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In this study, we report the degradation of smooth and rough lipopolysaccharides (LPS) from Gram-negative bacteria and of lipoteichoic acid (LTA) from Gram-positive bacteria by peptide-coated TiO2nanoparticles (TiO2NPs). While bare TiO2NPs displayed minor binding to both LPS and LTA, coating TiO2NPs with the antimicrobial peptide LL-37 dramatically increased the level of binding to both LPS and LTA, decorating these uniformly. Importantly, peptide coating did not suppress reactive oxygen species generation of TiO2NPs; hence, UV illumination triggered pronounced degradation of LPS and LTA by peptide-coated TiO2NPs. Structural consequences of oxidative degradation were examined by neutron reflectometry for smooth LPS, showing that degradation occurred preferentially in its outer O-antigen tails. Furthermore, cryo-TEM and light scattering showed lipopolysaccharide fragments resulting from degradation to be captured by the NP/lipopolysaccharide coaggregates. The capacity of LL-37-TiO2NPs to capture and degrade LPS and LTA was demonstrated to be of importance for their ability to suppress lipopolysaccharide-induced activation in human monocytes at simultaneously low toxicity. Together, these results suggest that peptide-coated photocatalytic NPs offer opportunities for the confinement of infection and inflammation.

The ageing of organic-coated aqueous aerosols at night is investigated by reacting NO3with binary surfactant mixtures floating on water. The surfactants are oleic acid (OA), methyl oleate (MO) and stearic acid (SA). Deuterated surfactants mixed with hydrogenous surfactants were studied using neutron reflectometry to determine the reaction kinetics of organic two-component monolayers with NO3at the air–water interface for the first time. We measured the rate coefficients for OA monolayers, mixed with hydrogenous co-surfactant MO or SA to be (3 ± 1) × 10−8cm2per molecule per s or (3.6 ± 0.9) × 10−8cm2per molecule per s and MO monolayers mixed with hydrogenous co-surfactant OA or SA to be (0.7 ± 0.4) × 10−8cm2per molecule per s or (3 ± 1) × 10−8cm2per molecule per s. The initial desorption lifetimes of NO3, τd,NO3,1, were 8 ± 3 ns, 14 ± 4 ns, 12 ± 3 ns and 21 ± 10 ns. The approximately doubled desorption lifetime for MO–SA compared to the other mixtures is consistent with a more accessible double bond associated with the larger area per molecule of MO in the presence of SA facilitating NO3attack. The significantly slower reactive loss of MO–OA compared to a MO monolayer demonstrates that multi-component surfactant mixtures need to be studied in addition to single-component monolayers. Such a retarded decay would cause the residence time to change from ca.4 to 22 minutes associated with increased transport distances of surfactant species together with any other pollutants that may be protected underneath the surfactant film.

The prospects for making a vast impact on the morbidity and mortality from breast cancer lie more likely in the area of chemoprevention. Tamoxifen was the first agent considered in a preventive setting. Different studies analyzed the role of tamoxifen in prevention and, although the first results were apparently contradictory, they showed notable reductions in breast cancer. In the same period, in the MORE trial, raloxifene unexpectedly produced a larger reduction of breast cancer than was seen for tamoxifen. This result led to other chemoprevention studies to establish the role of raloxifene. Particularly, the STAR trial showed that raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of adverse event. At the same time, the third-generation aromatase inhibitors (AIs) have shown good efficacy in advanced breast cancer and a low toxicity profile. They offer another approach to prevention, which may be superior or complimentary to the use of Selective Estrogen Receptor Modifiers (SERMs). Currently no AIs have yet been fully evaluated. New studies comparing the different agents together are needed and further follow up of the existing chemoprevention trials are necessary to determine which women will truly benefit from this kind of prophylaxis.

The aim of this review is to identify the evidence for the surveillance of women at high risk of breast cancer with the different modalities. The definition of high risk refers to the subpopulation of women with a family history of breast cancer, including both those with and without identified genetic mutations. The following topic has been evaluated: clinical breast examination (CBE), mammography, ultrasound and MRI accuracy of detecting breast cancer among women at high risk. The search was limited to full reports published in English and published between 1996 and March, 2010. We found consistent evidence that adding MRI provides a highly sensitive screening strategy (sensitivity range: 93-100) compared to mammography alone (32-86) or mammography plus ultrasound /- CBE (26-93). Three studies that compared MRI plus mammography versus mammography alone showed the sensitivity of MRI plus mammography as 93 (95 CI 86-100) and the incremental sensitivity of MRI as 60. Incremental sensitivity of MRI was lower when added to mammography plus ultrasound (43) or to the combination of mammography, ultrasound plus CBE. Estimates of screening specificity with MRI were less consistent but suggested a 3-5-fold higher risk of patient recall for investigation of false positive results. No studies assessed whether adding MRI reduces patient mortality, interval or advanced breast cancer rates, even if we found strong evidence that MRI leads to the detection of earlier stage disease. This review suggests that a surveillance strategy would be accurate and effective in improving health outcomes for women at high risk of breast cancer, but randomized studies should be considered for a better evaluation of these topics.

Aims and background Metronomic chemotherapy refers to the administration of low doses of cytotoxic agents over a prolonged period of time with no or only short drug-free intervals. It is designed to overcome acquired tumor resistance to chemotherapy and reduce neo-angiogenesis despite a lower toxicity than with standard chemotherapy. The role of metronomic chemotherapy remains controversial, and its optimal therapeutic use has not yet been defined.Methods and study design The present survey was designed as a short questionnaire and was sent to the medical oncologists registered with Medikey, a national database listing all the Italian oncology specialists linked with the Italian Council of Medical Oncology Hospital Consultants (Collegio Italiano Primari Oncologi Medici Ospedalieri, CIPOMO) and the Italian Association of Medical Oncology (Associazione Italiana di Oncologia Medica, AIOM). The questionnaire was completed on a voluntary basis and it was totally anonymous.Results The questionnaire was sent to 3,289 oncologists, and 191 (5.8%) actively participated in the survey. Seventy-two percent of responders declared that they had administered a regimen of metronomic chemotherapy at least once. Metronomic chemotherapy is commonly used in advanced breast cancer patients, and inmost cases it was prescribed after failure of at least two lines of treatment. Oral agents such as cyclophosphamide, capecitabine, methotrexate and vinorelbine were the most commonly prescribed drugs. Nearly 60% of responders was believed to have significantly less toxicity with metronomic chemotherapy than with standard chemotherapy.Conclusions The sample of oncologists who participated in the survey is small but it appears to be representative of the Italian medical oncology community. The answers to the questionnaire indicate a significant interest in metronomic chemotherapy, which is apparently widely prescribed. This is the first large national survey on the use of metronomic chemotherapy. Considering the results, larger research on metronomic chemotherapy is strongly warranted.

Emerging therapeutic treatments based on the production of proteins by delivering mRNA have become increasingly important in recent times. While lipid nanoparticles (LNPs) are approved vehicles for small interfering RNA delivery, there are still challenges to use this formulation for mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and a PEG-lipid. The structural characterization of mRNA-containing LNPs (mRNA-LNPs) is crucial for a full understanding of the way in which they function, but this information alone is not enough to predict their fate upon entering the bloodstream. The biodistribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNP administration, e.g., apolipoproteinE (ApoE). ApoE, being responsible for fat transport in the body, plays a key role in the LNP’s plasma circulation time. In this work, we use small-angle neutron scattering, together with selective lipid, cholesterol, and solvent deuteration, to elucidate the structure of the LNP and the distribution of the lipid components in the absence and the presence of ApoE. While DSPC and cholesterol are found to be enriched at the surface of the LNPs in buffer, binding of ApoE induces a redistribution of the lipids at the shell and the core, which also impacts the LNP internal structure, causing release of mRNA. The rearrangement of LNP components upon ApoE incubation is discussed in terms of potential relevance to LNP endosomal escape.