Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

Methotrexate analogues. 29. Effect of gamma-aminobutyric acid spacers between the pteroyl and glutamate moieties on enzyme binding and cell growth inhibition

A series of "stretched" methotrexate (MTX) analogues containing up to five 4-aminobutyryl (Gab) spacers between the 4-amino-4-deoxy-N10-methylpteroyl (MeAPA) moiety and the glutamate (Glu) side chain was prepared. Interest in these compounds stemmed from their relationship to MTX gamma-polyglutamates, from which they differ only in lacking "internal" alpha-carboxyl groups. The ability of the MeAPA-Gabn-Glu derivatives to inhibit dihydrofolate reductase (DHFR) and thymidylate synthase (TS) in vitro and to inhibit the growth of tumor cells in culture was evaluated. The IC50 for DHFR inhibition increased progressively from 0.082 to 0.84 microM as the number of Gab spacers was varied from one to five. At the same time the introduction of Gab spacers was found to produce substantial TS inhibition (Ki 0.1-0.4 microM) similar to that reported for MTX polyglutamates. Despite the activity of the MeAPA-Gabn-Glu derivatives as combined inhibitors of TS and DHFR, there was a steep loss of cell growth inhibitory potency as the number of Gab spacers was increased. This most likely reflects low cell uptake and the fact that when n greater than 1 there is almost total abolition of substrate activity for folylpolyglutamate synthetase, which had previously been observed with n = 1.     

Weight change adjusted equations for assessing resting metabolic rate in overweight and obese adults

BackgroundAlthough over one hundred equations have been developed to predict the energy expenditure of individuals, none are sensitive to weight change in assessment of resting metabolic rate (RMR) before and after weight loss.ObjectiveTo formulate adjusted equations for overweight and obese individuals and to compare their accuracy with existing prediction RMR equations before and after weight loss.Subjects/materialsThis is historical prospective study. Participants included 39 overweight and obese men and women before and after losing 10–20% from baseline weight on a diet and physical activity regimen for at least three months. Pre and post weight loss measured RMR results were compared to estimated RMR using several existing prediction equations: Harris and Benedict, Ravussin and Bogardus, and Mifflin et al. To improve the accuracy of these prediction equations, we suggest new equations adjusted for weight loss, based on measured RMR and evaluated their accuracy.ResultsPre and post weight loss data indicated: significant fat reduction in both genders; reduction in free-fat mass only in men, and a significant decrease in measured RMR only in women. Our suggested equations were the most accurate and closest to measured RMR in both genders, in comparison to the Harris and Benedict, Ravussin and Bogardus, and Mifflin et al equation results. Estimated RMR using the latter equations was significantly lower than measured RMR in both genders at pre and post weight loss (P < 0.01).ConclusionsThis study highlights the need for adjusting RMR equations before and after weight loss in overweight and obese individuals. Further research is needed to validate our suggested equations.     

Musculoskeletal injury survivors’ resiliency: A systematic review

BackgroundMusculoskeletal traumas are on the rise in the United States; however, limited studies are available to help trauma providers assess and treat concerns beyond the physical impact. Little is understood about the psychological, social, and spiritual factors that protect patients from adverse effects after a physical trauma or their experiences with each factor afterward.ObjectiveThis systematic review was conducted to investigate and review advancements in research related to risk and resiliency factors experienced by survivors of traumatic musculoskeletal injuries. The use of biopsychosocial-spiritual (BPS–S) framework and resiliency theory guided the analysis.MethodsResearchers reviewed 1003 articles, but only seven met the search criteria. Due to the complexity and uniqueness of traumatic brain injuries, studies on that target population were excluded.ResultsOf the seven articles reviewed, three identified psychological protective factors that protect against negative health outcomes; three identified negative psychological, social, or spiritual outcomes; and none investigated social or spiritual health.ConclusionsThere are significant gaps in the literature surrounding risk and resiliency factors related to the BPS-S health of musculoskeletal injury survivors.     

Antibody-mediated redirected cytolysis against murine melanoma cells in vivo

Cytotoxic T lymphocytes can lyse Fc receptor-bearing target cells in vitro in the presence of anti-CD3 antibodies. This "redirected" lysis is not restricted by major histocompatibility antigens nor does it require nominal antigen recognition by the CTL. The efficacy of redirected lysis in vivo was assessed by comparing the survival of mice inoculated with a melanoma cell line transfected with the gene for mouse Fc receptor versus the untransfected melanoma when inoculated with syngeneic mouse CTL and anti-CD3 antibody. Survival was significantly higher in the animals given injections of Fc receptor melanoma, CTL, and anti-CD3 monoclonal antibody. Delayed injection or i.v. injection of CTL failed to significantly improve survival. Redirected lysis does not preclude the establishment of tumor immunity, since animals that rejected the tumor as a result of redirected lysis exhibited an increased resistance to reinoculation with tumor cells.     

基于空洞卷积神经网络的心律失常分类算法

本文提出了一种基于卷积网络的心电信号分类算法,设计了空洞卷积池化金字塔模块,通过不同尺寸的空洞卷积提取信息,再将各通道的信息聚合,在增强网络的特征提取能力的同时可以降低参数量。本文聚焦于窦性心律、房性早搏、心动过速以及心动过缓4种分类,使用的心电图数据集来自医院的实测数据,数据集包含75000名不同检测者的心电记录。经过测试,本文提出的模型在该数据集上取得了0.89的F1值,另外在CinC2017数据集上也达到了0.87的F1值。实验结果表明该分类算法具有优秀的特征提取和分类能力,在心电信号的实时分类中具备应用前景。     

Differential influences of coping humor and humor bias on mood

The authors investigated relationships among sense of humor measured by a questionnaire, attentional bias toward humor measured by performance on a word-search task, and experimentally induced mood change through the use of sad and humorous cartoons. Mood was significantly altered in a negative direction after the sad cartoon. Coping humor, part of the sense of humor questionnaire, was associated with less negative mood ratings after the sad cartoon. In terms of main effects, only a modest change in mood was found after the humorous cartoon. Humor bias was associated with more positive mood ratings after the humorous cartoon. The authors suggest that coping humor serves a protective psychological function, helping screen the person from negative stimuli and, thus, from negative reactions. Attentional bias toward humor serves a different protective psychological function by helping the person focus on mood-enhancing stimuli in the environment.