¿Es el intervalo libre de docetaxel un factor predictivo para el cáncer de próstata resistente a la castración?

ObjectiveProstate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies.Material and methodsThis clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients’ progression time after Dx therapy and the effects on sequential treatment.ResultsAfter Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (P<.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months.ConclusionsOur findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information.     

Coupling online control and inhibitory systems in children with Developmental Coordination Disorder: Goal-directed reaching

For children with Developmental Coordination Disorder (DCD), the real-time coupling between frontal executive function and online motor control has not been explored despite reported deficits in each domain. The aim of the present study was to investigate how children with DCD enlist online control under task constraints that compel the need for inhibitory control. A total of 129 school children were sampled from mainstream primary schools. Forty-two children who met research criteria for DCD were compared with 87 typically developing controls on a modified double-jump reaching task. Children within each skill group were divided into three age bands: younger (6–7 years), mid-aged (8–9), and older (10–12). Online control was compared between groups as a function of trial type (non-jump, jump, anti-jump). Overall, results showed that while movement times were similar between skill groups under simple task constraints (non-jump), on perturbation (or jump) trials the DCD group were significantly slower than controls and corrected trajectories later. Critically, the DCD group was further disadvantaged by anti-jump trials where inhibitory control was required; however, this effect reduced with age. While coupling online control and executive systems is not well developed in younger and mid-aged children, there is evidence of age-appropriate coupling in older children. Longitudinal data are needed to clarify this intriguing finding. The theoretical and applied implications of these results are discussed.     

Mise à jour des croyances et congruence à l'humeur dans le trouble dépressif

Depressive disorder is characterized by a polymorphic symptomatology associating emotional, cognitive and behavioral disturbances. One of the most specific symptoms is negative beliefs, called congruent to mood. Despite the importance of these beliefs in the development, the maintenance, and the recurrence of depressive episodes, little is known about the processes underlying the generation of depressive beliefs. In this paper, we detail the link between belief updating mechanisms and the genesis of depressive beliefs. We show how depression alters information processing, generating cognitive immunization when processing positive information, affective updating bias related to the valence of belief and prediction error, and difficultie to disengage from negative information. We suggest that disruption of belief-updating mechanisms forms the basis of belief-mood congruence in depression.     

A cross-platform approach to characterize and screen potential neurovascular unit toxicants

Development of the neurovascular unit (NVU) is a complex, multistage process that requires orchestrated cell signaling mechanisms across several cell types and ultimately results in formation of the blood-brain barrier. Typical high-throughput screening (HTS) assays investigate single biochemical or single cell responses following chemical insult. As the NVU comprises multiple cell types interacting at various stages of development, a methodology combining high-throughput results across pertinent cell-based assays is needed to investigate potential chemical-induced disruption to the development of this complex cell system. To this end, we implemented a novel method for screening putative NVU disruptors across diverse assay platforms to predict chemical perturbation of the developing NVU. HTS assay results measuring chemical-induced perturbations to cellular key events across angiogenic and neurogenic outcomes in vitro were combined to create a cell-based prioritization of NVU hazard. Chemicals were grouped according to similar modes of action to train a logistic regression literature model on a training set of 38 chemicals. This model utilizes the chemical-specific pairwise mutual information score for PubMed MeSH annotations to represent a quantitative measure of previously published results. Taken together, this study presents a methodology to investigate NVU developmental hazard using cell-based HTS assays and literature evidence to prioritize screening of putative NVU disruptors towards a knowledge-driven characterization of neurovascular developmental toxicity. The results from these screening efforts demonstrate that chemicals representing a range of putative vascular disrupting compound (pVDC) scores can also produce effects on neurogenic outcomes and characterizes possible modes of action for disrupting the developing NVU.     

脂蛋白相关磷脂酶A2、胰岛素样生长因子-1与老年VD患者认知功能的关系及预测价值研究

目的 探讨脂蛋白相关磷脂酶A2（Lp-PLA2）、胰岛素样生长因子-1（IGF-1）与老年血管性痴呆（VD）患者认知功能的关系及预测价值。方法 选择2019 年3～6 月在我院接受治疗的VD 患者60 例为研究对象，同时选取同期在我院接受检查的健康者60 例为对照组，比较两组患者的Lp-PLA2、IGF-1、简易智力状态检查量表评分（MMSE）水平；采用Pearson 相关性分析法对Lp-PLA2、IGF-1 与MMSE 评分的相关性进行分析；采用受试者工作曲线（ROC）下面积（AUC）比较Lp-PLA2、IGF-1 对VD 的预测价值。结果 观察组患者的Lp-PLA2 水平明显高于对照组（P＜0.05），观察组患者的IGF-1、MMSE 评分明显低于对照组（P＜0.05）；Lp-PLA2 与MMSE 评分呈负相关性，IGF-1 与MMSE 评分呈正相关性；Lp-PLA2 与IGF-1 诊断VD 的AUC 值分别为0.940、0.954。结论Lp-PLA2 水平越低，IGF-1 水平越高，患者的认知功能越好，且Lp-PLA2、IGF-1 对老年VD 患者均具有较高的预测价值。     

An experimentally supported, mathematical explanation of the gas chromatographic elution behaviour of the long-chain carbon members of the homologous series

By substituting the saturated vapour phase tension of the pure normal hydrocarbons described by the Clausius-Clapeyron law into the accepted expression of the specific retention volume (V_g,T), a theoretically coherent and relatively simple mathematical evidence of the elution behaviour of the homologous members has been deduced. It gives exponential retention time dependence on carbon number for isothermal, and nearly equidistant (i.e., approximately linear retention-time dependence on carbon number) elution for linear temperature programmed gas chromatographic runs. The final equations are in close correlation with the experimental results. Special emphasis is placed on the fact that a good approximation—not strict physical laws—have been found.     

CS_2作业工人血清脂质过氧化水平与LDH同功酶谱研究

ＣＳ_２作业工人血清脂质过氧化水平与ＬＤＨ同功酶谱研究张文昌，连祥霖，张连娜，杨乃富（福建医学院劳动卫生学教研室，福州３５０００４）结果表明，高接触水平组（浓度为１０．４２～４６．５４ｍｇ／ｍ３或Σｍｇ·年≥５０）血清ＬＰＯ含量与对照比较，显著性增高?..     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.