环孢素脂质微粒经小鼠皮肤给药的渗透机理研究

目的　研究普通纳米脂质体、柔性纳米脂质体及胆酸钠-磷脂混合胶团对环孢素经小鼠皮肤给药的渗透机理。方法　将含药载体非封闭性应用于离体或在体小鼠皮肤,测定了皮肤、接收介质和血液中环孢素含量。结果 离体条件下,应用柔性纳米脂质体和混和胶团后均能在接收液中检测到药物,但普通脂质体却不能。在体条件下,应用柔性纳米脂质体后8 h血药浓度到达峰值,而应用普通脂质体和混合胶团后在血中几乎未检测到药物。结论 柔性纳米脂质体在皮肤水合压力下发生变形,携药透过皮肤;普通脂质体主要与皮肤发生融合产生蓄积作用;混合胶团在水溶液状态下发挥其渗透促进作用。     

Sexually Dimorphic Effects of a Western Diet on Brain Mitochondrial Bioenergetics and Neurocognitive Function

A Western diet (WD), high in sugars and saturated fats, impairs learning and memory function and contributes to weight gain. Mitochondria in the brain provide energy for neurocognitive function and may play a role in body weight regulation. We sought to determine whether a WD alters behavior and metabolic outcomes in male and female rodents through impacting hippocampal and hypothalamic mitochondrial bioenergetics. Results revealed a sexually dimorphic macronutrient preference, where males on the WD consumed a greater percentage of calories from fat/protein and females consumed a greater percentage of calories from a sugar-sweetened beverage. Both males and females on a WD gained body fat and showed impaired glucose tolerance when compared to same-sex controls. Males on a WD demonstrated impaired hippocampal functioning and an elevated tendency toward a high membrane potential in hippocampal mitochondria. Comprehensive bioenergetics analysis of WD effects in the hypothalamus revealed a tissue-specific adaption, where males on the WD oxidized more fat, and females oxidized more fat and carbohydrates at peak energy demand compared to same-sex controls. These results suggest that adult male rats show a susceptibility toward hippocampal dysfunction on a WD, and that hypothalamic mitochondrial bioenergetics are altered by WD in a sex-specific manner.     

Age-differences in cognitive flexibility when overcoming a preexisting bias through feedback

Introduction: Older adults are often worse than younger adults at adapting to changing situational demands, and this difference is commonly attributed to an age-related decline in acquiring and updating information. Previous research on aging and cognitive flexibility has used measures that require adapting to novel associations learned during a laboratory task (e.g., choice X led to positive outcomes but now leads to negative outcomes). However, in everyday life people must frequently overcome associations based on preexisting beliefs and biases (e.g., you like to eat cake, but your doctor said to limit your sugar intake). The goal of the present study was to examine possible age-differences in overcoming a preexisting bias and determine whether age-related changes in the acquisition and updating of information influence this form of flexibility.

Method: Older (n = 20) and younger (n = 20) adults completed a novel task in which repeated choices were made between a sure option (gain or loss) and one of two risky options that were initially ambiguous. Optimal performance required overcoming a framing bias toward being risk seeking to avoid a sure loss and risk averse when offered a sure gain. Probe questions assessed knowledge of choice outcomes, while skin conductance assessed physiological reactions to choices and choice outcomes.

Results: Both older and younger adults demonstrated flexibility by reducing the impact of bias over trials, but younger adults had better performance overall. Age-differences were associated with distinct aspects of processing. Young adults had more precise knowledge of choice outcomes and developed skin conductance responses in anticipation of bad choices that were not apparent in older adults.

Conclusions: Older adults showed significant improvement over trials in their ability to decrease bias-driven choices, but younger showed greater flexibility. Age-differences in task performance were based on differences in learning and corresponding representations of task-relevant information.     

代谢灵活性及其影响因素研究进展

代谢灵活性是机体为适应代谢需求调控营养物质可用性变化的能力。很多人关注代谢灵活性是因为它与胰岛素抵抗密切相关,众多研究证实,肥胖及糖尿病患者存在明显的代谢灵活性下降,而运动能够改善代谢灵活性,从而改善胰岛素抵抗。明确代谢灵活性在机体糖脂代谢中的作用及其影响因素,将为运动改善机体胰岛素抵抗、防治代谢性疾病提供新思路。     

接纳与承诺疗法对食管癌术后患者负性情绪及生活质量的影响

目的 探讨接纳与承诺疗法(acceptance and commitment therapy,ACT)对食管癌术后患者负性情绪及生活质量的影响.方法 选取2019年4月—2020年3月收治的100例食管癌术后患者为研究对象,采用随机数字表法将其分为对照组和观察组,各50例.对照组采用常规护理方法,观察组在常规护理的基础...     

Translational approaches to obsessive-compulsive disorder: from animal models to clinical treatment

Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.     

Bending properties of a new nickel-titanium alloy with a lower percent by weight of nickel

Introduction

The aim of the present study was to evaluate the bending properties of Hyflex instruments, which exhibit a lower percent in weight of nickel (52 Ni %wt) and compare them with other commercially available nickel-titanium (NiTi) rotary instruments.

Methods

Ten instruments with tip size 25, 0.06 taper of each of the following NiTi rotary instrumentation techniques were selected for the study: Hyflex, EndoSequence, ProFile, Hero, and Flexmasters. All instruments from each group were tested for stiffness by comparing their bending moment when they attained a 45-degree bend. Experimental procedures strictly followed testing methodology described in ISO 3630-1. All data were recorded and subjected to statistical evaluation by using analysis of variance test. Statistical significance was set at P < .05).

Results

Statistical analysis of the data revealed that Hyflex files were found to be the most flexible instruments, with a significant difference (P < .05) in comparison with the other instruments. Among the other files, a significant difference has been reported for EndoSequence instruments compared with ProFile, Hero, and FlexMaster (P < .05), whereas no significant differences have been reported among those 3 files (P > .05).

Conclusions

Results of the present study have illustrated an increased flexibility of the new NiTi alloy over conventional NiTi alloy, and they highlight the potential of the new manufacturing process.