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Molecular and pathophysiological basis of the brain glucose sensing ability 大脑葡萄糖感知能力的分子和病理生理基础
Pub Date : 2023-04-30 DOI: 10.32440/ar.2023.140.01.rev07
E. Blázquez Fernández
The presence of the messenger RNA for GLP-1 receptor (GLP-1R), GLUT-2 (isoform 2 of glucose transporter ) and GK (glucokinase) in brain areas might be related to the glucose sensing process that was recently described in pancreatic β cells. GLUT-2, GK and the regulatory protein of GK (GKRP) were identified in both human and rat brains. The GK gene expression generates a 52 kDa protein, identified by biochemical and immunochemical methods; it shows a high Km for glucose and a high capacity to phosphorylate glucose in the hypothalamus and in the brain cortex. Its physiological importance is related to its activation secondary to an increase in glycaemia related to food ingestion. GK and GKRP modulate the enzymatic activity according to the metabolic needs of the cells. This is necessary for the sensing process that is controlled by GK and GKRP, and could also contribute to a sensation of satiety. It would be interesting to know if mutations in the genes codifying the mentioned proteins can produce pathological alterations, or whether changes in the feeding behavior are related to the brain glucose sensing process. Until now, our work has focused on the role of hypothalamic glucokinase as a glucose sensor related to food behavior, but we cannot forget that this enzyme is widely expressed in the brain cortex, where it could also carry out other important functions. These observations, together with the anorexigenic activity of GLP-1 (glucagon-like peptide-1), suggest a combined role of these peptides on food intake control.
脑区GLP-1受体(GLP-1R)、GLUT-2(葡萄糖转运蛋白的亚型2)和GK(葡萄糖激酶)信使RNA的存在可能与最近在胰腺β细胞中描述的葡萄糖传感过程有关。GLUT-2、GK和GK调节蛋白(GKRP)在人和大鼠脑中均被鉴定。GK基因表达产生一个52kDa的蛋白质,通过生物化学和免疫化学方法鉴定;它显示出对葡萄糖的高Km和在下丘脑和大脑皮层中磷酸化葡萄糖的高能力。它的生理重要性与它的激活有关,其次是与食物摄入有关的血糖升高。GK和GKRP根据细胞的代谢需要调节酶活性。这对于由GK和GKRP控制的感知过程是必要的,也可能有助于饱腹感。我们很想知道编码上述蛋白质的基因突变是否会产生病理改变,或者进食行为的变化是否与大脑葡萄糖传感过程有关。到目前为止,我们的工作一直集中在下丘脑葡萄糖激酶作为与食物行为相关的葡萄糖传感器的作用上,但我们不能忘记,这种酶在大脑皮层中广泛表达,它也可以在大脑皮层执行其他重要功能。这些观察结果,加上GLP-1(胰高血糖素样肽-1)的厌食活性,表明这些肽在食物摄入控制中的联合作用。
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引用次数: 0
Deep Learning for Clinical Image Classification of Genital Lesions Caused by Sexually Transmitted Diseases 基于深度学习的性传播疾病生殖器病变临床图像分类
Pub Date : 2023-01-01 DOI: 10.32440/ar.2022.139.03.rev07
R. González-Alday, F. Peinado, D. Carrillo, V. Maojo
Sexually transmitted diseases (STDs) are one of the world’s major health emergencies. Given its incidence and prevalence, particularly in developing countries, it is necessary to find new methods for early diagnosis and treatment. However, this can be complicated in geographical areas where medical care is limited. In this article, we present the basis of a deep learning-based system for image classification of genital lesions caused by these diseases, built using a convolutional neural network model and methods such as transfer learning and data augmentation. In addition, an explainability method (GradCam) is employed to enhance the interpretability of the obtained results. Finally, we developed a web framework to facilitate additional data collection and annotation. This work aims to be a starting point, a “proof of concept” to test various different approaches, for the development of more robust and trustworthy Artificial Intelligence approaches for medical care in STDs, which could substantially improve medical assistance in the near future, particularly in developing regions.
性传播疾病是世界重大突发卫生事件之一。鉴于其发病率和流行率,特别是在发展中国家,有必要寻找早期诊断和治疗的新方法。然而,在医疗服务有限的地理区域,这可能会变得复杂。在这篇文章中,我们提出了一个基于深度学习的系统的基础,用于由这些疾病引起的生殖器病变的图像分类,该系统使用卷积神经网络模型和迁移学习和数据增强等方法构建。此外,采用可解释性方法(GradCam)来增强所得结果的可解释性。最后,我们开发了一个web框架,以方便额外的数据收集和注释。这项工作旨在成为一个起点,一个“概念验证”,以测试各种不同的方法,为性传播疾病的医疗保健开发更强大、更可靠的人工智能方法,这可以在不久的将来大大改善医疗援助,特别是在发展中地区。
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引用次数: 0
Spectral CT and Hounsfield Units: basis for correct interpretation 光谱CT和霍斯菲尔德单位:正确解释的基础
Pub Date : 2023-01-01 DOI: 10.32440/ar.2023.140.02.rev01
A. Armiñana, C. Montón-Gómez, A. Puig-Chilet, T. Infante-Fuenzalida, C. Fontenla-Martínez, I. Torres-Espallardó, L. Martí-Bonmatí
Dual energy CT is a recent upgrade to this diagnostic imaging technique. The purpose of this critical narrative review is to lay out the clinical applications of Hounsfield Units and their variation across the x-ray energy spectrum using DECT. We explore new reconstruction methods and parametric maps helpful for the diagnosis of prevalent pathologies such as fatty liver disease, urolithiasis, and to identify complications after interventions or determine the aggressiveness of tumoral lesions. The energy-resolving capabilities of DECT make it a reliable method for the characterisation of tissue and lesion composition. Lower energy monoenergetic images allow us to increase soft tissue contrast and easily identify tissues with higher contrast uptake. Higher energy monoenergetic images are useful to distinguish between contrast uptake and high attenuation calcium deposits and for metal artifact reduction. Parametric images showing uric acid, iodine, calcium, and other material decompositions can be obtained from spectral data for the diagnosis of tumoral or metabolic diseases, vascular lesions and characterisation of deposition arthritis and urolithiasis.
双能CT是该诊断成像技术的最新升级。这篇批判性的叙述性综述的目的是阐述Hounsfield单元的临床应用以及它们在使用DECT的x射线能谱上的变化。我们探索新的重建方法和参数图,以帮助诊断常见疾病,如脂肪肝、尿石症,并确定干预后的并发症或确定肿瘤病变的侵袭性。DECT的能量分辨能力使其成为表征组织和病变组成的可靠方法。低能量单能图像使我们能够增加软组织对比度,并容易识别具有高对比度摄取的组织。高能量单能图像有助于区分对比度吸收和高衰减钙沉积和金属伪影还原。从光谱数据中可以获得显示尿酸、碘、钙和其他物质分解的参数化图像,用于诊断肿瘤或代谢性疾病、血管病变以及沉积性关节炎和尿石症的特征。
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引用次数: 0
Adipokines, ageing, and vascular damage 脂肪因子,衰老和血管损伤
Pub Date : 2023-01-01 DOI: 10.32440/ar.2022.139.03.rev01
C. F. Sánchez Ferrer, I. Valencia Fernández, C. Peiró Vallejo
The main physiologic function of adipokines on the energy metabolism and the cardiovascular homeostasis, among others, are well known. In the last years, our laboratory is providing increasing evidence about the possible role of adipokines as mediators of vascular damage, by inducing different pro-inflammatory and pro-senescent mechanisms. The secretion of adipokines like visfatin or dipeptidylpeptidase-4 (DPP4) by adipose tissue, particularly by the visceral fat, is enhanced in obese and type 2 diabetic patients. Both adipokines are enzymes metabolically active that can induce the activation of specific receptors, namely type 4 “toll like receptors” (TLR4) for visfatin and “protease activated receptor 2” (PAR2) for DPP4. Stimulation of such receptors is triggering well known pro-inflammatory and pro-senescent mechanisms, like the nuclear transcription factor-κB (NF-κB) or the inflammasome NLRP3 (“nucleotide-binding, leucine-rich-repeat, pyrin domain containing 3”), a cell structure that transforms the immature forms of classic cytokines in their active derivates, interleukin-1β (IL-1β) or interleukin 18 (IL-18). It is worth to note that these classic cytokines are the final effectors for the harmful effects of the adipokines and its blockade can be a very relevant therapeutic approach. In our experiments, the specific antagonism of IL-1 receptors with anakinra prevents the inflammatory and senescent effects evoked by visfatin and DPP4. Moreover, this finding is in agreement with data from other researchers, as well as with the results of the CANTOS clinical trial, which demonstrate a very important cardioprotective cardiovascular effect mediated by the anti-inflammatory effect of the monoclonal antibody canakinumab. On the other hand, we have also provided experimental evidence about possible vasculopotective adipokines, such angiotensin-(1-7), which is able to induce, through activation of Mas receptors, the expression of klotho protein and the activation of antioxidant pathways, like the well known Nrf2-HO-1 (“nuclear factor erythroid-2 y hemoygenase-1”).
脂肪因子在能量代谢和心血管稳态等方面的主要生理功能是众所周知的。在过去的几年里,我们的实验室通过诱导不同的促炎和促衰老机制,提供了越来越多的关于脂肪因子作为血管损伤介质的可能作用的证据。在肥胖和2型糖尿病患者中,脂肪组织,特别是内脏脂肪分泌的脂肪因子如脂肪素或二肽基肽酶-4 (DPP4)增加。这两种脂肪因子都是具有代谢活性的酶,可以诱导特异性受体的激活,即visfatin的4型“toll样受体”(TLR4)和DPP4的“蛋白酶激活受体2”(PAR2)。对这些受体的刺激会触发众所周知的促炎和促衰老机制,如核转录因子-κB (NF-κB)或炎性小体NLRP3(“核苷酸结合,富含亮氨酸的重复序列,含有pyrin结构域3”),这是一种细胞结构,可将未成熟的经典细胞因子转化为其活性衍生物,白细胞介素-1β (IL-1β)或白细胞介素18 (IL-18)。值得注意的是,这些经典的细胞因子是脂肪因子有害作用的最终效应器,其阻断可能是一种非常相关的治疗方法。在我们的实验中,anakinra对IL-1受体的特异性拮抗作用可以防止visfatin和DPP4引起的炎症和衰老效应。此外,这一发现与其他研究人员的数据以及CANTOS临床试验的结果一致,这些结果表明单克隆抗体canakinumab的抗炎作用介导了非常重要的心血管保护作用。另一方面,我们也提供了关于可能的血管保护脂肪因子的实验证据,如血管紧张素-(1-7),它能够通过激活Mas受体,诱导klotho蛋白的表达和抗氧化途径的激活,如众所周知的Nrf2-HO-1(“核因子红细胞-2 y加氢酶-1”)。
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引用次数: 0
Health memories from Annual to Alhucemas: Medical advances between 1921 and 1925 从年度到老年的健康记忆:1921年至1925年的医学进步
Pub Date : 2023-01-01 DOI: 10.32440/ar.2022.139.03.rev05
R. Navarro-Suay, J. A. Rodríguez-Montes, F. Gilsanz Rodríguez, J. Sanz Serrulla, F. Vázquez de Quevedo, A. Campos Muñoz
Year 2021 marks a century since the Annual Disaster, an evento that ocurred in the Spanish Protectorate of Morocco bewtween July 21 and August 9 of that year, one of the most tragic defeats suffered by the Spanish Army through its history. Between September 8 and October 13, 1925, the SPanish Navy and Army in collaboration with French tropos, successfully landed at Alhucemas Bay, occupying and pacifying the área, which contributed to end the Rif War. The circumstances that occurred in this war period gave rise to important medical and health advances. In just a few years, wounded transport was improved emplying ambulances, hospital ships and medical planes; filed hospital were deployed in the Forefront to shorten the time from the battle field to the first treatment facility; surgical procedures were performed with innovative techniques at that time, epidural anesthesia was discovered and finally, thanks to an agile health system adapted to the área, sicks and wounded soldiers were recovered in hospital located in the Iberian Peninsula. Military and civil doctors, nurses from Spanish Red Cross, nuns, friars, health workers, soldiers, volunteers…applied their knowledge, tenacity and work for the sake of caring for patient, without any doubt, the ultimate goal for any health professional.
2021年是“年度灾难”发生100周年,这是当年7月21日至8月9日发生在西班牙保护国摩洛哥的事件,是西班牙军队历史上最悲惨的失败之一。1925年9月8日至10月13日之间,西班牙海军和陆军与法国军队合作,成功登陆阿尔赫马斯湾,占领并平息área,这有助于结束里夫战争。在这场战争期间发生的情况导致了重要的医疗和保健进步。在短短几年内,救护车、医疗船和医疗飞机的使用改善了伤员的运输;在前线部署了战地医院,以缩短从战场到第一个治疗设施的时间;当时,外科手术采用了创新技术,硬膜外麻醉被发现,最后,由于适应área的灵活医疗系统,生病和受伤的士兵在伊比利亚半岛的医院得到了康复。军队和民间医生、西班牙红十字会的护士、修女、修士、卫生工作者、士兵、志愿者……运用他们的知识、毅力和工作来照顾病人,毫无疑问,这是任何卫生专业人员的最终目标。
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引用次数: 0
Are the teachers disappearing? 老师们正在消失吗?
Pub Date : 2023-01-01 DOI: 10.32440/ar.2023.140.02.op01
M. Díaz-Rubio García
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引用次数: 0
Twenty years of biomedical network research 二十年的生物医学网络研究
Pub Date : 2023-01-01 DOI: 10.32440/ar.2022.139.03.ed01
P. Crespo Ferrer
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引用次数: 0
Development of bilateral circuits of the nervous system: From molecular mechanisms to the cerebellum and its implication in neurodevelopmental disorders 神经系统双侧回路的发育:从分子机制到小脑及其在神经发育障碍中的意义
Pub Date : 2023-01-01 DOI: 10.32440/ar.2022.139.03.rev02
J. A. Moreno Bravo
The brain is the most complex organ we have, and it is the one that defines us as human beings. It is the basis of intelligence, of our thoughts and memories. In addition, it interprets the world through the senses, initiates movement and controls our behaviors. The correct functioning of this organ is based on the correct establishment of connectivity patterns between the millions of neurons which enable a precise and efficient communication between them. These neural networks emerge during embryonic and postnatal development. The formation of proper neuronal circuitry relies on diverse and very precisely orchestrated events controlled by specific molecular mechanisms. Therefore, failures in these early events will lead to brain pathologies and complex disorders. In the last decades, remarkable progress has been made in identifying and in understanding the mechanisms of action of the molecular that direct axon and neural circuitry development. However, their role in vivo in many aspects of neural circuit formation remains largely unknown, particularly how the impairment of this initial connectivity derives in complex neurodevelopmental pathologies. Here, I highlight part of my contributions and recent advances that shed light on the complexity of mechanisms that regulate axon guidance and the wiring of the bilateral circuits of the central nervous system. Furthermore, I discuss about how understanding the development of bilateral circuits of the cerebellum is essential to understand the emergence of diverse neurodevelopmental pathologies.
大脑是我们拥有的最复杂的器官,是它定义了我们是人类。它是智力、思想和记忆的基础。此外,它通过感官解读世界,发起运动并控制我们的行为。这个器官的正确功能是建立在数以百万计的神经元之间正确的连接模式的基础上的,这使得它们之间能够进行精确和有效的交流。这些神经网络在胚胎和出生后发育期间出现。适当的神经回路的形成依赖于由特定分子机制控制的各种非常精确的精心安排的事件。因此,这些早期事件的失败将导致脑部病变和复杂的疾病。在过去的几十年里,在识别和理解指导轴突和神经回路发育的分子的作用机制方面取得了显著的进展。然而,它们在体内神经回路形成的许多方面的作用仍然很大程度上未知,特别是这种初始连接的损伤是如何在复杂的神经发育病理中产生的。在这里,我重点介绍了我的部分贡献和最近的进展,这些贡献和进展揭示了调节轴突引导和中枢神经系统双侧回路布线的机制的复杂性。此外,我还讨论了如何理解小脑双侧回路的发展对于理解各种神经发育病理学的出现至关重要。
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引用次数: 0
Primary prevention of chronic kidney disease 慢性肾脏疾病的初级预防
Pub Date : 2023-01-01 DOI: 10.32440/ar.2023.140.02.rev03
A. Ortiz, M.D. Sánchez-Niño
There are 850 million people in the world with chronic kidney disease (CKD), one of the fastest growing global causes of death that was the most important risk factor for fatal COVID-19. The remaining life expectancy of people with CKD on renal replacement therapy is up to 40 years less than in the general population. While healthy lifestyles and control of risk factors such as diabetes and hypertension can help protect against the development of CKD, the global burden of CKD continues to increase. Despite these poor results, recent clinical trials indicate that the concept of primary prevention of CKD must be developed. In post-hoc analyses of at least two clinical trials, SGLT2 inhibitors prevented the development of CKD in people without prior CKD but at high risk for CKD. We propose a working definition of primary prevention of CKD with the aim of preserving renal health, which should include the target population (who), the moment (when) and the intervention (what).
世界上有8.5亿人患有慢性肾脏疾病(CKD),这是全球增长最快的死亡原因之一,也是致命的COVID-19的最重要风险因素。CKD患者接受肾脏替代治疗的剩余预期寿命比普通人群少40年。虽然健康的生活方式和控制糖尿病和高血压等危险因素有助于预防CKD的发展,但CKD的全球负担仍在继续增加。尽管结果不佳,但最近的临床试验表明,必须发展CKD一级预防的概念。在至少两项临床试验的事后分析中,SGLT2抑制剂可预防无CKD但CKD高风险人群的CKD发展。我们提出了一个以维护肾脏健康为目的的CKD一级预防的工作定义,它应该包括目标人群(谁),时刻(何时)和干预(什么)。
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引用次数: 0
Cognitive performance in individuals with a first psychotic episode according to age at onset of psychotic symptoms and premorbid intelligence quotient 首次精神病发作个体的认知表现与精神病症状发病年龄和病前智商的关系
Pub Date : 2023-01-01 DOI: 10.32440/ar.2022.139.03.rev06
M. Molina-García, C. Arango
Introduction: There is great variability in the cognitive performance profile, clinical presentation, course of symptoms, and subsequent functioning in individuals with a first episode of psychosis (FEP). Premorbid IQ (pIQ) and age of onset are two important prognostic factors relevant to clinical practice and broadly explored in psychosis research (1,2) that could help to explain heterogeneity in cognitive performance after FEP. Methods: The present prospective longitudinal (two-year) observational study examines the neurocognitive performance profiles of 255 individuals with FEP and 326 controls. Using ANOVA, we compared four FEP subgroups according to the following criteria: age of onset before or after 18 years old, and pIQ below or above 85. We examined cognitive changes in the subgroups with pair-wise comparisons, two-way mixed ANOVA, and repeated measures ANOVA. General objective: to characterize the neuropsychological profiles of the four subsets of individuals with a FEP defined by age of onset of psychosis (<18 or ≥ 18) and p-IQ (low or average) and to compare these subgroups’ neuropsychological performance, at baseline and at two-year follow-up. Results: The subgroups with early-onset and adult-onset low pIQ showed cognitive deficits more than 1 SD below the control mean and significantly different from early- and adult-onset average pIQ subsets at both the baseline evaluation and the two-year follow-up. These deficits were in attention and processing speed (p <0.001), working memory (p <0.001), verbal learning and memory (p <0.001), executive function (p <0.001), and global cognition (p <0.001). Cognitive performance in the early-onset average pIQ subgroup did not differ from that of the adults with average pIQ, and the former subgroup showed improved scores over time. Discussion: Our results suggest that the presentation of psychotic symptoms in patients with a lower than average pIQ is associated with a globally impaired profile. Estimating pIQ in the early stages of the disorder can help identify individuals who require early personalized neurocognitive intervention.
首次精神病(FEP)患者在认知表现、临床表现、症状过程和随后的功能方面存在很大的差异。病前智商(pIQ)和发病年龄是与临床实践相关的两个重要的预后因素,在精神病研究中得到了广泛的探讨(1,2),这有助于解释FEP后认知表现的异质性。方法:本前瞻性纵向(两年)观察性研究检查了255名FEP患者和326名对照者的神经认知表现。采用方差分析,我们根据以下标准比较四个FEP亚组:发病年龄在18岁之前或之后,pIQ低于或高于85。我们通过两两比较、双向混合方差分析和重复测量方差分析检查了亚组的认知变化。总体目标:描述由精神病发病年龄(<18岁或≥18岁)和p-IQ(低或平均)定义的FEP个体的四个亚群的神经心理特征,并比较这些亚组在基线和两年随访时的神经心理表现。结果:在基线评估和两年随访中,早发性和成年性低pIQ亚组的认知缺陷比对照平均值低1 SD以上,与早期和成年性低pIQ亚组有显著差异。这些缺陷包括注意力和加工速度(p <0.001)、工作记忆(p <0.001)、言语学习和记忆(p <0.001)、执行功能(p <0.001)和整体认知(p <0.001)。早发的平均pIQ亚组的认知表现与平均pIQ的成年人没有差异,并且前亚组的得分随着时间的推移而提高。讨论:我们的研究结果表明,pIQ低于平均水平的患者出现精神病症状与整体受损相关。在障碍的早期阶段估计pIQ可以帮助识别需要早期个性化神经认知干预的个体。
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引用次数: 0
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Anales de la Real Academia Nacional de Medicina
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