Comparison between a liquid chromatography-tandem mass spectrometry assay and a fluorescent polarization immunoassay to measure whole blood everolimus concentration in heart and renal transplantations

Various methods [fluorescent polarization immunoassay (FPIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay] are used for therapeutic drug monitoring of everolimus. The aim of this study is to compare these assays in renal and heart transplantation. The correlation between results was investigated by linear regression in 44 patients (24 heart recipients and 20 renal recipients--137 samples). The comparison between assays was performed by a paired t-test. A highly significant correlation was found between FPIA and LC-MS/MS in heart and renal recipients [FPIA=0.851 x LC-MS/MS+1.773r(2)=0.8738 (P<0.001)]. Paired t-tests did not show a significant difference between everolimus whole blood concentrations in the populations of heart and renal recipients or heart recipients or renal recipients. FPIA and LC-MS/MS assays gave consistent overall results although some significant differences were observed in some samples between these methods indicating that FPIA assay has limitations that deserve further investigations.     

An Analysis of the Nursing Diagnosis Ineffective Management of Therapeutic Regimen Compared to Noncompliance and Orem's Self-Care Deficit Theory of Nursing

The authors compare the nursing diagnosis ineffective management of therapeutic regimen with that of noncompliance and with Orem's concept of self-care deficit. The article describes how the diagnosis of ineffective management of therapeutic regimen is more comprehensive than noncompliance. A question of patient autonomy is raised considering how the patient manages his or her therapeutic regimen. The major conclusion is that the nursing diagnosis of ineffective management of therapeutic regimen is based on continuous interaction between patient and nurse. The authors recommend that noncompliance be eliminated as a nursing diagnosis.     

Evidence-Based Practice and Reviews of Therapeutic Touch

Purpose: To present principles for accurately representing research for evidence-based practice and health care policies, and to evaluate how original research results indicated adherence to those principles in literature reviews of therapeutic touch.
Organizing constructs: Critical thinking and scientific integrity.
Sources: Reviews of therapeutic touch literature published in nursing journals between 1994 and 1998 and the research studies cited in those reviews.
Methods: Statements made in reviews about the efficacy of therapeutic touch were compared with the results and conclusions of the research cited. General conclusions reported in reviews were evaluated against a broad range of therapeutic touch (TT) research studies, including many not cited in reviews. How accurately reviewers represented the research studies was evaluated by comparing reviewers' conclusions with those of the researchers.
Findings were organized into principles to guide evidence-based reviews.
Findings: Literature reviews about therapeutic touch often cited only research with favorable findings. When citing studies with contradictory findings, only the favorable findings were usually mentioned. In many reviews, research cited as indicating the efficacy of therapeutic touch indicated it was ineffective. Every review examined had at least one significant mistake concerning how research studies were represented.
Conclusions: Accurate presentation of original research results is needed to make evidence-based decisions and to ensure that limited healthcare resources are used effectively and safely. Evidence-based principles should be followed in reviewing therapies and practices, including alternative therapies.     

Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer's disease and neuronal loss

Alzheimer's disease (AD) is the most prevalent age‐related neurodegenerative disorder, affecting over 35 million people worldwide. Pathologically, AD is characterized by the progressive accumulation of β‐amyloid (Aβ) plaques and neurofibrillary tangles within the brain. Together, these pathologies lead to marked neuronal and synaptic loss and corresponding impairments in cognition. Current treatments, and recent clinical trials, have failed to modify the clinical course of AD; thus, the development of novel and innovative therapies is urgently needed. Over the last decade, the potential use of stem cells to treat cognitive impairment has received growing attention. Specifically, neural stem cell transplantation as a treatment for AD offers a novel approach with tremendous therapeutic potential. We previously reported that intrahippocampal transplantation of murine neural stem cells (mNSCs) can enhance synaptogenesis and improve cognition in 3xTg‐AD mice and the CaM/Tet‐DT_A model of hippocampal neuronal loss. These promising findings prompted us to examine a human neural stem cell population, HuCNS‐SC, which has already been clinically tested for other neurodegenerative disorders. In this study, we provide the first evidence that transplantation of research grade HuCNS‐SCs can improve cognition in two complementary models of neurodegeneration. We also demonstrate that HuCNS‐SC cells can migrate and differentiate into immature neurons and glia and significantly increase synaptic and growth‐associated markers in both 3xTg‐AD and CaM/Tet‐DT_A mice. Interestingly, improvements in aged 3xTg‐AD mice were not associated with altered Aβ or tau pathology. Rather, our findings suggest that human NSC transplantation improves cognition by enhancing endogenous synaptogenesis. Taken together, our data provide the first preclinical evidence that human NSC transplantation could be a safe and effective therapeutic approach for treating AD. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

APOE ɛ4 constrains engagement of encoding‐related compensatory networks in amnestic mild cognitive impairment

People with amnestic mild cognitive impairment (aMCI), compared to healthy older adults (HO), benefit less from semantic congruent cues during episodic encoding. The presence of the apolipoprotein E (APOE) ?4 makes this congruency benefit smaller, but the neural correlates of this deficit are unknown. Here, we estimated the source generators of EEG oscillatory activity associated with successful encoding of face‐location associations preceded by semantically congruent and incongruent cues in HO (N = 26) and aMCI subjects (N = 34), 16 of which were ?4 carriers (?4⁺) and 18 ?4 noncarriers (?4^?). Source estimation was performed in those spectrotemporal windows where the power of low‐alpha, high‐alpha, and beta oscillatory activity differed either between congruent and incongruent faces or between groups. Differences in high‐alpha and beta‐oscillatory dynamics indicated that aMCI ?4⁺ are unable to activate lateral regions of the temporal lobe involved in associative memory and congruency benefit in HO. Interestingly, and regardless of APOE genotype, aMCI activated additional regions relative to HO, through alpha oscillations. However, only activation in a distributed fronto‐temporo‐parietal network in ?4 noncarriers was paralleled by enhanced memory. On the contrary, the redundant prefrontal activation shown by aMCI ?4⁺ did not prevent performance from decreasing. These results indicate that the effect of aMCI‐related degeneracy on functional networks is constrained by the presence of APOE ?4. Whereas individuals with aMCI ?4^? activate attentional, perceptual and semantic compensatory networks, aMCI ?4⁺ show reduced processing efficiency and capacity. © 2015 Wiley Periodicals, Inc.     

Posterior compensatory network in cognitively intact elders with hippocampal atrophy

Functional compensation in late life is poorly understood but may be vital to understanding long‐term cognitive trajectories. To study this we first established an empirically derived threshold to distinguish hippocampal atrophy in those with Mild Cognitive Impairment (MCI n = 34) from those with proficient cognition (PRO n = 22), using data from a population‐based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient individuals, either with (PRO_ATR) or without hippocampal atrophy (PRO_NIL). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM‐related networks. In those with hippocampal atrophy and under conditions of basic‐SWM demand, expression of a posterior compensatory network (PCN) comprised calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r = −0.96). In these individuals, basic level SWM response times were faster and no less accurate than in those with no hippocampal atrophy. Cognitively proficient older individuals with hippocampal atrophy may, therefore, uniquely engage posterior brain areas when performing simple spatial working memory tasks. © 2014 Wiley Periodicals, Inc.     

P2X7受体和肾脏疾病

P2X7受体是三磷酸腺苷(ATP)门控阳离子通道受体,是嘌呤受体P2X家族受体亚型之一。P2X7受体信号通路与IL-1β、IL-6、COX-2等多种炎症因子的生成和释放相关,在多种疾病的发病过程中起到了至关重要的作用。目前以此受体为治疗靶点的P2X7受体拮抗剂已进入临床试验阶段,表现出良好的安全性和疗效。最新研究表明P2X7受体与多种肾脏疾病有关,P2X7受体拮抗剂具有潜在的肾脏疾病治疗作用。本文综述P2X7受体在肾脏疾病中的作用及其可能的作用机制,以期为肾脏疾病治疗的新靶点和新策略提供理论依据。     

Do we over treat mild hypertension?

The important question whether ‘mild’ hypertension should or should not be treated by drugs is difficult to answer, because the only randomized controlled trials (RCTs) investigating this question were conducted when the definition of ‘mild’ hypertension was based on diastolic blood pressure only, whereas the present definition of grade 1 hypertension includes both systolic and diastolic values (SBP/DBP), and the concept of ‘mild’ hypertension also includes that of low-moderate cardiovascular risk (< 5% cardiovascular death rate in 5 years). Due to the lack of evidence from specific RCTs, guidelines recommend drug treatment of mild hypertension only on the basis of expert opinion. However, recent meta-analyses have provided some support to drug treatment intervention in low-moderate risk grade 1 hypertensives and have shown that, when treatment is deferred until organ damage or cardiovascular disease occur, absolute residual risk (events occurring despite treatment) markedly increases. Although evidence favoring therapeutic intervention in mild hypertension is nowadays stronger than expert opinion, meta-analyses are not substitutes for specific RCTs, and the wide BP spans defining grade 1 hypertension as well as the span defining low-moderate risk leave a wide space for individualized or personalized decisions.