Determination of Peripheral Neuropathy Prevalence and Associated Factors in Chinese Subjects with Diabetes and Pre-Diabetes – ShangHai Diabetic neuRopathy Epidemiology and Molecular Genetics Study (SH-DREAMS)

Objective

This study determined the prevalence and factors associated with peripheral neuropathy (PN) in subjects with diabetes mellitus, impaired glucose regulation (IGR), and normal glucose tolerance (NGT) in a community-based Chinese population.

Research Design and Methods

A total of 2035 subjects in Shanghai were classified as having NGT, IGR, or diabetes. All subjects underwent complete foot examination. PN was assessed according to the neuropathy symptom and neuropathy disability scores. Binary logistic regression was performed to analyze the contributions of factors to PN.

Results

The prevalence of PN was 8.4%, 2.8%, and 1.5% in diabetes mellitus, IGR, and NGT subjects, respectively (P<0.05 for diabetes vs. NGT, and IGR). The subjects with known diabetes had the highest frequency of PN (13.1%). Among the subjects without diabetes, those with PN were older, had a higher waist circumference and 2-h postprandial plasma glucose levels, and were more likely to be hypertensive. Among the IGR subjects, other than age, the 2-h postprandial plasma glucose level was an independent factor significantly associated with PN. Meanwhile, among the subjects with diabetes, PN was associated with fasting plasma glucose, duration of diabetes, and decreased estimated glomerular filtration rate.

Conclusions

The prevalence of PN is slightly higher in individuals with IGR than that in individuals with NGT, but small fibre damage in IGR as the earliest nerve fibre deficit may be underestimated in our study. As an independent risk factor, postprandial plasma glucose level may be an important target for strategies to prevent or improve PN in IGR subjects.     

Estimation of Wheat Agronomic Parameters using New Spectral Indices

Crop agronomic parameters (leaf area index (LAI), nitrogen (N) uptake, total chlorophyll (Chl) content ) are very important for the prediction of crop growth. The objective of this experiment was to investigate whether the wheat LAI, N uptake, and total Chl content could be accurately predicted using spectral indices collected at different stages of wheat growth. Firstly, the product of the optimized soil-adjusted vegetation index and wheat biomass dry weight (OSAVI×BDW) were used to estimate LAI, N uptake, and total Chl content; secondly, BDW was replaced by spectral indices to establish new spectral indices (OSAVI×OSAVI, OSAVI×SIPI, OSAVI×CI_{red edge}, OSAVI×CI_{green mode} and OSAVI×EVI2); finally, we used the new spectral indices for estimating LAI, N uptake, and total Chl content. The results showed that the new spectral indices could be used to accurately estimate LAI, N uptake, and total Chl content. The highest R² and the lowest RMSEs were 0.711 and 0.78 (OSAVI×EVI2), 0.785 and 3.98 g/m² (OSAVI×CI_{red edge}) and 0.846 and 0.65 g/m² (OSAVI×CI_{red edge}) for LAI, nitrogen uptake and total Chl content, respectively. The new spectral indices performed better than the OSAVI alone, and the problems of a lack of sensitivity at earlier growth stages and saturation at later growth stages, which are typically associated with the OSAVI, were improved. The overall results indicated that this new spectral indices provided the best approximation for the estimation of agronomic indices for all growth stages of wheat.     

Valproic Acid Treatment Inhibits Hypoxia-Inducible Factor 1α Accumulation and Protects against Burn-Induced Gut Barrier Dysfunction in a Rodent Model

Objective

Burn-induced gut dysfunction plays an important role in the development of sepsis and multiple organ dysfunction. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) is critical in paracelluar barrier functions via regulating vascular endothelial growth factor (VEGF) and myosin light chain kinase (MLCK) expression. Previous studies have also demonstrated that histone deacetylase inhibitors (HDACIs) can repress HIF-1α. This study aims to examine whether valproic acid (VPA), a HDACI, protects against burn-induced gut barrier dysfunction via repressing HIF-1α-dependent upregulation of VEGF and MLCK expression.

Methods

Rats were subjected to third degree 55% TBSA burns and treated with/ without VPA (300mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and histologic evaluation. Histone acetylation, tight junction protein zonula occludens 1 (ZO-1), VEGF, MLCK and HIF-1α were measured. In addition, CaCO₂ cells were transfected with siRNA directed against HIF-1α and were stimulated with CoCl2 (1mM) for 24 hours with/without VPA (2mM) followed by analysis of HIF-1α, MLCK, VEGF and ZO-1.

Results

Burn insults resulted in a significant increase in intestinal permeability and mucosal damage, accompanied by a significant reduction in histone acetylation, ZO-1, upregulation of VEGF, MLCK expression, and an increase in HIF-1α accumulation. VPA significantly attenuated the increase in intestinal permeability, mucosa damage, histone deacetylation and changes in ZO-1 expression. VPA also attenuated the increased VEGF, MLCK and HIF-1α protein levels. VPA reduced HIF-1α, MLCK and VEGF production and prevented ZO-1 loss in CoCl2-stimulated Caco-2 cells. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of MLCK and VEGF production, accompanied by upregulation of ZO-1.

Conclusions

These results indicate that VPA can protect against burn-induced gut barrier dysfunction. These protective effects may be due to its inhibitory action on HIF-1α, leading to a reduction in intestinal VEGF and MLCK expression and minimizing ZO-1 degradation.     

Genetic Variants of LRRK2 in Taiwanese Parkinson’s Disease

Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson’s disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset ≤ 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38–3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65–0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27–3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.     

Autophagic Protein Beclin 1 Serves as an Independent Positive Prognostic Biomarker for Non-Small Cell Lung Cancer

Beclin 1, a key regulator of autophagy, has been found to be aberrantly expressed in a variety of human malignancies. Herein, we employed immunohistochemistry (IHC) to detect the protein expression of Beclin 1 in non-small cell lung cancer (NSCLC) and paired normal adjacent lung tissues, and analyzed its clinicopathological/prognostic significance in NSCLC. Receiver operating characteristic (ROC) curve analysis was utilized to determine a cutoff point (>2 VS. ≤2) for Beclin 1 expression in a training set (n = 105). For validation, the ROC-derived cutoff value was subjected to analysis of the association of Beclin 1 with patients’ clinical characteristics and outcome in a testing set (n = 111) and the overall patient cohort (n = 216). Our data showed that Beclin 1 was significantly lower in NSCLC tissues compared with the adjacent normal tissues, negatively associating with tumor recurrence rate (65.8% VS 32.3%; p < 0.001). In the testing set and the overall patient cohort, low expression of Beclin 1 showed significantly inferior overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) compared to high expression of Beclin 1. In the testing set and the overall patient cohort, the median duration of OS for patients with high and low expression of Beclin 1 was 108 VS. 24.5 months (p < 0.001) and 108 VS. 28 months (p < 0.001), respectively. Furthermore, low expression of Beclin 1 was also a poor prognostic factor within each stage of NSCLC patients. Multivariate analysis identified that Beclin 1 was an independent prognostic factor for NSCLC. Our findings in the present study provided evidence that Beclin 1 may thus emerge as an independent prognostic biomarker in this tumor entity in the future.     

Equilibrium-Phase High Spatial Resolution Contrast-Enhanced MR Angiography at 1.5T in Preoperative Imaging for Perforator Flap Breast Reconstruction

Objectives

The aim was (i) to evaluate the accuracy of equilibrium-phase high spatial resolution (EP) contrast-enhanced magnetic resonance angiography (CE-MRA) at 1.5T using a blood pool contrast agent for the preoperative evaluation of deep inferior epigastric artery perforator branches (DIEP), and (ii) to compare image quality with conventional first-pass CE-MRA.

Methods

Twenty-three consecutive patients were included. All patients underwent preoperative CE-MRA to determine quality and location of DIEP. First-pass imaging after a single bolus injection of 10 mL gadofosveset trisodium was followed by EP imaging. MRA data were compared to intra-operative findings, which served as the reference standard.

Results

There was 100% agreement between EP CE-MRA and surgical findings in identifying the single best perforator branch. All EP acquisitions were of diagnostic quality, whereas in 10 patients the quality of the first-pass acquisition was qualified as non-diagnostic. Both signal- and contrast-to-noise ratios were significantly higher for EP imaging in comparison with first-pass acquisitions (p<0.01).

Conclusions

EP CE-MRA of DIEP in the preoperative evaluation of patients undergoing a breast reconstruction procedure is highly accurate in identifying the single best perforator branch at 1.5Tesla (T). Besides accuracy, image quality of EP imaging proved superior to conventional first-pass CE-MRA.     

Syphilis Screening among 27,150 Pregnant Women in South Chinese Rural Areas Using Point-of-Care Tests

Objectives

To determine the prevalence and correlates of syphilis among pregnant women in rural areas of South China.

Methods

Point-of-care syphilis testing was provided at 71 health facilities in less developed, rural areas of Guangdong Province. Positive samples were confirmed at a local referral center by toluidine red unheated serum tests (TRUST) and Treponema pallidum particle agglutination (TPPA) tests.

Results

Altogether 27,150 pregnant women in rural Guangdong were screened for syphilis. 106 (0.39%) syphilis cases were diagnosed, of which 78 (73.6%) received treatment for syphilis. Multivariate analysis revealed that older pregnant women (31–35 years old, aOR 2.7, 95% CI 0.99–7.32; older than 35 years old, aOR 5.9, 95% CI 2.13–16.34) and those with a history of adverse pregnant outcomes (aOR 3.64, 95% CI 2.30–5.76) were more likely to be infected with syphilis.

Conclusions

A high prevalence of syphilis exists among pregnant women living in rural areas of South China. Enhanced integration of syphilis screening with other routine women''s health services (OB GYN, family planning) may be useful for controlling China''s syphilis epidemic.