先天性肠闭锁166例临床分析

目的分析先天性肠闭锁病例的诊断及治疗,以提高治愈率及术后生活质量。方法回顾性分析166例先天性肠闭锁的临床资料。结果治愈142例,治愈率85.5%(142/166),其中包括18例二期手术治愈者;术中10例、术后8例放弃治疗;术后死亡6例。结论早期诊断和选择合理的术式是提高肠闭锁治愈率的关键,基础支持及手术技术改进能促进病情的恢复,改善预后。     

The Relationship between Vigorous Physical Activity and Juvenile Delinquency: A Mediating Role for Self-Esteem?

Many policy-related reviews of the potential social value of sport and physical activity list the prevention of juvenile delinquency. We examined the relationships among vigorous physical activity, self-esteem, and delinquent behavior among adolescents in a large cross-sectional survey of Ontario adolescents. Data are based on questionnaires from 3,796 students (range 11–20 years) derived from the 2005 Ontario Student Drug Use Survey. Negative binominal regression methods were used to estimate both additive and interactive models predicting delinquent behavior. Vigorous physical activity was positively associated with delinquent behavior; however, this pattern of association was observed only among male adolescents. There was no evidence of a mediating role for self-esteem. Our findings suggest that physical activity is not the solution for reducing juvenile delinquency.     

Quality of Life and Outcomes in African Americans with CKD

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.     

The effects of acute exercise on tobacco cravings and withdrawal symptoms in temporary abstinent pregnant smokers

Introduction

Smoking during pregnancy is common, and quitting at any point during pregnancy can yield benefits to both the fetus and mother. Smoking cessation is typically followed by withdrawal symptoms and a strong desire to smoke, both of which are likely to contribute to relapse. Research has shown that a bout of exercise minimizes cravings and tobacco withdrawal symptoms (TWS) after temporary abstinence in smokers, but these findings have not been replicated in pregnant smokers. This study examined the effect of 20 min of exercise on cravings (primary outcome) and TWS (secondary outcomes) among temporary abstinent, inactive pregnant smokers.

Methods

Thirty female smokers (Mean(M) age = 25.7 years, Standard Deviation(SD) = 5.5; M weeks pregnant = 18.2, SD = 5.3; Fagerstrom Test for Cigarette Dependence = 3.3, SD = 2.2; M 9.3 cigarettes/day, SD = 4.7; M hours abstained = 17.2, SD = 2.8) were randomized to 20 min of mild-to-moderate intensity exercise (EC; n = 14) or passive (PC; n = 16) condition. Cravings and TWS were assessed immediately before, during (at 10 min), immediately post, and at 10, 20, and 30 min post-condition.

Results

A 2 (condition) × 6 (time) repeated measures ANOVA revealed that the EC significantly (p < 0.05) reduced cravings (?² = 0.46) compared with the PC, across time. Non-significant, but nevertheless, large effects were evident favouring the EC over time for TWS restlessness (?² = 0.34), stress (?² = 0.24), irritability (?² = 0.21), tension (?² = 0.15), and depression (?² = 0.14).

Conclusions

Consistent with previous research, this study reveals that in pregnant smokers, a bout of exercise is associated with a reduction in cravings and similar patterns exist for TWS. Therefore, exercise may have the potential to assist in the initial stages of smoking cessation attempts during pregnancy.     

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in gamma-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance.     

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials

Lanthanides are a series of critical elements widely used in multiple industries, such as optoelectronics and healthcare. Although initially considered to be of low toxicity, concerns have emerged during the last few decades over their impact on human health. The toxicological profile of these metals, however, has been incompletely characterized, with most studies to date solely focusing on one or two elements within the group. In the current study, we assessed potential toxicity mechanisms in the lanthanide series using a functional toxicogenomics approach in baker’s yeast, which shares many cellular pathways and functions with humans. We screened the homozygous deletion pool of 4,291 Saccharomyces cerevisiae strains with the lanthanides and identified both common and unique functional effects of these metals. Three very different trends were observed within the lanthanide series, where deletions of certain proteins on membranes and organelles had no effect on the cellular response to early lanthanides while inducing yeast sensitivity and resistance to middle and late lanthanides, respectively. Vesicle-mediated transport (primarily endocytosis) was highlighted by both gene ontology and pathway enrichment analyses as one of the main functions disturbed by the majority of the metals. Protein–protein network analysis indicated that yeast response to lanthanides relied on proteins that participate in regulatory paths used for calcium (and other biologically relevant cations), and lanthanide toxicity included disruption of biosynthetic pathways by enzyme inhibition. Last, multiple genes and proteins identified in the network analysis have human orthologs, suggesting that those may also be targeted by lanthanides in humans.

Since their discovery, lanthanides have presented both difficulty and opportunity for researchers. As a series, these elements behave rather similarly: most of them form +3 ions in aqueous solution (1), prefer highly electronegative anionic ligands (2), and form insoluble hydroxide precipitates at neutral pH if not otherwise complexed (3). Although the chemical similarities between these elements made their initial isolation and characterization a significant challenge, they now have unique applications in industry and medicine. Several lanthanides have become critical materials for many clean and sustainable energy technologies that will drive the future of our societies and are used, for example, in the production of batteries, magnets, motors, and other electronic components (4); low-concentration mixtures of lanthanides are used in Chinese agriculture to increase body weight gain among livestock (5, 6); lanthanum carbonate (sold under the commercial name of Fosrenol) is a noncalcium phosphate binder used to control hyperphosphataemia (7); and gadolinium is employed in diagnostic medicine, as an essential component of MRI contrast agents (8, 9).The growing use of lanthanides has increased the potential for human exposure to large concentrations of these metals, requiring more detailed investigations into their toxicological properties. For instance, administration of gadolinium-based contrast agents has been associated with the development of nephrogenic systemic fibrosis in patients with compromised renal function (10–12). Moreover, accumulation of gadolinium in the brains of patients who received repeated doses of gadolinium-based contrast agents has also been reported (13). Despite the current ubiquity of lanthanides, their toxicological profile has been incompletely characterized because until recently they were considered to be of low toxicological concern (14, 15). Previous toxicity studies primarily focused on lanthanum or cerium (and, to a lesser extent, neodymium and gadolinium), with the notion that these metals were representative of the series (14, 16–18). However, to our knowledge, no comprehensive mechanistic assay has been conducted to evaluate metal toxicity across the series, and little is known about what toxicological mechanisms may be shared by the different lanthanides.Saccharomyces cerevisiae is one of the best-characterized model organisms (19, 20), and there are many tools available for analyzing its genomic data (21–23). For example, yeast functional toxicogenomic screening is a powerful tool for investigating cellular mechanisms of cytotoxicity (24, 25). This method makes use of the yeast deletion libraries generated by the Yeast Deletion Project (26), a consortium of researchers across the United States and Canada, to establish relationships between genes and chemical exposures. Researchers used heterozygous and homozygous deletion pools of barcoded yeast strains to derive mechanistic toxicological information about a wide array of chemicals, pharmaceuticals, metals, and biological compounds (27, 28). As eukaryotes, yeast and humans share many cellular pathways and functions, and many components of cell biology identified in S. cerevisiae have homologs in human biology (29–31). Consequently, functional toxicogenomic screening offers unique opportunities to evaluate the mechanisms of cytotoxicity and general biological activity across the lanthanide series in yeast and explore potentially conserved mechanisms in humans.Here, we identify fundamental cellular functions disrupted by lanthanides using functional toxicogenomics in S. cerevisiae. The metals studied had distinct behaviors: early lanthanides showed limited unique functional effects, while middle and late lanthanides had prominent and distinct ones. Although the functional effects of each lanthanide were different and suggested some very efficient element discrimination by endogenous molecules, we observed a few common trends. In particular, vesicle-mediated transport (primarily endocytosis) was perturbed by the majority of the lanthanides tested. Moreover, protein–protein network analysis suggested that lanthanides mimic calcium ions, interacting with calcium-binding proteins and disrupting processes regulated by this cation. Finally, several of the highly interconnected proteins targeted by multiple lanthanides in the network analysis are conserved in humans, suggesting their roles in the origin of the human health issues associated with lanthanide exposure and opening many directions for the determination of mechanisms associated with toxicity.     

MODES OF INACTIVATION OF NEUROHYPOPHYSIAL HORMONES: SIGNIFICANCE OF PLASMA DISAPPEARANCE RATE FOR THEIR PHYSIOLOGICAL RESPONSES

Analogues of oxytocin and deaminooxytocin with 4-glutamine replaced by 4-glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4-glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the 'oil-bath'technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these 'rapidly inactivated'analogues can be used as proof of some predictions of the three-compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed.