Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.     

Proteome alterations induced in human white blood cells by consumption of Brussels sprouts: Results of a pilot intervention study

Epidemiological studies indicate a correlation of cruciferous vegetables consumption with reduced incidence of cancer. This study was designed to investigate molecular mechanisms, which may help to understand the beneficial effects of Brussels sprout consumption. In order to avoid the limitations of in vitro model systems, we performed a dietary intervention study with five participants. We investigated, whether sprout consumption affects the proteome profile of primary white blood cells. In order to achieve maximal sensitivity in detecting specific adaptive proteome alterations, we metabolically labelled freshly isolated cells in the presence of ³⁵S‐methionine/cysteine and performed autoradiographic quantification of protein synthesis. Proteins were separated by 2‐DE and spots of interest were cut out, digested and identified by MS. After the intervention, we found a significant up‐regulation of the synthesis of manganese superoxide dismutase (1.56‐fold) and significant down‐regulation of the synthesis of heat shock 70 kDa protein (hsp70; 2.27‐fold). Both proteins play a role in malignant transformation of cells. Hsp‐70 is involved in the regulation of apoptosis, which leads to elimination of cancer cells, while SOD plays a key role in protection against reactive oxygen species mediated effects. Our findings indicate that the alteration of the synthesis of these proteins may be involved in the anticarcinogenic effects of cruciferous vegetables, which was observed in earlier laboratory studies with animals.     

Conjunctival nevi in Denmark 1960-1980. A 21-year follow-up

The clinicopathological characteristics of 343 naevi of the conjunctiva were studied. A significant increase in the number of naevi excised per year was observed. This may have been caused by an increased exposure to actinic rays. An approximately even distribution was found between the three main locations: caruncle, limbal area and eye ball. Intrastromal naevi were excised at a higher median age than compound naevi, and the lowest median age at excision was for junction naevi, which is in accordance with the known histopathological nature of naevi. Recurrence occurred in nine patients (2.7%), and one had transformed into a malignant melanoma. Eight of the recurring naevi were located in the limbal area. Eight of the nine patients were women, suggesting hormonal factors as a possible cause. Recommendations for the handling of conjunctival naevi are given, based on the present findings and on previous reports.     

Follow up after potential curative surgery of colorectal cancer. Guidelines from the Norwegian Gastrointestinal Cancer Group

In Norway, about 2,800 cases of colorectal cancer are diagnosed every year. Two-thirds of the patients undergo potentially curative surgery and almost half of them develop local or distant metastases. The follow-up of colorectal cancer patients involves four strategies: Educating the patients about the disease, symptoms of relapse, and risk of hereditariness; Early diagnosis of relapse, to make curative re-surgery possible; Diagnosis of metachronous/synchronous cancer(s); Recording the results of current surgical techniques. The Norwegian Gastrointestinal Cancer Group recommend a four-year follow-up programme (every third month for two years and then twice a year) of colorectal cancer patients. It is suggested that patients treated with low anterior resection are followed regularly by means of rectoscopy and local examination (digital or by ultrasound) undertaken by specialist (surgeon or gastroenterologist). The others should be followed up mainly by general practitioners. Carcinoembryonic antigen (CEA)-monitoring is suggested every third month for two years, and then every sixth month. Colonoscopy is recommended at one and four year follow-up. Patients with normal CEA levels prior to surgery should be evaluated by ultrasound of the liver every sixth month for four years.     

科帕卡格拉纳建筑 奥地利维亚纳

正科帕卡格拉纳位于新多瑙河12.5公里处,毗邻Reichsbrücke大桥。出于同旧有设计保持协调性考虑,力求能让大楼融入当地环境,迎合自身功能性需要,GERNER GERNER PLUS团队充分考虑现有周边环境,对大楼重新规划设计。新的设计突显建筑的特殊性和重要性,面向河流的立面是科帕卡格拉纳大楼最重要的部分,所以设计的重点也放在了这里。现有的城市中轴线是一个参照物,为了视觉上和氛围上形成一体化城市的感     

Recognition of handwritten musical notes by a modified Neocognitron

A neural network for recognition of handwritten musical notes, based on the well-known Neocognitron model, is described. The Neocognitron has been used for the what pathway (symbol recognition), while contextual knowledge has been applied for the where (symbol placement). This way, we benefit from dividing the process for dealing with this complicated recognition task. Also, different degrees of intrusiveness in learning have been incorporated in the same network: More intrusive supervised learning has been implemented in the lower neuron layers and less intrusive in the upper one. This way, the network adapts itself to the handwriting of the user. The network consists of a 13×49 input layer and three pairs of simple and complex neuron layers. It has been trained to recognize 20 symbols of unconnected notes on a musical staff and was tested with a set of unlearned input notes. Its recognition rate for the individual unseen notes was up to 93%, averaging 80% for all categories. These preliminary results indicate that a modified Neocognitron could be a good candidate for identification of handwritten musical notes.     

Lamotrigine toxicity secondary to sertraline

Branches of the extracranial internal carotid artery are very rare. A case is reported wherein an aberrant artery originated from the bulb of the internal carotid artery (ICA) approximately 2 cm from the bifurcation. The ICA was occluded distal to the branch's origin. Arteriography in this case gave the appearance of a carotid "string sign". Vascular surgeons and radiologists should be aware of this anomaly when interpreting carotid arteriograms.     

Near-infrared to visible photon upconversion in Mn and Yb containing materials

Near-infrared (NIR) laser excitation into the Yb^{3+ 2}F_7/2→²F_5/2 absorption transition around 10,200 cm⁻¹ at 12 K leads to red and green upconversion emission in MnCl₂:Yb³⁺ and Zn₂SiO₄:Yb³⁺; Mn²⁺, respectively. The photon upconversion (UC) emission is centered around 15,240 cm⁻¹ for MnCl₂:Yb³⁺ and around 19,050 cm⁻¹ for Zn₂SiO₄:Yb³⁺; Mn²⁺ and is ascribed to the Mn^{2+ 4}T₁→⁶A₁ transition in both compounds. The shift of the Mn²⁺ emission energy is due to the different coordination and ligand strength. Pulsed measurements indicate a sequence of ground-state absorption (GSA) and excited-state absorption (ESA) steps for the upconversion process. We conclude that the UC process in both compounds occurs by an exchange mechanism involving Yb³⁺ and Mn²⁺ ions. Zn₂SiO₄:Yb³⁺; Mn²⁺ is the first example of a Yb³⁺–Mn²⁺ upconversion system to show visible (VIS) by eye Mn²⁺ UC emission at room temperature.