Binocular vision in strabismic humans with alternating fixation

Grating acuity, interocular suppression and binocular interaction were evaluated at different positions in the visual field of strabismic humans with alternating fixation. In all cases, the suppression of the deviated eye was most intense in a region corresponding to the fovea of the fixating eye, but reduced or absent in the periphery. In addition, suppression was found in part of the peripheral visual field of the fixating eye. For most subjects, the monocular properties of both eyes were normal. However, for one subject with a strong preference for one of the eyes, visual acuity and luminance detection were selectively impaired in the chronically suppressed regions of the non-preferred eye. Regardless of which eye was currently used for fixation, the visual information available to the subject came from both eyes. In parts of the visual field, the two eyes tended to replace each other. In the far periphery, and especially in the upper and lower hemifield, signals from the two eyes were often combined in a binocular perception of depth.     

Biodistribution of Long-Circulating PEG-Grafted Nanocapsules in Mice: Effects of PEG Chain Length and Density

Purpose: To study the pharmacokinetics and biodistribution of novel polyethyleneglycol (PEG) surface-modified poly(rac-lactide) (PLA) nanocapsules (NCs) and to investigate the influence of PEG chain length and content. Methods: The biodistribution and plasma clearance in mice of different NC formulations were studied with [³H]-PLA. PLA-PEG copolymers were used in NC preparations at different chain lengths (5 kDa and 20 kDa) and PEG contents (10% and 30% w/w of total polymer). In vitro and in vivo stability were also checked. Results: Limited [³H]-PLA degradation was observed after incubation in mouse plasma for 1 h, probably because of to the large surface area and thin polymer wall. After injection into mice, NCs prepared with PLA-PEG copolymers showed an altered distribution compared to poloxamer-coated PLA NCs. An increased concentration in plasma was also observed for PLA-PEG NCs, even after 24 h. A dramatic difference in the pharmacokinetic parameters of PLA-PEG 45-20 30% NCs compared to poloxamer-coated NCs indicates that covalent attachment, longer PEG chain lengths, and higher densities are necessary to produce an increased half-life of NCs in vivo. Conclusions: Covalently attached PEG on the surface of NCs substantially can reduce their clearance from the blood compartment and alter their biodistribution.     

Protein threading by learning

By using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems.     

Stilbene analogues affect cell cycle progression and apoptosis independently of each other in an MCF-7 array of clones with distinct genetic and chemoresistant backgrounds

The development of chemoresistant breast cancer is poorly understood and second treatment options are barely investigated. The term 'chemoresistance' is ill-defined and thus, our experimental analyses aimed to disentangle the resistance to cell cycle arrest from the resistance to trigger apoptosis, both of which are important mechanisms to be targeted by anticancer therapy. Therefore, an MCF-7 array, which encompassed clones harboring distinct genetically- and pharmacologically-induced stages of resistance, was established. For this, MCF-7 cells were stably transfected with erbB2 cDNA and a dominant negative p53 mutation and the two clones were subjected to long-term treatment with the clinical agents 2'-deoxy-5-fluorouridine (5-FdUrd) or arabinosylcytosine (AraC) to develop specific chemoresistance. This array was tested with 3,4',5-trihydroxy-trans-stilbene (resveratrol) and the methoxylated paired stilbene analogue 3,4',5-trimethoxy-trans-stilbene (M5) to investigate whether these agents can overcome genetically- and pharmacologically-induced chemoresistance and to correlate the structure-activity relationship of resveratrol and M5. In all conditions tested, M5 exhibited stronger anticancer activity than resveratrol, but the cell cycle inhibitory properties of the tested drugs were dependent on the genetic background and the chemoresistant phenotype. In contrast, the proapoptotic properties were rather similar in the distinct genetic backgrounds of the clone array and therefore, apoptotic triggers and cell cycle checkpoints were distinctly affected and are thus independent of each other. The study demonstrates the merits or virtues of the genotypically- and phenotypically-defined clones of the MCF-7 array as a testing tool for novel drugs, which discriminates the two types of chemoresistance mechanisms.     

Nivolumab for advanced non-small cell lung cancer: an evaluation of a phase III study

Lung cancer still remains associated with a high mortality rate and more efficacious therapies are needed in order to improve the disease outcome. Nivolumab is a monoclonal antibody which blocks the programmed death-1 receptor which is currently evaluated in phase III clinical trials in advanced lung cancer. Here, we evaluate the results of a phase III study in which nivolumab efficacy and safety were compared to those of docetaxel. Nivolumab was able to improve survival and progression-free survival and exhibited a very good safety profile. Further clinical data are needed in order to better position this therapy among the existing methods. The promising results support the use of this therapy as a stand-alone approach.     

Natural orifice translumenal endoscopic surgery (NOTES) second-look peritoneoscopy for staging of limited peritoneal carcinomatosis

Background

Over the past decades, staging laparoscopy evolved as a useful tool in multimodality treatment of patients with abdominal malignancies, especially for detection of incurable peritoneal and liver metastasis. Natural orifice translumenal endoscopic surgery (NOTES) is a new, evolving technique which represents the next logical progression in minimally invasive surgery and has theoretical advantages in comparison with standard laparoscopic surgery. A review of the current literature revealed a continuous increasing number of fundamental and clinical studies addressing NOTES approach in multimodal management of oncologic patients. Technical possibility to use this new minimally invasive approach for oncological resection of abdominal malignancies was proved by some investigators.

Hypothesis

NOTES can be used as an alternative method for staging patients with limited peritoneal carcinomatosis and may have better results compared to current imaging techniques for small diameter metastatic disease.

Conclusions

With the continuous development of the NOTES techniques and technology, the second-look peritoneoscopy by NOTES may become an alternative method for staging in patients with peritoneal carcinomatosis. Nevertheless, NOTES is at a very early stage of its development, and its implementation in oncologic surgery should be made very caution, and only after careful evaluation.