Iron Oxide (Magnetite)-Based Nanobiomaterial with Medical Applications-Environmental Hazard Assessment Using Terrestrial Model Species.

Nanobiomaterials (NBMs) have tremendous potential applications including in cancer diagnosis and treatment. However, the health and environmental effects of NBMs must be thoroughly assessed to ensure safety. Fe3O4 (magnetite) nanoparticles coated with polyethylene glycol (PEG) and poly (lactic-co-glycolic acid) (PLGA) were one of the focus NBMs within the EU project BIORIMA. Fe3O4 PEG-PLGA has been proposed to be used as a contrast agent in magnetic resonance imaging for the identification of solid tumors and has revealed low cytotoxicity in several cell lines. However, the effects of Fe3O4 PEG-PLGA have not been assessed in terrestrial environments, the eventual final sink of most materials. In the present study, the effects of Fe3O4 PEG-PLGA and its precursor, (un-coated) Fe3O4 NMs, were assessed in soil model invertebrates Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola). The endpoints were survival, reproduction, and size, based on the standard OECD test (28 days) and its extension (56 days). The results showed no toxicity for any of the endpoints evaluated, indicating that the NBM Fe3O4 PEG-PLGA poses no unacceptable risk to the terrestrial environment.

Safe and sustainable by design Ag nanomaterials: A case study to evaluate the bio-reactivity in the environment using a soil model invertebrate.

Safe-and-sustainable-by-design (SSbD) nanomaterials (NMs) or NM-containing products are a priority. Silver (Ag) NMs have a vast array of applications, including biomedical and other products, even as nanopesticides. Thus, their release to the environment is expected to increase. The aim of the present study was to assess the ecotoxicity of the SSbD Ag NM to the soil model species Enchytraeus crypticus (Oligochaeta). The Ag NM tested consists in a SSbD Ag with biomedical applications, a hydroxyethyl cellulose (HEC) coated Ag NMs (AgHEC) and its toxicity was compared to the naked Ag NMs (Ag-Sigma), an Ag-based biomedical product (PLLA-Ag: Poly l-Lactide microfibers doped with Ag), and AgNO3. Effects were assessed both in soil and aqueous media, following the standard OECD guideline in soil (28 days) and the OECD extension (56 days), and short-term pulse (5 days) in aqueous media: reconstituted water (ISO water) and soil:water (S:W) extracts, followed by a 21-days recovery period in soil. Ag materials were thoroughly characterized as synthesized and during the test in media and animals. Results in S:W showed AgHEC was more toxic than Ag-Sigma (ca. 150 times) and PLLA-Ag (ca. 2.5 times), associated with a higher Ag uptake. Higher toxicity was related to a smaller hydrodynamic size and higher suspension stability, which in turn resulted in a higher bioavailability of Ag NMs and released ions, particularly in S:W. Toxicity was correlated with the main physicochemical features, providing useful prediction of AgNMs bioactivity. The ability to test E. crypticus in a range of media with different and/or increasing complexity (water, S:W extracts, soil) provided an excellent source to interpret results and is here recommended.

Pseudo-Bartter syndrome as the initial presentation of cystic fibrosis in children: an important diagnosis not to be missed.

Pseudo-Bartter syndrome (PBS) is characterised by hyponatraemic, hypochloraemic metabolic alkalosis that mimics Bartter syndrome, without renal tubular disease. We present a case of an infant with a positive cystic fibrosis (CF) newborn screening, hospitalised during the summer with dehydration, oliguria and apathy. Blood analysis revealed hypochloraemic metabolic alkalosis, hypokalaemia and hyponatraemia. Urine analysis showed leucocyturia with reduced sodium and chloride excretion fraction, and urinary culture was positive for Citrobacter koseri After antibiotherapy and intravenous rehydration with additional supplementation of sodium and chloride, the patient recovered completely. PBS is one of CF complications that is especially prevalent in infants and young children with increased sweating and/or other causes of additional loss of sodium and chloride. Clinical awareness of this syndrome and its strong clinical suspicion are extremely important for an early diagnosis and treatment of CF, particularly in countries where the universal screening of CF is not routinely performed.

Advanced materials - Food grade melatonin-loaded Lipid Surfactant Submicron Particles (LSSP)-environmental impacts.

Lipid-based nanoparticles (LNPs) are advanced materials (AdMa), particularly relevant for drug delivery of poorly water-soluble compounds, while also providing protection, stabilization, and controlled release of the drugs/active substances. The toxicological data available often focus on the specific applications of the LNPs-drug tested, with indication of low toxicity. However, the ecotoxicological effects of LNPs are currently unknown. In the present study, we investigated the ecotoxicity of a formulation of Lipid Surfactant Submicron Particles (LSSPs) loaded with melatonin at 1 mg/mL. The LSSPs formulation has been developed to be fully compliant with regulatory for its potential use in the market and all components are food additives. The same formulation without the thickening agent xanthan gum (stabilizer in water phase) designated as LSSP-xg, was also tested. Two soil model invertebrate species were tested in LUFA 2.2 soil: Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola). Effects were assessed based on the OECD standard guideline (28 days) and its extension, the longer-term exposure (56 days). Assessed endpoints were survival, reproduction, and size. LSSPs and LSSP-xg were toxic to E. crypticus and F. candida reducing their survival and reproduction in a dose-dependent way: e.g., 28-day exposure: E. crypticus: LC/EC50 = 30/15 mg LSSPs/kg soil and F. candida LC/EC50 = 55/44 mg LSSPs/kg soil, with similar values for LSSP-xg. Size was also reduced for F. candida but was the least sensitive endpoint. There were no indications that toxicity increased with longer term exposure. The results provide relevant information on ecotoxicity of a AdMa and highlights the need for awareness of the potential risks, even on products and additives usually used in food or cosmetic industry. Further information on single components and on their specific assembly is necessary for the interpretation of results, as it is not fully clear what causes the toxicity in this specific AdMa. This represents a typical challenge for AdMa hazard assessment scenario.

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites.

Three-dimensional (3D) printing technology has become a popular tool to produce complex structures. It has great potential in the regenerative medicine field to produce customizable and reproducible scaffolds with high control of dimensions and porosity. This study was focused on the investigation of new biocompatible and biodegradable 3D-printed scaffolds with suitable mechanical properties to assist tendon and ligament regeneration. Polylactic acid (PLA) scaffolds were reinforced with 0.5 wt.% of functionalized graphite nanoplatelets decorated with silver nanoparticles ((f-EG)+Ag). The functionalization of graphene was carried out to strengthen the interface with the polymer. (f-EG)+Ag exhibited antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), an important feature for the healing process and prevention of bacterial infections. The scaffolds' structure, biodegradation, and mechanical properties were assessed to confirm their suitability for tendon and ligamentregeneration. All scaffolds exhibited surface nanoroughness created during printing, which was increased by the filler presence. The wet state dynamic mechanical analysis proved that the incorporation of reinforcement led to an increase in the storage modulus, compared with neat PLA. The cytotoxicity assays using L929 fibroblasts showed that the scaffolds were biocompatible. The PLA+[(f-EG)+Ag] scaffolds were also loaded with human tendon-derived cells and showed their capability to maintain the tenogenic commitment with an increase in the gene expression of specific tendon/ligament-related markers. The results demonstrate the potential application of these new 3D-printed nanocomposite scaffolds for tendon and ligament regeneration.

Environmental hazards of WELGRO® Cu+Zn: A nano-enabled fertilizer.

Nanoagrochemicals have the potential to revolutionize agriculture towards a precision farming system, able to reduce application rates and consequently their environmental footprint, while keeping efficacy. Several nanoagrochemicals (including nanopesticides (Npes) and nanofertilizers (Nfer)) are already commercialized but the environmental risk assessment of these advanced materials is often lacking. In the present study, we studied the commercial fertilizer WELGRO® Cu + Zn and assessed its ecotoxicity to the soil invertebrate species Enchytraeus crypticus (Oligochaeta), further comparing it to its individual active substances CuO and ZnO. To get a comprehensive picture of possible effects, we used four types of highly relevant tests in LUFA 2.2 soil: 1) avoidance behaviour (2 days), 2) reproduction (OECD standard, 28 d), 3) its extension (56 d), and 4) the full life cycle (FLC) (46 d) - this high level of hazard screening allows for increased interpretation. The results confirmed the nano-features of WELGRO® and a higher toxicity than the mixture of the individual components CuO + ZnO. E. crypticus avoided the soil spiked with WELGRO® and CuO + ZnO, this being the most sensitive endpoint - avoidance behaviour. Both WELGRO® and the active substances were little to non-toxic based on the OECD standard test. However, the toxicity dramatically increased in the tests focussing on longer-term sustainability measures, i.e., 56 days, ca. 170 for WELGRO®. This seems related to the nano-features of WELGRO®, e.g., slow release of ions from the nanoparticles throughout time. The FLCt results showed WELGRO® affected hatching and juveniles' survival, being these the most sensitive life stages. Hence, under actual real world field usage scenarios, i.e., based on the recommended application rates, nanoenabled WELGRO® can affect oligochaete populations like enchytraeids, both via the immediate avoidance behaviour and also via prolonged exposure periods.

Environmental hazards of nanopesticides to non-target soil species - commercial nanoformulation versus its active substance (Karate Zeon® and lambda-cyhalothrin).

Nanopesticides (Npes) carry the potential of increased efficacy while reducing application rates, hence increasing agricultural productivity in a more sustainable way. However, given its novelty, the environmental risk assessment of these advanced materials is mostly absent. In the present study we investigated the ecotoxicity of a commercial insecticide, with reported nanofeatures, Karate Zeon®, and compared it to its active substance lambda-cyhalothrin. It is hypothesised that the use of the nanopesticide Karate Zeon® poses lower risk to enchytraeids than its active substance. The standard non-target soil invertebrate Enchytraeus crypticus was used, and exposure was done in LUFA 2.2 soil in 4 tests (endpoints: days): avoidance test [avoidance behaviour: 2 days], OECD standard reproduction test [survival, reproduction plus adults' size: 28 days] and its extension [total number organisms: 56 days], and Full Life Cycle (FLC) test [hatching and juveniles' size: 13 days; survival, reproduction and adults' size: 46 days]. Results showed that enchytraeids did not avoid Karate Zeon® nor its active substance lambda-cyhalothrin, which could be due to neurotoxicity. There was no indication of increased toxicity with prolonged exposure (46, 56d) compared to the standard (28d) for neither of the materials, being overall equally toxic in terms of hatching, survival, and reproduction. The FLCt results indicated that the juvenile stage was the most sensitive, resulting in higher toxicity for the adult animals when exposed from the cocoon stage. Although toxicity was similar between Karate Zeon and lambda-cyhalothrin, different patterns of uptake and elimination cannot be excluded. The benefits of using Karate Zeon will rely on reduced application rates.

Tentative Approaches for Extraction of Lanthanides from Wastewater with Low Metal Concentration.

Lanthanides are critical elements, and their recovery from wastewater increases the availability of these elements and reduces their impacts on the environment. In this study, tentative approaches to extract lanthanides from low-concentration aqueous solutions were investigated. PVDF membranes soaked with different active compounds or synthesized chitosan-based membranes containing these active compounds were used. The membranes were immersed in 10-4 M of aqueous solutions of selected lanthanides, and their extraction efficiency was assessed using ICP-MS. The PVDF membranes showed quite poor results, with only the membrane with oxamate ionic liquid giving some positive results (0.75 mg of Yb, 3 mg of lanthanides per gram of membrane). However, the chitosan-based membranes led to very interesting results, with the maximum concentration factor for the final solution relative to the initial solution being 13 times higher for Yb, which was obtained with the chitosan-sucrose-citric acid membrane. Several of the chitosan membranes, namely the one with 1-Butyl-3-methylimidazolium-di-(2-ethylhexyl)-oxamate, could extract around 10 mg of lanthanides per gram of membrane, with the better one being the membrane with sucrose/citric acid that achieved more than 18 mg/g of membrane. The use of chitosan for this purpose is a novelty. Since these membranes are easily prepared and have a very low cost, practical applications can be envisaged after further studies to better understand the underlying mechanism.

Nanoemulsion carriers for drug delivery: Assessment of environmental hazards.

Nanoemulsions (NEs) have been extensively studied as carriers for drug delivery, since these provide a good alternative to the existing non-nano systems, while promoting their target delivery and controlled release. NEs are considered safe drug carriers from a pre-clinical perspective, but there is currently no information on their ecotoxicological effects. In the present study we investigated the toxicity of a NE material (lecithin, sunflower oil, borate buffer) designed to be used as a liposomal excipient for eye drops, further referred to as (Lipid Particle:LP) LP_Eye and its dispersant (borate buffer) (LP_Eye disp.). Effects were assessed using two model species in soil ecotoxicology in LUFA 2.2 soil: Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola), based on the OECD standard guideline (28 days) and its extension, a longer-term exposure (56 days). The endpoints evaluated included survival, reproduction, and size. LP_Eye and LP_Eye disp. were toxic to E. crypticus and F. candida, affecting all measured endpoints. The toxicity of LP_Eye in E. crypticus seemed to be induced by the dispersant, whereas for F. candida, more sensitive, this was less explanatory. There were no indications that toxicity increased with longer exposure. Current results provide ecotoxicological data for a group of NMs that was absent, revealing toxicity to relevant environmental species. Indications were that the dispersant contributed to most of the observed effects, thus there is room to improve the formulation and achieve lower environmental impact.

TiO2 nanoparticles' library toxicity (UV and non-UV exposure) - High-throughput in vivo transcriptomics reveals mechanisms.

The hazards of nanomaterials/nanoparticles (NMs/NPs) are mostly assessed using individual NMs, and a more systematic approach, using many NMs, is needed to evaluate its risks in the environment. Libraries of NMs, with a range of identified different but related characters/descriptors allow the comparison of effects across many NMs. The effects of a custom designed Fe-doped TiO2 NMs library containing 11 NMs was assessed on the soil model Enchytraeus crypticus (Oligochaeta), both with and without UV (standard fluorescent) radiation. Effects were analyzed at organism (phenotypic, survival and reproduction) and gene expression level (transcriptomics, high-throughput 4x44K microarray) to understand the underlying mechanisms. A total of 48 microarrays (20 test conditions) were done plus controls (UV and non-UV). Unique mechanisms induced by TiO2 NPs exposure included the impairment in RNA processing for TiO2_10nm, or deregulated apoptosis for 2%FeTiO2_10nm. Strikingly apparent was the size dependent effects such as induction of reproductive effects via smaller TiO2 NPs (≤12 nm) - embryo interaction, while larger particles (27 nm) caused reproductive effects through different mechanisms. Also, phagocytosis was affected by 12 and 27 nm NPs, but not by ≤11 nm. The organism level study shows the integrated response, i.e. the result after a cascade of events. While uni-cell models offer key mechanistic information, we here deliver a combined biological system level (phenotype and genotype), seldom available, especially for environmental models.

Congenital adrenal hyperplasia with a CYP21A2 deletion overlapping the tenascin-X gene: an atypical presentation.

OBJECTIVES: Congenital Adrenal Hyperplasia (CAH) is a group of genetic diseases characterized by impaired cortisol biosynthesis. 95% of CAH cases result from mutation in the CYP21A2 gene encoding 21-hydroxilase. TNX-B gene partially overlaps CYP21A2 and encodes a matrix protein called Tenascin-X (TNX). Complete tenascin deficiency causes Enlers-Danlos syndrome (EDS). A mono allelic variant called CAH-X CH-1 was recently described, resulting from a CYP21A2 complete deletion that extends into the TNXB. This haploinsufficiency of TNX may be associated with a mild hypermobility form of EDS, as well as other connective tissue comorbidities such as hernia, cardiac defects and chronic arthralgia. CASE PRESENTATION: We report four patients heterozygous for a CAH-X CH-1 allele that do not present clinical manifestations of the EDS. CONCLUSIONS: All CAH patients, carriers of these TNXA/TNXB chimeras, should be evaluated for clinical manifestations related to connective tissue hypermobility, cardiac abnormalities and other EDS features, allowing for better clinical surveillance management.

A 3D printed hydrogel to promote human keratinocytes' spheroid-based growth.

Tissue engineering uses cells and biomaterials to develop bioartificial tissue substitutes for different purposes. For example, although several skin models have been developed for pharmaceutical and cosmetic research and skin wound healing, there are few studies on 3D cultures of keratinocytes in 3D printed scaffolds. So, this work aimed to develop a 3D-printed hydrogel scaffold to promote human keratinocyte growth. Mesh 3D scaffolds were printed using an extrusion-based method with a 20% gelatin/5% alginate hydrogel, where HaCaT cells were cultured for 7 days. Scaffolds kept their structure for over 1 week, and their stiffness only decreased after 7 days, showing good mechanical and structural characteristics and biodegradability (27% weight lost). Viable keratinocytes (MTT assay) are aggregated into spheroids, a 3D model capable of mimicking in vivo cell properties and phenotypes. Spheroids were formed on 47% of scaffolds pores and grew over time, showing promising cell proliferation. F-actin staining showed cells' irregular and interconnected shapes and organization over time. This method offers an easy and inexpensive solution for keratinocyte spheroid formation, which may be helpful in tissue engineering as a cell delivery system, for pharmacological or basic research, or wound healing medical applications.

Prospective study of loss of health-related quality adjusted life years in children and their families due to uncomplicated and hospitalised varicella.

INTRODUCTION AND AIMS: Although usually benign, varicella can lead to serious complications and sometimes long-term sequelae. Vaccines are safe and effective but not yet included in immunisation programmes in many countries. We aimed to quantify the impact on health-related quality of life (HRQoL) in terms of quality-adjusted life years (QALY) in children with varicella and their families, key to assessing cost-utility in countries with low mortality due to this infection. METHODS: Children with varicella in the community and admitted to hospitals in Portugal were included over 18 months from January 2019. Children's and carers' HRQoL losses were assessed prospectively using standard multi-attribute utility instruments for measuring HRQoL (EQ-5D and CHU9D), from presentation to recovery, allowing the calculation of QALYs. RESULTS: Among 109 families with children with varicella recruited from attendees at a pediatric emergency service (community arm), the mean HRQoL loss/child was 2.0 days (95 % CI 1.9-2.2, n = 101) (mean 5.4 QALYs/1000 children (95 % CI 5.3-6.1) and 1.3 days/primary carer (95 % CI 1.2-1.6, n = 103) (mean 3.6 QALYs /1000 carers (95 % CI 3.4-4.4). Among 114 families with children admitted to hospital because of severe varicella or a complication (hospital arm), the mean HRQoL loss/child was 9.8 days (95 % CI 9.4-10.6, n = 114) (mean 26.8 QALYs /1000 children (95 % CI 25.8-29.0) and 8.5 days/primary carer (95 % CI 7.4-9.6, n = 114) (mean 23.4 QALYs/1000 carers (95 % CI 20.3-26.2). Mean QALY losses/1000 patients were particularly high for bone and joint infections [67.5 (95 % CI 43.9-97.6)]. Estimates for children's QALYs lost using the CHU9D tool were well correlated with those obtained using EQ-5D, but substantially lower. CONCLUSIONS: The impact of varicella on HRQoL is substantial. We report the first measurements of QALYs lost in hospitalised children and in the families of children both in the community and admitted to hospital, providing important information to guide vaccination policy recommendations.

Tradução e adaptação para o português da Preterm Infant Breastfeeding Behaviour Scale / Traducción y adaptación al portugués de la Preterm Infant Breastfeeding Behaviour Scale / Translation and adaptation of Preterm Infant Breastfeeding Behavior Scale into Brazilian Portuguese

Resumo Objetivo Traduzir, adaptar culturalmente e validar o conteúdo da Preterm Infant Breastfeeding Behaviour Scale (PIBBS) Métodos Estudo metodológico, cujas etapas foram: tradução inicial; síntese das traduções; retrotradução; revisão das versões traduzidas; validação do conteúdo; pré-teste; e encaminhamento da documentação ao Comitê de Revisão da Adaptação Transcultural. Tanto a escala original quanto a traduzida e adaptada possuem seis itens e cada item contém 03 a 06 subitens com escores de pontuação que variam de 0 a 6. A pontuação total pode variar de 0 a 20. Para a etapa de validação foi realizado o cálculo do índice de validade de conteúdo (IVC) de todos os itens da escala. Foi considerado IVC mínimo de 0,8 como aceitável, para avaliação de cada item individualmente; e de 0,90, para avaliação geral do instrumento. Resultados A versão brasileira da escala PIBBS foi denominada de Escala Comportamental de amamentação do pré-termo. A escala foi traduzida, adaptada e seu conteúdo foi validado, alcançando equivalência conceitual e idiomática que variou de 83,3% a 100%. O índice de validade de conteúdo foi de 0,93. Conclusão Após a tradução, adaptação e validação pelos profissionais de saúde a escala se mostrou válida, de fácil aplicação e linguagem de fácil entendimento. A escala permitirá que os profissionais de saúde possam observar o comportamento do prematuro e orientar a mãe, estimulando assim o aleitamento materno exclusivo, já que o processo de amamentação do prematuro é complexo. Sua utilização em pesquisas futuras e prática clínica permitirá complementar as análises psicométricas mais robustas.

Resumen Objetivo Traducir, adaptar culturalmente y validar el contenido de la Preterm Infant Breastfeeding Behaviour Scale (PIBBS). Métodos Estudio metodológico, cuyas etapas fueron: traducción inicial, síntesis de las traducciones, retrotraducción, revisión de las versiones traducidas, validación de contenido, prueba piloto y envío de la documentación al Comité de Revisión de Adaptación Transcultural. Tanto la escala original, como la traducida y adaptada, contienen seis ítems y cada uno contiene de tres a seis subítems con puntuación que varía de 0 a 6. La puntuación total puede variar de 0 a 20. Para la etapa de validación se realizó el cálculo de índice de validez de contenido (IVC) de todos los ítems de la escala. Se consideró IVC mínimo de 0,8 como aceptable para la evaluación de cada ítem individualmente, y de 0,90 para la evaluación general del instrumento. Resultados La versión brasileña de la escala PIBBS fue denominada "Escala Comportamental de amamentação do pré-termo" (Escala de Comportamiento de Lactancia del Recién Nacido Prematuro). La escala fue traducida y adaptada, y su contenido fue validado, con una equivalencia conceptual e idiomática que varió de 83,3 % a 100 %. El índice de validez de contenido fue de 0,93. Conclusión Después de su traducción, adaptación y validación por parte de los profesionales de la salud, la escala demostró ser válida, de fácil aplicación y con un lenguaje de fácil comprensión. La escala permitirá que los profesionales de la salud puedan observar el comportamiento del prematuro y orientar a la madre, con el objetivo de estimular la lactancia materna exclusiva, ya que el proceso de lactancia del prematuro es complejo. Su uso en investigaciones futuras y en la práctica clínica permitirá complementar análisis psicométricos más sólidos.

Abstract Objective To translate, culturally adapt and validate the Preterm Infant Breastfeeding Behavior Scale (PIBBS) content Methods This is a methodological study, whose steps were: initial translation; synthesis of translations; back-translation; review of translated versions; content validity; pre-test; and sending the documentation to the Cross-Cultural Adaptation Review Committee. Both the original scale and the translated and adapted scale have six items, and each item contains 03 to 06 sub-items with score scores ranging from 0 to 6. The total score can range from 0 to 20. For the validity step, the Content Validity Index (CVI) of all scale items was calculated. A minimum CVI of 0.8 was considered acceptable for assessing each item individually, and 0.90, for generally assessing the instrument. Results The Brazilian version of PIBBS was called the "Escala Comportamental de Amamentação do Pré-Termo". The scale was translated, adapted and its content was validated, achieving conceptual and idiomatic equivalence ranging from 83.3% to 100%. The CVI was 0.93. Conclusion After translation, adaptation and validity by health professionals, the scale proved to be valid, easy to apply and easy to understand language. The scale will allow health professionals to observe preterm infants' behavior and guide mothers, thus encouraging exclusive breastfeeding, since the breastfeeding process of a preterm infant is complex. Its use in future research and clinical practice will complement more robust psychometric analyses.

Safer and Sustainable-by-Design Hydroxyapatite Nanobiomaterials for Biomedical Applications: Assessment of Environmental Hazards.

Developments in the nanotechnology area occur ensuring compliance with regulatory requirements, not only in terms of safety requirements, but also to meet sustainability goals. Hence, safer and sustainable-by-design (SSbD) materials are also aimed for during developmental process. Similar to with any new materials their safety must be assessed. Nanobiomaterials can offer large advantages in the biomedical field, in areas such as tissue repair and regeneration, cancer therapy, etc. For example, although hydroxyapatite-based nanomaterials (nHA) are among the most studied biomaterials, its ecotoxicological effects are mostly unknown. In the present study we investigated the toxicity of seven nHA-based materials, covering both different biomedical applications, e.g., iron-doped hydroxyapatite designed for theragnostic applications), hybrid collagen/hydroxyapatite composites, designed for bone tissue regeneration, and SSbD alternative materials such as titanium-doped hydroxyapatite/alginate composite, designed as sunscreen. The effects were assessed using the soil model Enchytraeus crypticus (Oligochaeta) in the natural standard LUFA 2.2 soil. The assessed endpoints included the 2, 3 and 4 days avoidance behavior (short-term), 28 days survival, size and reproduction (long term based on the OECD standard reproduction test), and 56 days survival and reproduction (longer-term OECD extension). Although overall results showed little to no toxicity among the tested nHA, there was a significant decrease in animals' size for Ti-containing nHA. Moreover, there was a tendency for higher toxicity at the lowest concentrations (i.e., 100 mg/kg). This requires further investigation to ensure safety.

Environmental Hazards of Nanobiomaterials (Hydroxyapatite-Based NMs)-A Case Study with Folsomia candida-Effects from Long Term Exposure.

Hydroxyapatite (HA) is a calcium phosphate used in many fields, including biomedical applications. In particular, ion-doped HA nanomaterials (nHA) are developed for their increased bioactivity, particularly in the fields of regenerative medicine and nanomedicine. In this study, we assessed the ecotoxicological impact of five nHA materials: a synthesized calcium hydroxyapatite (CaP-HA), superparamagnetic iron-doped hydroxyapatite (Fe-HA), titanium-doped hydroxyapatite (Ti-HA), alginate/titanium-doped hydroxyapatite hybrid composite (Ti-HA-Alg), and a commercial HA. The soil ecotoxicology model species Folsomia candida (Collembola) was used, and besides the standard reproduction test (28 days), an extension to the standard for one more generation was performed (56 days). Assessed endpoints included the standard survival and reproduction, and additionally, growth. Exposure via the standard (28 days) did not cause toxicity, but reproduction increased in commercial HA (significantly at 320 mg HA/kg) whereas via the extension (56 days) it decreased in all tested concentrations. Juveniles' size (56 days) was reduced in all tested nHA materials, except commercial HA. nHA materials seem to trigger a compromise between reproduction and growth. Long-term effects could not be predicted based on the standard shorter exposure; hence, the testing of at least two generations (56 days) is recommended to assess the toxicity of nanomaterials, particularly in F. candida. Further, we found that the inclusion of size as additional endpoint is highly relevant.

Cerebrospinal fluid hypotension following fall in a child: Case report.

CSF hypotension arises in the context of a leak of CSF which causes negative intracranial pressure. Sacral fractures result from high-energy trauma which are frequently underdiagnosed. A ten-year-old boy presented with hip pain, after a fall. He mobilized both lower limbs, reported no leg pain, irradiation nor lack of sphincter control. The neurological examination was normal. When asked to stand, he began biparietal headache, nausea and vomiting, which improved laying down. CT scan showed an occult intrasacral meningocele; the MRI revealed collections of CSF along the spine, a S3 fracture with potential laceration of the meningocele and opening of a CSF fistula. Our diagnosis was the CSF hypotension, secondary to the fistula opening. The diagnosis was challenging. The child first presented with symptoms of CSF hypotension without evident cause. The discovery of the meningocele led us to hypothesize the opening of a fistula, a rare diagnosis, later confirmed by MRI.

Impacts of Longer-Term Exposure to AuNPs on Two Soil Ecotoxicological Model Species.

The production, use and disposal of nanoparticles (NPs) has been increasing continuously. Due to its unique properties, such as a high resistance to oxidation, gold NPs (AuNPs) are persistent in the environment, including the terrestrial, one of the major sinks of NPs. The present study aimed to assess the effects of AuNPs (from 10 to 1000 mg/kg) on two OECD standard ecotoxicological soil model species, Enchytraeus crypticus and Folsomia candida, based on the reproduction test (28 days) and on a longer-term exposure (56 days), and survival, reproduction, and size were assessed. AuNPs caused no significant hazard to F. candida, but for E. crypticus the lowest tested concentrations (10 and 100 mg AuNPs/kg) reduced reproduction. Further, AuNPs' toxicity increased from the 28th to the 56th day mainly to F. candida, as observed in animals' size reduction. Therefore, longer-term exposure tests are recommended as these often reveal increased hazards, not predicted when based on shorter exposures. Additionally, special attention should be given to the higher hazard of low concentrations of NPs, compared to higher concentrations.