Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin

Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy

[Level of functionality among senior citizen packers in a chain of Mexican supermarkets]

OBJECTIVE: To identify socio-demographic characteristics and general health conditions among senior citizens working as volunteer packers in a supermarket chain in Mexico. MATERIAL AND METHODS: From May to July 2008 we carried out a cross-sectional analysis in 416 volunteers aged 60 or more years. RESULTS: Mean age was 69.4 years, (range 60-87). Mean level of schooling was elementary school. Men's prior occupation was in the formal sector of the economy vs. women participants who were not. Men were mostly from lower middle class strata and women from lower strata. Most participant's self-perception of health was good although there was an inherent risk of developing obesity. Depression rating scale scores were within normal limits. They had sought work as packers due to financial constraints. CONCLUSIONS: Senior citizens working as paid volunteers seems to promote their physical, mental, social and financial well being. Our findings suggest gender differences within the context of a bleak socio-economic and epidemiological panorama

[Level of functionality among senior citizen packers in a chain of Mexican supermarkets]

OBJECTIVE: To identify socio-demographic characteristics and general health conditions among senior citizens working as volunteer packers in a supermarket chain in Mexico. MATERIAL AND METHODS: From May to July 2008 we carried out a cross-sectional analysis in 416 volunteers aged 60 or more years. RESULTS: Mean age was 69.4 years, (range 60-87). Mean level of schooling was elementary school. Men's prior occupation was in the formal sector of the economy vs. women participants who were not. Men were mostly from lower middle class strata and women from lower strata. Most participant's self-perception of health was good although there was an inherent risk of developing obesity. Depression rating scale scores were within normal limits. They had sought work as packers due to financial constraints. CONCLUSIONS: Senior citizens working as paid volunteers seems to promote their physical, mental, social and financial well being. Our findings suggest gender differences within the context of a bleak socio-economic and epidemiological panorama