Limb Idleness Index (LII): a novel measurement of pain in a rat model of osteoarthritis

SummaryObjectivesMechanical allodynia during ambulation in osteoarthritis (OA) animal models can be assessed as decreased extent of loading or decreased duration of loading. We propose to measure gait adaptation to pain by both mechanisms with the development of Limb Idleness Index (LII) in a rat model of knee OA.MethodsRats were assigned to anterior cruciate ligament transection (ACLT), Sham, or Normal group (n = 6). Gait data were collected at pre-injury, 1, 2, 3 and 6 months post-injury. Ratios of target print intensity, anchor print intensity, and swing duration were combined to obtain LII. The association of gait changes with pain was assessed by buprenorphine treatment at 3 and 6 months post-injury. At 6 months, OA-related structural changes in knee joints were examined by μCT and results from histological scoring were correlated with LII.ResultsAs compared to pre-injury level (range 0.75–1.20), LII in ACLT group was increased at 6 months post-injury, which was significantly higher than that in Sham and Normal groups (P = 0.024). The increase in LII in ACLT group was effectively reversed by buprenorphine treatment (P = 0.004). ACLT group exhibited a significantly higher maximum Osteoarthritis Research Society International (OARSI) score as compared to Sham (P = 0.005) and Normal (P = 0.006) groups. Significant correlation was found between LII and side-to-side difference in OARSI score (r = 0.893, P < 0.001).ConclusionsLII presents a good measurement for OA-related knee pain in rat model

Evolution Of Myrmecophytism In Western Malesian Macaranga (Euphorbiaceae)

Plants inhabited by ants (myrmecophytes) have evolved in a diversity of tropical plant lineages. Macaranga includes approximately 300 paleotropical tree species; in western Malesia there are 26 myrmecophytic species that vary in morphological specializations for ant association. The origin and diversification of myrmecophytism in Macaranga was investigated using phylogenetic analyses of morphological and nuclear ITS DNA characters and studies of character evolution. Despite low ITS variation, the combined analysis resulted in a well-supported hypothesis of relationships. Mapping myrmecophytism on all most parsimonious trees resulting from the combined analysis indicated that the trait evolved independently between two and four times and was lost between one and three times (five changes). This hypothesis was robust when tested against trees constrained to have three or fewer evolutionary transformations, although increased taxon sampling for the ITS analysis is required to confirm this. Mapping morphological traits on the phylogeny indicated that myrmecophytism was not homologous among lineages; each independent origin involved a suite of different specializations for ant-plant association. There was no evidence that myrmecophytic traits underwent sequential change through evolution; self-hollowing domatia evolved independently from ant-excavated domatia, and different food-body production types evolved in different lineages. The multiple origins of myrmecophytism in Macaranga were restricted to one small, exclusively western Malesian lineage of an otherwise large and nonmyrmecophytic genus. Although the evolution of aggregated food-body production and the formation of domatia coincided with the evolution of myrmecophytism in all cases, several morphological, ecological, and biogeographic factors appear to have facilitated and constrained this radiation of ant-plants

Effect of the addition of diblock copolymer nanoparticles on the evaporation kinetics and final particle morphology for drying aqueous aerosol droplets

A deeper understanding of the key processes that determine the particle morphologies generated during aerosol droplet drying is highly desirable for spray-drying of powdered pharmaceuticals and foods, predicting the properties of atmospheric particles, and monitoring disease transmission. Particle morphologies are affected by the drying kinetics of the evaporating droplets, which are in turn influenced by the composition of the initial droplet as well as the drying conditions. Herein, we use polymerization-induced self-assembly (PISA) to prepare three types of sterically stabilized diblock copolymer nanoparticles comprising the same steric stabilizer block and differing core blocks with z-average diameters ranging from 32 to 238 nm. These well-defined nanoparticles enable a systematic investigation of the effect of the nanoparticle size and composition on the drying kinetics of aqueous aerosol droplets (20-28 μm radius) and the final morphology of the resulting microparticles. A comparative kinetics electrodynamic balance was used to obtain evaporation profiles for 10 examples of nanoparticles at a relative humidity (RH) of 0, 45, or 65%. Nanoparticles comprising the same core block with mean diameters of 32, 79, and 214 nm were used to produce microparticles, which were dried under different RH conditions in a falling droplet column. Scanning electron microscopy was used to examine how the drying kinetics influenced the final microparticle morphology. For dilute droplets, the chemical composition of the nanoparticles had no effect on the evaporation rate. However, employing smaller nanoparticles led to the formation of dried microparticles with a greater degree of buckling

Dimensional Dependence of Black Hole Formation in Self-Similar Collapse of Scalar Field

We study classical and quantum self-similar collapses of a massless scalar field in higher dimensions, and examine how the increase in the number of dimensions affects gravitational collapse and black hole formation. Higher dimensions seem to favor formation of black hole rather than other final states, in that the initial data space for black hole formation enlarges as dimension increases. On the other hand, the quantum gravity effect on the collapse lessens as dimension increases. We also discuss the gravitational collapse in a brane world with large but compact extra dimensions.Comment: Improved a few arguments and added a figur

SSTR2 in Nasopharyngeal Carcinoma:Relationship with Latent EBV Infection and Potential as a Therapeutic Target

SIMPLE SUMMARY: Nasopharyngeal cancer (NPC) is a malignant epithelial tumor endemic to parts of Asia and associated with infection by the Epstein–Barr virus (EBV) in these regions. The cancer is often detected at a late stage which is associated with poor outcomes (63% 5-year survival). Advances for the management of this disease have remained largely stagnant and treatment relies primarily on radiotherapy and chemotherapy, as well as surgery when indicated. Nevertheless, our understanding of its underlying biology has grown rapidly in the past two decades, laying the foundation for the development of improved therapeutics which have the potential to improve outcomes. This review offers a comprehensive, up-to-date summary of this disease, with a focus on the role of somatostatin receptor 2 (SSTR2) in NPC and how this increased knowledge may lead to improved diagnosis and management of this disease. ABSTRACT: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor, most commonly located in the pharyngeal recess and endemic to parts of Asia. It is often detected at a late stage which is associated with poor prognosis (5-year survival rate of 63%). Treatment for this malignancy relies predominantly on radiotherapy and/or systemic chemotherapy, which can be associated with significant morbidity and impaired quality of life. In endemic regions NPC is associated with infection by Epstein–Barr virus (EBV) which was shown to upregulate the somatostatin receptor 2 (SSTR2) cell surface receptor. With recent advances in molecular techniques allowing for an improved understanding of the molecular aetiology of this disease and its relation to SSTR2 expression, we provide a comprehensive and up-to-date overview of this disease and highlight the emergence of SSTR2 as a key tumor biomarker and promising target for imaging and therapy

Human Metapneumovirus Detection in Patients with Severe Acute Respiratory Syndrome

We used a combination approach of conventional virus isolation and molecular techniques to detect human metapneumovirus (HMPV) in patients with severe acute respiratory syndrome (SARS). Of the 48 study patients, 25 (52.1%) were infected with HMPV; 6 of these 25 patients were also infected with coronavirus, and another 5 patients (10.4%) were infected with coronavirus alone. Using this combination approach, we found that human laryngeal carcinoma (HEp-2) cells were superior to rhesus monkey kidney (LLC-MK2) cells commonly used in previous studies for isolation of HMPV. These widely available HEp-2 cells should be included in conjunction with a molecular method for cell culture followup to detect HMPV, particularly in patients with SARS

Reversal of cardiac damage in patients with symptomatic severe aortic stenosis following transcatheter aortic valve implantation: An echocardiographic study

Background: Severe aortic stenosis (AS) results in cardiac damages, such as left ventricular hypertrophy, left atrial enlargement, pulmonary pressure elevation and in advanced stage, right ventricular damage. Généreux and colleagues proposed a staging classification based on these extra-valvular damages in 2017, with increasing stage representing more cardiac damage. While regression of these cardiac damages is expected following aortic valve replacement, the reversal of cardiac damage based on this staging system has not been described. Purpose: This study aimed to describe and stage the changes in cardiac structure and function at 6 months and 1 year after transcatheter aortic valve implantation (TAVI) in patients with symptomatic severe AS. Methods: This was a retrospective, single center, longitudinal observational study. Echocardiographic data of patients who underwent TAVI were retrieved and analysed. Results: From May 2018 to Feb 2021, 31 patients underwent TAVI. 5 patients were excluded due to death <6 months post-procedure (n=2) and incomplete echocardiographic data (n=3). The mean age of the remaining 26 patients was 70.9±9.4 years, 57.7% were male, and 34.6% bicuspid aortic valve. After TAVI, transvalvular aortic mean pressure gradient reduced from 45.2±14.5 mmHg to 8.0±5.4 mmHg (p<0.001), and aortic valve area increased from 0.57±0.21 cm2 to 1.75±0.68 cm2 (p<0.001). At baseline, 6-month and 1-year, the left ventricular mass index (LVMi) were 183.4±60.7g/m2, 150.8±55.3 g/m2 and 126.8±42.1 g/m2 (p<0.001) respectively; left-atrial volume index (LAVI) were 60.4±22.8 ml/m2 , 51.7±23.8ml/m2, and 48.1±23.6ml/m2 (p=0.009) respectively; left ventricular ejection fraction (LVEF) were 52.3±25.4%, 64.2±29.3%, and 62.4±12.1% (p=0.005) respectively. Based on the proposed cardiac damage staging for AS, at baseline 38% of patients were stage 1, 65.4% stage 2, 7.7% stage 3 and 23.1% stage 4. At 1 year, 8.3% were stage 0, 29.2% stage 1, 58.3% stage 2, and 4.2% stage 4. 12 patients (46%) showed improvement in cardiac damage staging, and the other 14 (54%) remained in the same stage. Conclusion: In patients with symptomatic severe AS, there were overall significant regression in LVMi and LAVI, and improvement in LVEF at 1 year after TAVI. However, improvement in cardiac damage staging was observed in only 46% of patients

Recommendations for Epstein-Barr virus–based screening for nasopharyngeal cancer in high- and intermediate-risk regions

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)–based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program

d-alpha Correlation functions and collective motion in Xe+Au collisions at E/A=50 MeV

The interplay of the effects of geometry and collective motion on d-$\alpha$ correlation functions is investigated for central Xe+Au collisions at E/A=50 MeV. The data cannot be explained without collective motion, which could be partly along the beam axis. A semi-quantitative description of the data can be obtained using a Monte-Carlo model, where thermal emission is superimposed on collective motion. Both the emission volume and the competition between the thermal and collective motion influence significantly the shape of the correlation function, motivating new strategies for extending intensity interferometry studies to massive particles.Comment: Accepted for publication on Physics Letters