Derivation and Validation of a Risk Score for Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

BACKGROUND: Compared with methicillin sensitive Staphylococcus aureus (MSSA), the prognosis of patients with methicillin resistant Staphylococcus aureus (MRSA) bloodstream infection is poor. Therefore, the construction of MRSA and MSSA identification model has certain value for the selection of antibiotics and treatment outcome control. This study aimed to derive and validate a simple risk prediction model for MRSA bloodstream infection in Chinese patients. METHODS: Three hundred and thirty-five patients with Staphylococcus aureus (S. aureus) bloodstream infection were retrospectively analyzed and divided into three groups. The first group was used for the risk score derivation (n = 163), the second group was used for internal validation (n = 80), and the third group was used for external validation (n = 92). According to the odds ratio (OR) obtained from multivariate logistic regression, the risk prediction model for MRSA bloodstream infection was established, and the prediction efficiency of the model in three cohorts were evaluated. RESULTS: Hospital stay before BSI ≥ 7 days, hospital acquired BSI, infection source ≥ 2 sites, indwelling gastric tube before BSI and carbapenems used before BSI and after admission were independent influencing factors of MRSA in the derivation group, the above influencing factors were scored 3, 5, 4, 3, and 3, respectively. The derivation, internal and external validation groups showed adequate discrimination (the AUCs were 0.788, 0.780, and 0.742, respectively) and good calibration (H-L tests were χ2 = 3.896, p = 0.306; χ2 = 4.221, p = 0.298; and χ2 = 3.974, p = 0.352, respectively). The risk scores were further divided into very low-risk (score 0 - 3), low-risk (score 4 - 7), high-risk (score 8 - 12), and very high-risk (score ≥ 13) layers. CONCLUSIONS: The simple risk score model for predicting MRSA bloodstream infection has good predictive effect, high predictive accuracy, and good clinical applicability, which can help clinicians choose sensitive antibiotics and reduce the adverse prognosis of patients.

Pretreatment Depressive Status Associated with Poor Nutrition and Prognosis in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

The prevalence of pretreatment depression in breast cancer patients and its impact on nutrition and prognosis during neoadjuvant chemotherapy remain unknown. One hundred twenty-one patients with previously untreated breast cancer undergoing neoadjuvant chemotherapy (NAC) were enrolled. Patients completed the Self-rating Depressive symptoms Scale (SDS) before treatment and were divided into two groups (non-depressive group and depressive group). The nutrition risk screening-2002 (NRS-2002), and nutritional and prognostic indicators, including neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI), were collected at baseline (pretreatment) and post-treatment. One- and two-year progression-free survival (PFS) in both groups were also calculated. We found that 38.84% patients experienced pretreatment depressive symptoms. Patients in the depressive group had higher nutritional risk and lower body mass index, potassium, sodium, total cholesterol, total protein, and fasting blood glucose levels than those in pretreatment non-depressive group after NAC (all p < 0.05). And higher NLR (p = 0.039) and lower PNI level (p = 0.0021) after NAC were found in patients with pretreatment depressive status. Multivariable Cox analysis showed pretreatment depressive status (HR: 1.893; 95% CI: 1.047-3.426; p = 0.034) were a significant predictor of PFS. This study provides evidence for early identification of pretreatment depression in patients receiving NAC, which would certainly favor nutrition and survival outcome.

ABAD/17ß-HSD10 reduction contributes to the protective mechanism of huperzine a on the cerebral mitochondrial function in APP/PS1 mice.

Huperzine A (HupA) is a kind of Lycopodium alkaloid with potential disease-modifying qualities that has been reported to protect against ß-amyloid (Aß)-mediated mitochondrial damage in Alzheimer's disease. However, the fundamental molecular mechanism underlying the protective action of HupA against Aß-mediated mitochondrial malfunction is not completely understood. Recently, the mitochondrial enzyme amyloid-binding alcohol dehydrogenase (ABAD) protein has been reported to facilitate Aß-induced mitochondrial damage, resulting in mitochondrial malfunction and cell death. Our study found that HupA, but not the acetylcholinesterase inhibitor tacrine, reduced the deposition of Aß and the ABAD level, and further reduced Aß-ABAD complexes, thereby improving cerebral mitochondrial function in APP/PS1 mice. This was accompanied by attenuated reactive oxygen species overload, as well as increases adenosine triphosphate levels. Moreover, HupA decreased the release of cytochrome-c from mitochondria and the level of cleaved caspase-3, thereby increasing dissociated brain cell viability in APP/PS1 mice. Thus, our study demonstrated that a reduction in ABAD was involved in the protective mechanism of HupA on the cerebral mitochondrial function in APP/PS1 mice.

An improved Ultra-High Performance Liquid chromatography-tandem mass spectrometry method for simultaneous quantitation of cytochrome P450 metabolites of arachidonic acid in human plasma.

This study aims to develop a straightforward, sensitive UHPLC-MS/MS method to quantify 15 eicosanoids derived from arachidonic acid in human plasma. Tert-Butyl methyl ether was used on the liquid-liquid extraction method and significantly reduced the expense and time. The method showed excellent linearity for all analytes, with regression coefficients higher than 0.99 over a wide range of concentrations from 0.01 ng mL-1 to 100 ng mL-1. The recovery rates were over 65.00%, and the matrix effects ranged from 8.42% to 40.00%. The limits of detection ranged from 6 pg mL-1 to 10 pg mL-1, and all of the limits of quantification were 20 - 33 pg mL-1. For the broad concentration range, the RE% for accuracy and precision were less than ±â€¯15%. Moreover, trans-4-{4-[3-(4-Trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB) pretreatment extended the window of detection for as much as 30 days. Eicosanoid signaling is altered in various neurological diseases, including pain, Alzheimer's disease and major depressive disorder. Therefore, this rapid, robust quantitative profiling of 15 eicosanoids in plasma could provide a distinct eicosanoid fingerprint for precision medicine in these patients.

Blocking mPTP on Neural Stem Cells and Activating the Nicotinic Acetylcholine Receptor α7 Subunit on Microglia Attenuate Aß-Induced Neurotoxicity on Neural Stem Cells.

ß-Amyloid (Aß) can stimulate microglia to release a variety of proinflammatory cytokines and induce neurotoxicity. Nicotine has been reported to inhibit TNF-α, IL-1, and ROS production in microglia. Mitochondrial permeability transition pore (mPTP) plays an important role in neurotoxicity as well. Here, we investigated whether activating the microglial α7-nAChR has a neuroprotective role on neural stem cells (NSCs) and the function of mPTP in NSCs in this process. The expression of α7-nAChR in rat NSCs was detected by immunocytochemistry and RT-PCR. The viability of microglia and NSCs was examined by MTT assay. The mitochondrial membrane potential (ΔΨm) and morphological characteristics of NSCs was measured by JC-1 staining and transmission electron microscopy respectively. The distribution of cytochrome c in the subcellular regions of NSCs was visualized by confocal laser scanning microscopy, and the expression levels of cyclophilin D and cleaved caspase-3 were assayed by western blot. The apoptotic rate of NSCs was measured by flow cytometry. The expression of α7-nAChR was detected in microglial cells, but no expression was found in NSCs. The viability of rat microglial cells and NSCs was not affected by reagents or coculture itself. Aß1-42-mediated microglial activation impaired the morphology and the ΔΨm of mitochondria of NSCs as well as increased cell apoptosis. However, the damage was attenuated when the α7-nAChRs on microglial cells were activated or the mPTPs on NSCs were blocked. Blockade of mPTPs on NSCs and activation of α7-nAChRs on microglia exhibit neuroprotective roles in Aß-induced neurotoxicity of NSCs.