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1.
J Pediatr Orthop ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016260

ABSTRACT

BACKGROUND: The aim of this study was to determine whether height differences in the levels of the iliac crests and femoral heads on erect spinal radiographs can be used as indirect measurements for the screening and surveillance of limb length discrepancy (LLD) in patients with scoliosis. METHODS: Whole body posteroanterior (PA) and lateral erect radiographs of patients with adolescent idiopathic scoliosis (AIS) were retrospectively reviewed. Patients with congenital, syndromic, and neuromuscular scoliosis were excluded. A direct measurement of each limb was taken from the highest point of the femoral head to the middle of the tibial plafond; any difference between the sides was recorded as the LLD. In addition, the PACS Software tool was used to measure femoral head height difference (FHHD) and iliac crest height difference (ICHD). Pearson's correlation, linear regression, and Bland-Altman plots were used to determine the relationships between LLD and FHHD, and LLD and ICHD. RESULTS: Radiographs of 141 patients (92 women, 49 men) with an average age of 12.0±2.65 years were analyzed. A strong correlation (r=0.730, P<0.001) was found between LLD and FHHD; the correlation between LLD and ICHD was weaker (r=0.585, P<0.001). The Bland-Altman analysis showed good agreements of LLD with FHHD and ICHD. Linear regression analysis predicted an LLD of ≤10 mm based on an FHHD of ≤11.5 mm or an ICHD of ≤15.3 mm. CONCLUSIONS: FHHD and ICHD on spinal PA radiographs can be used for the screening and monitoring of LLD in patients with AIS with FHHD being the preferred indirect measurement. These measurements are readily learned and quick to perform. The FHHD and ICHD can be measured on any erect scoliosis PA radiograph. Therefore, these proxy measurements can be used to screen and monitor for LLD in patients with AIS. LEVEL OF EVIDENCE: Level III.

2.
Article in English | MEDLINE | ID: mdl-38722724

ABSTRACT

The olfactory system enables humans to smell different odors, which are closely related to emotions. The high temporal resolution and non-invasiveness of Electroencephalogram (EEG) make it suitable to objectively study human preferences for odors. Effectively learning the temporal dynamics and spatial information from EEG is crucial for detecting odor-induced emotional valence. In this paper, we propose a deep learning architecture called Temporal Attention with Spatial Autoencoder Network (TASA) for predicting odor-induced emotions using EEG. TASA consists of a filter-bank layer, a spatial encoder, a time segmentation layer, a Long Short-Term Memory (LSTM) module, a multi-head self-attention (MSA) layer, and a fully connected layer. We improve upon the previous work by utilizing a two-phase learning framework, using the autoencoder module to learn the spatial information among electrodes by reconstructing the given input with a latent representation in the spatial dimension, which aims to minimize information loss compared to spatial filtering with CNN. The second improvement is inspired by the continuous nature of the olfactory process; we propose to use LSTM-MSA in TASA to capture its temporal dynamics by learning the intercorrelation among the time segments of the EEG. TASA is evaluated on an existing olfactory EEG dataset and compared with several existing deep learning architectures to demonstrate its effectiveness in predicting olfactory-triggered emotional responses. Interpretability analyses with DeepLIFT also suggest that TASA learns spatial-spectral features that are relevant to olfactory-induced emotion recognition.


Subject(s)
Algorithms , Attention , Deep Learning , Electroencephalography , Emotions , Neural Networks, Computer , Odorants , Humans , Electroencephalography/methods , Emotions/physiology , Attention/physiology , Male , Adult , Female , Smell/physiology , Memory, Short-Term/physiology , Young Adult
3.
J Thorac Dis ; 16(4): 2225-2235, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38738232

ABSTRACT

Background: Management of acute type A intramural hematoma (IMH) is a controversial topic, and variable treatment strategies have been reported. Upfront aortic replacement may not be necessary in all cases. The goal of our study was to evaluate clinical outcomes of patients with acute type A IMH or thrombosed false lumen (FL) treated with upfront surgery or watchful waiting. Methods: Patients admitted to our hospital with type A IMH or aortic dissection with thrombosed ascending FL from December 2012 to February 2023 were retrospectively reviewed. Results: Among the 93 patients with type A IMH, 36 (38.7%) patients underwent upfront aortic surgery (Group S), and 57 (61.3%) patients were offered watchful waiting with medical surveillance (Group W). Of the 57 patients in Group W, 32 were treated conservatively with medical therapy alone (Group C). Patients in Group S had larger ascending aortic diameter (47.8±5.3 vs. 44.4±4.2 mm: P=0.001), higher frequency of pericardial effusion (38.9% vs. 10.5%; P=0.001) and cardiac tamponade (16.7% vs. 1.8%; P=0.008). The overall mortality rate was 4.3% in the whole cohort over a median follow up of 40.5 months. Overall survival for Group S was 100% at 30 days and 1 year, and 96.2% at 5 years. Overall survival for Group W was 98.2% at 30 days, 96.3% at 1 year and 95.2% at 5 years. The difference in overall survival was not statistically significant (P=0.64). Overall survival for Group C was 100% at 30 days and 1 year, and 90.9% at 5 years. Conclusions: Survival outcomes in selected patients with type A IMH were satisfactory. An individualized approach to patients with uncomplicated type A IMH was feasible. Upfront surgery was not necessary in all cases.

4.
J ISAKOS ; 9(3): 326-333, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38428820

ABSTRACT

PURPOSE: To report short-term results and clinical outcomes of arthroscopic deepening trochleoplasty combined with medial patellofemoral ligament (MPFL) reconstruction utilizing standard arthroscopic instruments in patients of recurrent patellar dislocation and trochlear dysplasia. METHODS: This is a case series of 13 patients between the ages of 14 and 20 years who presented with recurrent patellar dislocation and severe trochlear dysplasia (Dejour grade D). They were treated surgically using an arthroscopic technique from February 2017 to January 2019 and were followed for 18 months. Patients were assessed preoperatively and postoperatively (at 6, 12, and 18 months) with clinical scores (Tegner Activity Score, Lysholm Knee Score, and Kujala Score). RESULTS: There were 69.2% females, and the mean age was 16.4 â€‹± â€‹2.0 years. There were statistically significant improvements in the mean Lysholm and Kujala scores when comparing pre-operative and post-operative scores at every follow-up landmark (p â€‹< â€‹0.05). Comparing the preoperative and 18-month postoperative scores-the Lysholm score improved from 68.2 â€‹± â€‹10.3 to 98.7 â€‹± â€‹2.1 (p â€‹< â€‹0.001), and the Kujala score improved from 50.3 â€‹± â€‹12.0 to 95.4 â€‹± â€‹4.8 (p â€‹< â€‹0.001). Five patients were able to achieve premorbid Tegner activity levels at 12 months, with an additional 5 patients achieving the same premorbid Tegner activity at the 18-month mark. The remaining 3 patients were able to attain >90% of their activity level at 18 months' follow-up. No complications were observed during the follow-up period. CONCLUSIONS: This proposed arthroscopic deepening trochleoplasty technique combined with MPFL reconstruction has demonstrated excellent and reproducible early clinical outcomes. LEVEL OF EVIDENCE: IV.


Subject(s)
Arthroscopy , Patellar Dislocation , Humans , Female , Arthroscopy/methods , Male , Adolescent , Young Adult , Patellar Dislocation/surgery , Treatment Outcome , Plastic Surgery Procedures/methods , Patellofemoral Joint/surgery , Ligaments, Articular/surgery , Recurrence
5.
J Pediatr Orthop ; 44(5): 322-326, 2024.
Article in English | MEDLINE | ID: mdl-38389197

ABSTRACT

BACKGROUND: The lower extremity functional scale (LEFS) is a patient-reported outcome measure for assessment of lower extremity function. It has been validated in adults but not in children or adolescents. METHODS: Patients 8 to 18 years of age who were treated for a lower limb fracture, injury, or other conditions were invited to join the study. LEFS and Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) were administered. Reliability and validity of the LEFS were determined for the entire cohort and for 2 age groups (children: 8 to 12 years; adolescents 13 to 18 years) using PedsQL as comparison. RESULTS: A total of 178 patients were recruited into this study. In the entire cohort, internal consistency of LEFS was excellent (0. 972) with acceptable floor (0%) and ceiling (12%) effects. Correlation between LEFS and PedsQL physical functioning component was high ( r =0.859). Construct validity was acceptable, with all 8 hypotheses demonstrating statistical significance. Factor analysis showed that item 15 (sitting for 1 hour) may contribute to measurement error in the pediatric population. Results remained similar when comparing the 2 age groups. CONCLUSIONS: The LEFS is overall an acceptable patient-reported outcome assessment of children and adolescents with various lower limbs disorders. LEVEL OF EVIDENCE: Level II.


Subject(s)
Disability Evaluation , Quality of Life , Adult , Humans , Child , Adolescent , Reproducibility of Results , Lower Extremity , Patient Reported Outcome Measures , Psychometrics/methods , Surveys and Questionnaires
6.
Eur J Orthop Surg Traumatol ; 34(4): 1803-1809, 2024 May.
Article in English | MEDLINE | ID: mdl-38416233

ABSTRACT

PURPOSE: Bracing for adolescents with idiopathic scoliosis (AIS) is a treatment option to prevent curve progression to surgical level. This study aimed to assess the efficacy of a 3D fully customized over corrective brace, "ScoliBrace," an orthosis treatment for AIS. METHODS: This was a prospective pilot study of AIS female patients with inclusion criteria followed recommended Scoliosis Research Society (SRS) Guidelines. Cobb angles measured at: baseline (T0), 21 months (T5-2), skeletal maturity (T6), 6 months post-brace (T7), along with hours of brace wear using a thermal sensor and health-related quality of life (HRQoL) using the SRS-22r questionnaire. RESULTS: A total of 30 female AIS patients with mean age 11.85 ± 0.68 years, predominantly Risser 0 (70%), and median Cobb angle 29° were recruited; 21 patients were included for the final analysis. Results showed significant difference in Cobb angle between T0 and T5-2 (median = 22.5° vs. 28.5°, p = 0.0082). 57.14% had reduction in Cobb angle by ≥ 5° at skeletal maturity. Cobb angle reduced 0.794° for each additional hour of dosage (p = 0.036, 95% CI = - 1.532°, - 0.056°). Although pain level was increased at T6 (4.37 ± 0.51vs.4.70 ± 0.41, p = 0.014), patients reported significantly greater satisfaction with management of their condition (3.90 ± 0.90vs.3.29 ± 0.88, p = 0.020). CONCLUSION: Results show similar findings to the BRAIST study, whereby curves remained under surgical threshold and showed improvement. More than half had curve reduction of ≥ 5° at skeletal maturity. Increased dose was also associated with improved outcomes. Using "ScoliBrace" as a non-surgical treatment, maintained curves below surgical threshold and showed curve reduction, improving patient satisfaction with management.


Subject(s)
Braces , Quality of Life , Scoliosis , Humans , Scoliosis/therapy , Female , Pilot Projects , Prospective Studies , Child , Adolescent , Treatment Outcome , Patient Satisfaction
7.
J Pediatr Orthop ; 44(3): 157-163, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37994645

ABSTRACT

BACKGROUND: Cast immobilization is the mainstay of treatment for stable pediatric supracondylar humeral fractures (SCHFs). In recent years, a waterproof and breathable hybrid-mesh (HM) cast has emerged and been marketed to address common complaints such as itch, skin irritation, and malodor. Hence, this randomized controlled trial seeks to assess the overall satisfaction, comfort, and clinical outcomes of using HM casts in the conservative treatment of stable pediatric SCHF. METHODS: Seventy-nine patients (age range: 1 to 10 y) with modified Gartland's classification Type I and Type IIa SCHF were recruited and randomized for immobilization with either fiberglass or HM long-arm cast for 3 weeks. During follow-up visits, patients were assessed for any loss of reduction and skin rash. The weight of casts, the presence of cast breakage, the duration of cast application, and removal were recorded. A self-reported patient comfort and satisfaction questionnaire was also administered during the same visit. RESULTS: The final analysis included 38 patients immobilized with fiberglass casts and 39 patients with HM casts. Despite the significantly longer duration required for HM cast removal (4.18±1.25 min vs. 2.25±0.55 min, P <0.001), the HM cast was significantly lighter than its fiberglass counterpart (162.82±23.94 g vs. 203.95±36.52 g, P <0.001). The HM casts have better comfort (4.05±0.887 vs. 3.47±0.951, P =0.007) and satisfaction (3.69±1.055 vs. 3.11±0.953, P =0.012) scores as compared to fiberglass casts for immobilizing pediatric SCHF without compromising clinical outcome. CONCLUSIONS: HM casts have better comfort and overall satisfaction as compared to conventional fiberglass casts for immobilizing pediatric SCHF without compromising clinical outcomes. LEVEL OF EVIDENCE: Level II-therapeutic studies-investigating the results of treatment.


Subject(s)
Casts, Surgical , Humeral Fractures , Child , Child, Preschool , Humans , Infant , Conservative Treatment , Prostheses and Implants
8.
Am J Clin Nutr ; 119(3): 788-799, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38035997

ABSTRACT

BACKGROUND: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. OBJECTIVES: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. METHODS: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. RESULTS: In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. CONCLUSION: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov as NCT05259475.


Subject(s)
Diet, Mediterranean , Fatty Acids , Non-alcoholic Fatty Liver Disease , Female , Humans , Non-alcoholic Fatty Liver Disease/prevention & control , Liver/metabolism , Weight Loss , Fatty Acids, Unsaturated , Cholesterol
10.
Article in English | MEDLINE | ID: mdl-38083323

ABSTRACT

Emotion recognition from electroencephalogram (EEG) requires computational models to capture the crucial features of the emotional response to external stimulation. Spatial, spectral, and temporal information are relevant features for emotion recognition. However, learning temporal dynamics is a challenging task, and there is a lack of efficient approaches to capture such information. In this work, we present a deep learning framework called MTDN that is designed to capture spectral features with a filterbank module and to learn spatial features with a spatial convolution block. Multiple temporal dynamics are jointly learned with parallel long short-term memory (LSTM) embedding and self-attention modules. The LSTM module is used to embed the time segments, and then the self-attention is utilized to learn the temporal dynamics by intercorrelating every embedded time segment. Multiple temporal dynamics representations are then aggregated to form the final extracted features for classification. We experiment on a publicly available dataset, DEAP, to evaluate the performance of our proposed framework and compare MTDN with existing published results. The results demonstrate improvement over the current state-of-the-art methods on the valence dimension of the DEAP dataset.


Subject(s)
Electroencephalography , Emotions , Memory, Long-Term , Recognition, Psychology
11.
Bone Jt Open ; 4(9): 689-695, 2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37673418

ABSTRACT

Aims: To determine whether side-bending films in scoliosis are assessed for adequacy in clinical practice; and to introduce a novel method for doing so. Methods: Six surgeons and eight radiographers were invited to participate in four online surveys. The generic survey comprised erect and left and right bending radiographs of eight individuals with scoliosis, with an average age of 14.6 years. Respondents were asked to indicate whether each bending film was optimal (adequate) or suboptimal. In the first survey, they were also asked if they currently assessed the adequacy of bending films. A similar second survey was sent out two weeks later, using the same eight cases but in a different order. In the third survey, a guide for assessing bending film adequacy was attached along with the radiographs to introduce the novel T1-45B method, in which the upper endplate of T1 must tilt ≥ 45° from baseline for the study to be considered optimal. A fourth and final survey was subsequently conducted for confirmation. Results: Overall, 12 (86%) of 14 respondents did not use any criteria to assess the bending film adequacy; the remaining two each described a different invalidated method. In total, 12 (86%) of the respondents felt T1-45B was easy to learn and apply. There was fair to substantial intra-rater reliability (k = 0.25 to 0.88) which improved to fair to almost perfect (k = 0.38 to 0.88) post-introduction of the guide. Inter-rater reliability varied considerably among the rater groups but similarly increased following introduction of the guide (kS1 = 0.19 to 0.34, kS2 = 0.33 to 0.43 vs kS3 = 0.49 to 0.5, kS4 = 0.35 to 0.43). Conclusion: Many surgeons and radiographers do not assess spinal bending films for adequacy. We propose that the change in the plane of the upper endplate of T1 on side-bending can be used in this evaluation. In the T1-45B method, a change of ≥ 45° on side bending qualifies as an adequate bend effort.

13.
Eur Spine J ; 32(11): 3987-3995, 2023 11.
Article in English | MEDLINE | ID: mdl-37428212

ABSTRACT

PURPOSE: To determine if the novel 3D Machine-Vision Image Guided Surgery (MvIGS) (FLASH™) system can reduce intraoperative radiation exposure, while improving surgical outcomes when compared to 2D fluoroscopic navigation. METHODS: Clinical and radiographic records of 128 patients (≤ 18 years of age) who underwent posterior spinal fusion (PSF), utilising either MvIGS or 2D fluoroscopy, for severe idiopathic scoliosis were retrospectively reviewed. Operative time was analysed using the cumulative sum (CUSUM) method to evaluate the learning curve for MvIGS. RESULTS: Between 2017 and 2021, 64 patients underwent PSF using pedicle screws with 2D fluoroscopy and another 64 with the MvIGS. Age, gender, BMI, and scoliosis aetiology were comparable between the two groups. The CUSUM method estimated that the MvIGS learning curve with respect to operative time was 9 cases. This curve consisted of 2 phases: Phase 1 comprises the first 9 cases and Phase 2 the remaining 55 cases. Compared to 2D fluoroscopy, MvIGS reduced intraoperative fluoroscopy time, radiation exposure, estimated blood loss and length of stay by 53%, 62% 44%, and 21% respectively. Scoliosis curve correction was 4% higher in the MvIGS group, without any increase in operative time. CONCLUSION: MvIGS for screw insertion in PSF contributed to a significant reduction in intraoperative radiation exposure and fluoroscopy time, as well as blood loss and length of stay. The real-time feedback and ability to visualize the pedicle in 3D with MvIGS enabled greater curve correction without increasing the operative time.


Subject(s)
Pedicle Screws , Scoliosis , Spinal Fusion , Surgery, Computer-Assisted , Humans , Scoliosis/diagnostic imaging , Scoliosis/surgery , Retrospective Studies , Blood Loss, Surgical/prevention & control , Spinal Fusion/methods , Fluoroscopy/methods , Surgery, Computer-Assisted/methods , Radiation, Ionizing
14.
AME Case Rep ; 7: 15, 2023.
Article in English | MEDLINE | ID: mdl-37122961

ABSTRACT

Background: Syphilitic ostial coronary stenosis is an uncommon manifestation of cardiovascular syphilis, characterized by concomitant aortic regurgitation and isolated or bilateral ostial involvement. Although much has been written about syphilis in the pre-antibiotic era, the key imaging and operative findings were rarely reported in the modern literature. Through multimodality imaging and operative videos, we demonstrate the unique diagnostic and therapeutic hurdles associated with the condition. Case Description: A 47-year-old woman presented with acute decompensated heart failure due to bilateral ostial coronary stenosis and severe aortic insufficiency, which raises suspicion for underlying syphilis. She underwent successful aortic valve replacement, right coronary ostioplasty and bypass grafting of the left coronary system. The syphilitic process was confirmed by histopathological examination of the aortic valve and aortic wall as well as serological tests. She recovered from the operation uneventfully. Conclusions: The manifestations of cardiovascular syphilis are protean and can pose significant diagnostic challenges even in the modern era. The presence of isolated coronary ostial stenosis should raise suspicion for syphilis. Timely surgery and antibiotics can lead to successful outcomes. Furthermore, the evolution and nuances of surgical techniques addressing ostial coronary stenosis was reviewed. Surgical strategy should be individualized based on preoperative multimodality imaging.

16.
Curr Protoc ; 3(4): e745, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37071053

ABSTRACT

Fluorescent proteins (FPs) have become an essential tool for biological research. Since the isolation and description of green FP, hundreds of FPs have been discovered and created with various characteristics. The excitation of these proteins ranges from ultraviolet (UV) up to near infrared (NIR). Using conventional cytometry, with each detector assigned to a fluorochrome, great care must be taken when selecting the optimal bandpass filters to minimalize the spectral overlap as the emission spectra of FPs are broad. Full-spectrum flow cytometers eliminate the need to change optical filters for analyzing FPs, which simplifies instrument setup. In experiments where more than one FP is used, single-color controls are required. These can be cells expressing each of the proteins separately. In the case of the confetti system, for instance, when four FPs are used, all these proteins will need to be expressed separately so that compensation or spectral unmixing can be performed, and this can be inconvenient and expensive. An appealing alternative is to produce FPs in Escherichia coli, purify them, and covalently couple them to carboxylate polystyrene microspheres. Such microspheres are ready to use and can be stored at 4°C for months or even years without any deterioration in fluorescence. The same procedure can be used to couple antibodies or other proteins to these particles. Here, we describe how to express and purify FPs, how to couple them to microspheres, and how to evaluate the fluorescent properties of the particles. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Escherichia coli expression and purification of recombinant mPlum Basic Protocol 2: Coupling fluorescent proteins to polystyrene microspheres Support Protocol 1: Comparing the cell-bound and bead-bound fluorescence signatures Support Protocol 2: Comparing spectral signatures via the similarity index, complexity matrix, and spillover spread matrix of fluorescent protein-coupled beads.


Subject(s)
Fluorescent Dyes , Polystyrenes , Microspheres , Fluorescence , Luminescent Proteins/genetics , Luminescent Proteins/metabolism
17.
J Biol Chem ; 299(2): 102889, 2023 02.
Article in English | MEDLINE | ID: mdl-36634847

ABSTRACT

Osteoporosis is a chronic skeletal condition characterized by low bone mass and deteriorated microarchitecture of bone tissue and puts tens of millions of people at high risk of fractures. New therapeutic agents like i-bodies, a class of next-generation single-domain antibodies, are needed to overcome some limitations of conventional treatments. An i-body is a human immunoglobulin scaffold with two long binding loops that mimic the shape and position of those found in shark antibodies, the variable new antigen receptors of sharks. Its small size (∼12 kDa) and long binding loops provide access to drug targets, which are considered undruggable by traditional monoclonal antibodies. Here, we have successfully identified a human receptor activator of nuclear factor-κB ligand (RANKL) i-body, ADR3, which demonstrates a high binding affinity to human RANKL (hRANKL) with no adverse effect on the survival or proliferation of bone marrow-derived macrophages. Differential scanning fluorimetry suggested that ADR3 is stable and able to tolerate a wide range of physical environments (including both temperature and pH). In addition, in vitro studies showed a dose-dependent inhibitory effect of ADR3 on osteoclast differentiation, podosome belt formation, and bone resorption activity. Further investigation on the mechanism of action of ADR3 revealed that it can inhibit hRANKL-mediated signaling pathways, supporting the in vitro functional observations. These clues collectively indicate that hRANKL antagonist ADR3 attenuates osteoclast differentiation and bone resorption, with the potential to serve as a novel therapeutic to protect against bone loss.


Subject(s)
Bone Resorption , Osteoclasts , RANK Ligand , Single-Domain Antibodies , Humans , Bone Resorption/genetics , Bone Resorption/metabolism , Cell Differentiation/genetics , Macrophages/cytology , Macrophages/metabolism , Osteoclasts/cytology , RANK Ligand/metabolism , Signal Transduction , Single-Domain Antibodies/metabolism
18.
Spine (Phila Pa 1976) ; 48(9): 617-624, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36716381

ABSTRACT

STUDY DESIGN: Prospective cohort study. OBJECTIVE: The purpose of this study was to evaluate the relationship between patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) in adolescent idiopathic scoliosis (AIS) managed nonsurgically with bracing or observation. SUMMARY OF BACKGROUND DATA: PREMs and PROMs are increasingly used to assess the effectiveness of patient-centered health care provision. To date, no study has attempted to study the relationship between PREMs and PROMs in AIS. METHODS: All patients who visited our one-stop, tertiary center for AIS between 2020 and 2021, were asked to complete pairs of PREMs and PROMs questionnaires. PREMs were evaluated using our institution's outpatient experience survey adapted from Hospital Consumer Assessment of Healthcare Providers and Systems survey. PROMs were determined via the Scoliosis Research Society-22 revised (SRS-22r) and European Quality of Life Five-Dimension Five-Level (EQ-5D-5L) forms. RESULTS: In total, we included 730 patients who completed pairs of PREMs and PROMs questionnaires. 451 patients were treated by observation and 279 were braced. In the observation group, there was no association between patient experience and SRS-22r or EQ-5D-5L scores. In the brace group, improved SRS-22r were associated with higher PREM scores. In particular, having confidence and trust in treating physicians ( r =0.34), reporting that their worries and concerns were addressed during treatment ( r =0.34) and being taught self-care ( r =0.33, P <0.0001 for all) were most highly correlated with better SRS-22r scores. CONCLUSIONS: In patients with AIS treated with bracing, improved patient experience was positively correlated with better patient reported outcomes, especially if patients' concerns were addressed during treatment and they received supportive care and education on self-care. In contrast, patient experience did not correlate with PROMs in children and adolescents with AIS who were under observation.


Subject(s)
Kyphosis , Scoliosis , Child , Humans , Adolescent , Quality of Life , Prospective Studies , Scoliosis/therapy , Surveys and Questionnaires , Patient Reported Outcome Measures , Outpatients
19.
Int J Mol Sci ; 24(2)2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36674774

ABSTRACT

We report enzymes from the berberine bridge enzyme (BBE) superfamily that catalyze the oxidative cyclization of the monoterpene moiety in cannabigerolic acid (CBGA) to form cannabielsoin (CBE). The enzymes are from a variety of organisms and are previously uncharacterized. Out of 232 homologues chosen from the enzyme superfamily, four orthologues were shown to accept CBGA as a substrate and catalyze the biosynthesis of CBE. The four enzymes discovered in this study were recombinantly expressed and purified in Pichia pastoris. These enzymes are the first report of heterologous expression of BBEs that did not originate from the Cannabis plant that catalyze the production of cannabinoids using CBGA as substrate. This study details a new avenue for discovering and producing natural and unnatural cannabinoids.


Subject(s)
Cannabinoids , Cannabis , Cannabinoids/metabolism , Cannabis/genetics , Cannabis/chemistry , Oxidation-Reduction , Catalysis , Nitric Oxide Synthase/metabolism
20.
Aust J Gen Pract ; 51(9): 713-720, 2022 09.
Article in English | MEDLINE | ID: mdl-36045629

ABSTRACT

BACKGROUND AND OBJECTIVES: General practitioners (GPs) play a central role in healthcare, serving as the first point of contact, making appropriate referrals and coordinating care for chronic conditions such as heart failure (HF). We sought to determine healthcare use by people with HF in primary care. METHOD: In this Study of Heart failure in the Australian Primary carE setting (SHAPE), we analysed records of 1.93 million adult patients who attended a total of 43 practices between 1 July 2013 and 30 June 2018. We identified and examined the data of 20,219 patients with HF to describe the frequency of visits and use of Medicare Benefits Schedule items. RESULTS: Patients with HF saw GPs 14.4 times per annum on average; 59.5% had a General Practice Management Plan (GPMP), 2.9% of GPMPs were reviewed annually or more frequently, and 46.8% of patients had been referred to a cardiologist. A total of 3761 had coexisting anxiety or depression, and of these 37.1% had a mental health plan. DISCUSSION: Patients with HF visit their GP frequently, with many not reaching guideline therapy nor referred to cardiologists. Low use of care planning and reviews presents an opportunity for GPs to improve care.


Subject(s)
General Practitioners , Heart Failure , Adult , Aged , Australia , Delivery of Health Care , General Practitioners/psychology , Heart Failure/epidemiology , Heart Failure/therapy , Humans , National Health Programs
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