Toxicity of a serotonin-derived neuromelanin

Postoperative Cognitive Dysfunction (POCD) is associated with increased mortality in the elderly and may occur from lipid peroxidation in aging. We previously showed that sevoflurane sequesters acrolein, which promotes the formation of a novel species of a putative neuromelanin. The current study examined the properties of this serotonin-derived melanoid (SDM). The interaction of SDM with unilamellar vesicles (ULVs) was examined using lipid membrane probes. Vesicle disruption was investigated by leakage of dye from calcein-loaded ULVs. We observed that SDM decreased diphenyl-hexatriene fluorescence anisotropy and increased the temperature-dependent change in anisotropy. SDM changed the absorbance of merocyanin-bound ULVs. SDM increased detergent-mediated calcein leakage. SDM structure was dramatically altered upon interaction with ULVs. We also observed that SDM enhanced detergent-mediated leakage of loaded ULVs, suggesting that SDM may be neurotoxic. We propose that inhalational agents, which sequester acrolein, may promote the production of certain species of neuromelanin that depletes local serotonin and enhances neuronal vulnerability.     

Linking ecology,morphology, and metabolism: Niche differentiation in sympatric populations of closely related species of the genus Littorina (Neritrema)

Divergence of ecological niches in phylogenetically closely related species indicates the importance of ecology in speciation, especially for sympatric species are considered. Such ecological diversification provides an advantage of alleviating interspecies competition and promotes more efficient exploitation of environmental resources, thus being a basis for ecological speciation. We analyzed a group of closely related species from the subgenus Neritrema (genus Littorina, Caenogastropoda) from the gravel‐bouldery shores. In two distant sites at the Barents and Norwegian Sea, we examined the patterns of snail distribution during low tide (quantitative sampling stratified by intertidal level, presence of macrophytes, macrophyte species, and position on them), shell shape and its variability (geometric morphometrics), and metabolic characteristics (metabolomic profiling). The studied species diversified microbiotopes, which imply an important role of ecological specification in the recent evolution of this group. The only exception to this trend was the species pair L. arcana / L. saxatilis, which is specifically discussed. The ecological divergence was accompanied by differences in shell shape and metabolomic characteristics. Significant differences were found between L. obtusata versus L. fabalis and L. saxatilis / L. arcana versus L. compressa both in shell morphology and in metabolomes. L. saxatilis demonstrated a clear variability depending on intertidal level which corresponds to a shift in conditions within the occupied microhabitat. Interestingly, the differences between L. arcana (inhabiting the upper intertidal level) and L. compressa (inhabiting the lower one) were analogous to those between the upper and lower fractions of L. saxatilis. No significant level‐dependent changes were found between the upper and lower fractions of L. obtusata, most probably due to habitat amelioration by fucoid macroalgae. All these results are discussed in the contexts of the role of ecology in speciation, ecological niche dynamics and conservatism, and evolutionary history of the Neritrema species.     

自拟益气通阳活血方治疗阿尔茨海默病的临床研究

摘要 目的：分析自拟益气通阳活血方治疗阿尔茨海默病的临床效果。方法：选取2020年10月~2022年4月于中国人民解放军空军军医大学第一附属医院接受治疗的阿尔茨海默病患者104例，依据入院先后顺序编号，按单双号分为对照组（n=52）和研究组（n=52）。对照组进行常规西药治疗，研究组在此基础上进行自拟益气通阳活血方治疗。比较两组临床疗效、治疗前后中医证候积分、日常生活活动能力、认知功能、血清去甲肾上腺素（NE）、多巴胺（DA）、乙酰胆碱转移酶（ChAT）水平、β淀粉样蛋白前体（APP）、β淀粉样蛋白1-42（Aβ1-42）、丙二醛（MDA)、超氧化物歧化酶（SOD）水平，并比较两组安全性。结果：治疗后，两组中医证候积分均降低，且研究组显著低于对照组（P<0.05）；研究组总有效率为94.23%，明显高于对照组的78.85%（P<0.05）；治疗后，两组简易智能精神状态检查量表（MMSE）评分与蒙特利尔认知评估量表（MoCA）评分研究组均高于对照组（P<0.05）；治疗后，两组barthel指数评分及日常生活能力量表（ADL）评分研究组均显著高于对照组（P<0.05）；治疗后，两组DA、NE、ChAT水平均升高，且研究组明显高于对照组（P<0.05）；治疗后，两组SOD水平升高，APP、Aβ1-42、MDA水平均降低（P<0.05），且与对照组相比研究组各指标变化更显著（P<0.05）；两组治疗期间的不良反应均较轻微，经对症处理后均缓解，不良反应发生率比较无明显差异（P>0.05）。结论：自拟益气通阳活血方治疗阿尔茨海默病疗效显著，可降低中医证候积分，提高认知功能，调节NE、DA、ChAT水平，抑制APP、Aβ1-42水平，提高其日常生活活动能力，且安全性高。     

帕金森病患者血清klk6、HSP70检测的临床意义研究

摘要 目的：探讨帕金森病（PD）患者血清激肽释放酶6（klk6）、热休克蛋白70（HSP70）水平与病情严重程度以及PD轻度认知障碍（PD-MCI）的关系。方法：选择2021年2月至2022年2月徐州医科大学附属医院收治的165例PD患者（PD组），根据修订的Hoehn-Yahr分级将PD患者分为早期组（1.0~2.5级，59例）、中期组（3.0级，65例）和晚期组（4.0~5.0 级，41例），根据是否存在PD-MCI将PD患者分为PD-MCI组（66例）和非PD-MCI组（99例），另选择同期72例于我院门诊体检的健康志愿者为对照组。检测血清klk6、HSP70水平，比较不同分组血清klk6、HSP70水平差异，多因素Logistic回归分析影响PD患者发生PD-MCI的因素。结果：PD组血清klk6水平高于对照组（P＜0.05），HSP70水平低于对照组（P＜0.05），晚期组血清klk6水平高于早期组和中期组，且中期组血清klk6水平均高于早期组（P＜0.05），晚期组血清HSP70水平低于早期组和中期组，且中期组血清HSP70水平低于早期组（P＜0.05）；PD-MCI组血清klk6水平高于非PD-MCI组（P＜0.05），HSP70水平低于非PD-MCI组（P＜0.05）。多因素Logistic回归分析结果显示年龄偏高、修订的Hoehn-Yahr分级晚期、高水平klk6是PD患者发生PD-MCI的危险因素（P＜0.05），高水平HSP70是PD患者发生PD-MCI的保护因素（P＜0.05）。结论：PD患者血清klk6水平增高，HSP70水平降低与修订的Hoehn- Yahr分级增加以及PD-MCI有关，检测血清klk6、HSP70水平有助于评估PD病情以及PD-MCI风险。     

Formación de cuidadores en un programa de estimulación cognitiva: efectos diferenciales según el tipo de cuidador

Background and objectivesThe ageing population and the increasing dependency associated with it, makes the caregiver a highly relevant figure nowadays. The present study analyzes the socio-demographic differences between family and professional caregivers and their satisfaction and implication in a training program for caregivers.MethodsThe sample consisted of 59 caregivers of older people (37 were family caregivers and 22 professional caregivers) which received and implemented a caregivers training program in their daily care functions. These caregivers were trained in communication skills and cognitive stimulation strategies so they could use them in their daily care activities with the older adults under their care during a period of 3 months. All the participants were assessed with a socio-demographic questionnaire, 2 questionnaires to analyze their satisfaction with their work and the training received and one questionnaire to analyze their ability to detect and react to memory and behavior problems in the older adults they attended.ResultsThe results showed socio-demographic differences, improvements in satisfaction in family caregivers and a greater commitment in their daily work after the treatment in both groups although these effects could be due to different reasons.ConclusionsThe research shows the benefits of carrying out training programs for caregivers as they significantly increase the quality and satisfaction with caregiving. The study also displays the need to adjust such programs taking into account that the socio-demographic characteristics and training needs are different depending on whether de caregiver is a family member or a professional.     

Resveratrol improves cognitive function in mice by increasing production of insulin-like growth factor-I in the hippocampus

We examined whether resveratrol increases insulin-like growth factor-I (IGF-I) production in the hippocampus by stimulating sensory neurons in the gastrointestinal tract, thereby improving cognitive function in mice. Resveratrol increased calcitonin gene-related peptide (CGRP) release from dorsal root ganglion (DRG) neurons isolated from wild-type (WT) mice. Increases in tissue levels of CGRP, IGF-I, and IGF-I mRNA and immunohistochemical expression of IGF-I were observed in the hippocampus at 3 weeks after oral administration of resveratrol in WT mice. Significant enhancement of angiogenesis and neurogenesis was observed in the dentate gyrus of the hippocampus in these animals (P<.01). Improvement of spatial learning in the Morris water maze was observed in WT mice after administration of resveratrol. None of the effects of resveratrol observed in WT mice were seen after resveratrol administration in CGRP-knockout (CGRP^−/−) mice. Although red wine containing 20 mg/L of resveratrol produced effects similar to those of resveratrol administrationl in WT mice, neither red wine containing 3.1 mg/L of resveratrol nor white wine exhibited such effects in WT mice. Resveratrol was undetectable in the hippocampus of WT mice administered resveratrol and red wine containing 20 mg/L of resveratrol. These observations strongly suggest that resveratrol increases hippocampal IGF-I production via sensory neuron stimulation in the gastrointestinal tract, thereby improving cognitive function in mice.     

Cognitive individualism and the child as scientist program

In this paper, I examine the charge that Gopnik and Meltzoff’s ‘Child as Scientist’ program, outlined and defended in their 1997 book Words, Thoughts and Theories is vitiated by a form of ‘cognitive individualism’ about science. Although this charge has often been leveled at Gopnik and Meltzoff’s work, it has rarely been developed in any detail.I suggest that we should distinguish between two forms of cognitive individualism which I refer to as ‘ontic’ and ‘epistemic’ cognitive individualism (OCI and ECI respectively). I then argue - contra Ronald Giere – that Gopnik and Meltzoff’s commitment to OCI is relatively unproblematic, since it is an easily detachable part of their view. By contrast, and despite their explicit discussion of the issue, their commitment to ECI is much more problematic.     

红景天苷对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制

目的：探讨红景天苷（Sal）对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制。方法：将30只成年雄性SD大鼠随机分为健康对照组、模型组（Model组）、Sal[按体重1g／（kg·d）]治疗组（sal组）。采用Morris水迷宫实验方法捡测缺氧后大鼠学习记忆功能变化,同时检测脑组织匀浆中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）、谷胱甘）lk（GSH）、丙二醛（MDA）的水平。结果：（1）模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义（P〈0．05）,Sal组寻找平台的潜伏期相对于模型组显著缩短（P〈0．05）。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组（P〈0．05）,Sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长（P〈0．05）。（2）模型组SOD、GSH—PX、GSH显著下降,MDA明显增高,Sal干预组SOD、GSH．PX、GSH显著增高,而MDA明显下降,具有统计学意义（P〈O．05）。结论：Sal可改善高原缺氧大鼠认知功能,其可能机制是通过减轻海马区的氧化应激反应减轻海马区的损伤,从而实现改善认知功能。     

认知风格、内外向和情绪对军人认知反应能力的影响

该文主要通过测评研究认知风格、内外向和情绪对军人认知反应能力的影响。结果表明,场独立性者对图形的认知反应能力比场依赖性者强。情绪稳定性高者的认知反应能力好于情绪稳定性低者,外向性格者的认知反应能力总体上要高于内向性格者。