Laser-Activatable CuS Nanodots to Treat Multidrug-Resistant Bacteria and Release Copper Ion to Accelerate Healing of Infected Chronic Nonhealing Wounds

Chronic nonhealing wounds have imposed serious challenges in the clinical practice, especially for the patients infected with multidrug-resistant microbes. Herein, we developed an ultrasmall copper sulfide (covellite) nanodots (CuS NDs) based dual functional nanosystem to cure multidrug-resistant bacteria-infected chronic nonhealing wound. The nanosystem could eradicate multidrug-resistant bacteria and expedite wound healing simultaneously owing to the photothermal effect and remote control of copper-ion release. The antibacterial results indicated that the combination treatment of photothermal CuS NDs with photothermal effect initiated a strong antibacterial effect for drug-resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase Escherichia coli both in vitro and in vivo. Meanwhile, the released Cu2+ could promote fibroblast cell migration and endothelial cell angiogenesis, thus accelerating wound-healing effects. In MRSA-infected diabetic mice model, the nanosystem exhibited synergistic wound healing effect of infectious wounds in vivo and demonstrated negligible toxicity and nonspecific damage to major organs. The combination of ultrasmall CuS NDs with photothermal therapy displayed enhanced therapeutic efficacy for chronic nonhealing wound in multidrug-resistant bacterial infections, which may represent a promising class of antibacterial strategy for clinical translation.Peer reviewe

Smaller baseline subcortical infarct volume predicts good outcomes in patients with a large core in early acute ischemic stroke after endovascular treatment

BackgroundPatients with acute ischemic stroke (AIS) and a large core may benefit from endovascular treatment (EVT) in the early time window.PurposeTo examine the prognostic factors for good outcomes in patients with a large core (70–130 ml) after EVT.Materials and methodsWe retrospectively reviewed 40 patients who met the criteria from October 2019 to April 2021. Based on the modified Rankin Score (mRS) at 90 days, the patients were divided into a good outcome group (mRS 0–2) and a poor outcome group (mRS 3–6). Baseline and procedural characteristics were collected for unilateral and multivariate regression analyses to explore the factors that influence good outcomes. In particular, the infarct territories were quantified as subcortical infarct volume (SIV) and cortical infarct volume (CIV).ResultsOf the 40 patients included, good outcomes were observed in 11 (27.5%) patients. Younger age, smaller SIV and larger mismatch volume were noted in the good outcome group than in the poor outcome group (all P < 0.05). Multivariate logistic regression analysis showed that only a smaller SIV [odds ratio (OR) 0.801; 95% CI 0.644–0.996; P = 0.046] was an independent predictor for good outcomes. The receiver operating characteristic curve indicated a moderate value of SIV for predicting good outcomes, with an area under the receiver operating characteristic curve of 0.735 (95% CI 0.572–0.862; P = 0.007).ConclusionSubcortical infarct volume was a potential useful predictor of good outcomes in patients with a large core after EVT in the early time window

The Ninth Visual Object Tracking VOT2021 Challenge Results

acceptedVersionPeer reviewe

Metabolic Causes of Epileptic Encephalopathy

Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria) and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies). Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category

Anti-Cancer Drug Sensitivity Assay with Quantitative Heterogeneity Testing Using Single-Cell Raman Spectroscopy

A novel anti-cancer drug sensitivity testing (DST) approach was developed based on in vitro single-cell Raman spectrum intensity (RSI). Generally, the intensity of Raman spectra (RS) for a single living cell treated with drugs positively relates to the sensitivity of the cells to the drugs. In this study, five cancer cell lines (BGC 823, SGC 7901, MGC 803, AGS, and NCI-N87) were exposed to three cytotoxic compounds or to combinations of these compounds, and then they were evaluated for their responses with RSI. The results of RSI were consistent with conventional DST methods. The parametric correlation coefficient for the RSI and Methylthiazolyl tetrazolium assay (MTT) was 0.8558 ± 0.0850, and the coefficient of determination was calculated as R2 = 0.9529 ± 0.0355 for fitting the dose⁻response curve. Moreover, RSI data for NCI-N87 cells treated by trastuzumab, everolimus (cytostatic), and these drugs in combination demonstrated that the RSI method was suitable for testing the sensitivity of cytostatic drugs. Furthermore, a heterogeneity coefficient H was introduced for quantitative characterization of the heterogeneity of cancer cells treated by drugs. The largest possible variance between RSs of cancer cells were quantitatively obtained using eigenvalues of principal component analysis (PCA). The ratio of H between resistant cells and sensitive cells was greater than 1.5, which suggested the H-value was effective to describe the heterogeneity of cancer cells. Briefly, the RSI method might be a powerful tool for simple and rapid detection of the sensitivity of tumor cells to anti-cancer drugs and the heterogeneity of their responses to these drugs

Quantitation of gamma-hydroxybutyric acid in dried blood spots: Feasibility assessment for newborn screening of succinic semialdehyde dehydrogenase (SSADH) deficiency

OBJECTIVE: SSADH deficiency, the most prevalent autosomal recessive disorder of GABA degradation, is characterized by elevated gamma-hydroxybutyric acid (GHB). Neurological outcomes may be improved with early intervention and anticipatory guidance. Morbidity has been compounded by complications, e.g. hypotonia, in undiagnosed infants with otherwise routine childhood illnesses. We report pilot methodology on the feasibility of newborn screening for SSADH deficiency. METHOD: Dried blood spot (DBS) cards from patients affected with SSADH deficiency were compared with 2831 archival DBS cards for gamma-hydroxybutyric acid content. Following extraction with methanol, GHB in DBS was separated and analyzed using ultra high-performance liquid chromatography tandem mass spectrometry. RESULTS: Methodology was validated to meet satisfactory accuracy and reproducibility criteria, including intra-day and inter-day validation. Archival refrigerated dried blood spots samples of babies, infants and children (N=2831) were screened for GHB, yielding a mean +/- S.D. of 8 ± 5 nM (99.9 %-tile 63 nM) (Min 0.0 Max 78 nM). The measured mean and median concentrations in blood spots derived from seven SSADH deficient patients were 1182 nM and 699 nM respectively (Min 124, Max 4851nM). CONCLUSIONS: GHB concentration in all 2831 dried blood spot cards was well below the lowest concentration of affected children. These data provide proof-of-principle for screening methodology to detect SSADH deficiency with applicability to newborn screening and earlier diagnosis

Separation of Minor Actinides from High-Level Liquid Waste Using Novel Silica-Based Butyl-BTP Adsorbents

To separate the long-lived minor actinides (MA = Am, Cm) from high-level liquid waste (HLLW), we have been studying an advanced separation process via selective adsorption that uses minimal amounts of organic solvent and compact equipment. The process consists of two separation columns packed with a CMPO (octyl(phenyl)-N,N-diisobutylcarbamoyl-methyl phosphine oxide) adsorbent for elemental group separation and a soft-donor named the R-BTP (2,6-bis-(5,6-dialkyl-1,2,4-triazine-3-yl) pyridine) adsorbent for the isolation of MA from lanthanides (Ln). In this work, the effects of nitrate ion (NO3−) on the adsorption behavior of Am(III) and a typical fission product Ln(III) onto the isoBu-BTP/SiO2-P adsorbent were studied experimentally. Then, the desorption properties of the adsorbed element were examined using different eluting agents. A hot test for the separation of MA from the fission product Ln in a genuine MA containing effluent from the irradiated MOX-fuel treatment process was carried out using a nBu-BTP/SiO2-P packed column. It was found that the separation factor between Am(III) and Ln(III)-FP is over 100 in the measured 0.5–4 M NO3−. The adsorbed elements could be effectively eluted off using a complexing agent such as DTPA or pure water. Complete separation between MA and Ln was achieved in the column results, indicating that the proposed MA separation process is feasible in principle