18 research outputs found
Neonatal encephalopathic cerebral injury in south india assessed by perinatal magnetic resonance biomarkers and early childhood neurodevelopmental outcome
Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR) biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India.
Methods
We recruited consecutive term or near term infants with evidence of perinatal asphyxia and a Thompson encephalopathy score ≥6 within 6 h of birth, over 6 months. We performed conventional MR imaging, diffusion tensor MR imaging and thalamic proton MR spectroscopy within 3 weeks of birth. We computed group-wise differences in white matter fractional anisotropy (FA) using tract based spatial statistics. We allocated Sarnat encephalopathy stage aged 3 days, and evaluated neurodevelopmental outcomes aged 3½ years using Bayley III.
Results
Of the 54 neonates recruited, Sarnat staging was mild in 30 (56%); moderate in 15 (28%) and severe in 6 (11%), with no encephalopathy in 3 (6%). Six infants died. Of the 48 survivors, 44 had images available for analysis. In these infants, imaging indicated perinatal rather than established antenatal origins to injury. Abnormalities were frequently observed in white matter (n = 40, 91%) and cortex (n = 31, 70%) while only 12 (27%) had abnormal basal ganglia/thalami. Reduced white matter FA was associated with Sarnat stage, deep grey nuclear injury, and MR spectroscopy N-acetylaspartate/choline, but not early Thompson scores. Outcome data were obtained in 44 infants (81%) with 38 (79%) survivors examined aged 3½ years; of these, 16 (42%) had adverse neurodevelopmental outcomes.
Conclusions
No infants had evidence for established brain lesions, suggesting potentially treatable perinatal origins. White matter injury was more common than deep brain nuclei injury. Our results support the need for rigorous evaluation of the efficacy of rescue hypothermic neuroprotection in low- and middle-income countries
Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth.
The design of cancer-targeting particles with precisely tuned physicochemical properties may enhance the delivery of therapeutics and access to pharmacological targets. However, a molecular-level understanding of the interactions driving the fate of nanomedicine in biological systems remains elusive. Here, we show that ultrasmall (<10 nm in diameter) poly(ethylene glycol)-coated silica nanoparticles, functionalized with melanoma-targeting peptides, can induce a form of programmed cell death known as ferroptosis in starved cancer cells and cancer-bearing mice. Tumour xenografts in mice intravenously injected with nanoparticles using a high-dose multiple injection scheme exhibit reduced growth or regression, in a manner that is reversed by the pharmacological inhibitor of ferroptosis, liproxstatin-1. These data demonstrate that ferroptosis can be targeted by ultrasmall silica nanoparticles and may have therapeutic potential
Correction to Cancer-Targeting Ultrasmall Silica Nanoparticles for Clinical Translation: Physicochemical Structure and Biological Property Correlations
Neonatal Encephalopathic Cerebral Injury in South India Assessed by Perinatal Magnetic Resonance Biomarkers and Early Childhood Neurodevelopmental Outcome
Cancer-Targeting Ultrasmall Silica Nanoparticles for Clinical Translation: Physicochemical Structure and Biological Property Correlations
Although
a large body of literature exists on the potential use
of nanoparticles for medical applications, the number of probes translated
into human clinical trials is remarkably small. A major challenge
of particle probe development and their translation is the elucidation
of safety profiles associated with their structural complexity, not
only in terms of size distribution and heterogeneities in particle
composition but also their effects on biological activities and the
relationship between particle structure and pharmacokinetics. Here,
we report on the synthesis, characterization, and long-term stability
of ultrasmall (<10 nm diameter) dual-modality (optical and positron
emission tomography) and integrin-targeting silica nanoparticles (cRGDY–PEG–Cy5–C′
dots and <sup>124</sup>I-(or <sup>131</sup>I-) cRGDY–PEG–Cy5–C′dots)
and the extent to which their surface ligand density differentially
modulates key in vitro and in vivo biological activities in melanoma
models over a range of ligand numbers (i.e., ∼6–18).
Gel permeation chromatography, established as an important particle
characterization tool, revealed a two-year shelf life for cRGDY–PEG–Cy5–C′
dots. Radiochromatography further demonstrated the necessary radiochemical
stability for clinical applications. The results of subsequent ligand
density-dependent studies elucidate strong modulations in biological
response, including statistically significant increases in integrin-specific
targeting and particle uptake, cellular migration and adhesion, renal
clearance, and tumor-to-blood ratios with increasing ligand number.
We anticipate that nanoprobe characteristics and a better understanding
of the structure–function relationships determined in this
study will help guide identification of other lead nanoparticle candidates
for in vitro and in vivo biological assessments and product translation
Glioma Grading and Determination of IDH Mutation Status and ATRX loss by DCE and ASL Perfusion
Early childhood outcomes of infants according to Sarnat neonatal encephalopathy staging.
<p>Values are frequency (% of n);</p><p>*Normal outcome defined as Bayley III cognitive score ≥85 and motor composite score ≥82; with normal head growth; normal neurological examination; normal vision and hearing; and no ongoing seizures at 3½ years.</p