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PurposeThis study aimed to assess the association between motor and non-motor symptoms of Parkinson’s disease (PD) and iron accumulation within the deep gray matter of the brain by Quantitative Susceptibility Mapping (QSM).MethodsFifty-six PD patients and twenty-nine healthy controls were recruited in this study. According to the Hoehn and Yahr (H-Y) stage score, PD patients were divided into early stage (H-Y ≤ 2) and advanced stage (H-Y > 2) groups. Specifically, the Regions of Interest (ROIs) encompassed the substantia nigra (SN), red nucleus (RN), caudate nucleus (CN), globus pallidus (GP) and putamen (PT). Meanwhile, various rating scales were used to assess the clinical symptoms of PD.ResultsCompared to healthy controls (HCs), PD patients showed a significant increase in magnetic susceptibility values (MSVs) within the SN and GP. Further comparisons indicated that the MSVs of the SN, PT, GP and CN are all higher in advanced stages than in early stages. Significant positive correlations were observed between the MSVs of the SN and scores on the UPDRS-III, HAMA, and HAMD (r = 0.310, p = 0.020; r = 0.273, p = 0.042; r = 0.342, p = 0.010, respectively). Likewise, the MSVs of the GP demonstrated notable correlations with HAMA and HAMD scores (r = 0.275, p = 0.040; r = 0.415, p = 0.001). Additionally, a significant correlation was found between the MSVs of the PT and HAMD scores (r = 0.360, p = 0.006). Furthermore, we identified a significant negative correlation between MMSE scores and the MSVs of both the PT and GP (r = −0.268, p = 0.046; r = −0.305, p = 0.022).ConclusionOur study revealed that QSM possesses the capability to serve as a biomarker for PD. Significant correlations were found between clinical features and the iron deposition in the nigrostriatal system.

ABSTRACT Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0–24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0–24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.

Background: The functional improvement following bone marrow stromal cells (BMSCs) transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke. Methods: Rat transient middle cerebral artery occlusion (MCAO) model was established. Two separate MCAO groups were administered with either MCI-186 or phosphate-buffered saline (PBS) solution to evaluate the expression of stromal cell-derived factor-1 (SDF-1) in ischemic brain, and compared to that in sham group (n = 5/ group/time point[at 1, 3, and 7 days after operation]). The content of chemokine receptor-4 (CXCR4, a main receptor of SDF-1) at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs (2 × 106), or a combination of MCI-186 and BMSCs (n = 10/group). 5-bromo-2-deoxyuridine (BrdU) and Nestin double-immunofluorescence staining was performed to identify the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome. Results: MCI-186 upregulated the expression of SDF-1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI-186, BMSCs, or a combination of MCI-186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group (P < 0.01 or 0.05, respectively). Combination therapy represented a further restoration, increased the number of BMSCs and Nestin+ cells in ischemic brain as compared with BMSCs monotherapy (P < 0.01). The number of engrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain (r = 0.72 , P < 0.01) and the improvement of foot-fault (r = 0.70, P < 0.01). Conclusion: MCI-186 might promote BMSCs migration to the ischemic brain, amplify the neurogenesis, and improve the effects of cell therapy.

A novel electrochemiluminescence (ECL) luminophor of amoxicillin was studied and found to generate ECL following the oxidation or reduction of amoxicillin. The amoxicillin oxidation state was also found to eliminate the reduction state, generating ECL. When solutions of amoxicillin were scanned between þ1.5 V and 1.0 V with a graphite electrode in the presence of cetyltrimethyl ammonium bromide using KC1 as the supporting electrolyte, ECL emissions were observed at potentials of -0.7 V and þ0.5 V. The ECL intensity at -0.7 V was enhanced by H2O2. Based on these findings, an ECL method for the determination of the amoxicillin concentration is proposed. The ECL intensities were linear with amoxicillin concentrations in the range of 1.8 x 10-8 g/mL to 2.5 x 10-7 g/mL, and the limit of detection (signal/noise ¼ 3) was 5 x 10-9 g/mL. The florescence of amoxicillin had the greatest emission intensity in a neutral medium, with the emission wavelength dependent on the excitation wavelength. The experiments on the ECL mechanism for amoxicillin found that the electrochemical oxidation products of dissolved oxygen and active oxygen species contributed to the ECL process. The data also suggest that the hydroxyl group of amoxicillin contributed to its ECL emission. [ABSTRACT FROM AUTHOR]

A facile approach was established for fabricating photothermo-responsive nanogels for simultaneous optical temperature-sensing, cell imaging, and combined chemo-photothermal treatment. The strategy for preparing the hybrid Au@IPN-pNIPAAm nanogels involved two steps, consisting of growing an acrylamide monolayer on a single gold nanoparticle, followed by in situpolymerization and crosslinking of N-isopropylacrylamide and acrylamide. The hybrid Au@IPN-pNIPAAm nanogels exhibited not only biocompatibility at low concentration <200 μg ml−1, but also good function on cellular imaging by using dark-field microscopy. Furthermore, the integration of the unique scattering properties of AuNP core and the reversible thermo-responsive volume phase transition of IPN-pNIPAAm shell could offer a thermo-/photo-triggered release of a model anticancer drug 5-fluorouracil from Au@IPN-pNIPAAm nanogels. Hence, the hybrid Au@IPN-pNIPAAm nanogels, may offer broad opportunities for combined diagnosis and therapy. [ABSTRACT FROM AUTHOR]