Elasticity evaluation of the plantar fascia: A shear wave elastography study involving 33 early-stage plantar fasciopathy subjects

Background: Plantar fasciopathy, the most common foot condition seen in elderly and athletic populations, can be diagnosed and differentially diagnosed with imaging modalities such as ultrasound shear wave elastography (SWE). However, standard guidelines for ultrasound elastography of the plantar fascia are lacking. The purpose of this study was to determine the impact of the region of interest (ROI) on the evaluation of the plantar fascia elasticity and confirm the screening accuracy of SWE in the early-stage of plantar fasciopathy.Methods: This was an observational case‒control study involving 50 feet of 33 early-stage plantar fasciopathy subjects (the plantar fasciopathy group) and 96 asymptomatic feet of 48 healthy volunteers (the non-pain group). Clinical information, including age, gender, height, weight, visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Scale score (AOFAS), and the symptom duration, were recorded. All participants underwent both conventional ultrasound and SWE evaluation. The plantar fascia elastic parameters included SWEsingle-point, calculated with a single-point ROI set at the greatest thickness of the plantar fascia, and SWEmulti-point, calculated by multipoint ROIs set continuously from the origin at the calcaneus to about 2 cm from the calcaneal origin.Results: The plantar fasciopathy group presented a higher VAS score (median [IQR), 4.00 (3.00) vs. 0.00 (0.00), p < 0.001] and lower AOFAS score [median (IQR), 79.50 (3.00) vs. 100.00 (10.00), p < 0.001] than the non-pain group. The median plantar fascia thickness of the plantar fasciopathy group was significantly greater than that of the non-pain group [median (IQR), 3.95 (1.37) mm vs 2.40 (0.60) mm, p < 0.001]. Abnormal ultrasound features, including echogenicity, border irregularities, and blood flow signals, were more prominent in the plantar fasciopathy group than in the non-pain group (29% vs. 0%, p < 0.001; 26% vs. 1%, p < 0.001; 12% vs. 0%, p < 0.001, respectively). Quantitative analysis of the plantar fascia elasticity revealed that the difference between the value of SWEsingle-point and SWEmultipoint was significant [median (IQR), 65.76 (58.58) vs. 57.42 (35.52) kPa, p = 0.02). There was a moderate and significant correlation between the value of SWEsingle-point and heel pain. However, there was no correlation between the value of SWEmultipoint and heel pain. Finally, we utilized the results of SWEsingle-point as the best elastic parameter reflecting clinical heel pain and found that SWEsingle-point could provide additional value in screening early-stage plantar fasciopathy, with an increase in sensitivity from 76% to 92% over conventional ultrasound alone. Additionally, compared with conventional ultrasound and SWE, the use of both improved the accuracy of screening for plantar fasciopathy. Although there were no significant differences in the negative predictive value of conventional ultrasound, SWE, and their combination, the positive predictive value when using both (90.20%) was significantly greater than that when using conventional ultrasound (74.50%) or SWE alone (76.50%).Conclusion: The plantar fascia elastic parameter calculated with single-point ROIs set at the greatest thickness of the plantar fascia is positively correlated with fascia feel pain. Single-point analysis is sufficient for the screening of the early-stage plantar fasciopathy using SWE. SWEsingle-point may provide additional valuable information for assessing the severity of plantar fasciopathy

Alternative splicing and trans-splicing events revealed by analysis of the Bombyx mori transcriptome

Alternative splicing and trans-splicing events have not been systematically studied in the silkworm Bombyx mori. Here, the silkworm transcriptome was analyzed by RNA-seq. We identified 320 novel genes, modified 1140 gene models, and found thousands of alternative splicing and 58 trans-splicing events. Studies of three SR proteins show that both their alternative splicing patterns and mRNA products are conserved from insect to human, and one isoform of Srsf6 with a retained intron is expressed sex-specifically in silkworm gonads. Trans-splicing of mod(mdg4) in silkworm was experimentally confirmed. We identified integrations from a common 5′-gene with 46 newly identified alternative 3′-exons that are located on both DNA strands over a 500-kb region. Other trans-splicing events in B. mori were predicted by bioinformatic analysis, in which 12 events were confirmed by RT-PCR, six events were further validated by chimeric SNPs, and two events were confirmed by allele-specific RT-PCR in F 1 hybrids from distinct silkworm lines of JS and L10, indicating that trans-splicing is more widespread in insects than previously thought. Analysis of the B. mori transcriptome by RNA-seq provides valuable information of regulatory alternative splicing events. The conservation of splicing events across species and newly identified trans-splicing events suggest that B. mori is a good model for future studies. Published by Cold Spring Harbor Laboratory Press. Copyrigh

Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery

Purpose: To investigate the efficacy, safety, and mechanisms of Sirolimus sustained delivery film on prevention of scar formation in a rabbit model of glaucoma filtration surgery. Methods: Sixty-four New Zealand white rabbits who underwent trabeculectomy in the right eye were randomly allocated to one of the four treatment regimens: Sirolimus sustained delivery film treatment group (Group A), or drug-free film treatment group (Group B), or 30 ng/ml Sirolimus-soaked sponge treatment group (Group C), or no adjunctive treatment group (Group D), and each group consists of 16 rabbits. Intraocular pressure (IOP), morphologic changes of bleb, anterior chamber flare, and corneal endothelial cell count and complications were evaluated over a 28-day period follow-up time. Aqueous humor samples were gathered from Group A, and the concentration of Sirolimus was measured regularly post-operation. Rabbits were sacrificed on the 7th, 14th, and 28th day post-operation separately, and the fibroblast hypertrophy, infiltration of inflammatory, and proliferation of new collagen fiber formation in each group were evaluated with HE and Masson staining. Proliferative cell nuclear antigen (PCNA) and fibroblast apoptosis were evaluated by immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay at the 28th day post-operation. Results: Both Sirolimus sustained delivery film (Group A) and Sirolimus alone (Group C) were well tolerated in this model, and significantly prolonged bleb survival compared with no drug treatment group (Group B and D; p<0.001). Group A had the longest bleb survival time in comparison with other groups (p<0.001). There were significant differences in IOP readings between Group A and other groups at the last follow-up (p<0.05). The concentration of Group A maintained stable for over 2 weeks, drops from (10.56 +/- 0.05) ng/ml at day 3 to (7.74 +/- 0.05) ng/ml at day 14. The number of corneal endothelial cells of Group A was not statistically significant between pre and post-operation. Histologic examination demonstrated that eyes treated with Sirolimus, especially the Sirolimus sustained delivery film, showed an obvious reduction in subconjunctival fibroblast scar tissue formation compared with no drug treatment groups, and had minimal evidence of inflammatory cell infiltration and new collagen deposition in the subconjunctiva. Immunohistochemistry assay showed that PCNA-expression was lower in the Group A (16.25 +/- 3.24%) compared to other groups (p<0.01). TUNEL assay showed a significant increase in the number of apoptotic fibroblasts around the surgical area in Group A and Group C (9.75 +/- 1.71% and 8.50 +/- 1.92%) compared to the Group B and D (p<0.01). Conclusions: Sirolimus drug sustained delivery film can inhibit inflammatory cell activity, impede fibroblast proliferation activity, and induce fibroblast apoptosis in the filtration surgery sites in rabbit. The results indicate a safe and effective treatment strategy in anti-scaring treatment in glaucoma surgery.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000295289900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologyOphthalmologySCI(E)9ARTICLE270-712495-25061

Lipodystrophy, Diabetes and Normal Serum Insulin in PPARγ-Deficient Neonatal Mice

Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ. PPARγ-rescued placentas support development of PPARγ-deficient embryos that are viable and born in near normal numbers. However, PPARγ-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPARγ2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPARγ1 in the neonatal period either alone or in combination with PPARγ2 in lipid metabolism, glucose homeostasis and insulin sensitivity

Lower Extremity Peripheral Arterial Disease Is an Independent Predictor of Coronary Heart Disease and Stroke Risks in Patients with Type 2 Diabetes Mellitus in China

We aimed to determine the relationship between lower extremity peripheral arterial disease (PAD), 10-year coronary heart disease (CHD), and stroke risks in patients with type 2 diabetes (T2DM) using the UKPDS risk engine. We enrolled 1178 hospitalized T2DM patients. The patients were divided into a lower extremity PAD group (ankle-brachial index≤0.9 or >1.4; 88 patients, 7.5%) and a non-PAD group (ankle-brachial index>0.9 and ≤1.4; 1090 patients, 92.5%). Age; duration of diabetes; systolic blood pressure; the hypertension rate; the use of hypertension drugs, ACEI /ARB, and statins; CHD risk; fatal CHD risk; stroke risk; and fatal stroke risk were significantly higher in the PAD group than in the non-PAD group (P<0.05 for all). Logistic stepwise regression analysis indicated that ABI was an independent predictor of 10-year CHD and stroke risks in T2DM patients. Compared with those in the T2DM non-PAD group, the odds ratios (ORs) for CHD and stroke risk were 3.6 (95% confidence interval (CI), 2.2–6.0; P<0.001) and 6.9 (95% CI, 4.0–11.8; P<0.001) in those with lower extremity PAD, respectively. In conclusion, lower extremity PAD increased coronary heart disease and stroke risks in T2DM

CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer's Disease

Protein phosphatase 2A (PP2A) inhibition causes hyperphosphorylation of tau and APP in Alzheimer's disease (AD). However, the mechanisms underlying the downregulation of PP2A activity in AD brain remain unclear. We demonstrate that Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is overexpressed in AD brain. CIP2A-mediated PP2A inhibition drives tau/APP hyperphosphorylation and increases APP beta-cleavage and A beta production. Increase in CIP2A expression also leads to tau mislocalization to dendrites and spines and synaptic degeneration. In mice, injection of AAV-CIP2A to hippocampus induced AD-like cognitive deficits and impairments in long-term potentiation (LTP) and exacerbated AD pathologies in neurons. Indicative of disease exacerbating the feedback loop, we found that increased CIP2A expression and PP2A inhibition in AD brains result from increased A beta production. In summary, we show that CIP2A overexpression causes PP2A inhibition and AD-related cellular pathology and cognitive deficits, pointing to CIP2A as a potential target for AD therapy