Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

Background: Tau hyper-phosphorylation has been considered a major contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies, and has gained prominence in therapeutic development for AD. To elucidate the pathogenic mechanisms underlying AD and evaluate therapeutic approaches targeting tau, numerous transgenic mouse models that recapitulate critical AD-like pathology have been developed. Tau P301S transgenic mice is one of the most widely used mouse models in AD research. Extensive studies have demonstrated that sex significantly influences AD pathology, behavioral status, and therapeutic outcomes, suggesting that studies using mouse models of AD must consider sex-and age-related differences in neuropathology, behavior, and plasma content. Method: We systematically investigated differences in tau P301S transgenic mice (PS19 line) and wildtype littermates of different sex behavioral performance, tau neuropathology, and biomarkers in plasma and brain. Results: Male P301S transgenic mice exhibited significant changes in weight loss, survival rate, clasping, kyphosis, composite phenotype assessment, nest building performance, tau phosphorylation at Ser202/Thr205, and astrocyte activation compared to that of wild-type littermates. In contrast, female P301S transgenic mice were only sensitive in the Morris water maze and open field test. In addition, we characterized the absence of macrophage-inflammatory protein (MIP-3α) and the upregulation of interferon (IFN)-γ, interleukin (IL)-5, and IL-6 in the plasma of P301S transgenic mice, which can be served as potential plasma biomarkers in P301S Tg mice. Male P301S transgenic mice expressed more monokine induced by IFN-γ (MIG), tumor necrosis factor-α (TNF-α), IL-10, and IL-13 than those of female P301S mice. Conclusion: Our findings highlight sexual dimorphism in the behavior, neuropathology, and plasma proteins in tau P301S transgenic AD mice, indicating that the use of male P301S transgenic mice may be more suitable for assessing anti-phosphorylated tau therapeutic strategies for AD and related tauopathies, and the MIP-3α may be a new potential plasma biomarker.

Hypoxia-inducible factor-1a (HIF-1a) plays a beneficial role during cerebral ischemia reperfusion (IR), but the underlying molecular mechanisms are not completely understood. Here, we aimed to investigate the effects and molecular regulation of HIF-1a on brain cell apoptosis and autophagy during IR. We found that augmentation of HIF-1a in re-perfused hematopoietic cells significantly reduced brain damage, alleviated brain edema and improved neural function during IR, seemingly through two HIF-1a target genes BNIP3 and NIX, which were critical regulators for cell apoptosis and autophagic cell survival. in vitro, HIF-1a induced up-regulation of BNIP3 and NIX in human cortical neuron cells, HCN-1A. Inhibition of BNIP3 and NIX significantly attenuated HIF-1a-suppressed cell apoptosis and HIF-1a-induced cell autophagy. Together, these data suggest that HIF-1a may ameliorate brain damages during IR through BNIP3 and NIX -dependent augmentation of autophagic cell survival and reduction in cell apoptosis.

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Background: Fertility is an important economic trait in the production of meat goat, and follicular development plays an important role in fertility. Although many mRNAs and microRNAs (miRNAs) have been found to play critical roles in ovarian biological processes, the interaction between mRNAs and miRNAs in follicular development is not yet completely understood. In addition, less attention has been given to the study of single follicle (dominant or atretic follicle) in goats. This study aimed to identify mRNAs, miRNAs, and signaling pathways as well as their interaction networks in the ovarian follicles (large follicles and small follicles) of uniparous and multiple Chuanzhong black goats at estrus phase using RNAsequencing (RNA-seq) technique. Results: The results showed that there was a significant difference in the number of large follicles between uniparous and multiple goats (P < 0.05), but no difference in the number of small follicles was observed (P > 0.05). For the small follicles of uniparous and multiple goats at estrus phase, 289 differentially expressed mRNAs (DEmRNAs) and 16 DEmiRNAs were identified; and for the large follicles, 195 DEmRNAs and 7 DEmiRNAs were identified. The functional enrichment analysis showed that DE genes in small follicles were significantly enriched in ovarian steroidogenesis and steroid hormone biosynthesis, while in large follicles were significantly enriched in ABC transporters and steroid hormone biosynthesis. The results of quantitative real-time polymerase chain reaction were consistent with those of RNA-seq. Analysis of the mRNA-miRNA interaction network suggested that CD36 (miR-122, miR-200a, miR-141), TNFAIP6 (miR-141, miR-200a, miR-182), CYP11A1 (miR-122), SERPINA5 (miR-1, miR-206, miR-133a-3p, miR-133b), and PTGFR (miR-182, miR-122) might be related to fertility, but requires further research on follicular somatic cells. Conclusions: This study was used for the first time to reveal the DEmRNAs and DEmiRNAs as well as their interaction in the follicles of uniparous and multiple goats at estrus phase using RNA-seq technology. Our findings provide new clues to uncover the molecular mechanisms and signaling networks of goat reproduction that could be potentially used to increase ovulation rate and kidding rate in goat.

This study investigated the effects of dexmedetomidine on heart-type fatty acid binding protein (H-FABP), creatine kinase isoenzymes (CK-MB), and troponin I (cTnI) levels, neurological function and near-term prognosis in patients undergoing heart valve replacement. Patients undergoing heart valve replacement were randomly allocated to remifentanil anesthesia (control group, n=48) or dexmedetomidine anesthesia (observation group, n=48). Hemodynamic parameters were measured before anesthesia induction (T1), 1 min after intubation (T2), 10 min after start of surgery (T3), and on completion of surgery (T4). Levels of plasma H-FABP, CK-MB and cTnI were measured 10 min before anesthesia induction (C1), 10 min after start of surgery (C2), on completion of surgery (C3), 6 h after surgery (C4), and 24 h after surgery (C5). S100β protein and serum neuron-specific enolase (NSE) were detected 10 min before anesthesia induction (C1), and 24 h after surgery (C5). Neurological and cardiac function was evaluated 24 h after surgery. Incidence of cardiovascular adverse events was recorded for 1 year of follow-up. There were no significant differences in the average heart rate between the two groups during the perioperative period. The mean arterial pressure in the observation group was significantly lower than control group (P<0.05). Levels of H-FABP, CK-MB and cTnI at C2, C3, C4 and C5, were significantly higher than C1, but significantly lower in the observation versus control group (P<0.05). Twenty-four hours after surgery, levels of S100β and NSE in both groups were higher than those before induction (P<0.05), but significantly lower in the observation versus control group (P<0.05). Twenty-four hours after surgery, neurological function scores were better, and myocardial contractility and arrhythmia scores significantly lower in the observation versus control group (P<0.05 for all). After follow-up for 1 year, incidence of cardiovascular adverse events was significantly lower in the observation versus control group (P<0.05). Dexmedetomidine anesthesia can effectively maintain hemodynamic stability, reduce myocardial injury and the occurrence of cognitive dysfunction, and improve prognosis in patients undergoing heart valve replacement.

The abnormal deposition of amyloid-β (Aβ) peptides in the brain is the main neuropathological hallmark of Alzheimer's disease (AD). Amyloid deposits are formed by a heterogeneous mixture of Aβ peptides, among which the most studied are Aβ40 and Aβ42. Aβ40 is abundantly produced in the human brain, but the level of Aβ42 is remarkably increased in the brain of AD patients. Aside from Aβ40 and Aβ42, recent data have raised the possibility that Aβ43 peptides may be instrumental in AD pathogenesis. Besides its length, whether the Aβ aggregated form accounts for the neurotoxicity is also particularly controversial. Aβ fibrils are generally considered as key pathogenic substances in AD pathogenesis. Nevertheless, recent data implicated soluble Aβ oligomers as the main cause of synaptic dysfunction and memory loss in AD. To further address this uncertainty, we analyzed the neurotoxicity of different Aβ species and Aβ forms at the cellular level. The results showed that Aβ42 could form oligomers significantly faster than Aβ40 and Aβ43 and Aβ42 oligomers showed the greatest level of neurotoxicity. Regardless of the length of Aβ peptides, Aβ oligomers induced significantly higher cytotoxicity compared with the other two Aβ forms. Surprisingly, the neurotoxicity of fibrils in PC12 cells was only marginally but not significantly stronger than monomers, contrary to previous reports. Altogether, our findings demonstrate the high pathogenicity of Aβ42 among the three Aβ species and support the idea that Aβ42 oligomers contribute to the pathological events leading to neurodegeneration in AD. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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