5s to segment one tract). In addition, we showed that the method successfully generalizes to diffusion scans from an external dementia dataset (N ​= ​58, 3T MRI). In two proof-of-principle experiments, we associated WM microstructure obtained using the proposed method with age in a normal elderly population, and with disease subtypes in a dementia cohort. In concordance with the literature, results showed a widespread reduction of microstructural organization with aging and substantial group-wise microstructure differences between dementia subtypes. In conclusion, we presented a highly reproducible and fast method for WM tract segmentation that has the potential of being used in large-scale studies and clinical practice.A variety of psychiatric, behavioral and cognitive phenotypes have been linked to brain ”functional connectivity” — the pattern of correlation observed between different brain regions. Most commonly assessed using functional magnetic resonance imaging (fMRI), here, we investigate the connectivity-phenotype associations with functional connectivity measured with electroencephalography (EEG), using phase-coupling. We analyzed data from the publicly available Healthy Brain Network Biobank. This database compiles a growing sample of children and adolescents, currently encompassing 1657 individuals. Among a variety of assessment instruments we focus on ten phenotypic and additional demographic measures that capture most of the variance in this sample. The largest effect sizes are found for age and sex for both fMRI and EEG. We replicate previous findings of an association of Intelligence Quotient (IQ) and Attention Deficit Hyperactivity Disorder (ADHD) with the pattern of fMRI functional connectivity. We also fnectivity predict individual phenotypes.Since its first description and development in the late 20th century, diffusion magnetic resonance imaging (dMRI) has proven useful in describing the microstructural details of biological tissues. Signal generated from the protons of water molecules undergoing Brownian motion produces contrast based on the varied diffusivity of tissue types. Images employing diffusion contrast were first used to describe the diffusion characteristics of tissues, later used to describe the fiber orientations of white matter through tractography, and most recently proposed as a functional contrast method capable of delineating neuronal firing in the active brain. Thanks to the molecular origins of its signal source, diffusion contrast is inherently useful at describing features of the microenvironment; however, limitations in achievable resolution in magnetic resonance imaging (MRI) scans precluded direct visualization of tissue microstructure for decades following MRI’s inception as an imaging modality. Even after advancements in MRI hardware had permitted the visualization of mammalian cells, these specialized systems could only accommodate fixed specimens that prohibited the observation and characterization of physiological processes. The goal of the current study was to visualize cellular structure and investigate the subcellular origins of the functional diffusion contrast mechanism (DfMRI) in living, mammalian tissue explants. Using a combination of ultra-high field spectrometers, micro radio frequency (RF) coils, and an MRI-compatible superfusion device, we are able to report the first live, mammalian cells-α-motor neurons-visualized with magnetic resonance microscopy (MRM). We are also able to report changes in the apparent diffusion of the stratum oriens within the hippocampus-a layer comprised primarily of pyramidal cell axons and basal dendrites-and the spinal cord’s ventral horn following exposure to kainate.How to overcome the cell membrane barriers and achieve release payloads efficiently in the cytoplasm have been major challenges for anticancer drug delivery and therapeutic effects with nanosystems. In this study, bovine serum albumin (BSA) was modified with folate acid and histamine, which was then used as the nanocarrier for the antitumor agent doxorubicin (DOX). The DOX-loaded nanoparticles (DOX/FBH-NPs) were prepared via a crosslinking method, and the release of DOX from these nanoparticles (NPs) exhibited pH/reduction-responsive behaviors in vitro. selleckchem These NPs interacted with the folate receptor overexpressed on the cell membrane of 4 T1 cells and achieved enhanced endocytosis. Afterwards, these NPs exhibited pH-responsiveness within endo-lysosomes and escaped from endosomes due to the „proton sponge” effect, and then completed release of DOX was triggered by high concentration of glutathione (GSH) in cytoplasm. Thus, DOX/FBH-NPs exhibited excellent cytotoxicity against 4 T1 cells in vitro. Benefited from the enhanced permeability and retention (EPR) effect and folate receptor-mediated endocytosis, these NPs gained satisfied tumor-targeting effects in vivo and efficient delivery of DOX to tumor tissues. As a result, these NPs exhibited enhanced antitumor effects and reduced side effects in vivo. In conclusion, these BSA-based NPs modified with both folate acid and histamine showed enhanced tumor-targeting effects in vivo with good biocompatibility and intracellular pH/reduction-responsive behaviors, providing a promising strategy for the efficient delivery of antitumor agents.Nowadays, novel less-expensive nanoformulations for in situ-controlled and safe delivery of photosensitisers (PSs) against opportunistic pathogens in body-infections areas need to be developed. Antimicrobial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections that are recalcitrant to antibiotics. In this paper, we propose the design and characterization of a novel nanophototherapeutic based on the trade cyclodextrin CAPTISOL® (sulfobutylether-beta-cyclodextrin, SBE-βCD) and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine tetrakis(p-toluenesulfonate) (TMPyP) to fabricate efficient biocompatible systems for aPDT. Spherical nanoassemblies of about 360 nm based on CAPTISOL®/TMPyP supramolecular complexes with 11 stoichiometry and apparent equilibrium binding constant (Kb ≅ 1.32 × 105 M-1) were prepared with entrapment efficiency of ≅ 100% by simple mixing in aqueous media and freeze-drying. These systems have been characterized by complementary spectroscopy and microscopy technility thus optimizing the PDT effect at the site of action. These results can open routes for in vivo translational studies on nano(photo)drugs and nanotheranostics based on less expensive formulations of CD and PS.Chemotherapy in drug-resistant cancers remains a challenge. Owing to associated poor bioavailability, oral administration of hydrophobic anticancer drugs like paclitaxel has been quite challenging, with the scenario being further complicated by Pgp efflux in drug-resistant tumours. We developed a novel nanocochleates (CPT) system encapsulating paclitaxel (PTX) to treat resistant colon cancer by oral administration. link2 PTX encapsulated nanocochleates (PTX-CPT), made up of phosphatidylserine in size range of 350-600 nm with -20 ± 5.2 mV zeta potential were protected from degradation at acidic gastric pH and showed sustained PTX release over 48 hours under intestinal pH condition. In vitro cytotoxicity studies on HCT-116 & HCT-15 cells (multi-drug resistant) established IC50 value of less then 10 and 69 nM, respectively, which was significantly lower when compared to commercial Taxol formulation. Further, the in vivo efficacy with five oral doses of 30mg/kg PTX-CPT in an HCT-15 drug-resistant colon cancer xenograft mouse model showed more than 25 fold reduction in the tumour growth inhibition as compared to intravenous Taxol which showed just 1.94 % inhibition. Interestingly, PTX-CPT treated mice also showed significantly lower proliferation index and microvessel density when compared to Taxol treated mice. Nanocochleates showed lower toxicity with at LD-50 value greater than 300 mg/kg as described in OECD 423 guideline. The enhanced efficacy of PTX-CPT speculated due to its internalization by active endocytosis, ability to escape Pgp efflux, and due to a combined effect of the pro-apoptotic and antiangiogenic role. Taken together, the results suggested the PTX-CPT a promising strategy for efficiently treating drug-resistant colon cancer orally.Objectives To analyze the impact of desensitizing (D) and/or whitening (W) dentifrices on erosion and erosion-abrasion. Methods Enamel specimens were allocated into 10 groups (n = 20) 1. Artificial saliva (control); 2. Sensodyne Repair&Protect (SRP-D); 3. Sensodyne Repair&Protect Whitening (SRP-W); 4. Colgate Sensitive Pro-Relief (CSPR-D); 5. Colgate Sensitive Pro-Relief Real White (CSPR-W); 6. Colgate Total 12 (CT); 7. Colgate Total 12 Professional Whitening (CTP-W); 8. Sensodyne True White (ST-W); 9. Curaprox Black is White (CB-W); 10. Oral-B 3D White Perfection (OB3D – W). For abrasion (n = 10), 30,000 brushing strokes were performed and surface roughness (SR) was evaluated. Erosion-abrasion (n = 10) consisted of 1 % citric acid (2 min), artificial saliva (60 min); 6×/day; 5 days. Toothbrushing was carried out 2×/day (45 strokes). Surface loss (SL) was determined with an optical profilometer. Data were statistically analyzed (α = 0.05). Results Relative to SR, only OB3D-W had a significantly rougher surface than the control (p = 0.014). SRP-D, CSPR-D and ST-W showed no difference from the baseline. High SL was observed for ST-W, OB3D-W and CTP-W, without significant differences from the control. CT showed the lowest SL, not differing from SRP-D and SRP-W. There was a weak negative correlation between SL and concentration of free fluoride in the slurries, SL and SR, and SL and pH, all p > 0.05. Conclusions Only one dentifrice increased surface roughness of enamel to a higher degree than brushing with saliva. Brushing with the test dentifrices did not cause higher enamel erosive wear than brushing with saliva. link3 Clinical significance This study enhances our knowledge on the effect of desensitizing and whitening dentifrices, indicating that they do not worsen enamel loss due to abrasion and they might be a safe option for individuals with erosive tooth wear.Objectives The objective of this study was to quantify the changes in mineral and selected element concentrations within residual carious dentine and restorative materials following incomplete carious lesion removal (ICLR) using different cavity liners, with non-destructive subtraction 3D-X-ray Microtomography (XMT, QMUL, London, UK). Materials and methods A total of 126 extracted teeth with deep dental caries were assessed using International Caries Risk and Assessment (ICDAS). Eight teeth were subsequently selected after radiographic evaluation. Each lesion was removed, leaving a thin layer of leathery dentine at the deepest part of cavity. Different cavity lining materials were placed; Mineral Trioxide Aggregate (MTA), calcium hydroxide, (Ca(OH)2), resin-based material (RBM). For each, the restorative material was an encapsulated glass ionomer (GIC) and the control group had a GIC restoration alone. Each tooth was immediately placed in Simulated Body Fluid (SBF). All samples were then imaged using XMT at baseline, and three weeks after treament.