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Background: When tying knots, some surgeons do not pay particular attention to the direction in which they pull to lay down throws. We examine to what extent does pulling direction influence on knot security., Methods: A total of 368 residents were instructed to tie knots with from 2 to 7 throws using silk braided suture in 3-0 gauge. The direction in which they pulled to lay down throws was recorded. Only the knots tied either by pulling in alternate directions (Group A) or in constant direction (Group C) from the first throw to the last were involved in statistical analysis. Tensile strength and untying rate of the knots were then measured for comparative analysis., Results: For knots with from 2 to 7 throws, the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively. For knots with from 5 to 7 throws, the untying rate of the ones from Group A was significantly lower than that of the ones from Group C (p < 0.05), respectively. For the unraveled knots with from 2 to 7 throws (except for the ones with 5 throws), the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively., Conclusion: Pulling in constant direction results in inferior knot security. Surgeons must ascertain the influence of pulling direction on knot security, and try to achieve superior security with fewer throws to ensure patient safety., Competing Interests: Declarations of competing interest None., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Olfactory damage develops at the early stages of Alzheimer's disease (AD). While amyloid-β (Aβ) oligomers are shown to impair inhibitory circuits in the olfactory bulb (OB), its underlying mechanisms remain unclear. Here, we investigated the olfactory dysfunction due to impaired inhibitory transmission to mitral cells (MCs) of the OB in APP/PS1 mice. Using electrophysiological studies, we found that MCs exhibited increased spontaneous firing rates as early as 3 months, much before development of Aβ deposits in the brain. Furthermore, the frequencies but not amplitudes of MC inhibitory postsynaptic currents decreased markedly, suggesting that presynaptic GABA release is impaired while postsynaptic GABA A receptor responses remain intact. Notably, muscimol, a GABA A receptor agonist, improved odor identification and discrimination behaviors in APP/PS1 mice, reduced MC basal firing activity, and rescued inhibitory circuits along with reducing the Aβ burden in the OB. Our study links the presynaptic deficits of GABAergic transmission to olfactory dysfunction and subsequent AD development and implicates the therapeutic potential of maintaining local inhibitory microcircuits against early AD progression., (Copyright © 2021. Published by Elsevier Inc.)

Synthetic grafts are of limited use in small-diameter vessels (Φ<6mm) due to the poor patency rate. The inability of such grafts to achieve early endothelialization together with the compliance mismatch between the grafts and the native vessels promote thrombosis, which eventually leads to graft occlusion. In the current study, stromal cell-derived factor (SDF)-1α/vascular endothelial growth factor (VEGF)-loaded polyurethane (PU) conduits were simply prepared via electrospinning. The mechanical property, drug release behavior and cytocompatibility of the conduits were investigated. The effects of the conduits on endothelial progenitor cell (EPC) mobilization and differentiation were examined in vitro. Then, the conduits were implanted as canine femoral artery interposition grafts. The results revealed that SDF-1α and VEGF were quickly released shortly after implantation, and the conduits exhibited slow and sustained release thereafter. The cytokines had definite effects on EPC mobilization and differentiation in vitro and promoted conduit endothelialization in vivo. The conduits had good tissue compatibility and favorable compliance. All of these features inhibited the conduits from being occluded, thereby improving their long-term patency rate. At 6th month postoperatively, 5 of the 8 grafts were patent while all the 8 grafts without the cytokines were occluded. These findings provide a simple and effective method for the construction of small-diameter artificial blood vessels with the aim of facilitating early endothelialization and improving long-term patency. STATEMENT OF SIGNIFICANCE: (1) SDF-1α/VEGF loaded PU conduits were simply prepared by electrospinning. The cytokines with definite and potent effects on angiogenesis were used to avoid complicated mechanism researches. Compared with most of the current vascular grafts which are of poor strength or elasticity, the conduits have favorable mechanical property. All of these inhibit the conduits from occlusion, and thus improve their long-term patency rate. (2) For the in vivo tests, the dogs did not receive any anticoagulant medication in the follow-up period to expose the grafts to the strictest conditions. In vivo endothelialization of the conduits was thoroughly investigated by Sonography, HE staining, SEM and LSCM. The study will be helpful for the construction of small-diameter artificial blood vessels., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Although early olfactory dysfunction has been found in patients with Alzheimer's disease, the underlying mechanisms remain unclear. In this study, we investigated whether and how oligomeric amyloid-β peptide (Aβ) affects the responses of mitral cells (MCs). We found that oligomeric Aβ1-42 increased spontaneous and evoked firing rates but decreased the ratio of evoked to spontaneous firings in MCs. Aβ1-42 oligomers showed no impact on the hyperactivity exerted by pharmacological blockage of GABA A receptors, suggesting an involvement of GABAergic inhibitory transmission in Aβ1 to 42-induced over-excitability. It was further determined that Aβ1-42 oligomers inhibited the frequency of spontaneous inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents, as well as the amplitude of miniature inhibitory postsynaptic currents in MCs. Both recurrent and lateral inhibition of MCs, which are critical for odor discrimination, were also disrupted by Aβ1-42 oligomers. The above data indicate that Aβ impairs local inhibitory circuits and thereby leads to perturbations of olfactory information output in the olfactory bulb. This study reveals a cellular and synaptic basis of olfactory deficits associated with Alzheimer's disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Oligomeric amyloid-β peptide (Aβ) has been found to be associated with the pathogenesis of Alzheimer's disease (AD). Numerous studies have reported Aβ neurotoxicity, but the underlying molecular mechanisms remain to be fully illuminated. In the present study, we investigated the Aβ-induced activation and regulation of P38MAPKs in rat hippocampus in vivo. The results showed that intracerebroventricular injection of oligomeric Aβ25-35 increased the activation (phosphorylation) of P38MAPKs, and the level of cleaved caspase-3, but decreased the number of neurons in rat hippocampal CA1 and CA3 subfields. Downregulation of P38MAPK activity by SB239063 protected against the Aβ neurotoxicity. Pretreatment with NMDA and non-NMDA receptor antagonists respectively suppressed P38MAPK activation induced by Aβ25-35 oligomers and presented neuroprotective effect. Taken together, these data suggest that P38MAPK activation via NMDA and non-NMDA receptors is a key signal cascade in Aβ-induced neuronal death. Inhibition of P38MAPK cascades may be a promising treatment in AD., (Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)