Higher frequency of septic shock in septic patients with the 47C allele (rs4880) of the SOD2 gene

Aim

To analyze the effect of the two different versions of the manganese superoxide dismutase gene (SOD2) on sepsis. The SOD2 gene presents the 47C > T single nucleotide polymorphism (SNP; ID: rs4880) which produces MnSOD with different activities. The − 9Val MnSOD (47T allele) is less efficient than the − 9Ala version (47C allele). During sepsis there are abundance of ROS, high SOD2 expression and excess of H₂O₂ synthesis. High concentrations of H₂O₂ could affect the sepsis scenario and/or the sepsis outcome.

Methods

We determined the 47C > T single nucleotide polymorphism (SNP) frequencies in 529 critically ill patients with or without sepsis, facing outcome. To collect information on population frequencies, we obtained a pilot 47C > T genotypic and allelic frequencies in a random group of 139 healthy subjects.

Results

We compared the 47C allele carriers (47CC + 47CT genotypes) with 47TT homozygotes and noticed a significant association between 47C allele carriers and septic shock in septic patients (P = 0.025). With an adjusted binary multivariate logistic regression, incorporating 47C > T SNP and the main clinical predictors, we showed high SOFA scores [P < 0.001, OR = 9.107 (95% CI = 5.319–15.592)] and 47C allele [P = 0.011, OR = 2.125 (95% CI = 1.190–3.794)] were significantly associated with septic shock outcome. With this information we presented a hypothesis suggesting that this negative outcome from sepsis is possibly explained by effects on cellular stress caused by 47C allele.

Conclusion

In our population there was a significant higher frequency of septic shock in septic patients with the 47C allele of the SOD2 gene. This higher 47C allele frequency in septic patients with negative outcome could be explained by effects of higher activity MnSOD on cellular stress during the sepsis.     

Identification of MRI1, encoding translation initiation factor eIF-2B subunit alpha/beta/delta-like protein,as a candidate locus for infantile epilepsy with severe cystic degeneration of the brain

Several neurodegenerative disorders are known to predominantly affect the white matter of the brain including vanishing white matter disease (VWMD), an autosomal recessive disorder characterized by leukodystrophy of varying severity in addition to variable systemic involvement. We report a consanguineous Arab family with three affected children, all of whom presented with severe neonatal epilepsy and profound neurodegenerative disease characterized by marked leukodystrophy with white matter cavitation mimicking VWMD. We combined autozygome and exome analysis to identify a novel variant in the gene encoding a member of the eIF2B-related family of proteins (MRI1). This is a poorly understood family of proteins of unclear function. Our results represent the first link between a variant in a member of this family and a human disease, and suggest that it converges with the highly homologous eIF2B, known to be mutated in VWMD, on the molecular pathogenesis of neurodegeneration.     

EVI-1 modulates arsenic trioxide induced apoptosis through JNK signalling pathway in leukemia cells

High expression of the oncogene ecotropic viral integration site-1 (EVI-1) is an independent negative prognostic indicator of survival in leukemia patients. This study aimed to examine the effects of arsenic trioxide (ATO) on EVI-1 in acute myeloid leukemia (AML). Mononuclear cells were isolated from the bone marrow and peripheral blood of AML patients and healthy donors. EVI-1 expression in hematopoietic cells was evaluated by RT-qPCR and Western blot analysis. EVI-1 was highly expressed in both primary AML and leukemia cell lines (THP-1 and K562). ATO down-regulated EVI-1 mRNA in zebrafish in vivo as well as in primary leukemia cells and THP-1 and K562 cells in vitro. Additionally, ATO treatment induced apoptosis, down-regulated both EVI-1 mRNA and oncoprotein expression, increased the expression of pro-apoptosis proteins, and decreased the expression of anti-apoptotic proteins in leukemia cells in vitro. EVI-1 expression in leukemia cells (THP-1 and K562) transduced with EVI-1 siRNA was significantly reduced. Silencing EVI-1 had a significant effect on the activation of the JNK pathway and the induction of leukemia cell apoptosis. ATO may downregulate EVI-1 mRNA and oncoprotein levels and block the inhibitory effects of EVI-1 on the JNK pathway, which activates the JNK apoptotic pathway, thereby leading to the apoptosis of EVI-1 in AML patients.     

Competing Responsibilities: Moving Beyond Neoliberal Responsibilisation

Ideas of responsibility pervade social life, underpinning forms of governance, subjectivities, and collective relations. Inspired by current analyses of neoliberal projects of ‘responsibilisation’, this paper examines modes of responsibility that extend, challenge, or co-exist with neoliberal ideals. Our aim is twofold: first, we wish to broaden current scholarly understandings of how neoliberal ‘responsible’ subjects are nested within multiple frames of dependencies, reciprocities, and obligations. Secondly, we articulate a framework for conceptualising responsibility that places responsibilisation alongside relations of care and social contract ideologies—three modes of inter-relationship that we see as underlying the ‘competing responsibilities’ inherent in contemporary social life.     

Seed Pro-Nutra Care: A tool for characterization of seed storage proteins and database of bioactive peptides having potential health benefits

Seed storage proteins, the major food proteins, possess unique physicochemical characteristics which determine their nutritional importance and influence their utilization by humans. Here, we describe a database driven tool named Seed Pro-Nutra Care which comprises a systematic compendium of seed storage proteins and their bioactive peptides influencing several vital organ systems for maintenance of health. Seed Pro-Nutra Careis an integrated resource on seed storage protein. This resource help in the (I) Characterization of proteins whether they belong to seed storage protein group or not. (II) Identification the bioactive peptides with their sequences using peptide name (III) Determination of physico chemical properties of seed storage proteins. (IV) Epitope identification and mapping (V) Allergenicity prediction and characterization. Seed Pro-Nutra Care is a compilation of data on bioactive peptides present in seed storage proteins from our own collections and other published and unpublished sources. The database provides an information resource of a variety of seed related biological information and its use for nutritional and biomedical application.

Availability

http://www.gbpuat-cbsh.ac.in/departments/bi/database/seed_pro_nutra_care/     

临床护理路径管理糖尿病足患者效果评价

目的:观察临床护理路径对糖尿病足患者的效果。方法:将100例糖尿病足患者随机分为两组:实验组(50例)应用临床护理路径模式,对照组采用常规护理模式,比较两组患者的住院时间、医疗费用、患者满意率、血糖、溃疡愈合时间和糖尿病足知识评分。结果:实验组患者的住院日数、医疗费用、血糖和溃疡愈合时间显著低于对照组(P<0.05),患者满意率和糖尿病足知识评分显著高于对照组(P<0.05)。结论:应用临床护理路径可以有效地降低糖尿病患者的血糖、溃疡愈合时间、住院时间和医疗费用,提高患者糖尿病足知识水平和满意率。     

Parental care and EGG size in salamanders: An examination of the safe harbor hypothesis

The safe harbor hypothesis includes the suggestion that parental care causes the embryonic stage to be the safest harbor, and, therefore, egg size will increase in populations with parental care to decrease the duration of subsequent, higher risk stages. Neither the safe habor hypothesis nor r and K theory seem adequate to explain the correlation between egg size and the presence/absence of parental care among salamanders, a group in which there is a further correlation between the larval (hatchling) habitat and egg size/parental care. Pond-breeding salamanders generally have small eggs and lack parental care, and stream-breeding salamanders generally have large eggs and parental care. I argue that the fundamental difference in the food available to hatchling salamanders between lentic (plankton-rich) and lotic (plankton-poor) environments selects for relatively lower parental investment in the lentic environment. From the standpoint of parental fitness, small (more numerous) hatchlings have a greater payoff where the available food is mall and dense (zooplankton in lentic environments), and large hatchlings are selectively advantageous where the food is of large size and less dense (benthic invertebrates in lotic environments). Selection for larger hatchlings in lotic environments results in longer embryonic periods and, ceteris paribus, greater total embryonic mortality. Embryo hiding and guarding have evolved among lotic-breeding salamanders as compensatory mechanisms to reduce the rate of embryonic mortality. In this view, parental care is a consequence of selection for larger egg size and not an umbrella that allows egg size to increase, contrary to the safe harbor hypothesis. The relationship between variance in parental investment and food available to offspring, developed here for salamanders, may be of general significance. YosiakiItô , a critic of r and K theory, independently arrived at a similar conclusion from a broader data base.     

容积减影成像计算机自动化技术与实现

探讨在PC机上对容积CT灌注（CTP）源影像全自动生成减影CTP源影像的方法。首先在WindowsXP操作系统中使用Matlab,对4层螺旋CTP源影像进行DICOM文件格式解析,获得CT成像设备的球管每转一周扫描层数及容积减影方法需要的其它参数信息,然后经过容积的CT值集合读、容积的CT值集合减以及容积的CT值集合写等几个步骤,生成减影CTP源影像的DICOM文件序列。使用该容积减影方法得到的减影CTP源影像,在定性肉眼观察和定量CT值矩阵比对上,与使用CT影像工作站上的减影软件手工逐层半自动减影得到的结果类同。容积减影方法实现了容积CTP源影像的自动化减影处理与成像,为最终形成一个一站式的减影CTP软件奠定了基础。     

Administrative gatekeeping - a third way between unrestricted patient advocacy and bedside rationing

The inevitable need for rationing of healthcare has apparently presented the medical profession with the dilemma of choosing the lesser of two evils. Physicians appear to be obliged to adopt either an implausible version of traditional professional ethics or an equally problematic ethics of bedside rationing. The former requires unrestricted advocacy of patients but prompts distrust, moral hazard and unfairness. The latter commits physicians to rationing at the bedside; but it is bound to introduce unfair inequalities among patients and lack of political accountability towards citizens. In this paper I shall argue that this dilemma is false, since a third intermediate alternative exists. This alternative, which I term 'administrative gatekeeping', makes it possible for physicians to be involved in rationing while at the same time being genuine advocates of their patients. According to this ideal, physicians are required to follow fair rules of rationing adopted at higher organizational levels within healthcare systems. At the same time, however, they are prohibited from including considerations of cost in their clinical decisions.