Fat embolism after intraosseous catheters in pediatric forensic autopsies.

In our center, we performed the autopsy of a child who died from drowning and presented, at autopsy, a major pulmonary fat embolism (PFE). A cardiopulmonary resuscitation (CPR) was performed, including infusion by intraosseous catheter (IIC). No other traumatic lesions and diseases classically related to a risk of PFE were detected. According to some animal studies, we considered the IIC as the only possible cause for PFE. However, we could not find literature to confirm this hypothesis in humans, especially in a pediatric population. To verify the occurrence of PFE after IIC in a pediatric population, we retrospectively selected 20 cases of pediatric deaths autopsied in our center, in which a CPR was performed, without bone fractures or other possible causes of PFE: 13 cases with IIC (group A) and 7 cases without IIC (group B). Several exclusion criteria were considered. The histology slides of the pulmonary tissue were stained by Oil Red O. PFE was classified according to the Falzi scoring system. In group A, 8 cases showed PFE: 4 cases with a score 1 of Falzi and 4 cases with a score 2 of Falzi. In group B, no case showed PFE. The difference between the two groups was statistically significant. The results of our study seem to confirm that IIC can lead to PFE in a pediatric population and show that the PFE after IIC can be important (up to score 2 of Falzi). To the best of our knowledge, our study is the first specifically focused on the occurrence of PFE after IIC in a pediatric population by using autoptic data.

Creation of a Forensic Pathology Biobank in Switzerland: which issues and research opportunities?

A biobank is a collection of biological material associated with health database. The field of biobanking has significantly developed over the past 30 years. Research based on biobank material gives access to data of a large number of people and can often significantly accelerate the understanding of disease and improve the quality of care. In the University Center of Legal Medicine Lausanne-Geneva, samples collected during autopsies are used for forensic investigations. The legal and ethical framework to use these samples for research is often complex and confused, which is unfortunate given the potential of these biospecimens. Indeed, forensic samples are valuable for research because they originate in part from young (including pediatrics cases) and healthy people who are poorly represented in worldwide institutional biobanks. In this context at the beginning of the year 2019, the Forensic Pathology Biobank was created. Creation of a forensic pathology biobank is the best way to standardize local conservation practices and improve personal data management, thus providing a very valuable biological material for scientific projects. Its development gives rise to many questions about technical standards, ethical and legal issues but also many research opportunities.

Biophysical rhizosphere processes affecting root water uptake.

Background Recent advances in imaging techniques now make it possible to visualize the biogeochemical and physical environment around the roots, the rhizosphere. Detailed images of pore space geometry and water content dynamics around roots have demonstrated the heterogeneity of the rhizosphere compared with the soil far from the roots. These findings have inspired new models of root water uptake which aim to describe such small-scale heterogeneity. However, the question remains of how far these image-based findings have really advanced our understanding of how roots extract water from soils. Scope The rhizosphere processes affecting root water uptake are reviewed. Special attention is dedicated to the role of mucilage exuded by roots. Mucilage increases the soil moisture at negative water potentials and it keeps the rhizosphere wet when plants take up water, possibly maintaining the hydraulic connection between roots and soil. However, mucilage becomes viscous and hydrophobic upon severe drying and it limits the water fluxes across the rhizosphere during the rewetting phase. The role of mucilage in maintaining the hydraulic contact between the root surface and the surrounding soil, thereby softening the drops in water potential around the roots in dry soils, remains to be demonstrated. Conclusion Despite detailed images of water content, water fluxes and soil structure in the rhizosphere, a general understanding of how the rhizosphere affects root water uptake is still lacking. The missing elements of the puzzle are the gradient in water potential around roots. Measurements of the xylem water potential at varying soil water potentials and transpiration rates supported by numerical models of root water uptake would allow the estimation of the water potential across the rhizosphere. Such measurements are crucial to comprehend how water enters the roots.

Hydraulic contacts controlling water flow across porous grains.

Water flow between porous grains varies widely depending on the water distribution in contacts between grains. The hydraulic behavior of contacts varies from highly conductive when water fills the contacts to a bottleneck to flow as water pressure drops and contact asperities rapidly drain. Such changes greatly impact the hydraulic conductivity of porous grain packs such as aggregated soil. The dominant driving force of water flow across contacts is capillarity, often quantified relative to gravity and viscous forces using the capillary and Bond numbers. For fast water infiltration, viscous forces dominate. For simplicity we modeled the water distribution between spherical porous grains whose surfaces are covered by spherical bumps of much smaller radii. We provide experimental evidence obtained by neutron radiography and synchrotron-based x-ray tomographic microscopy documenting transitions in the flow behavior across contacts.

Evaluation of the health of free-ranging greater rheas (Rhea americana) in Argentina.

The health of 22 free-ranging adult rheas (Rhea americana) examined and sampled during a translocation/reintroduction project and six juvenile rheas kept in semicaptivity was investigated, and details of their haematology and plasma biochemistry are presented. Serological testing for antibodies to infectious agents was negative for infectious laryngotracheitis, avian adenovirus, avian influenza, avian reovirus, infectious bursal disease, infectious bronchitis virus, paramyxovirus types 1, 2, and 3, fowlpox and Salmonella Pullorum. Antibodies to Chlamydophila species were found in 25 of 27 of the birds, and 22 of 25 had antibodies to Aspergillus species. Ova of gastrointestinal nematodes of the genus Capillaria were identified, and the anoplocephalid cestode Monoecocestus cf rheiphilus was identified in R americana for the first time.

Pathways and kinetics of aqueous decomposition and carbamoylating activity of new anticancer nitroimidazole-linked 2-chloroethylnitrosoureas.

The products of decomposition in anaerobic aqueous solution at pH 7.1 and 37 degrees were determined for two series of novel anticancer agents incorporating both nitroimidazole and 2-chloroethylnitrosourea moieties (NI-CENUs) and examples of which exhibit preferential hypoxic toxicity against HeLa-MR cells. The decomposition products identified were vinyl chloride, acetaldehyde, 2-chloroethanol, ethylene glycol and imidazole-bearing compounds of the type including oxazolidinone, ethylamine or urea moieties. Series A NI-CENUs, which contain a 2-hydroxypropyl unit, gave rise to the oxazolidinone intramolecularly compared with the series B agents which gave rise to the imidazole-ethylamine and ureas. The half-lives of the B series agents were comparable with those of 1,3-bis(2-chloroethyl)nitrosourea (BCNU), 2-cyclohexyl-1-(2-chloroethyl)-1-nitrosourea (CCNU) and streptozotocin. The carbamoylation activity of the series B agents was approximately ten times that of series A compounds. This latter property may be related to the greater potency of series B than series A NI-CENUs against Mer+ HeLa-S3 cells via inhibition of relevant repair enzymes.

Chemosensitization at reduced nitroimidazole concentrations by mixed-function compounds combining 2-nitroimidazole and chloroethylnitrosourea.

A mixed-function compound (I-278) combining 2-nitroimidazole and chloroethylnitrosourea has been shown to be greater than 2-fold more toxic to hypoxic HeLa-MR cells than to cells similarly exposed under aerobic conditions, consistent with chemosensitization of nitrosourea toxicity by the 2-nitroimidazole Misonidazole (MISO). However, in the case of I-278, the enhancement resulted from micromolar concentrations of 2-nitroimidazole as opposed to the millimolar quantities required for a similar enhancement by MISO. These experiments provide evidence (1) that the enhanced hypoxic toxicity of I-278 is not attributable to additional, independent hypoxic cell killing by the nitroimidazole group and (2) that the interaction between the two functions under hypoxic conditions results in increased crosslink formation typical of chemosensitization. The data strongly suggest that the chemosensitizing efficiency of nitroimidazoles can be dramatically improved by covalent linkage to a chloroethylating species.

On a new class of mixed-function drugs associating nitroimidazoles and CENU: the NICE-NU.

Two series of (2-chloroethyl) nitrosoureas (NICE-NU) bearing a nitroimidazole group have been synthesized for anti-tumor evaluation with the aim of chemopotentiation of their biological activity. Their anti-tumor activity against L1210 in vivo in mice is excellent especially for the series A derivatives where a hydroxy function provides assistance to decomposition. However, the activity of NICE-NU against B16 melanoma is lower.

Aerobic and hypoxic toxicity of a new class of mixed-function drugs associating nitroimidazoles and chloroethylnitrosourea in nitrosourea-sensitive (Mer-) and -resistant (Mer+) human tumor cells.

The cytotoxicity of two series (A and B) of novel mixed-function compounds (NI-CENU) combining nitroimidazole (NI) and chloroethylnitrosourea (CENU) functions were examined in Mer- HeLa-MR and Mer+ HeLa-S3 cells. Series A compounds differed from those in Series B by having a hydroxypropyl as opposed to an ethyl group linking the imidazole ring and the nitrosoureido function. Four analogues, including the imidazole and the 2-, 4-, and 5-NO2 derivatives, were evaluated in each series. Cells were exposed to the various compounds for 4 h under aerobic and hypoxic conditions, and toxicity was assessed by clonogenic assay. Corresponding analogues in Series A and B were equally toxic to HeLa-MR cells. Preferential hypoxic toxicity was observed only with the 2-NO2 derivative in either series (I-278, Series A; I-282, Series B). For either compound a dose enhancement factor of 2.4 was observed for hypoxic exposures. The Mer+ HeLa-S3 cells were considerably more resistant to the NI-CENU than were their HeLa-MR counterparts. In further contrast to the HeLa-MR data, the Series B compounds were consistently more effective against the HeLa-S3 cells than were their corresponding Series A analogues. The enhanced effectiveness of the Series B compounds in HeLa-S3 cells may be related to the fact that these compounds express carbamoylating activity whereas Series A compounds lack this property. Again only I-278 and I-282 were preferentially toxic to hypoxic cells; however, the aerobic/hypoxic differential was dramatically reduced (dose enhancement factor = 1.3) as compared to that observed with the HeLa-MR cells. The enhanced hypoxic toxicity of the 2-NO2 NI-CENUs was not due to direct hypoxic toxicity of the nitro moiety but presumably is the result of enhancement of CENU toxicity (i.e., chemosensitization). The data suggest that much lower concentrations of NI may be required to observe chemosensitization when the NI and chemotherapeutic agent are administered as a single mixed-function compound.