0.05) and tended to lower (P < 0.01) starch intake compared to CON calves. The HAY calves had a higher rumination time (P < 0.01), ruminal pH (P < 0.01), and acetate-to-propionate ratio (P = 0.05) compared to the CON calves. Spearman correlation analysis showed that rumination time was positively related to the ruminal pH at d 84 (P = 0.01) and 196 (P = 0.02). The HAY calves had similar apparent total-tract digestibility of dry matter (DM), NDF and ether extract (EE), but lower digestibility of organic matter (OM, P = 0.03), crude protein (CP, P < 0.01) and starch (P < 0.01) compared to those of the CON calves at week 12. Furthermore, there were no positive relationships between rumination time and nutrient digestibility or between rumination time per kilogram DM and nutrient digestibility. In conclusion, feeding hay to calves fed a high milk level improved rumination during the post-weaning period only, without a concomitant effect on growth performance throughout the experimental period, suggesting no detrimental effect of feeding forage in calves fed high milk level.

Pediatric and Adolescent Gynecology WebEd: A Brief Report of an Underutilized Online Learning Module.

Pediatric and adolescent gynecology (PAG) is a unique subspecialty for which accessible educational resources and clinical exposure have historically been limited; surveys show that trainees in both obstetrics and gynecology and pediatrics agree. In 2014, the North American Society for Pediatric and Adolescent Gynecology (NASPAG) introduced PAG WebEd, an original and interactive online case-based curriculum designed to bridge this learning gap. As of 2023, there are 35 published PAG WebEd clinical cases with key learning points that present, test, and discuss a variety of current PAG topics. The NASPAG Resident Education Committee (REC) compiled and reviewed administrative data from the module platform to investigate trainee utilization and performance. The activity data and assessment scores for 161 registered users are included and reported in this article. This brief report highlights that a relatively small number of medical trainees use PAG WebEd and aims to raise awareness of this resource through publication. There is potential for many more users to benefit from this resource; its efficacy as an examination and clinical practice tool could also be measured. The NASPAG REC hopes to ultimately show, with increased utilization, that PAG WebEd deserves to be a key piece of PAG-focused medical education. For PAG WebEd information and faculty registration, as well as a link that allows faculty to submit new learners, please visit https://www.naspag.org/pagwebed-information.

Intravenous Ketamine for Pain Control in First-Trimester Surgical Abortion: Interim Analysis of a Randomized Controlled Trial.

OBJECTIVES: Surgical abortion is common, with most completed in the first trimester. Gold standard pain control is intravenous (IV) fentanyl and midazolam, requiring continuous cardio-respiratory monitoring, a potential challenge where this monitoring is unavailable. Ketamine is a sedative and analgesic without the cardio-respiratory depression risk associated with IV opioids, representing a potential alternative. Investigating non-opiate pain control methods is imperative given the context of the opioid crisis. This is an interim analysis of 45 participants from a randomized controlled trial comparing IV ketamine, oral morphine, and IV fentanyl for pain control in first-trimester surgical abortion. We hypothesize that ketamine will provide better pain control than morphine. METHODS: This is a double-blind, single-centre superiority trial of 3 parallel groups. Participants were ≥18 years old with confirmed intrauterine pregnancy of gestational age <12 weeks. Pain was assessed using the Visual Analogue Scale and the Wong-Baker Faces Pain Rating Scale. RESULTS: In total, 2 participants were excluded post-randomization for 43 treated. Findings indicate that ketamine (n = 14; M = 0.7; 95% CI 0.1-1.3) provides better intra-operative pain control than morphine (n = 15, M = 4.4, 95% CI 2.9-5.9) and fentanyl (n = 14; M = 4.3; 95% CI 3.0-5.6; P < 0.001). The ketamine group was more satisfied with the anaesthetic method than the morphine group (P = 0.017). No group experienced serious adverse events. CONCLUSIONS: Findings support continuation of the randomized controlled trial and highlight ketamine as a compelling non-opiate pain control option in first-trimester surgical abortion. Ketamine use may represent more optimal pain control in settings where continuous cardio-respiratory monitoring is unavailable.

The effect of parenteral vitamin B12 on the growth rate of dairy calves over the summer and autumn on seven farms from the Central Plateau, New Zealand.

AIMS: To investigate the effect of parenteral vitamin B12 supplementation on the growth rate of dairy heifer calves over the summer and autumn on seven farms from the Central Plateau of New Zealand, an area historically associated with low cobalt levels in grazing pasture. METHODS: This was a controlled clinical trial conducted on a convenience sample of seven farms with young female calves randomly assigned to three vitamin B12 treatment groups and followed through a grazing season. Two treatment groups received either monthly SC injections of a short-acting (SA) B12 formulation or 3-monthly injections of a long-acting (LA) B12 formulation and the third group received no treatment (NT). No additional parenteral vitamin B12 was given; however, all calves received additional cobalt (0.04-0.4 mg Co/kg liveweight) in the mineralised anthelmintic drenches given orally every month. Liveweight was recorded in December/January and at the end of the trial in May/June/July depending on farm. Pasture cobalt concentrations (mg/kg DM) were measured every month using 500-g herbage samples from 100-m transects in the area about to be grazed by the trial groups. RESULTS: There was evidence for a difference in growth rate between groups with mean final weight of 228 (95% CI = 212-243) kg for the LA groups, 224 (95% CI = 209-239) kg for the SA groups and 226 (95% CI = 211-241) kg for the NT groups respectively, (global p-value = 0.014). Calves given SA vitamin B12 were 3.77 (95% CI = 0.71-6.82) kg lighter than calves given LA vitamin B12 (p = 0.011). There was no evidence for a change in pasture cobalt concentrations (p = 0.32). CONCLUSIONS AND CLINICAL RELEVANCE: The results of this trial raise the question as to whether the routine use of vitamin B12 supplementation in young cattle from areas traditionally thought to be cobalt deficient is necessary, and further raise the possibility that vitamin B12 supplementation by repeated injection of SA products may negatively impact growth rates.

Bovine milk microbiota: Key players, origins, and potential contributions to early-life gut development.

BACKGROUND: Bovine milk is a significant substitute for human breast milk and holds great importance in infant nutrition and health. Apart from essential nutrients, bovine milk also contains bioactive compounds, including a microbiota derived from milk itself rather than external sources of contamination. AIM OF REVIEW: Recognizing the profound impact of bovine milk microorganisms on future generations, our review focuses on exploring their composition, origins, functions, and applications. KEY SCIENTIFIC CONCEPTS OF REVIEW: Some of the primary microorganisms found in bovine milk are also present in human milk. These microorganisms are likely transferred to the mammary gland through two pathways: the entero-mammary pathway and the rumen-mammary pathway. We also elucidated potential mechanisms by which milk microbiota contribute to infant intestinal development. The mechanisms include the enhancing of the intestinal microecological niche, promoting the maturation of immune system, strengthening the intestinal epithelial barrier function, and interacting with milk components (e.g., oligosaccharides) via cross-feeding effect. However, given the limited understanding of bovine milk microbiota, further studies are necessary to validate hypotheses regarding their origins and to explore their functions and potential applications in early intestinal development.

Validating low-fidelity arthroscopic simulation in medical students: a feasibility trial.

INTRODUCTION: With surgical opportunities becoming increasingly restricted for orthopaedic trainees, simulation training is a valuable alternative at providing sufficient practice. This pilot study aims to assess the potential effectiveness of low-fidelity simulation in teaching medical students basic arthroscopic skills and the feasibility of its incorporation into formal student training programmes. METHODS: Twenty-two medical students completed pre- and post-training tests on the Probing (Task 1) and Maze (Task 2) exercises from the Sawbones 'Fundamentals of Arthroscopy Surgery Training' (FAST) programme. Training consisted of practising horizon control, deliberate linear motion and probing within 25min over a period of days. Completion time and error frequency were measured. The difference in performance was assessed using a paired two-tailed t-test. Qualitative data were collected. RESULTS: Test completion time decreased significantly by a mean of 83s (±46s, 95% confidence intervals [CI] 37 to 129) for Task 1 (p=0.001) and 105s (±55s, 95% CI 50 to 160) for Task 2 (p=0.0007). Frequency of direct visualisation errors decreased significantly by a mean of 1.0 errors (±1.0 errors, 95% CI 0.1 to 2.0) for Task 1 (p = 0.04) and 0.8 errors (±0.8 errors, 95% CI 0.1 to 1.6) for Task 2 (p = 0.04). At post-training, 82% of participants were willing to incorporate FAST into formal training. CONCLUSIONS: Low-fidelity simulators such as FAST can potentially teach basic arthroscopic skills to medical students and are feasible for incorporation into formal training. They also give students a cost-effective and safe basic surgical training experience.

Risk factors for horse falls in New Zealand Thoroughbred jumps racing.

This study aimed to determine the incidence of, and risk factors for race-day horse falls in Thoroughbred jumps (hurdle and steeplechase) racing in New Zealand. Incidence rates for race-day horse falls in jumps races from 2005/6 - 2018/19 racing seasons (n = 13,648 race day starts) were calculated per 1000 starts. Univariable and multivariable analyses of race-, horse- and jockey-level risk factors for horse falls were conducted using Poisson regression in a generalised linear mixed model. The incidence rate of horse falls in jumps races was 42 (95 % confidence intervals [CI], 39 - 45) per 1000 starts. Horse falls in steeplechase races were 1.6 (95 % CI, 1.4 - 1.9) times more likely than hurdle races. The incidence rate ratio (IRR) for horses falling at the last three jumps in comparison with the first three jumps was 3.1 (95 % CI, 2.8 - 3.5) for hurdle and 4.4 (95 % CI, 3.9 - 5.0) for steeplechase races. Greater jockey (age, P = 0.02) and horse experience (P = 0.001) were associated with a lower IRR of falls (P = 0.05). Longer races (P = 0.02) and those held in autumn compared to winter (IRR 1.4; 95 % CI, 1.0 - 1.8; P = 0.05) were associated with a higher rate of falling in steeplechase races. A regulatory change enhancing discretionary ability of jockeys to pull up 'in-race' was associated with reduced horse falls (IRR 0.65; 95 % CI, 0.51 - 0.82; P = 0.001). Pragmatic rule changes within the industry can have a positive effect on reducing risk and improving equine welfare.

Long Curriculum 3.0 in Resident Education: Comprehensive Curriculum in Pediatric and Adolescent Gynecology for Postgraduate Trainees in Obstetrics/Gynecology, Pediatrics, and Adolescent Medicine.

In 2015, the Resident Education Committee of the North American Society for Pediatric and Adolescent Gynecology published the Long Curriculum in Resident Education to provide educators with a comprehensive document to be used in postgraduate medical education. The original curriculum was designed to meet the resident learning objectives for the Council on Resident Education in Obstetrics and Gynecology, the American Board of Pediatrics, and the Royal College of Physicians and Surgeons of Canada and to provide a more intensive, broader learning experience. The curriculum was updated in 2018. This Committee Document is the third updated version (3.0) of the Long Curriculum in Resident Education.

Virtual reality promotes greater improvements than video-stimulation screen on perceptual-cognitive skills in young soccer athletes.

Background The literature has shown the positive effect of virtual reality (VR) in percepto-cognitive skills. However, the literature lacks findings about at what extent VR would be better than video. Purpose This study aimed to analyze the chronic effect of VR and video-stimulation screen training on passing decision-making, visual search behavior, and inhibitory control performance in young soccer athletes. Method A total of 26 young soccer players underwent an 8-week training protocol after being randomly assigned to the VR (n = 13) or video-screen (VID, n = 13) group. Passing decision-making, visual search behavior, and inhibitory control performance were measured before and after both interventions. Results A group x time interaction was found for decision-making performance (p < 0.01) and visual search behavior (p < 0.01). Both groups improved both decision-making performance (p < 0.01) and visual search behavior (p < 0.01); however, greater improvements were verified in VR (p < 0.01). Both VR and VID improved inhibitory control (p < 0.01), but no group interaction effect was observed (p > 0.05). Conclusion Our results suggest that VR leads to greater improvements in decision-making and visual search behavior in young soccer athletes than VID.

Estimating the potential impact of interventions to reduce over-calling and under-calling of melanoma.

BACKGROUND: Pathologists sometimes disagree over the histopathologic diagnosis of melanoma. 'Over-calling' and 'under-calling' of melanoma may harm individuals and healthcare systems. OBJECTIVES: To estimate the extent of 'over-calling' and 'under-calling' of melanoma for a population undergoing one excision per person and to model the impact of potential solutions. METHODS: In this epidemiological modelling study, we undertook simulations using published data on the prevalence and diagnostic accuracy of melanocytic histopathology in the U.S. POPULATION: We simulated results for 10 000 patients each undergoing excision of one melanocytic lesion, interpreted by one community pathologist. We repeated the simulation using a hypothetical intervention that improves diagnostic agreement between community pathologist and a specialist dermatopathologist. We then evaluated four scenarios for how melanocytic lesions judged to be neither clearly benign (post-test probability of melanoma < 5%), nor clearly malignant (post-test probability of melanoma > 90%) might be handled, before sending for expert dermatopathologist review to decide the final diagnosis. These were (1) no intervention before expert review, (2) formal second community pathologist review, (3) intervention to increase diagnostic agreement and (4) both the intervention and formal second community pathologist review. The main outcomes were the probability of 'over-calling' and 'under-calling' melanoma, and number of lesions requiring expert referral for each scenario. RESULTS: For 10 000 individuals undergoing excision of one melanocytic lesion, interpreted by a community pathologist, a hypothetical intervention to improve histopathology agreement reduced the number of benign lesions 'over-called' as melanoma from 308 to 164 and the number of melanomas 'under-called' from 289 to 240. If all uncertain diagnoses were sent for expert review, the number of referrals would decrease from 1500 to 737 cases if formal second community pathologist review was used, and to 701 cases if the hypothetical intervention was additionally used. CONCLUSIONS: Interventions to improve histopathology agreement may reduce melanoma 'over-calling' and 'under-calling'.

Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis.

PURPOSE: Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres. METHODS: Thirty-eight patients, median age = 60 (45-83), attended for GAE using 100-300 µm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0-100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively. RESULTS: Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53-66) at baseline to 36 (SD = 24, 95% CI 28-44) at 3 months (p < 0.001) and 45 (SD = 30, 95% CI 30-60) at 1-year (p < 0.05). All KOOS subscales showed a significant improvement at 6-weeks, 3-months, and 1-year follow-up, except function in daily living, which reached borderline significance (p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p < 0.05). There were no cases of osteonecrosis. CONCLUSION: GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.

Latent-transforming growth factor beta-binding protein-2 (LTBP-2) is required for longevity but not for development of zonular fibers.

Latent-transforming growth factor beta-binding protein 2 (LTBP-2) is a major component of arterial and lung tissue and of the ciliary zonule, the system of extracellular fibers that centers and suspends the lens in the eye. LTBP-2 has been implicated previously in the development of extracellular microfibrils, although its exact role remains unclear. Here, we analyzed the three-dimensional structure of the ciliary zonule in wild type mice and used a knockout model to test the contribution of LTBP-2 to zonule structure and mechanical properties. In wild types, zonular fibers had diameters of 0.5-1.0 micrometers, with an outer layer of fibrillin-1-rich microfibrils and a core of fibrillin-2-rich microfibrils. LTBP-2 was present in both layers. The absence of LTBP-2 did not affect the number of fibers, their diameters, nor their coaxial organization. However, by two months of age, LTBP-2-depleted fibers began to rupture, and by six months, a fully penetrant ectopia lentis phenotype was present, as confirmed by in vivo imaging. To determine whether the seemingly normal fibers of young mice were compromised mechanically, we compared zonule stress/strain relationships of wild type and LTBP-2-deficient mice and developed a quasi-linear viscoelastic engineering model to analyze the resulting data. In the absence of LTBP-2, the ultimate tensile strength of the zonule was reduced by about 50%, and the viscoelastic behavior of the fibers was altered significantly. We developed a harmonic oscillator model to calculate the forces generated during saccadic eye movement. Model simulations suggested that mutant fibers are prone to failure during rapid rotation of the eyeball. Together, these data indicate that LTBP-2 is necessary for the strength and longevity of zonular fibers, but not necessarily for their formation.

Developing immune-regulatory materials using immobilized monosaccharides with immune-instructive properties.

New strategies for immune modulation have shown real promise in regenerative medicine as well as the fight against autoimmune diseases, allergies, and cancer. Dendritic cells (DCs) are gatekeepers of the immune system and their ability in shaping the adaptive immune responses makes DCs ideal targets for immune modulation. Carbohydrates are abundant in different biological systems and are known to modulate DC phenotype and function. However, how simple monosaccharides instruct DC function is less well understood. In this study, we used a combinatorial array of immobilized monosaccharides to investigate how they modulate DC phenotype and function and crucially the impact of such changes on downstream adaptive immune responses. Our data show that a selection of monosaccharides significantly suppress lipopolysaccharide-induced DC activation as evidenced by a reduction in CD40 expression, IL-12 production, and indoleamine 2,3-dioxygenase activity, while inducing a significant increase in IL-10 production. These changes are indicative of the induction of an anti-inflammatory or regulatory phenotype in DCs, which was further confirmed in DC-T cell co-cultures where DCs cultured on the 'regulatory' monosaccharide-coated surfaces were shown to induce naïve T cell polarization toward regulatory phenotype. Our data also highlighted a selection of monosaccharides that are able to promote mixed Treg and Th17 cell differentiation, a T cell phenotype expected to be highly immune suppressive. These data show the potential immunomodulatory effects of immobilized monosaccharides in priming DCs and skewing T cell differentiation toward an immune-regulatory phenotype. The ability to fine-tune immune responses using these simple carbohydrate combinations (e.g. as coatings for existing materials) can be utilized as novel tools for immune modulation with potential applications in regenerative medicine, implantable medical devices, and wound healing where reduction of inflammatory responses and maintaining immune homeostasis are desirable.