Cellular Uptake of Upconversion Nanoparticles Based on Surface Polymer Coatings and Protein Corona.

Upconversion nanoparticles (UCNPs) are materials that provide unique advantages for biomedical applications. There are constantly emerging customized UCNPs with varying compositions, coatings, and upconversion mechanisms. Cellular uptake is a key parameter for the biological application of UCNPs. Uptake experiments have yielded highly varying results, and correlating trends between cellular uptake with different types of UCNP coatings remains challenging. In this report, the impact of surface polymer coatings on the formation of protein coronas and subsequent cellular uptake of UCNPs by macrophages and cancer cells was investigated. Luminescence confocal microscopy and elemental analysis techniques were used to evaluate the different coatings for internalization within cells. Pathway inhibitors were used to unravel the specific internalization mechanisms of polymer-coated UCNPs. Coatings were chosen as the most promising for colloidal stability, conjugation chemistry, and biomedical applications. PIMA-PEG (poly(isobutylene-alt-maleic) anhydride with polyethylene glycol)-coated UCNPs were found to have low cytotoxicity, low uptake by macrophages (when compared with PEI, poly(ethylenimine)), and sufficient uptake by tumor cells for surface-loaded drug delivery applications. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) studies revealed that PIMA-coated NPs were preferentially internalized by the clathrin- and caveolar-independent pathways, with a preference for clathrin-mediated uptake at longer time points. PMAO-PEG (poly(maleic anhydride-alt-1-octadecene) with polyethylene glycol)-coated UCNPs were internalized by energy-dependent pathways, while PAA- (poly(acrylic acid)) and PEI-coated NPs were internalized by multifactorial mechanisms of internalization. The results indicate that copolymers of PIMA-PEG coatings on UCNPs were well suited for the next-generation of biomedical applications.

The variation of anticoagulation prescribed in foot and ankle surgery in the UK - UK foot and ankle thrombo-embolism audit (UK-FATE).

INTRODUCTION: Venous thrombo-embolism (VTE) is a recognised complication of foot and ankle surgery. There are multiple possible anticoagulation treatments available in the UK to mitigate the risk of developing VTE. Our primary objective was to assess the variability of chemical anticoagulation prescribed in patients undergoing foot and ankle procedures. METHODS: This was a UK-based national, multicenter, prospective audit spanning a collection duration of 9 months on all foot and ankle procedures, carried out in 68 UK centers between 1st June 2022 and 30th November 2022, with a further 3-month follow up period. All patients who underwent a foot and ankle surgical procedure (including Achilles tendon rupture treatment) were included in this study. RESULTS: Data on a total of 13,569 patients was submitted. Following data cleansing, 11,363 patients were available for further analysis, with anticoagulation data available for 11,099 patients. There were eleven different chemical anticoagulation treatments recorded across the cohort. A total of 3630 (31.95 %) patients received no chemical anticoagulation. The patients receiving chemical anticoagulation medication could be split into 4 main groups. The most common chemical anticoagulation received was low molecular weight heparin (LMWH) (6303, 84.4 % of patients receiving chemical anticoagulation). Aspirin was given in 4.1 % (308 patients), a Factor Xa inhibitor in 10 % (744 patients) and other anticoagulants (e.g. Warfarin) in 1.5 % (114 patients). The overall VTE rate in this sub analysis of patients receiving chemical anticoagulation, was 1.1 % (83 cases out of 7469). There was no significant difference seen in incidence of VTE between types of anticoagulants, when confounding factors were considered. The duration of post-operative chemical prophylaxis used by participants for most chemical anticoagulants was 6 weeks (64.50 %). CONCLUSION: There was significant variability of chemical anticoagulants reported in the study, with five different categories of anticoagulants used (including no chemical anticoagulation), and none clearly superior/inferior. The duration of anticoagulation was consistent across types of thromboprophylaxis.

Lung Manifestation of Dengue Fever: A Retrospective Study.

Introduction Dengue fever, caused by the dengue virus transmitted by Aedes aegypti mosquitoes, is a significant public health concern globally. Its resurgence in recent years, particularly in low- and middle-income countries, has led to increased morbidity and mortality rates. Atypical manifestations, involving the cardiac, liver, gut, renal, blood, bone, nervous, and respiratory systems, in dengue, can complicate both diagnosis and management. This study aimed to investigate the incidence of lung manifestations in dengue-infected individuals and their correlation with patient outcomes. Background The prevalence of dengue fever has risen dramatically over the past two decades, with Asia bearing the brunt of the burden, particularly India. The pathophysiology of lung complications in dengue remains unclear but is thought to be related to capillary leak syndrome and thrombocytopenia. Studies suggest that respiratory symptoms may be associated with severe cases and increased mortality rates. Despite limited research in India, understanding lung manifestations in dengue is crucial for improving diagnostic accuracy and patient care. Methods A retrospective study was conducted at K.S. Hegde Hospital, a tertiary care facility located in Mangalore, India, involving patients aged 18 years and above diagnosed with dengue fever between January and December 2019. Data gathered comprised patient demographics, clinical symptoms, laboratory findings, imaging results including radiographs, computed tomography (CT) scans of the chest (if accessible), ultrasound examinations of the chest and abdomen, and 2D echocardiograms, as well as patient outcomes. Diagnosis of lung manifestation was established through clinical assessment, chest X-ray interpretation, and ultrasound of the chest. Statistical analysis was conducted using SPSS Statistics (version 20), with a significance set at p<0.05. Results Out of 255 dengue cases, 10.19% (n=26) exhibited pulmonary manifestations, with pleural effusion being the most common. Older age (>50 years) and comorbidities were associated with a higher incidence of lung involvement. Respiratory symptoms, such as breathlessness, were more prevalent in patients with pulmonary complications. Laboratory parameters indicated distinct profiles in patients with lung manifestations, including elevated total count, urea, bilirubin, and liver enzymes, and reduced platelet counts. Mortality rates were higher in patients with lung involvement, older age, and comorbidities. Discussion The study findings highlight the importance of recognizing respiratory symptoms in dengue fever, particularly in older patients and those with underlying health conditions. The association between pulmonary involvement and adverse outcomes underscores the need for early detection and appropriate management strategies. Future research should focus on elucidating the pathophysiology of lung complications in dengue and developing targeted interventions to improve patient outcomes. Conclusion Lung manifestations in dengue fever represent a significant clinical challenge and are associated with increased morbidity and mortality. Early recognition of respiratory symptoms, along with prompt diagnostic evaluation and appropriate management, is essential for improving patient prognosis. Further studies are warranted to deepen our understanding of lung involvement in dengue and optimize therapeutic approaches to mitigate its impact on patient outcomes.

Characteristics of Patients Not Receiving Chemical Thromboprophylaxis Following Foot and Ankle Surgery: Data From the Multicenter, Prospective UK Foot and Ankle Thrombo-Embolism Audit (UK-FATE).

BACKGROUND: Although the rate of venous thromboembolism (VTE) after foot and ankle surgery is low, multiple factors influence risk for individual patients. Furthermore, there are no clear guidelines on which patients may benefit from chemical thromboprophylaxis. Our aim was to assess patients not treated with chemical thromboprophylaxis after foot and ankle surgery, and to report on their specific patient and surgical risk factors for VTE. METHODS: This was a multicenter, prospective, national audit of patients undergoing foot and ankle surgery (including Achilles tendon ruptures) from 68 participating UK centers. The study was conducted between June 1, 2022, and November 30, 2022, with a further 3-month follow-up. Following data cleansing, 3309 patients were included who did not receive postoperative thromboprophylaxis. RESULTS: Most patients were elective cases (2589 patients, 78.24%) with ASA grade I or II (2679 patients, 80.96%), fully weightbearing postoperatively (2752 patients, 83.17%), and either without ankle splintage, or splinted in a plantigrade boot (2797 patients, 84.53%). The VTE rate was 0.30% overall (11 cases), with no VTE-related mortality. No single demographic, surgical, or postoperative factor was associated with reduced risk of VTE. However, patients who had elective or trauma surgery not involving the ankle, who were ASA grade I or II and who were weightbearing immediately postoperatively (without splinting or in a plantigrade boot) had a VTE rate of 0.05% (1 of 1819 patients), compared with 0.67% (10 of 1490 patients, P = .002). CONCLUSION: Patients not receiving chemical thromboprophylaxis had a low incidence of symptomatic VTE, although they do represent a curated group considered lower risk. Within this group we describe characteristics associated with a substantially lower risk of VTE. All patients should be assessed on an individual basis, and further work is required to substantiate our findings.

Classifications in adult pes cavus - A scoping review.

AIMS: The adult cavus foot represents a challenging clinical problem, with varied aetiology and complex, 3-dimensional deformities. Thus far, the cavus foot has eluded a unified classification. The aim of this paper was to appraise the literature to identify classification systems which guide the operative management of neurological cavus feet in adults. METHODS: As the aim of this paper was broad, a scoping review was conducted. The review was conducted in line with published frameworks. Our principal research question was 'what classification systems that guide surgical management currently exist for neurological cavus feet in adults'. We searched CINAHL, Embase, OVID, Proquest, Pubmed, Scopus and Web of Science databases using MESH and non-MESH terms. Two authors independently reviewed abstracts / papers and a data extraction sheet was used to collect the relevant data. RESULTS: A total of 1140 articles were initially screened, identifying 125 articles for which a full text review was performed. Only three articles met all our inclusion criteria. All these articles reported an anatomical classification with suggestions for treatment based on the classification. All were considered to comprise Level V evidence, and none reported outcomes of treatment based on the classification. CONCLUSIONS: There is currently a paucity of robust classifications to guide treatment in neurological cavus feet in adults. The few classifications systems that exist are varied and do not as yet have sufficient evidence to support their widespread use. Further work is required, aimed at identifying specific features of cavus feet that would guide operative treatment.

Forefoot Morphotypes in Cavovarus Feet: A Novel Assessment of Deformity.

BACKGROUND: The cavovarus foot is a complex 3-dimensional deformity. Although a multitude of techniques are described for its surgical management, few of these are evidence based or guided by classification systems. Surgical management involves realignment of the hindfoot and soft tissue balancing, followed by forefoot balancing. Our aim was to analyze the pattern of residual forefoot deformities once the hindfoot is corrected, to guide forefoot correction. METHODS: We included 20 cavovarus feet from 16 adult patients with Charcot-Marie-Tooth who underwent weightbearing CT (mean age 43.4 years, range: 22-78 years, 14 males). Patients included had flexible deformities, with no previous surgery. Using specialized software (Bonelogic 2.1, Disior) a 3-dimensional, virtual model was created. Using morphologic data captured from normal feet in patients without pathology as a guide, the talonavicular joint of the cavovarus foot was digitally reduced to a "normal" position to simulate the correction that would be achieved during surgical correction. Models of the corrected position were exported and geometrically analyzed using Blender 3.64 to identify anatomical trends. RESULTS: We identified 4 types of cavovarus forefoot morphotypes. Type 0 was defined as a balanced forefoot (2 cases, 10%). Type 1 was defined as a forefoot where the first metatarsal was relatively plantarflexed to the rest of the foot, with no significant residual adduction after talonavicular joint correction (12 cases, 60%). Type 2 was defined as a forefoot where the second and first metatarsals were progressively plantarflexed, with no significant adduction (4 cases, 20%). Type 3 was defined as a forefoot where the metatarsals were adducted after talonavicular derotation (2 cases, 10%). CONCLUSION: In this relatively small cohort, we identified 4 forefoot morphotypes in cavovarus feet that might help surgeons to recognize and anticipate the residual forefoot deformities after hindfoot correction. Different treatment strategies may be required for different morphotypes to achieve balanced correction. LEVEL OF EVIDENCE: Level IV, retrospective case series.

The position, orientation, and relative size of the fibularis longus tubercle in normal patients: A weightbearing CT assessment.

The fibularis longus attaches to the base of the first metatarsal at the fibularis/peroneus longus tubercle (FLT/PLT). Theoretically, differences in FLT morphology may reflect changes in the function of the fibularis longus. This study defines the normal limits of the FLT position, orientation, and size in patients with morphologically normal foot anatomy. A retrospective analysis of 131 feet without deformity in 72 patients undergoing weightbearing CT (WBCT) at a single center was conducted. The position and morphology of the FLT was assessed with novel measurements including tubercle-floor distance, tubercle-metatarsal angle, and the angle between the floor and a line bisecting the FLT (bisecting angle). Roundness of the FLT was compared to a triangle limiting its shape (triangular ratio), with lower values indicating increasing roundness. We also report relative size of the FLT to the first metatarsal (X/Y ratio), and relative size of the first metatarsal and FLT to the second metatarsal (XY/Z ratio). There were no significant side to side differences for any measurement (p > 0.05). Mean values were: tubercle-floor distance 28.02 ± 2.63 mm, tubercle-metatarsal angle 32.7 ± 6.32 degrees, bisecting angle 65.58 ± 6.27 degrees, triangular ratio 0.69 ± 0.04, X/Y ratio 1.13 ± 0.20, and XY/Z ratio 3.44 ± -0.72. Bisecting angle strongly correlated with tubercle-metatarsal angle (Pearson correlation 0.840, p < 0.001) suggesting FLT rotation occurred independent of foot position. ICC was >0.943 for all measurements. This study reports the morphology of the FLT in individuals with normal feet. This normative data may be used in future studies examining differences between groups of patients with foot pathology, helping us better understand the role of fibularis longus in the development and treatment of foot disorders.

Structural validation of the Manchester-Oxford Foot Questionnaire for use in foot and ankle surgery.

Aims: The Manchester-Oxford Foot Questionnaire (MOxFQ) is an anatomically specific patient-reported outcome measure (PROM) currently used to assess a wide variety of foot and ankle pathology. It consists of 16 items across three subscales measuring distinct but related traits: walking/standing ability, pain, and social interaction. It is the most used foot and ankle PROM in the UK. Initial MOxFQ validation involved analysis of 100 individuals undergoing hallux valgus surgery. This project aimed to establish whether an individual's response to the MOxFQ varies with anatomical region of disease (measurement invariance), and to explore structural validity of the factor structure (subscale items) of the MOxFQ. Methods: This was a single-centre, prospective cohort study involving 6,637 patients (mean age 52 years (SD 17.79)) presenting with a wide range of foot and ankle pathologies between January 2013 and December 2021. To assess whether the MOxFQ responses vary by anatomical region of foot and ankle disease, we performed multigroup confirmatory factor analysis. To assess the structural validity of the subscale items, exploratory and confirmatory factor analyses were performed. Results: Measurement invariance by pathology was confirmed, suggesting the same model can be used across all foot and ankle anatomical regions. Exploratory factor analysis demonstrated a two- to three-factor model, and suggested that item 13 (inability to carry out work/everyday activities) and item 14 (inability to undertake social/recreational activities) loaded more positively onto the "walking/standing" subscale than their original "social interaction" subscale. Conclusion: This large cohort study supports the current widespread use of the MOxFQ across a broad range of foot and ankle pathologies. Our analyses found indications that could support alterations to the original factor structure (items 13 and 14 might be moved from the "social interaction" to the "walking/standing" subscale). However, this requires further work to confirm.

Talar neck rotation angle in adults with clubfoot deformity: Observed values and intra- and inter-observer reliability using weightbearing CT.

INTRODUCTION: Adults presenting with symptomatic clubfoot represent a challenging cohort of patients. An appreciation of the location and degree of deformities is essential for management. Talar anatomy is often abnormal with varus within the talar neck, however, there are few reproducible methods which quantify talar neck deformity in adults. We describe a technique of assessing talar neck deformity, and report on observed values and intra- / inter-observer reliability. METHODS: This was a single-centre, retrospective study including 96 feet from 56 adult patients with clubfeet (82 feet had clubfoot deformity, 14 were normal). Mean age was 34.3 ± 16.9 years and 31 (55.3%) were male. Weight-bearing CT scans captured as part of routine clinical care were analysed. Image reformats were oriented parallel to the long axis of the talus in the sagittal plane. In the corresponding axial plane two lines were drawn (on separate slices): 1) a line perpendicular to the intermalleolar axis, 2) a line connecting the midpoints of the talar head and narrowest part of the talar neck. The talar neck rotation angle (TNR angle) was the angle formed between these lines. Intraclass correlation coefficients (ICC) were performed for intra- and inter-observer reliability. RESULTS: Mean TNR angle in clubfeet was 27.6 ± 12.2 degrees (95%CI = 25.0 to 30.2 degrees). Mean TNR angle in normal feet was 18.7 ± 5.1 degrees (95%CI = 16.0 to 21.4 degrees) (p < 0.001). The ICC for clubfeet was 0.944 (95%CI = 0.913 to 0.964) for intra-observer agreement, and 0.896 (95%CI = 0.837 to 0.932) for inter-observer agreement. CONCLUSION: This measurement technique demonstrated excellent intra- and inter-observer agreement. It also demonstrated that compared to normal feet, clubfeet had about 9 degrees of increased varus angulation of the talar neck. This technique and data may be used for future research into clubfoot deformity and in planning treatment. LEVEL OF CLINICAL EVIDENCE: 3.

Outcomes of Tenosynovial Giant Cell Tumor of the Foot and Ankle.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a benign proliferative disease affecting synovial membranes. There are 2 forms, localized (L-TGCT) and diffuse (D-TGCT), which although histologically similar behave differently. It is locally invasive and is treated in most cases by operative excision. The aim of this study was to assess current practice, how the patients' presentation affected their outcome, as well as review the recurrence rates and complications. METHODS: A retrospective analysis of 123 cases was performed in patients treated between 2003 and 2019 with TGCT of the foot and/or ankle. Data were collected on age at presentation, radiologic pattern of disease, location of disease, treatment provided, and recurrence rates. The minimum follow-up was 2 years with a mean of 7.7 years. RESULTS: There were 61.7% female patients with a mean age of 39 (range, 11-76) years. L-TGCT accounted for 85 (69.1%) cases and D-TGCT for 38 (30.9%). The most prevalent preoperative symptoms were a palpable mass (78/123) and pain (65/123). Radiologically confirmed recurrence in the operative group was noted in 14.5% (16/110) cases. This comprised 4% (3/75) of operatively treated L-TGCT and 37% (13/35) of operatively treated D-TGCT. Patients with pain on presentation and those with erosive changes on presenting magnetic resonance imaging (MRI) were more likely to have persistent postoperative pain (P < .001 for both). Where patients had both preoperative pain and erosive changes, 57.1% had postoperative pain. Thirteen cases were managed nonoperatively where symptoms were minimal, with 1 case requiring surgery at a later date. CONCLUSION: Outcomes of TGCT management are dependent on the disease type, extent of preoperative erosive changes, and presence of preoperative pain. These data are useful for counseling patients regarding the outcomes of surgical intervention and help guide the timing of intervention. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

CYP2D6 Activity Is Correlated with Changes in Plasma Concentrations of Taurocholic Acid during Pregnancy and Postpartum in CYP2D6 Extensive Metabolizers.

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of >20% of marketed drugs. CYP2D6 expression and activity exhibit high interindividual variability and is induced during pregnancy. The farnesoid X receptor (FXR) is a transcriptional regulator of CYP2D6 that is activated by bile acids. In pregnancy, elevated plasma bile acid concentrations are associated with maternal and fetal risks. However, modest changes in bile acid concentrations may occur during healthy pregnancy, thereby altering FXR signaling. A previous study demonstrated that hepatic tissue concentrations of bile acids positively correlated with the hepatic mRNA expression of CYP2D6. This study sought to characterize the plasma bile acid metabolome in healthy women (n = 47) during midpregnancy (25-28 weeks gestation) and ≥3 months postpartum and to determine if plasma bile acids correlate with CYP2D6 activity. It is hypothesized that during pregnancy, plasma bile acids would favor less hydrophobic bile acids (cholic acid vs. chenodeoxycholic acid) and that plasma concentrations of cholic acid and its conjugates would positively correlate with the urinary ratio of dextrorphan/dextromethorphan. At 25-28 weeks gestation, taurine-conjugated bile acids comprised 23% of the quantified serum bile acids compared with 7% ≥3 months postpartum. Taurocholic acid positively associated with the urinary ratio of dextrorphan/dextromethorphan, a biomarker of CYP2D6 activity. Collectively, these results confirm that the bile acid plasma metabolome differs between pregnancy and postpartum and provide evidence that taurocholic acid may impact CYP2D6 activity during pregnancy. SIGNIFICANCE STATEMENT: Bile acid homeostasis is altered in pregnancy, and plasma concentrations of taurocholic acid positively correlate with CYP2D6 activity. Differences between plasma and/or tissue concentrations of farnesoid X receptor ligands such as bile acids may contribute to the high interindividual variability in CYP2D6 expression and activity.

Dressing Materials: A Comprehensive Review.

Injury to the skin provides a difficult challenge, as wound healing is a complex and dynamic process. Wound healing process recruits three different phases: inflammation, proliferation, and maturation. The sequence of events involved in wound healing can be affected by numerous disease processes, resulting in chronic, non-healing wounds that give significant discomfort and distress to the patients while draining the medical fraternity of enormous resources. Wound tissue never reaches its pre-injured strength and multiple aberrant healing states can result in chronic non-healing wounds. There is a growing concern about the usage of correct materials for wound dressings. The development of new and effective treatments in wound care still remains an area of intense research. There are a number of wound dressings available in the market. The objective of the article is to enhance knowledge about characteristics of an ideal wound dressing and guide in finding the correct dressing material. It also provides a detailed classification of traditional and modern wound dressings.

An Updated Review on Current Treatment of Alopecia Areata and Newer Therapeutic Options.

Alopecia areata (AA) is a dermatological disease that causes nonscarring hair loss. It can occur at any age and has an unpredictable and variable evolution in individuals. The aim of this review is to provide an update on the novel therapies currently being used, as well as upcoming therapeutic options in the treatment of AA.

First Metatarsal Rotation After Scarf Osteotomy for Hallux Valgus.

BACKGROUND: Recurrence after surgical correction of hallux valgus may be related to coronal rotation of the first metatarsal. The scarf osteotomy is a commonly used procedure for correcting hallux valgus but has limited ability to correct rotation. Using weight-bearing computed tomography (WBCT), we aimed to measure the coronal rotation of the first metatarsal before and after a scarf osteotomy, and correlate these to clinical outcome scores. METHODS: We retrospectively analyzed 16 feet (15 patients) who had a WBCT before and after scarf osteotomy for hallux valgus correction. On both scans, hallux valgus angle (HVA), intermetatarsal angle (IMA), and anteroposterior/lateral talus-first metatarsal angle were measured using digitally reconstructed radiographs. Metatarsal pronation angle (MPA), alpha angle, sesamoid rotation angle, and sesamoid position were measured on standardized coronal WBCT slices. Preoperative and postoperative (12 mo) clinical outcome scores (Manchester Oxford Foot Questionnaire and Visual Analogue Scores) were captured. RESULTS: Mean HVA was 28.6 ± 10.1° preoperatively and 12.1 ± 7.7° postoperatively (P < .001). Mean IMA was 13.7 ± 3.8° preoperatively and 7.5 ± 3.0° postoperatively (P < .001). Before and after surgery, there were no significant differences in MPA (11.4 ± 7.7 and 11.4 ± 9.9°, respectively; P = .75) or alpha angle (10.9 ± 8.0 and 10.7 ± 13.1°, respectively; P = .83). There were significant improvements in sesamoid rotation angle (SRA) (26.4 ± 10.2 and 15.7 ± 10.2°, respectively; P = .03) and sesamoid position (1.4 ± 1.0 and 0.6 ± 0.6, respectively; P = .04) after a scarf osteotomy. There were significant improvements in all outcome scores after surgery. Poorer outcome scores correlated with greater postoperative MPA and alpha angles (r = .76 (P = .02) and .67 (P = .03), respectively). CONCLUSION: A scarf osteotomy does not correct first metatarsal coronal rotation, and worse outcomes are linked to greater postoperative metatarsal rotation. Rotation of the metatarsal needs to be measured and considered when planning hallux valgus surgery. Further work was needed to compare postoperative outcomes with rotational osteotomies and modified Lapidus procedures when addressing rotation.Level of Evidence: 4.

3-D joint space mapping at the ankle from weight-bearing CT: reproducibility, repeatability, and challenges for standardisation.

OBJECTIVES: We present a 3-D approach to joint space width (JSW) measurement across the ankle from weight-bearing CT (WBCT) to demonstrate inter-operator reproducibility, test-retest repeatability, and how differences in angulation affect ankle JSW distribution. METHODS: One side from repeat WBCT imaging of both feet and ankles was analysed from 23 individuals as part of their routine clinical care pathway. Joint space mapping was performed at four facets across the talus: talonavicular, talar dome and medial gutter (dome-medial), lateral gutter, and posterior subtalar. Inter-operator reproducibility was calculated for two users, while test-retest repeatability was calculated by comparing the two visits, both presented as Bland-Altman statistics. Statistical parametric mapping determined any significant relationships between talocrural joint space angulation and 3-D JSW distribution. RESULTS: The average ± standard deviation interval between imaging was 74.0 ± 29.6 days. Surface averaged bias ± limits of agreement were similar for reproducibility and repeatability, the latter being: talonavicular 0.01 ± 0.26 mm, dome-medial 0.00 ± 0.28 mm, lateral gutter - 0.02 ± 0.40 mm, and posterior subtalar 0.02 ± 0.34 mm. Results are presented as 3-D distribution maps, with optimum test-retest repeatability reaching a smallest detectable difference of ± 0.15 mm. CONCLUSIONS: Joint space mapping is a robust approach to 3-D quantification of JSW measurement, inter-operator reproducibility, and test-retest repeatability at the ankle, with sensitivity reaching a best value of ± 0.15 mm. Standardised imaging protocols and optimised metal artefact reduction will be needed to further understand the clinical value of these 3-D measures derived from WBCT. CLINICAL RELEVANCE STATEMENT: Weight-bearing computed tomography is an increasingly important tool in the clinical assessment of orthopaedic ankle disorders. This paper establishes the performance of measuring 3-D joint space width using this technology, which is an important surrogate marker for severity of osteoarthritis. KEY POINTS: • Joint space width values and error metrics from across the ankle measured from weight-bearing CT can be presented as 3-D maps that show topographic variation. • The best sensitivity for detecting meaningful change in 3-D joint space width at the ankle was ± 0.15 mm, a value less than the isotropic imaging voxel dimensions. • Standardised imaging protocols and optimised metal artefact reduction will be needed to understand the clinical value of 3-D measures from weight-bearing CT.

Assessing the coronal plane deformity in Charcot Marie Tooth Cavovarus feet using automated 3D measurements.

BACKGROUND: This study assesses the coronal-plane deformities in cavovarus feet secondary to Charcot-Marie-Tooth disease (CMT) using Weightbearing-CT (WBCT) and semi-automated 3D-segmentation software. METHODS: WBCTs from 30 CMT-cavovarus feet were matched to 30 controls and analysed using semi-automatic 3D-segmentation (Bonelogic, DISIOR). The software used automated cross-section sampling with subsequent straight-line representation of weighted centre points to calculate 3D axes of bones in the hindfoot, midfoot and forefoot. Coronal relationships of these axes were analysed. Supination/pronation of the bones in relation to the ground and within each joint were measured and reported. RESULTS: The most significant deformity in CMT-cavovarus feet occurred at the talonavicular joint (TNJ) with 23 degrees more supination than normal feet (6.4 ± 14.5 versus 29.4 ± 7.0 degrees, p < 0.001). This was countered by relative pronation at the naviculo-cuneiform joints (NCJ) of 7.0 degrees (-36.0 ± 6.6 versus -43.0 ± 5.3 degrees, p < 0.001). Combined hindfoot varus and TNJ supination resulted in an additive supination effect not compensated by NCJ pronation. The cuneiforms in CMT-cavovarus feet were therefore supinated by 19.8 degrees to the ground relative to normal feet (36.0 ± 12.1 versus 16.2 ± 6.8 degrees, p < 0.001). The forefoot-arch and 1st metatarsal-ground angles demonstrated similar supination to the cuneiforms suggesting no further significant rotation occurred distally. CONCLUSION: Our results demonstrate coronal plane deformity occurs at multiple levels in CMT-cavovarus feet. Majority of the supination arises at the TNJ, and this is partially countered by pronation distally, mainly at the NCJ. An understanding of the location of coronal deformities may help when planning surgical correction. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Lanthanide-Doped Upconversion Nanoparticles: Exploring A Treasure Trove of NIR-Mediated Emerging Applications.

Lanthanide-doped upconversion nanoparticles (UCNPs) possess the remarkable ability to convert multiple near-infrared (NIR) photons into higher energy ultraviolet-visible (UV-vis) photons, making them a prime candidate for several advanced applications within the realm of nanotechnology. Compared to traditional organic fluorophores and quantum dots (QDs), UCNPs possess narrower emission bands (fwhm of 10-50 nm), large anti-Stokes shifts, low toxicity, high chemical stability, and resistance to photobleaching and blinking. In addition, unlike UV-vis excitation, NIR excitation is nondestructive at lower power intensities and has high tissue penetration depths (up to 2 mm) with low autofluorescence and scattering. Together, these properties make UCNPs exceedingly favored for advanced bioanalytical and theranostic applications, where these systems have been well-explored. UCNPs are also well-suited for bioimaging, optically modulating chemistries, forensic science, and other state-of-the-art research applications. In this review, an up-to-date account of emerging applications in UCNP research, beyond bioanalytical and theranostics, are presented including optogenetics, super-resolution imaging, encoded barcodes, fingerprinting, NIR vision, UCNP-assisted photochemical manipulations, optical tweezers, 3D printing, lasing, NIR-II imaging, UCNP-molecule nanohybrids, and UCNP-based persistent luminescent nanocrystals.

Semi-automated 3-dimensional analysis of the normal foot and ankle using weight bearing CT - A report of normal values and bony relationships.

BACKGROUND: Foot and ankle deformities have translational and rotational components in multiple planes, at multiple levels. Semi-automatic segmentation is a relatively new technology, which when used with weight-bearing CT (WBCT), can build an accurate model of the foot and calculate the orientation and relationships of bones under physiological load. However, few papers report reference values using these techniques. We report normative values for key bony relationships based on semi-automated analysis of WBCT. METHODS: This was a single-centre, retrospective analysis of 100 feet without deformity from 55 adult patients undergoing WBCT as part of routine clinical activity (mean age 40.5 ± 17.3 years). Imaging was analysed using Bonelogic 2.1 (DISIOR, Finland). Semi-automatic segmentation was used to compute the various bony axes in 3-dimensional space. Selected coronal, axial and sagittal plane relationships were then calculated for bones of the hindfoot, midfoot and forefoot. RESULTS: Data is presented on axial and sagittal plane relationships between the metatarsals in the forefoot, and the metatarsals and cuneiforms in the midfoot. In the hindfoot, the calcaneal pitch, talar-first-metatarsal angles, talonavicular coverage angles and Saltzman angles are reported. Coronal plane axes and their relationships are reported at multiple levels from hindfoot to forefoot. Results are presented as mean values with standard deviations and 95% confidence intervals. CONCLUSIONS: We present an observational analysis of the normal values from non-deformed feet. We highlight the major relationships in the axial, sagittal and coronal planes as obtained by semi-automated analysis of WBCT. This data may serve as a reference for future research. LEVEL OF EVIDENCE: Basic science study.

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants.

The cytochrome P450 monooxygenase (CYP) superfamily comprises hemethiolate enzymes that perform remarkable regio- and stereospecific oxidative chemistry. As such, CYPs are key agents for the structural and functional tailoring of triterpenoids, one of the largest classes of plant natural products with widespread applications in pharmaceuticals, food, cosmetics, and agricultural industries. In this review, we provide a full overview of 149 functionally characterised CYPs involved in the biosynthesis of triterpenoids and steroids in primary as well as in specialised metabolism. We describe the phylogenetic distribution of triterpenoid- and steroid-modifying CYPs across the plant CYPome, present a structure-based summary of their reactions, and highlight recent examples of particular interest to the field. Our review therefore provides a comprehensive up-to-date picture of CYPs involved in the biosynthesis of triterpenoids and steroids in plants as a starting point for future research.

Unlocking Long-Term Stability of Upconversion Nanoparticles with Biocompatible Phosphonate-Based Polymer Coatings.

Achieving long-term (>3 months) colloidal stability of upconversion nanoparticles (UCNPs) in biologically relevant buffers has been a major challenge, which has severely limited practical implementation of UCNPs in bioimaging and nanomedicine applications. To address this challenge, nine unique copolymers formulations were prepared and evaluated as UCNP overcoatings. These polymers consisted of a poly(isobutylene-alt-maleic anhydride) (PIMA) backbone functionalized with different ratios and types of phosphonate anchoring groups and poly(ethylene glycol) (PEG) moieties. The syntheses were done as simple, one-pot nucleophilic addition reactions. These copolymers were subsequently coated onto NaYF4:Yb3+,Er3+ UCNPs, and colloidal stability was evaluated in 1 × PBS, 10 × PBS, and other buffers. UCNP colloidal stability improved (up to 4 months) when coated with copolymers containing greater proportions of anchoring groups and higher phosphonate valences. Furthermore, small molecules could be conjugated to these overcoated UCNPs by use of copper-free click chemistry, as was done to demonstrate suitability for sensor and bioprobe development.