Nanoparticle tracking analysis (NTA) has been one of several characterization methods used for extracellular vesicle (EV) research since 2006. Many consider that NTA instruments and their software packages can be easily utilized following minimal training and that size calibration is feasible in-house. As both NTA acquisition and software analysis constitute EV characterization, they are addressed in Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018). In addition, they have been monitored by Transparent Reporting and Centralizing Knowledge in Extracellular Vesicle Research (EV-TRACK) to improve the robustness of EV experiments (e.g., minimize experimental variation due to uncontrolled factors). Despite efforts to encourage the reporting of methods and controls, many published research papers fail to report critical settings needed to reproduce the original NTA observations. Few papers report the NTA characterization of negative controls or diluents, evidently assuming that commercially available products, such as phosphate-buffered saline or ultrapure distilled water, are particulate-free. Similarly, positive controls or size standards are seldom reported by researchers to verify particle sizing. The Stokes-Einstein equation incorporates sample viscosity and temperature variables to determine particle displacement. Reporting the stable laser chamber temperature during the entire sample video collection is, therefore, an essential control measure for accurate replication. The filtration of samples or diluents is also not routinely reported, and if so, the specifics of the filter (manufacturer, membrane material, pore size) and storage conditions are seldom included. The International Society for Extracellular Vesicle (ISEV)\'s minimal standards of acceptable experimental detail should include a well-documented NTA protocol for the characterization of EVs. The following experiment provides evidence that an NTA analysis protocol needs to be established by the individual researcher and included in the methods of publications that use NTA characterization as one of the options to fulfill MISEV2018 requirements for single vesicle characterization.

Solid lipid nanoparticles (SLNs) are presently being promoted to improve bioavailability of encapsulated drugs. These are well tolerated in living systems, as they are made from biocompatible material. Despite finding extensive applicability, these systems have not been sufficiently investigated for the toxicity so far. We have reported use of SLNs to improve plasma bioavailability of isoniazid (INH), a hepatotoxic, antitubercular drug. Presently we evaluate acute and repeated (28-day) oral dose toxicity, with satellite group, of developed INH loaded COMBI-SLN. In addition to high bioavailability, the COMBI-SLN exhibited 3 times higher LD50 (2000 mg/kg BW) versus 650 mg/kg BW for free INH. Results were complemented with histopathological evidence in brain, sciatic nerve and liver tissue all of which indicated enhanced safety of INH upon incorporation into SLNs. In the repeated dose study at doses selected as per Organisation for Economic Co-operation and Development (OECD) guidelines, a series of behavioural and haematological tests, clinical biochemistry (kidney and liver function, lipid profile) and histopathological studies were performed to evaluate the effect of low (250 mg/kg BW), medium (500 mg/kg BW) and high oral dose (1000 mg/kg BW). Absence of adverse effects like hepatotoxicity and peripheral neuropathy observed in rats at an oral intake level of 500 and 1000 mg/kg BW of COMBI-SLN, that is 20-40 folds above the anticipated human intake levels (after normalizing the surface area correction for rats), supports the conclusion that SLN are an intrinsically safe nanocarrier system that improves both the efficacy and the safety of INH.

Introduction: The World Health Organization (WHO) points out that 3 million deaths per year caused by cardiopulmonary diseases are related to exposure to air pollution. Objective: To estimate areas of concentration of PM2.5 in Bogotá according to the WHO Air Quality Guidelines (AQG) for cardiopulmonary diseases during the period 2014-2015. Materials and methods: We conducted an ecological study with geostatistical techniques. We calculated the PM2.5 averages for six hour-periods distributed throughout the day in four time slots, which were classified according to daily and annual WHO AQG. Results: The locality of Kennedy presented the highest concentrations of PM2.5 in all time slots. The values registered in this area classified within the daily and annual AQG showed that the locality would present an increase of 1.2% and 9% in cardiopulmonary mortality in the short and long term, respectively. Conclusion: The time slots from 0:00 to 6:00 h y from 12:00 to 18:00 h met the annual AQG value of 10 μg/m3 in a part of the eastern zone of the city; in the rest of the city, in these same time slots, intermediate objectives 2 and 3 were met, which means increases by 9% and 3% in the cardiopulmonary mortality according to the AQG, respectively.
Introducción. La Organización Mundial de la Salud señala que tres millones de muertes al año por enfermedades cardiopulmonares están relacionadas con la exposición a la contaminación del aire. Objetivo. Estimar las superficies de concentración de partículas en suspensión de menos de 2,5 μm (Particulate Matter, PM2,5) en Bogotá entre el 2014 y el 2015, clasificándolas según las guías de calidad del aire de la Organización Mundial de la Salud para enfermedades cardiopulmonares. Materiales y métodos. Se hizo un estudio ecológico mediante técnicas geoestadísticas. Se calcularon los promedios de PM2,5 en lapsos de seis horas a lo largo del día en cuatro franjas horarias. Las concentraciones se clasificaron según los valores diarios y anuales de las guías de calidad del aire de la OMS. Resultados. La localidad de Kennedy presentó las mayores concentraciones de PM2,5 en todas las franjas horarias. Los valores registrados en esta zona y clasificados según las guías diarias y anuales de calidad del aire, evidenciaron que la localidad presentaría un incremento de 1,2 % en la mortalidad cardiopulmonar en el corto plazo y de 9 % en el largo plazo. Conclusión. Las franjas horarias de las 0:00 a las 6:00 h y de las 12:00 a las 18:00 h, cumplieron con el valor anual de las guías de calidad del aire de 10 μg/m3 en una parte de la zona oriental de la ciudad. En el resto de la ciudad, en las franjas horarias de las 6:00 h a las 12:00 h y de las 18:00 h a las 24:00 h se registraron valores que cumplían los objetivos intermedios 2 y 3, lo que representa incrementos de 9 y 3 % en la mortalidad cardiopulmonar, respectivamente.

Metal occupational exposure limits mainly focus on total content of the respective metals of interest. The methods applied for trace metal analysis in occupational health and safety laboratories are usually standardized to pragmatic consensus digestion schemes, ensuring comparability of results. The objective of the present study entailed the evaluation of a recently developed HNO3-only microwave-assisted digestion procedure by comparison with the German consensus hot-block digestion and other national digestion schemes. An inter-laboratory comparison test with participation of nine national occupational health and safety laboratories from Europe and North America was organized. For adequate emulation of what workers are at risk of inhaling four different industrial metal processing workplace dusts (electronic recycling, high-speed steel grinding, cylinder head cleaning, and battery combustion ash) were homogenized and sieved to the particle size < 100 µm diameter at IFA. The participants were asked to process air sample-typical amounts according to the German hot-plate technique, the IFA microwave-assisted digestion scheme as well as their national or in-house conventional digestion method for airborne dust and analyze for Cd, Co, Cr, Co, Fe, Mg, Ni, Pb, and Zn. Recoveries (relative to consensus open-vessel digestion) obtained for the new IFA microwave-assisted digestion were between 88 and 114% and relative reproducibility standard deviations were <10% for most metals of interest. The in-house digestion procedures applied varied widely but (whether microwave, hot block, or open vessel) yielded comparable results for the predominantly elemental alloy type dusts supplied. Results become more diverse for the combustion dust, especially if a combination of microwave-assisted digestion procedures with high temperatures and hydrofluoric acid is applied. ISO 15202-2 is currently being revised; this digestion procedure will be included as a possible variant in annex 2.

The number of poorly soluble drug candidates is increasing, and this is also seen in the research interest towards drug nanoparticles and (nano-)cocrystals; improved solubility is the most important application of these nanosystems. In order to confirm the functionality of these nanoparticles throughout their lifecycle, repeatability of the formulation processes, functional performance of the formed systems in pre-determined way and system stability, a thorough physicochemical understanding with the aid of necessary analytical techniques is needed. Even very minor deviations in for example particle size or size deviation in nanoscale can alter the product bioavailability, and the effect is even more dramatic with the smallest particle size fractions. Also, small particle size sets special requirements for the analytical techniques. In this review most important physicochemical properties of drug nanocrystals and nano-cocrystals are presented, suitable analytical techniques, their pros and cons, are described with the extra input on practical point of view.

BACKGROUND: There is an ongoing debate about the optimal use of metal-on-metal (MoM) bearings in total hip replacement, since there are uncertainties about local and systemic adverse effects due to wear and corrosion of these bearings. Despite various national recommendations, efforts to achieve international harmonization of specific evidence-based recommendations for best practice are still lacking.
OBJECTIVE: An international consensus study group should be able to develop recommendations on the use and monitoring of MoM bearings, preferably at the European level, through a multidisciplinary approach, by integrating the perspectives of various stakeholders.
METHODS: Twenty-one experts representing three stakeholder groups and eight countries participated in this European consensus study, which consisted of a consensus meeting, subsequent structured discussion, and consensus voting.
RESULTS: The current statement defines first of all benefits, local and systemic risks, as well as uncertain issues related to MoM bearings. Safety assessment after implantation of MoM comprises all patients. A closer follow-up is recommended for large head MoM (≥36mm) and resurfacing. In these implants basic follow-up should consist of x-rays and metal ion measurement of cobalt in whole blood, performed with GF-AAS or ICP-MS. Clinical and/or radiographic abnormality as well as elevated ion levels needs additional imaging (ultrasound, CT-scan and/or MARS-MRI). Cobalt values less than 2 μg/L are probably devoid of clinical concern, the threshold value for clinical concern is expected to be within the range of 2-7 μg/L.
CONCLUSIONS: This is the first multinational, interdisciplinary, and multiprofessional approach for developing a recommendation for the use and monitoring of MoM bearings in total hip replacement. The current recommendations are in partial agreement with previous statements regarding the extent of follow-up and imaging techniques. They however differ from previous communications regarding measurement of metal ions and especially the investigated medium, technique, and eventual threshold levels.
METHODS: Level V, expert opinion/agreement conference.

This feature review provides an overview of the state-of the art and recent developments in tip-enhanced Raman spectroscopy (TERS), in-depth information about the different available types of instruments including their (dis-)advantages and capabilities as well as a short glance at a number of samples that have recently been investigated using TERS. Issues concerning the progression of TERS from point spectroscopy to an imaging technique are discussed, as well as problems arising from background and contamination signals. This review is concluded with a short TERS \'user guideline\', trying to aid researchers new in the field to properly align and test their own TERS setups. Finally, a short outlook is given and some critical issues are raised that need to be solved by the community sooner or later, in order to promote TERS towards a \'push-button\' operation.

A major weakness of sediment quality guidelines (SQGs) is their poor ability to predict how toxicity thresholds change for different sediment types. Using species sensitivity distributions (SSDs) of copper effects data, new guidelines were derived for copper in non-sulfidic marine sediments in which organic carbon (OC) and particle size strongly influence copper bioavailability. The derived SQGs varied in a predictable manner with changes in sediment particle size and organic carbon (OC), and were shown to offer a significant improvement on the existing \'single value\' SQG. Adequate protection for all benthic organisms is expected to be achieved for a OC-normalised copper concentration of 3.5 mg Cu g(-1) OC in the <63 μm sediment fraction. For short-term exposures, the equivalent acute guideline is 11 mg<63 μm Cu g(-1) OC. The new SQGs incorporate a high degree of conservatism owing to the use of copper-spiked sediments and laboratory-based bioassays that were expected to result in greater metal exposure of organisms to bioavailable copper than would be expected for field-contaminated sediments with similar total copper concentrations. SQGs that vary with sediment properties were prepared in an easily referenced tabular format.

暂无摘要。

Virus filters are membrane-based devices that remove large viruses (e.g., retroviruses) and/or small viruses (e.g., parvoviruses) from products by a size exclusion mechanism. In 2002, the Parenteral Drug Association (PDA) organized the PDA Virus Filter Task Force to develop a common nomenclature and a standardized test method for classifying and identifying viral-retentive filters. One goal of the task force was to develop a test method for small virus-retentive filters. Because small virus-retentive filters present unique technical challenges, the test method development process was guided by laboratory studies to determine critical variables such as choice of bacteriophage challenge, choice of model protein, filtration operating parameters, target log10 reduction value, and filtration endpoint definition. Based on filtration, DLS, electrospray differential mobility analysis, and polymerase chain reaction studies, a final rating based on retention of bacteriophage PP7 was chosen by the PDA Virus Filter Task Force. The detailed final consensus filter method was published in the 2008 update of PDA Technical Report 41. Virus Filtration.