Robust and Biocompatible Functionalization of ZnS Nanoparticles by Catechol-Bearing Poly(2-Methyl-2-Oxazoline)s.

Zinc sulfide (ZnS) nanoparticles (NPs) are particularly interesting materials for their electronic and luminescent properties. Unfortunately, their robust and stable functionalization and stabilization, especially in aqueous media, has represented a challenging and not yet completely accomplished task. In this work, we report the synthesis of colloidally stable, photoluminescent and biocompatible core\u2013polymer shell ZnS and ZnS:Tb NPs by employing a water-in-oil miniemulsion (ME) process combined with surface functionalization via catechol-bearing poly-2-methyl-2-oxazoline (PMOXA) of various molar masses. The strong binding of catechol anchors to the metal cations of the ZnS surface, coupled with the high stability of PMOXA against chemical degradation, enable the formation of suspensions presenting excellent colloidal stability. This feature, combined with the assessed photoluminescence and biocompatibility, make these hybrid NPs suitable for optical bioimaging

Percutaneous Trans-Thoracic Procedures in Children With Tumors of Thoracic Wall, Mediastinum and Lung. The Experience of a Single Institution

Background While percutaneous trans-thoracic procedures (PTTP) are commonly performed in adults with tumors of thoracic wall, mediastinum and lung, the experience is limited in children, in whom however less invasive methods should be the choice for the diagnosis or the identification of small pulmonary nodules that need to be removed, sparing lung tissue. The results of the PTTP performed by the interventional radiologists in our Pediatric Surgery Department are analyzed. Methods CT-guided biopsies, utilizing a 64-slice CTscanner, with low-radiation dose, were performed applying the coaxial technique with 16-18G needles with a single tissue path. For localization of lung nodules before surgery, two 20G-hook wires were positioned beyond the nodule. CT images after each manipulation of the needles were obtained. US-guided biopsies were performed either with or without coaxial technique through a needle bracket. Younger patients required sedation. All patients underwent a chest radiogram two hours after the procedure and remained under observation for 24 hours. Results From January 2015 to March 2019, 23 procedures were performed in 22 patients (Age:16M- 19Y): 6 patients underwent CT-guided biopsy (4 lung nodules, 2 mediastinal mass); 3 underwent 4 CT-guided hook-wire localization of pulmonary nodules, just before surgery; 13 underwent US-guided biopsy (posterior mediastinum 2; anterior mediastinum 5, thoracic/intrathoracic mass 5). Adequate core biopsies were obtained in all patients, except three, who underwent thoracoscopy/thoracotomy. The hook-wires were successfully positioned in all cases, as confirmed by histology. After the procedure, two patients presented perilesional hemorrhage and one pneumothorax, but they did not required treatment. Conclusion PTTP were successful in most patients, without significant complications. These techniques should be encouraged to avoid diagnostic aggressive surgical approaches in children with cancer. For all cases a multidisciplinary team is essential to discuss the indications and planning the procedures

Effects of Simulated Microgravity on Embryonic Stem Cells

There have been many studies on the biological effects of simulated microgravity (SMG) on differentiated cells or adult stem cells. However, there has been no systematic study on the effects of SMG on embryonic stem (ES) cells. In this study, we investigated various effects (including cell proliferation, cell cycle distribution, cell differentiation, cell adhesion, apoptosis, genomic integrity and DNA damage repair) of SMG on mouse embryonic stem (mES) cells. Mouse ES cells cultured under SMG condition had a significantly reduced total cell number compared with cells cultured under 1 g gravity (1G) condition. However, there was no significant difference in cell cycle distribution between SMG and 1G culture conditions, indicating that cell proliferation was not impaired significantly by SMG and was not a major factor contributing to the total cell number reduction. In contrast, a lower adhesion rate cultured under SMG condition contributed to the lower cell number in SMG. Our results also revealed that SMG alone could not induce DNA damage in mES cells while it could affect the repair of radiation-induced DNA lesions of mES cells. Taken together, mES cells were sensitive to SMG and the major alterations in cellular events were cell number expansion, adhesion rate decrease, increased apoptosis and delayed DNA repair progression, which are distinct from the responses of other types of cells to SMG

Bacillus Calmette-Guérin-related cold thigh abscess as an unusual cause of thigh swelling in infants following BCG vaccine administration: a case series

<p>Abstract</p> <p>Introduction</p> <p>Thigh swelling in an infant can be a symptom of a simple benign condition or a life-threatening condition. We observed a cluster of thigh swelling episodes in infants in which the cause was Bacillus Calmette-Guérin-related cold thigh abscess. We report this unusual case series to raise awareness about this diagnosis.</p> <p>Case presentations</p> <p>We performed a retrospective review of five infants (four boys and one girl) who presented with Bacillus Calmette-Guérin-related left thigh abscess. The swelling was noticed by the parents at a mean period of three months prior to presentation. The ages at presentation were five, five, eight and nine months for the boys, and six months for the girl. All of the patients were healthy Saudi infants, and received the Bacillus Calmette-Guérin vaccine at birth. Clinically, all of the patients were well and did not demonstrate signs of systemic infection. All patients underwent needle aspiration, with subsequent incision and drainage in four of the five cases. The cultures obtained from the abscess fluids were the key to establishing the diagnosis. Only three patients (60%) received antituberculosis drugs. Wound healing lasted for a mean period of approximately seven months. Two-year follow-up was unremarkable for all of our patients.</p> <p>Conclusions</p> <p>Technical errors continue to be significant in the development of vaccine-related complications. Bacillus Calmette-Guérin-related cold thigh abscess is an extremely rare entity.</p

Analysis of miRNA and mRNA Expression Profiles Highlights Alterations in Ionizing Radiation Response of Human Lymphocytes under Modeled Microgravity

BACKGROUND: Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of \u3b3-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. CONCLUSIONS/SIGNIFICANCE: On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL

The effect of low-level laser irradiation (In-Ga-Al-AsP - 660 nm) on melanoma in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>It has been speculated that the biostimulatory effect of Low Level Laser Therapy could cause undesirable enhancement of tumor growth in neoplastic diseases. The aim of the present study is to analyze the behavior of melanoma cells (B16F10) <it>in vitro </it>and the <it>in vivo </it>development of melanoma in mice after laser irradiation.</p> <p>Methods</p> <p>We performed a controlled <it>in vitro </it>study on B16F10 melanoma cells to investigate cell viability and cell cycle changes by the Tripan Blue, MTT and cell quest histogram tests at 24, 48 and 72 h post irradiation. The <it>in vivo </it>mouse model (male Balb C, n = 21) of melanoma was used to analyze tumor volume and histological characteristics. Laser irradiation was performed three times (once a day for three consecutive days) with a 660 nm 50 mW CW laser, beam spot size 2 mm², irradiance 2.5 W/cm²and irradiation times of 60s (dose 150 J/cm²) and 420s (dose 1050 J/cm²) respectively.</p> <p>Results</p> <p>There were no statistically significant differences between the <it>in vitro </it>groups, except for an increase in the hypodiploid melanoma cells (8.48 ± 1.40% and 4.26 ± 0.60%) at 72 h post-irradiation. This cancer-protective effect was not reproduced in the <it>in vivo </it>experiment where outcome measures for the 150 J/cm²dose group were not significantly different from controls. For the 1050 J/cm²dose group, there were significant increases in tumor volume, blood vessels and cell abnormalities compared to the other groups.</p> <p>Conclusion</p> <p>LLLT Irradiation should be avoided over melanomas as the combination of high irradiance (2.5 W/cm²) and high dose (1050 J/cm²) significantly increases melanoma tumor growth <it>in vivo</it>.</p

3D-Printed Architected Materials Inspired by Cubic Bravais Lattices

Learning from Nature and leveraging 3D printing, mechanical testing, and numerical modeling, this study aims to provide a deeper understanding of the structure-property relationship of crystal-lattice-inspired materials, starting from the study of single unit cells inspired by the cubic Bravais crystal lattices. In particular, here we study the simple cubic (SC), body-centered cubic (BCC), and face-centered cubic (FCC) lattices. Mechanical testing of 3D-printed structures is used to investigate the influence of different printing parameters. Numerical models, validated based on experimental testing carried out on single unit cells and embedding manufacturing-induced defects, are used to derive the scaling laws for each studied topology, thus providing guidelines for materials selection and design, and the basis for future homogenization and optimization studies. We observe no clear effect of the layer thickness on the mechanical properties of both bulk material and lattice structures. Instead, the printing direction effect, negligible in solid samples, becomes relevant in lattice structures, yielding different stiffnesses of struts and nodes. This phenomenon is accounted for in the proposed simulation framework. The numerical models of large arrays, used to define the scaling laws, suggest that the chosen topologies have a mainly stretching-dominated behavior- A hallmark of structurally efficient structures-where the modulus scales linearly with the relative density. By looking ahead, mimicking the characteristic microscale structure of crystalline materials will allow replicating the typical behavior of crystals at a larger scale, combining the hardening traits of metallurgy with the characteristic behavior of polymers and the advantage of lightweight architected structures, leading to novel materials with multiple functions

Bystander response in human lymphoblastoid TK6 cells

The mechanisms of the medium-mediated bystander response induced by gamma-rays in non-irradiated TK6 cells were investigated. Cell cultures were irradiated and the culture medium discarded immediately after irradiation and replaced with a fresh one. In cells incubated with conditioned medium from irradiated cells (CM), a significant decrease in cell viability and cloning efficiency was observed, together with a significant increase in apoptosis, also in directly irradiated cells. To examine whether bystander apoptosis involved the extrinsic pathway, an inhibitor of caspase-8 was added to CM cultures, which significantly decreased apoptosis to control levels. The addition to CM of ROS scavengers, Cu-Zn superoxide dismutase and N-acetylcysteine did not affect the induction of apoptosis. To assess whether CM treatment activates a DNA damage response, also the formation of gamma-H2AX foci, as markers of double-strand breaks and their colocalisation with 53-binding protein 1 (53BP1) and the protein mutated in the Nijmegen breakage syndrome 1 (NBS1) was analysed. In cultures treated for 2h with CM, 9-11% of cells showed gamma-H2AX foci, which partially or totally lacked colocalisation with 53BP1 and NBS1 foci. About 85% of irradiated cells were positive for gamma-H2AX foci, which colocalised with 53BP1 and NBS1 proteins. At 24h from irradiation, very few irradiated cells retained foci, fitting DNA repair kinetics. The number of foci-positive bystander cells also decreased to background values 24h after CM incubation. Our results suggest that irradiated TK6 cells release into the medium some soluble factors, not ROS, which are responsible for the cytotoxic effects induced in bystander cells. In our experimental system, the role of ROS appeared to be of minor importance in inducing cell mortality, but probably critical in activating the DNA damage response in the responsive fraction of bystander cells

Analysis of point mutations in HPRT mutant T-lymphocytes derived from coke-oven workers.

We studied mutations in exon 3 of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus in 113 6-thioguanine-resistant T-cell clones derived from coke-oven workers and control subjects in order to analyse possible changes in the mutational spectrum associated with the exposure to polycyclic aromatic hydrocarbons (PAHs). In 99 mutants, HPRT exon 3 was analysed by means of genomic polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP). Products for which SSCP indicated the presence of a mutation were further analysed by DNA sequencing. In addition, HPRT cDNA from 14 clones was analysed by reverse transcription (RT) PCR and DNA sequencing. In total, 18/113 mutants (16%) had a mutation in exon 3. This frequency was similar in PAH-exposed (9/57) and non-exposed (9/56) subjects. Base substitutions caused 14 mutations at 13 different sites. Three +/- 1 bp frameshifts and one 6 bp deletion were identified. No significant differences between PAH-exposed and non-exposed workers were observed in this limited mutational spectrum. These results indicate that deletions/insertions at the HPRT exon 3 account for 22% of the mutations, and base substitutions for 78%