Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases.     

Incidence and costs of bicycle-related traumatic brain injuries in the Netherlands

The main cause of death and serious disability in bicycle accidents is traumatic brain injury (TBI). The aim of this population-based study was to assess the incidence and costs of bicycle-related TBI across various age groups, and in comparison to all bicycle-related injuries, to identify main risk groups for the development of preventive strategies.Data from the National Injury Surveillance System and National Medical Registration were used for all patients with bicycle-related injuries and TBI who visited a Dutch emergency department (ED) between 1998 and 2012. Demographics and national, weighted estimates of injury mechanism, injury severity and costs were analysed per age group. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model.Between 1998 and 2012, the incidence of ED treatments due to bicycle-related TBI strongly increased with 54%, to 43 per 100,000 persons in 2012. However, the incidence of all bicycle-related injuries remained stable, from 444 in 1998 to 456/100,000 in 2012. Incidence of hospital admission increased in both TBI (92%) and all injuries from cycling (71%). Highest increase in incidence of both ED treatments and hospital admissions was seen in adults aged 55+. The injury rate of TBI per kilometre travelled increased (44%) except in children, but decreased (−4%) for all injuries, showing a strong decrease in children (−36%) but an increase in men aged 25+, and women aged 15+. Total costs of bicycle-related TBI were €74.5 million annually. Although bicycle-related TBI accounted for 9% of the incidence of all ED treatments due to cycling, it accounted for 18% of the total costs due to all bicycle-related injuries (€410.7 million). Children and adolescents (aged 0–24) had highest incidence of ED treatments due to bicycle-related injuries. Men in the working population (aged 15–64) had highest indirect costs following injuries from cycling, including TBI. Older cyclists (aged 55+) were identified as main risk group for TBI, as they had highest ED attendance, injury rate, injury severity, admission to hospital or intensive care unit, and costs.Incidence of ED treatments due to cycling are high and often involve TBI, imposing a high burden on individuals and society. Older cyclists aged 55+ were identified as main risk group for TBI to be targeted in preventive strategies, due to their high risk for (serious) injuries and ever-increasing share of ED visits and hospital admissions.     

Omega-6支撑身体，Omega-3支撑大脑：均衡摄入对儿童大脑发育的影响（网络首发、推荐阅读）

人体大脑和身体的发育，需要从食物中摄取均衡的营养物质。人类大脑是区分人类和其他动物的特征。食物中的必需脂肪酸是机体组织结构和功能的必要组成部分。Omega-6（O6）亚油酸（LA6）是皮肤组织的组成成分，且是炎症、血栓形成、免疫和其他信号分子的前体；Omega-3（O3）α-亚麻酸（ALA3），特别是其长链代谢产物——二十二碳六烯酸（DHA3），是大脑、视网膜和部分神经组织中的关键组分。从富含LA6脂肪酸（缺乏O3脂肪酸）的植物籽中提取出的廉价而优质油脂，是20世纪的西方国家食品工业生产的主要脂肪来源。在代谢通路中，高浓度的LA6脂肪酸可拮抗O3脂肪酸代谢，造成O3脂肪酸不足，因此，在给怀孕动物的饲料中，只提供富含LA6但缺乏O3脂肪酸的油脂作为唯一的脂肪来源，会导致幼崽大脑发育不良。过去20~30年的研究表明，低含量LA6且含DHA3的油脂可改善大脑的功能。近年来的研究较多集中在营养因素对大脑发育的影响，最新研究数据表明，脂肪酸平衡对营养不良儿童的大脑发育尤为重要。世界卫生组织（WHO）越来越重视大脑的营养健康，通过其下属的食品法典委员会，建议用于治疗严重急性营养不良儿童的即食治疗食品中，使用含有均衡脂肪酸组成/构成的脂肪。同样，脂肪酸均衡对老年人可能也很重要。目前，业界已经有了调整油脂成分的方法，以确保脂肪酸均衡，从而维持人体整个生命周期的大脑健康。     

Fast Positive Feedback Between the Adrenocortical Stress Response and a Brain Mechanism Involved in Aggressive Behavior.

Aggressive behavior induces an adrenocortical stress response, and sudden stressors often precipitate violent behavior. Experiments in rats revealed a fast, mutual, positive feedback between the adrenocortical stress response and a brain mechanism controlling aggression. Stimulation of the aggressive area in the hypothalamus rapidly activated the adrenocortical response, even in the absence of an opponent and fighting. Hypothalamic aggression, in turn, was rapidly facilitated by a corticosterone injection in rats in which the natural adrenocortical stress response was prevented by adrenalectomy. The rapidity of both effects points to a fast, mutual, positive feedback of the controlling mechanisms within the time frame of a single conflict. Such a mutual facilitation may contribute to the precipitation and escalation of violent behavior under stressful conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Verbal Representation and Therapeutic Change in Anaclitic and Introjective Inpatients.

This study examined the relation between changes in clinical functioning and changes in verbal expression in 81 seriously disturbed and treatment-resistant young adults seen in a comprehensive, psychoanalytically oriented inpatient treatment. Clinical functioning was evaluated with a battery of clinical and social measures. Verbal representations were assessed using computer-assisted scoring of Thematic Apperception Test responses. Changes in the frequency of verbal content and style in the narratives of these patients covaried with changes in clinical functioning. Significantly different covariations of verbal and clinical change, particularly differences in covariates of referential activity, were found for patients with anaclitic versus introjective personality configurations. The implications of these findings for understanding and treating severe psychopathology are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

聚合物降解产物伤害与糖甙键特异酶破胶技术

综述了钻井，完井，尤其是水力压裂作业中产生的多糖类聚合物伤害和应用糖甙键特异酶破胶，解除多糖类聚合物伤害的技术。第一节报道了聚合物降解产物造成的伤害，指出冻胶破胶液粘度低并不代表压裂液已从充填裂缝中充分返排，氧化破胶剂和普通酶破胶剂不能使多糖类聚合物充分降解，产生的大分子量，水不溶的降解产物可对地层造成伤害，消除伤害的办法是采用对糖甙键有特异性的各种水解酶作压裂液破胶剂或伤害地层处理剂。第二节报道了各种聚合物（纤维素，瓜尔胶，淀粉）糖甙键特异酶降解聚合物的机理。第三节报道了糖甙键特异酶（主要针对瓜尔胶）的应用性能测试及结果，包括岩心流动实验，含糖量和分子量测定，传导性测试。第四节介绍了糖甙键特异酶消除聚合物伤害和用作压裂液破胶剂的现场应用，包括选井原则，实施工艺要点及3个典型井例。     

Neuroticism and depressive symptoms among spouse caregivers: Do health behaviors mediate this relationship?

This study examined the mediating role of health behaviors in the relationship between neuroticism and depressive symptoms among spouse caregivers. Path analysis was used to test a model of the caregiver stress process among 233 caregivers of people with dementia. Results indicate that neuroticism has a significant direct effect on depressive symptoms and also indirectly influences depressive symptoms through health behaviors and perceived stress. When individual health behaviors were examined in the path model, only physical activity served a significant mediating role. These findings suggest that neuroticism may lead to depressive symptoms among caregivers partly through declines in physical activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of stimulus emotionality and sentence generation on memory for words in adults with unilateral brain damage.

Does sentence generation and/or stimulus emotionality enhance verbal memory in patients with neurological impairment? This question was addressed by testing 40 patients with unilateral stroke (20 with left-brain and 20 with right-brain damage) and 20 healthy control participants for recall and recognition of 48 target words. During encoding, emotional and nonemotional words were either presented in sentences (read condition) or used to form sentences (generate condition). Both word emotionality and generative processing improved memory performance in all groups. The authors suggest that a similar influence (i.e., cognitive activation) underlies both of these memory-enhancing effects, although the putative origins of the 2 effects are quite different. Neuropsychological underpinnings and clinical implications of these phenomena are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Terminally ill patients and volunteer support: Is it the right intervention?

Comments on the article by K. T. Herbst-Damm and J. A. Kulik (see record 2005-02260-012) entitled Volunteer support, marital status, and the survival times of terminally ill patients. Can a simple and low-cost intervention, such as a visit by a volunteer, extend the life of terminally ill patients? The answer, according to a study by Herbst-Damm and Kulik (2005), is yes. When it comes to quality of life, however, the effects of volunteer visits remain murky. Thus, it is critical that we look beyond effects on longevity and assess how such a program would influence quality of life. Extending the life of terminally ill patients might not always a blessing. Prolonging their life might even cause harm, as it can extend unwanted physical and mental suffering. It may also go against some patients' desire to hasten their death. Despite Herbst-Damm and Kulik's important findings, the current author remains unconvinced as to the merits of implementing volunteer visits as an intervention policy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)