Моксифлоксацин в сравнении с комбинацией офлоксацин плюс метронидазол при неосложнённых воспалительных заболеваниях органов малого таза: результаты многоцентрового, двойного слепого, рандомизированного клинического исследования

МОКСИФЛОКСАЦИНТА

Rhesus macaques vaccinated with consensus envelopes elicit partially protective immune responses against SHIV SF162p4 challenge

The development of a preventative HIV/AIDS vaccine is challenging due to the diversity of viral genome sequences, especially in the viral envelope (Env160). Since it is not possible to directly match the vaccine strain to the vast number of circulating HIV-1 strains, it is necessary to develop an HIV-1 vaccine that can protect against a heterologous viral challenge. Previous studies from our group demonstrated that a mixture of wild type clade B Envgp160s were able to protect against a heterologous clade B challenge more effectively than a consensus clade B Envgp160 vaccine. In order to broaden the immune response to other clades of HIV, in this study rhesus macaques were vaccinated with a polyvalent mixture of purified HIV-1 trimerized consensus Envgp140 proteins representing clades A, B, C, and E. The elicited immune responses were compared to a single consensus Envgp140 representing all isolates in group M (Con M). Both vaccines elicited anti- Envgp140 IgG antibodies that bound an equal number of HIV-1 Envgp160 proteins representing clades A, B and C. In addition, both vaccines elicited antibodies that neutralized the HIV-1SF162 isolate. However, the vaccinated monkeys were not protected against SHIV SF162p4 challenge. These results indicate that consensus Env gp160 vaccines, administered as purified Envgp140 trimers, elicit antibodies that bind to Envgp160s from strains representing multiple clades of HIV-1, but these vaccines did not protect against heterologous SHIV challenge. © 2013 Eugene et al.; licensee BioMed Central Ltd

Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging

Fibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scattering (SAXS), with in situ mechanics and correlative imaging, can provide quantitative and position-resolved information on the fibrotic matrix nanostructure and its mechanical properties. We use as an example the case of keloid scarring in skin. SAXS mapping reveals heterogeneous gradients in collagen fibrillar concentration, fibril pre-strain (variations in D-period) and a new interfibrillar component likely linked to proteoglycans, indicating evidence of a complex 3D structure at the nanoscale. Furthermore, we demonstrate a proof-of-principle for a diffraction-contrast correlative imaging technique, incorporating, for the first time, DIC and SAXS, and providing an initial estimate for measuring spatially resolved fibrillar-level strain and reorientation in such heterogeneous tissues. By application of the method, we quantify (at the microscale) fibrillar reorientations, increases in fibrillar D-period variance, and increases in mean D-period under macroscopic tissue strains of ~20%. Our results open the opportunity of using synchrotron X-ray nanomechanical imaging as a quantitative tool to probe structure–function relations in keloid and other fibrotic disorders in situ

Twitter-based analysis of the dynamics of collective attention to political parties

Large-scale data from social media have a significant potential to describe complex phenomena in real world and to anticipate collective behaviors such as information spreading and social trends. One specific case of study is represented by the collective attention to the action of political parties. Not surprisingly, researchers and stakeholders tried to correlate parties' presence on social media with their performances in elections. Despite the many efforts, results are still inconclusive since this kind of data is often very noisy and significant signals could be covered by (largely unknown) statistical fluctuations. In this paper we consider the number of tweets (tweet volume) of a party as a proxy of collective attention to the party, identify the dynamics of the volume, and show that this quantity has some information on the elections outcome. We find that the distribution of the tweet volume for each party follows a log-normal distribution with a positive autocorrelation of the volume over short terms, which indicates the volume has large fluctuations of the log-normal distribution yet with a short-term tendency. Furthermore, by measuring the ratio of two consecutive daily tweet volumes, we find that the evolution of the daily volume of a party can be described by means of a geometric Brownian motion (i.e., the logarithm of the volume moves randomly with a trend). Finally, we determine the optimal period of averaging tweet volume for reducing fluctuations and extracting short-term tendencies. We conclude that the tweet volume is a good indicator of parties' success in the elections when considered over an optimal time window. Our study identifies the statistical nature of collective attention to political issues and sheds light on how to model the dynamics of collective attention in social media.Comment: 16 pages, 7 figures, 3 tables. Published in PLoS ON

Actin binding proteins:their ups and downs in metastatic life

In order to metastasize away from the primary tumor site and migrate into adjacent tissues, cancer cells will stimulate cellular motility through the regulation of their cytoskeletal structures. Through the coordinated polymerization of actin filaments, these cells will control the geometry of distinct structures, namely lamella, lamellipodia and filopodia, as well as the more recently characterized invadopodia. Because actin binding proteins play fundamental functions in regulating the dynamics of actin polymerization, they have been at the forefront of cancer research. This review focuses on a subset of actin binding proteins involved in the regulation of these cellular structures and protrusions, and presents some general principles summarizing how these proteins may remodel the structure of actin. The main body of this review aims to provide new insights into how the expression of these actin binding proteins is regulated during carcinogenesis and highlights new mechanisms that may be initiated by the metastatic cells to induce aberrant expression of such proteins. © 2013 Landes Bioscience

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Successful treatment of Mycobacterium ulcerans osteomyelitis with minor surgical debridement and prolonged rifampicin and ciprofloxacin therapy: a case report

ABSTRACT: INTRODUCTION: Treatment for osteomyelitis-complicating Mycobacterium ulcerans infection typically requires extensive surgery and even amputation, with no reported benefit from adjunctive antibiotics. CASE PRESENTATION: We report a case of an 87-year-old woman with M. ulcerans osteomyelitis that resolved following limited surgical debridement and 6 months of therapy with rifampicin and ciprofloxacin. CONCLUSION: M. ulcerans osteomyelitis can be successfully treated with limited surgical debridement and adjunctive oral antibiotics

Impetigo herpetiformis during the puerperium triggered by secondary hypoparathyroidism: a case report

A 38-year-old multiparous woman with post thyroidectomy hypoparathyroidism developed pruritic erythematous patches with multiple pustules on its margins on her thighs and groin accompanied by fever few days after delivery by caesarean section. Impetigo herpetiformis was diagnosed based on the typical clinicopathological findings. The patient was treated with intravenous fluids, calcium, Calcitrol and corticosteroids. The correction of hypocalcaemia was accompanied with rapid improvement of her skin disease and general condition. Our case is the fourth case of impetigo herpetiformis initially presented during puerperium and the first case of puerperal impetigo herpetiformis that is precipitated by secondary hypoparathyroidism. The awareness of the possible occurrence of impetigo herpetiformis during the puerperium allows early diagnosis, treatment and prevention of maternal complications