Establishing a multidisciplinary diabetic foot team in a large tertiary hospital: a workshop

Every year, over 1 million people with diabetes lose a leg due to diabetic foot disease. Most amputations are preceded by a foot ulcer. Causes for the development of foot ulcers are generally multifactorial and may include neuropathy, peripheral vasculopathy, abnormal foot mechanics and infection. Multidisciplinary approach to the patient with acute diabetic foot is mandatory and has been shown to reduce amputation rate. In our article we describe the establishment of a multidisciplinary diabetic foot team in a large tertiary hospital and its outcomes. Copyright © 2014 John Wiley & Sons, Ltd.     

Cytocompatibility of novel extracellular matrix protein analogs of biodegradable polyester polymers derived from α-hydroxy amino acids

One of the challenges in regenerative medicine is the development of novel biodegradable materials to build scaffolds that will support multiple cell types for tissue engineering. Here we describe the preparation, characterization, and cytocompatibility of homo- and hetero-polyesters of α-hydroxy amino acid derivatives with or without lactic acid conjugation. The polymers were prepared by a direct condensation method and characterized using gel permeation chromatography, ¹H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, optical activity, and solubility. The surface charge of the polymers was evaluated using zeta potential measurements. The polymers were coated onto glass cover slips followed by characterization using nano-surface profiler, thin film reflectometry, and atomic force microscopy (AFM). Their interaction with endothelial and neuronal cells was assessed using adhesion, proliferation, and differentiation assays. Of the characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12 pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of endothelial cells, but did not affect PC12 cell differentiation. NGF-induced Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar to the effect observed for cells cultured on collagen type I. While no significant association could be established between charge and the differentiative/proliferative properties of the polymers, AFM analysis indicated augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces. We conclude that overall selective cytocompatibility and bioactivity might render α-hydroxy amino acid polymers useful as extracellular matrix-mimicking materials for tissue engineering.     

缺血性卒中或短暂性脑缺血发作的双重抗血小板治疗

2013年美国心脏协会/美国卒中协会颁布的缺血性卒中早期处理指南推荐单用阿司匹林进行抗血小板治疗,并未推荐其他抗血小板药,更未推荐联合应用多种抗血小板药.然而,2013年之后发表的大量文献显示,双重抗血小板药在防治缺血性卒中和短暂性脑缺血发作方面优于单个抗血小板药,并评估了双重抗血小板药治疗的安全性.     

Red Blood Cell Distribution Width (RDW) and long-term survival in patients with ST Elevation Myocardial Infarction

Introduction

High RDW values are associated with adverse prognosis in many clinical conditions including short and medium term outcome of patients with ST Elevation Myocardial Infarction (STEMI). The aim of the present study was to evaluate the association between RDW and long term mortality in STEMI patients undergoing primary angioplasty (PPCI).

Material and methods

A cohort of 535 STEMI patients undergoing PPCI were divided into two groups (RDW > 14%, RDW ≤ 14%) using CHAID and CART methods. The association between RDW and 5-year all-cause mortality was assessed using Cox’s proportional hazards analysis.

Results

A total of 37 patients died during follow up of 5 years (mean: 1059, median: 1013, range 2–2130 days). RDW > 14% was associated with increased risk of all-cause mortality (HR = 5, CI 95% 2.7– 9.9, p < 0.001). In multivariate analysis, RDW > 14 remained significantly associated with increased risk for all-cause mortality (HR = 3.8, CI 95% 1.8– 7.99, p < 0.001). Patients with RDW above 14% did not have lower ejection fraction, higher CPK or more conventional risk factors.

Conclusion

RDW value above 14 is independently associated with increased long term all-cause mortality in patients with STEMI undergoing PPCI.     

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1?? resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.     

Downregulation of Notch-1/Jagged-2 in human colon tissues from Hirschsprung disease patients

Purpose  

Recent studies have shown that the Notch pathways play important roles in the differentiation and development of neurons. Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the nerve plexuses of the distal gut. However, putative Notch function in enteric nervous system (ENS) development and the etiology of HSCR is unknown.     

A single pentylenetetrazole-induced clonic-tonic seizure episode is accompanied by a slowly developing cognitive decline in rats

According to different studies, between 5% and 10% of people suffer a single isolated seizure episode at some time in their life. However, little is known about the effects of a single seizure episode on cognitive function, and clinical investigations of this issue are not easy to perform. In this situation, animal models may be a reasonable choice. The aim of our study was to follow the time course of delayed effects of generalized clonic-tonic convulsions on learning and memory functions in rats. A clonic-tonic seizure episode was induced by a single i.p. injection of pentylenetetrazole (70 mg/kg). Different behavioral tests were performed between days 10 and 100 after the convulsant administration. A single seizure episode resulted in a gradual decline in short-term memory function as assessed by novel object recognition and social recognition tests. The seizure episode induced a quick increase in hippocampal cell proliferation; however, the excessive newly generated cells seemed to be eliminated by the time of obvious cognitive impairment. These observations are indicative of a slowly developing and long-lasting influence of a single seizure episode on cognitive function. A rather long time period between the seizure episode and the manifestations of cognitive decline provides a window for a possible therapeutic intervention, and an elaboration of such “post-conditioning” treatments may be a promising opportunity to prevent subsequent mental impairments in patients.     

Evaluating reliability of ultra-short ECG indices of heart rate variability in diabetes mellitus patients

Our aim was to investigate the reliability of ultra-short HRV in patients with DM. A good correlation was found between the 1 minute and 5 minute parameters for maximal-RR, minimal-RR, average-RR, SDNN, RMSSD, pNN50, and total power. Also, a good correlation between 10 second and 5 minute parameters was found for maximal-RR, minimal-RR, average-RR, and RMSSD. We suggest that certain ultra-short HRV parameters can be used efficiently in DM patients for autonomic evaluation.