Novel CSF1R variant in adult-onset leukoencephalopathy masquerading as frontotemporal dementia: a follow-up study.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter degenerative disease manifesting as progressive cognitive decline, pyramidal, and extrapyramidal features resulting from mutations in the colony-stimulating factor-1 receptor (CSF1R) gene. We describe a sporadic case of a young man who developed five months history of progressive cognitive decline with predominant neuropsychiatric symptoms, suggestive of frontotemporal dementia. Brain magnetic resonance imaging (MRI) showed bilateral frontotemporal atrophy, high signal intensities in frontal and high parietal deep white matter with persistent diffusion restriction on follow-up imaging. Genetics showed a novel heterozygous mutation in CSF1R gene confirming the diagnosis of ALSP. Being a rare disease, and given its particular adult-onset presentation especially presenile cognitive impairment, it can pose a unique diagnostic challenge. The study highlights the importance of recognizing the disease early and broadens the clinical, genetic, and imaging spectrum of CSF1R gene mutation.

A study of Titanium and Magnesium particle-induced oxidative stress and toxicity to human osteoblasts.

Hybrid implants combine both Titanium (Ti) and Magnesium (Mg) are prevalent nowadays. The long-term implications of Ti and Mg implants within the human body are not yet fully understood. Many implant failure cases due to inflammation, allergic responses, and aspect loosening have been reported frequently. Particles generated through daily wear and tear of implants may worsen the situation by causing acute complications. An in-depth understanding of the behavior of metal particles with human osteoblasts is necessary. In this study, a novel and systematic attempt was made to understand the effects of different concentrations of Ti and Mg particles to the osteoblastic SAOS2 cell: toxicity, alterations to mitochondria, and changes to the specific gene and protein expression. Ti particles were found toxic to SAOS2 cells at different dosages, while Mg particles at lower concentrations could improve cell viability. To understand this phenomenon better, we have measured cellular reactive oxygen species (ROS) production and cell apoptosis & necrosis percentage. We also have checked the mitochondrial structure with transmission electron microscope (TEM), and mitochondrial function using Tetramethyl rhodamine, ethyl ester staining (TMRE). NDUFB6, SDHC, and ATP5F1 were the essential mitochondrial genes involved in the ROS production and ATP production. Immunocytochemistry (ICC) and real-time polymerase chain reaction (qPCR) were implemented to check the regulations of these related genes.

Fabrication of Ti + Mg composites by three-dimensional printing of porous Ti and subsequent pressureless infiltration of biodegradable Mg.

A semi-degradable Ti + Mg composite with superior compression and cytotoxicity properties have been successfully fabricated using ink jet 3D printing followed by capillary mediated pressureless infiltration technique targeting orthopaedic implant applications. The composite exhibited low modulus (~5.2 GPa) and high ultimate compressive strength (~418 MPa) properties matching that of the human cortical bone. Ti + Mg composites with stronger 3D interconnected open-porous Ti networks are possible to be fabricated via 3D printing. Corrosion rate of samples measured through immersion testing using 0.9%NaCl solution at 37 °C indicate almost negligible corrosion rate for porous Ti (~1.14 µm/year) and <1 mm/year for Ti + Mg composites for 5 days of immersion, respectively. The composite significantly increased the SAOS-2 osteoblastic bone cell proliferation rate when compared to the 3D printed porous Ti samples and the increase is attributed to the exogenous Mg2+ ions originating from the Ti + Mg samples. The cell viability results indicated absent to mild cytotoxicity. An attempt is made to discuss the key considerations for net-shape fabrication of Ti + Mg implants using ink jet 3D printing followed by infiltration approach.

Zika virus alters DNA methylation status of genes involved in Hippo signaling pathway in human neural progenitor cells.

Aim: This study was aimed to understand if Zika virus (ZIKV) alters the DNA methylome of human neural progenitor cells (hNPCs). Materials & methods: Whole genome DNA methylation profiling was performed using human methylationEPIC array in control and ZIKV infected hNPCs. Results & conclusion: ZIKV infection altered the DNA methylation of several genes such as WWTR1 (TAZ) and RASSF1 of Hippo signaling pathway which regulates organ size during brain development, and decreased the expression of several centrosomal-related microcephaly genes, and genes involved in stemness and differentiation in human neural progenitor cells. Overall, ZIKV downregulated the Hippo signaling pathway genes which perturb the stemness and differentiation process in hNPCs, which could form the basis for ZIKV-induced microcephaly.