Research of fetal ECG extraction using wavelet analysis and adaptive filtering

Extracting clean fetal electrocardiogram (ECG) signals is very important in fetal monitoring. In this paper, we proposed a new method for fetal ECG extraction based on wavelet analysis, the least mean square (LMS) adaptive filtering algorithm, and the spatially selective noise filtration (SSNF) algorithm. First, abdominal signals and thoracic signals were processed by stationary wavelet transform (SWT), and the wavelet coefficients at each scale were obtained. For each scale, the detail coefficients were processed by the LMS algorithm. The coefficient of the abdominal signal was taken as the original input of the LMS adaptive filtering system, and the coefficient of the thoracic signal as the reference input. Then, correlations of the processed wavelet coefficients were computed. The threshold was set and noise components were removed with the SSNF algorithm. Finally, the processed wavelet coefficients were reconstructed by inverse SWT to obtain fetal ECG. Twenty cases of simulated data and 12 cases of clinical data were used. Experimental results showed that the proposed method outperforms the LMS algorithm: (1) it shows improvement in case of superposition R-peaks of fetal ECG and maternal ECG; (2) noise disturbance is eliminated by incorporating the SSNF algorithm and the extracted waveform is more stable; and (3) the performance is proven quantitatively by SNR calculation. The results indicated that the proposed algorithm can be used for extracting fetal ECG from abdominal signals.     

Brain-targeting delivery for RNAi neuroprotection against cerebral ischemia reperfusion injury

Nanoparticles (NPs) with modification of brain-targeting molecules have been extensively exploited for therapeutic gene delivery across the blood–brain barrier (BBB). As one of the effective RNA interference (RNAi) approaches, short hairpin RNA (shRNA) has been proved to be promising in the field of gene therapy. Apoptosis signal-regulating kinase 1 (Ask1) has been reported to be an important target for gene therapy against cerebral ischemia reperfusion injury. In this study, dendrigraft poly-l-lysine (DGL) was decorated by dermorphin (a μ-opiate receptor agonist) through PEG for efficient brain-targeting, then complexed with anti-Ask1 shRNA plasmid DNA, yielding the DGL-PEG-dermorphin/shRNA NPs. The DGL-PEG-dermorphin/shRNA NPs were characterized and estimated the brain-targeting ability. In vitro, increased cellular uptake and transfection efficiency were explored; in vivo, preferable accumulation and gene transfection in brain were showed in images. The DGL-PEG-dermorphin/shRNA NPs also revealed high efficiency of neuroprotection. As a result of RNAi, corresponding mRNA was distinctly degraded, expression of Ask1 protein was obviously suppressed, apoptotic cell death was apparently decreased and cerebral infarct area was significantly reduced. Above all, DGL-PEG-dermorphin/shRNA NPs were proved to be efficient and safe for brain-targeting RNAi neuroprotection against cerebral ischemia reperfusion injury.     

Serum Levels of Calreticulin in Correlation with Disease Activity in Patients with Rheumatoid Arthritis

Objective

The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA).

Methods

Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative.

Results

Serum CRT levels in RA patients (4.817?±?2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574?±?0.942 ng/ml), SLE (4.013?±?1.536 ng/ml), other autoimmune diseases (3.882?±?0.837 ng/ml) and HC (3.726?±?0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P?<?0.01).

Conclusion

Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.     

Molecular Identification of Bacterial DNA in the Chorioretinal Scars of Chronic Granulomatous Disease

Purpose

Chronic granulomatous disease (CGD) is an inherited disorder characterized by defects in phagocyte-derived nicotinamide adenine dinucleotide phosphate oxidase. It is typically diagnosed in childhood and leads to severe, recurrent bacterial or fungal infections. Chorioretinal lesions are the most common ocular manifestation. We sought to determine whether there are infectious agents in CGD-associated chorioretinopathy.

Methods

Medical records and ocular histopathology from CGD cases from January 1983 to January 2012 at the National Institutes of Health were retrospectively reviewed. Chorioretinal cells from normal and lesional tissues of the same eye were microdissected. Primers for Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia sp., and a panbacterial 16S ribosomal DNA were used for polymerase chain reaction.

Results

Seventeen CGD patients had ocular tissues (16 autopsied cases and 1 chorioretinal biopsy) examined. Of these 17, 8 demonstrated CGD-associated chorioretinal lesions in at least one eye on histopathology. Of these 8, 7 showed amplification of 16S ribosomal DNA within the lesion; of these 7, two also amplified S. epidermidis and one P. aeruginosa. One had no bacterial DNA amplified. Importantly, no microbial DNA was amplified from the normal, non-lesional ocular tissues of these 8 cases. Furthermore, only 1 of the 9 eyes without chorioretinopathy had amplified Burkholderia DNA, that patient had a history of Burkholderia infection.

Conclusions

We detected bacterial DNA in 7 of 8 (88 %) cases with CGD-associated chorioretinopathy and only in 1 normal ocular tissue of 17 CGD cases. Bacterial infection may play a role in the pathogenesis of CGD-associated chorioretinal lesions.     

Repairing Defect and Preventing Collapse of Canine Femoral Head Using Titanium Implant Enhanced by Autogenous Bone Graft and rhBMP-2

There is a direct relationship between mechanical stress and the progressive collapse of the necrotic region in osteonecrosis of the femoral head. The titanium implant combined with autogenous bone graft and recombinant human bone morphogenetic protein (rhBMP)-2 to repair the defect and prevent collapse of the femoral head was investigated. The femoral head defects were made by the trapdoor procedure and then the defects were filled, respectively, with the titanium implant combined with autogenous bone graft and rhBMP-2, with autogenous bone graft and rhBMP-2, and with autogenous bone graft alone. Roentgenographic and histological examinations were performed at various times postoperatively. The defects were repaired completely and the titanium implant was integrated with the surrounding bone tissues. The defects healed faster than did without rhBMP-2. No trapdoor cartilage collapsed and joint space narrowed. The titanium implant combined with autogenous bone graft and rhBMP-2 can enhance the repairing procedure and prevent the collapse of the femoral head.     

Expression of Interleukin‐22 in Myasthenia Gravis

IL‐17 and IL‐22 are implicated in the pathogenesis of autoimmune diseases. The roles of IL‐22 in the pathophysiology of myasthenia gravis (MG) remain unsettled. The aim of this study was to investigate the possible relationship between serum IL‐22, IL‐17 levels, anti‐acetylcholine receptor antibody (anti‐AChR Ab) titres and clinical parameters in patients with MG. The serum IL‐22, IL‐17 levels and anti‐AChR Ab titres were tested by enzyme‐linked immunosorbent assay (ELISA), while the expression of IL‐22 and IL‐17 mRNAs in peripheral blood mononuclear cells (PBMC) from healthy and MG subjects were detected by quantitative real‐time PCR (qRT‐PCR). Furthermore, PBMC from 12 patients with generalized MG were purified and treated with recombinant human IL‐22 (rhIL‐22), the IL‐17 levels of supernatant were detected by ELISA. We found that the IL‐17 levels were significantly increased, but IL‐22 levels were significantly decreased in the serum of patients with MG compared with healthy controls. Consistantly, a significant decrease in IL‐22 mRNA levels and an increase in IL‐17 mRNA levels were detected in PBMC collected from patients with MG, compared with healthy controls. A negative correlation between IL‐22 mRNA in PBMC, serum IL‐22 and serum anti‐AChR Ab levels was found in patients with MG. Moreover, in cultured MG PBMC treated with recombinant human IL‐22 (rhIL‐22), the IL‐17 levels were decreased in a dose‐dependent manner. Our findings indicated a possible role of IL‐22 as a protective factor in MG.     

In vitro biocompatibility evaluation of bioresorbable copolymers prepared from l-lactide, 1, 3-trimethylene carbonate,and glycolide for cardiovascular applications

PLLA-TMC-GA terpolymer was prepared by ring-opening polymerization of l-lactide, 1, 3-trimethylene carbonate (TMC), and glycolide (GA). The biocompatibility of terpolymer was evaluated in comparison with PLLA and PLLA-TMC with the aim of assessing their potential in the development of bioresorbable cardiovascular stents. Various aspects of in vitro biocompatibility were considered, including MTT assay, hemolytic test, dynamic clotting time, platelet adhesion, platelet activation, protein adsorption, plasma recalcification time and release of cytokines. The results revealed that the terpolymer presents good cytocompatibility and hemocompatibility. Moreover, no significant increase in the release of cytokines was detected. It is thus concluded that these polymers, in particular PLLA-TMC-GA terpolymer present good biocompatibility for cardiovascular applications.     

Inhibition of EGF Signaling Protects the Diabetic Retina from Insulin-Induced Vascular Leakage

Diabetes mellitus is a disease with considerable morbidity and mortality worldwide. Breakdown of the blood–retinal barrier and leakage from the retinal vasculature leads to diabetic macular edema, an important cause of vision loss in patients with diabetes. Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes, insulin therapies for control of glucose metabolism cannot prevent long-term retinal complications. The phenomenon of temporary paradoxical worsening of diabetic macular edema after insulin treatment has been observed in a number of studies. In prospective studies on non–insulin-dependent (type 2) diabetes mellitus patients, a change in treatment from oral drugs to insulin was often associated with a significant increased risk of retinopathy progression and visual impairment. Although insulin therapies are critical for regulation of the metabolic disease, their role in the retina is controversial. In this study with diabetic mice, insulin treatment resulted in increased vascular leakage apparently mediated by betacellulin and signaling via the epidermal growth factor (EGF) receptor. In addition, treatment with EGF receptor inhibitors reduced retinal vascular leakage in diabetic mice on insulin. These findings provide unique insight into the role of insulin signaling in mediating retinal effects in diabetes and open new avenues for therapeutics to treat the retinal complications of diabetes mellitus.Diabetic maculopathy, an important cause of vision loss in patients with type 2 diabetes, is characterized by hyperpermeability of retinal blood vessels and subsequent formation of macular edema and hard exudates. Although the increase in retinal vascular permeability occurs both diffusely and in focal regions, the basic physiological defect that causes retinal vascular leakage is unknown. The blood–retinal barrier (BRB) isolates the retina from the bloodstream, establishing a favorable environmental milieu with the regulation of ionic balance, nutrient availability, and blockage of potentially toxic molecules that allows for optimal retinal function. The BRB consists of an inner BRB, formed by endothelial cells lining the retinal blood vessels and the outer BRB formed by the retinal pigment epithelium (RPE), a layer of epithelial cells between the retina and the non-neuronal choroid.^1,2 Disruption of the BRB is an important feature of diabetic retinopathy.Based on data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a prospective population-based cohort study of patients with type 1 and 2 diabetes mellitus, the prevalence of clinically significant macular edema is 5.9% for type 1 and 7.5% for type 2 diabetes.³ Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes,⁴ insulin therapies for control of glucose metabolism may not prevent long-term complications.^5,6 Even though both laser photocoagulation and anti-VEGF therapies have shown significant promise in the treatment of proliferating vessels in proliferative diabetic retinopathy, diabetic macular edema (DME) appears to be more resistant to these treatment approaches, suggesting that other factors might contribute to this complication. We have recently reported the potential role of betacellulin (Btc) in inducing retinal vascular permeability in diabetes.⁷ Clinical trials and other studies have determined that initiation of acute intensive insulin therapy in patients with long-standing poor glycemic control results in a transient worsening of diabetic retinopathy.^8–13 A change in treatment from oral drugs to insulin in patients with non–insulin-dependent (type 2) diabetes mellitus was associated with a significantly increased risk of retinopathy progression and visual impairment.^14–16 In addition, it has been reported that patients who undergo total pancreatectomy for cancer develop severe diabetes because of the complete absence of insulin but rarely if ever develop proliferative diabetic retinopathy,¹⁷ even when they survive for more than one or two decades. These reports led us to model and evaluate the pathophysiological effects of insulin on the retinal vasculature and the potential crosstalk between insulin and Btc in the regulation of retinal vascular permeability.