Propofol infusion syndrome in a super morbidly obese patient (BMI = 75)

Propofol infusion syndrome (PRIS) is a rare but often fatal complication as a result of large doses of propofol infusion (4–5 mg/kg/hr) for a prolonged period (>48 h). It has been reported in both children and adults. Besides large doses of propofol infusion, the risk factors include young age, acute neurological injury, low carbohydrate and high fat intake, exogenous administration of corticosteroid and catecholamine, critical illness, and inborn errors of mitochondrial fatty acid oxidation. PRIS manifestation include presence of metabolic acidosis with a base deficit of more than 10 mmol/l at least on one occasion, rhabdomyolysis or myoglobinuria, acute renal failure, sudden onset of bradycardia resistant to treatment, myocardial failure, and lipemic plasma. The pathophysiology of PRIS may be either direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. We report a case of supermorbidly obese patient who received propofol infusion by total body weight instead of actual body weight and developed PRIS.

Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism

Chronic fatigue syndrome (CFS) is characterized by idiopathic fatigue of greater than 6 months' duration with postexertional exacerbation and many other symptoms. A trend toward relative hypocortisolism is described in CFS. Twin and family studies indicate a substantial genetic etiologic component to CFS. Recently, severe corticosteroid-binding globulin (CBG) gene mutations have been associated with CFS in isolated kindreds. Human leukocyte elastase, an enzyme important in CBG catabolism at inflammatory sites, is reported to be elevated in CFS. We hypothesized that CBG gene polymorphisms may act as a genetic risk factor for CFS. A total of 248 patients with CFS defined by Centers for Disease Control criteria, and 248 controls were recruited. Sequencing and restriction enzyme testing of the CBG gene coding region allowed detection of severe CBG gene mutations and a common exon 3 polymorphism (c.825G --> T, Ala-Ser(224)). Plasma CBG levels were measured in 125 CFS patients and 198 controls by radioimmunoassay. Total and free (calculated and measured) cortisol levels were ascertained in single samples between 8-10 a.m. The age of onset (mid 30s) and gender ratio (2.2:1, female:male) of the patients were similar to those reported in U.S. epidemiologic studies. A trend toward a preponderance of serine(224) homozygosity among the CFS patients was noted, compared with controls (chi(2) = 5.31, P = 0.07). Immunoreactive-CBG (IR-CBG) levels were higher in Serine/Alanine (Ser/Ala) than Ala/Ala subjects and higher again in Ser/Ser subjects, this effect was strongest in controls; Ser/Ser: 46.1 +/- 1.8 (n = 31, P = 0.03) vs. Ser/Ala: 42.4 +/- 1.0 (n = 56, P = 0.05) vs. Ala/Ala: 40.8 +/- 1.7 mug/mL (n = 21). Despite higher CBG levels, there was a nonsignificant trend toward lower total and free plasma cortisol in serine allele positive patients, total cortisol: Ser/Ser: 13.3 +/- 1.4 (n = 34) vs. Ser/Ala: 14.0 +/- 0.7 (n = 66) vs. Ala/Ala: 15.4 +/- 1.0 (n = 23). Homozygosity for the serine allele of the CBG gene may predispose to CFS, perhaps due to an effect on hypothalamic-pituitary-adrenal axis function related to altered CBG-cortisol transport function or immune-cortisol interactions.

Inhibition of 19-kDa C-terminal region of merozoite surface protein-1-specific antibody responses in neonatal pups by maternally derived 19-kDa C-terminal region of merozoite surface protein-1-specific antibodies but not whole parasite-specific antibodies

Immunizing pregnant women with a malaria vaccine is one approach to protecting the mother and her offspring from malaria infection. However, specific maternal Abs generated in response to vaccination and transferred to the fetus may interfere with the infant's ability to respond to the same vaccine. Using a murine model of malaria, we examined the effect of maternal 19-kDa C-terminal region of merozoite surface protein-1 (MSP1(19)) and Plasmodium yoelii Abs on the pups' ability to respond to immunization with MSP1(19). Maternal MSPI,g-specific Abs but not A yoelii-specific Abs inhibited Ab production following MSP1(19) immunization in 2-wk-old pups. This inhibition was correlated with the amount of maternal MSP1(19) Ab present in the pup at the time of immunization and was due to fewer specific B cells. Passively acquired Ab most likely inhibited the development of an Ab response by blocking access to critical B cell epitopes. If a neonate's ability to respond to MSP1(19) vaccination depends on the level of maternal Abs present at the time of vaccination, it may be necessary to delay immunization until Abs specific for the vaccinating Ag have decreased.

Normal HPRT coding region in a male with gout due to HPRT deficiency (Brief Communication)

A deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) is associated with a spectrum of disease that ranges from gouty arthritis (OMIM 300323) to the more severe Lesch-Nyhan syndrome (OMIM 300322). To date, all cases of HPRT deficiency have shown a mutation within the HPRT cDNA. In the present study of an individual with gout due to HPRT deficiency, we found a normal HPRT cDNA sequence. This is the first study to provide an example of HPRT deficiency which appears to be due to a defect in the regulation of the gene. © 2005 Elsevier Inc. All rights reserved.

Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes

Despite the identification of SRY as the testis-determining gene in mammals, the genetic interactions controlling the earliest steps of male sex determination remain poorly understood. In particular, the molecular lesions underlying a high proportion of human XY gonadal dysgenesis, XX maleness and XX true hermaphroditism remain undiscovered. A number of screens have identified candidate genes whose expression is modulated during testis or ovary differentiation in mice, but these screens have used whole gonads, consisting of multiple cell types, or stages of gonadal development well beyond the time of sex determination. We describe here a novel reporter mouse line that expresses enhanced green fluorescent protein under the control of an Sf1 promoter fragment, marking Sertoli and granulosa cell precursors during the critical period of sex determination. These cells were purified from gonads of male and female transgenic embryos at 10.5 dpc (shortly after Sry transcription is activated) and 11.5 dpc (when Sox9 transcription begins), and their transcriptomes analysed using Affymetrix genome arrays. We identified 266 genes, including Dhh, Fgf9 and Ptgds, that were upregulated and 50 genes that were downregulated in 11.5 dpc male somatic gonad cells only, and 242 genes, including Fst, that were upregulated in 11.5 dpc female somatic gonad cells only. The majority of these genes are novel genes that lack identifiable homology, and several human orthologues were found to map to chromosomal loci implicated in disorders of sexual development. These genes represent an important resource with which to piece together the earliest steps of sex determination and gonad development, and provide new candidates for mutation searching in human sexual dysgenesis syndromes.

PAX2 activates WNT4 expression during mammalian kidney development

The transcription factor PAX2 is expressed during normal kidney development and is thought to influence outgrowth and branching of the ureteric bud. Mice with homozygous null Pax2 mutations have developmental defects of the midbrain-hindbrain region, optic nerve, and ear and are anephric. During nephrogenesis, PAX2 is also expressed by mesenchymal cells as they cluster and reorganize to form proximal elements of each nephron, but the function of PAX2 in these cells is unknown. In this study we hypothesized that PAX2 activates expression of WNT4, a secreted glycoprotein known to be critical for successful nephrogenesis. PAX2 protein was identified in distal portions of the S-shaped body, and the protein persists in the emerging proximal tubules of murine fetal kidney. PAX2 activated WNT4 promoter activity 5-fold in co-transfection assays with JTC12 cells derived from the proximal tubule. Inspection of the 5'-flanking sequence of the human WNT4 gene identified three novel PAX2 recognition motifs; each exhibited specific PAX2 protein binding in electromobility shift assays. Two motifs were contained within a completely duplicated 0.66-kb cassette. Transfection of JTC12 cells with a PAX2 expression vector was associated with a 7-fold increase in endogenous WNT4 mRNA. In contrast, Wnt4 mRNA was decreased by 60% in mesenchymal cell condensates of fetal kidney from mice with a heterozygous Pax2 mutation. We speculated that a key function of PAX2 is to activate WNT4 gene expression in metanephric mesenchymal cells as they differentiate to form elements of the renal tubules.

Simulation of Brugada syndrome using cellular and three-dimensional whole-heart modeling approaches

Brugada syndrome (BS) is a genetic disease identified by an abnormal electrocardiogram ( ECG) ( mainly abnormal ECGs associated with right bundle branch block and ST-elevation in right precordial leads). BS can lead to increased risk of sudden cardiac death. Experimental studies on human ventricular myocardium with BS have been limited due to difficulties in obtaining data. Thus, the use of computer simulation is an important alternative. Most previous BS simulations were based on animal heart cell models. However, due to species differences, the use of human heart cell models, especially a model with three-dimensional whole-heart anatomical structure, is needed. In this study, we developed a model of the human ventricular action potential (AP) based on refining the ten Tusscher et al (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573 - 89) model to incorporate newly available experimental data of some major ionic currents of human ventricular myocytes. These modified channels include the L-type calcium current (ICaL), fast sodium current (I-Na), transient outward potassium current (I-to), rapidly and slowly delayed rectifier potassium currents (I-Kr and I-Ks) and inward rectifier potassium current (I-Ki). Transmural heterogeneity of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by varying the maximum conductance of IKs and Ito. The modified AP models were then used to simulate the effects of BS on cellular AP and body surface potentials using a three-dimensional dynamic heart - torso model. Our main findings are as follows. (1) BS has little effect on the AP of endocardial or mid-myocardial cells, but has a large impact on the AP of epicardial cells. (2) A likely region of BS with abnormal cell AP is near the right ventricular outflow track, and the resulting ST-segment elevation is located in the median precordium area. These simulation results are consistent with experimental findings reported in the literature. The model can reproduce a variety of electrophysiological behaviors and provides a good basis for understanding the genesis of abnormal ECG under the condition of BS disease.

Phototrophic microendoliths bloom during coral "white syndrome"

Following rapid lesion progression of white syndrome in tabular Acropora spp., the white bare skeleton gradually changes to green, a result of endolithic algae blooms (primarily Ostreobium spp.). Endolithic algal biomass and chlorophyll concentration were found to be an order of magnitude higher in the green zone compared with healthy appearing parts of each colony. Chl b to Chl a ratio increased from 1:1.6 in the healthy area to 1:2 and 1:3.5 in the white exposed skeleton and green zones, respectively. These observations together with pulse amplitude modulated (PAM) fluorometry suggest photoacclimation of the endoliths in the green zone. Histopathological microscopy revealed that the endolithic algal filaments penetrate the coral tissue. This study highlights the interaction of endolithic algae with both the skeleton and host tissue. This may have a critical role in the processes that accompany the post-disease state in reef-building corals.

Bringing hope to crisis: critical thinking, ethical action and social change

This paper departs from this point to consider whether and how crisis thinking contributes to practices of affirmative critique and transformative social action in late-capitalist societies. I argue that different deployments of crisis thinking have different ‘affect-effects’ and consequences for ethical and political practice. Some work to mobilize political action through articulating a politics of fear, assuming that people take most responsibility for the future when they fear the alternatives. Other forms of crisis thinking work to heighten critical awareness by disrupting existential certainty, asserting an ‘ethics of ambiguity’ which assumes that the continuous production of uncertain futures is a fundamental part of the human condition (de Beauvoir, 2000). In this paper, I hope to illustrate that the first deployment of crisis thinking can easily justify the closing down of political debate, discouraging radical experimentation and critique for the sake of resolving problems in a timely and decisive way. The second approach to crisis thinking, on the other hand, has greater potential to enable intellectual and political alterity in everyday life—but one that poses considerable challenges for our understandings of and responses to climate change...

Size frequency distribution of beta-amyloid (Abeta) deposits in dementia with Lewy bodies

In Alzheimer's disease (AD) and Down's syndrome (DS), the size frequency distribution of the beta-amyloid (Abeta) deposits can be described by a log-normal model and may indictae the growth of the deposits. This study determined the size frequency distribution of the Abeta deposits in the temporal lobe in 8 casaes of dementia with Lewy bodies (DLB) with associated AD pathology (DLB/AD. The size distributions of Abeta deposits were unimodal and positively skewed; the mean size of deposi and the degree of skew varying with deposit type and brain region. Size distributions of the primitive deposits had lower means and were less skewed compared with the diffuse and classic deposits. In addition, size distributions in the hippocampus and parahippocampal gyrus (PHG) had larger means and a greater degree of skew compared with other cortical gyri. All size distributions deviated significantly from a log-normal model. There were more Abeta deposits than expected in the smaller size classes and fewer than expected near the mean and in the larger size classes. The data suggest thatthe pattern of growth of the Abeta deposits in DLB/AD depends both on deposit morphology and brain area. In addition, Abeta deposits in DLB appear to grow to within a more restricted size range than predicted and hence, to have less potential for growth compared with cases of 'pure' AD and DS.

"Crack down on the celebrity junkies": does media coverage of celebrity drug use pose a risk to young people?

This study analysed news media content to examine the role played by celebrity drug use in young people's perceptions of drug use. We know that young people have access to discourses of drug use through music and other media which may emphasise short term gains (of pleasure or sexual success) over longer term health and social problems. This study goes beyond a simple modelling approach by using Media Framing Analysis (MFA) to take an in-depth look at the messages themselves and how they are 'framed'. New stories about Amy Winehouse's drug use were used and we conducted focus groups with young people asking them questions about drugs, celebrity and the media. Frames identified include: 'troubled genius', 'losing patience' and 'glamorization or gritty realism'. Initially, the press championed Winehouse's musical talent but soon began to tire of her recklessness; the participants tended to be unimpressed with Winehouse's drug use, characterising her as a promising artist who had 'gone off the rails'. Young people were far more critical of Winehouse than might be expected, demonstrating that concerns about the influence of celebrity drug use and its impact on future health risk behaviour among young people may have been over-simplified and exaggerated. This study illustrates the need to understand young people and their frames of reference within popular culture when designing drug awareness information relevant to them. Furthermore, it indicates that critical media skills analysis may contribute to health risk education programmes related to drug use.

An examination of the determinants of entrepreneurship at the regional level:the case of East Midlands region

Despite the importance of new firms to the economy, determinants of start-ups have mainly been examined at a country level and discussion of regional entrepreneurial activity has received less attention. Since there are significant variations in entrepreneurship rates across and within countries, such an investigation at a regional level would help in gaining an in depth understanding of the impact of the individual level resource endowments and neighbourhood characteristics on an individual’s decision to engage in entrepreneurial activity. The main aim of the thesis is to explore various theories of entrepreneurship and develop integrated frameworks for examining the determinants of entrepreneurial activity at a neighbourhood level in the East Midlands region in England. The specific objectives of the thesis are to examine how the individual level resources and the neighbourhood characteristics: (i) combine to influence an individual to engage in the different stages of the entrepreneurial process, (ii) influence natives and migrants to engage in start up activity and (iii) influence women and men to become self-employed and ambitious entrepreneurs. In terms of the methodology, the empirical analysis is based on two databases combined: 2006 to 2009 GEM East Midlands region and the English Index of Multiple Deprivation dataset. Based on the critical review of the literature on entrepreneurship the thesis develop theoretical frameworks which led to formulate hypotheses related to the differentiated impact of both individual and neighbourhood level factors on the propensity of an individual to be involved in entrepreneurial activity. The findings indicate that the determinants of entrepreneurial activity vary with human, financial and the local environment factors affecting the entrepreneurial process. Finally, the thesis calls for caution when developing and applying generic and specific policy measures aimed at promoting entry into entrepreneurship.

Hogyan bonthatók le a látható és láthatatlan falak? – Kooperatív kutatás a megváltozott munkaképességűek foglalkoztatásával kapcsolatos mentális gátak lebontásáról (How to break down the visible and unvisible walls? – A cooperative research about the breaking down of mental barriers of the employment of disabled people)

A szerzők tanulmányukban egy kooperatív kutatási projekt eredményeit mutatják be, melyet emberierőforrás- menedzsment szakos master hallgatókkal folytattak megváltozott munkaképességűek foglalkoztatásával kapcsolatban. Magyarországon rendkívül magas a munkanélküliség a fogyatékkal élők körében, és a szerzők úgy vélik, hogy a HR-szakértőknek kulcsfontosságú szerepük van abban, hogy a foglalkoztatási korlátokat fenntartják-e, vagy változtatnak a jelenlegi helyzeten. A kritikai emberierőforrás-fejlesztés és a kritikai pedagógia hagyományait követve kutatásuk kettős célt tűzött ki. Céljuk volt egyrészt a jövő HRszakembereinek megváltozott munkaképességűek foglalkoztatásával kapcsolatos mentális mintázatainak, attitűdjeinek és hiedelmeinek feltárása, amelyek az elnyomás, diszkrimináció vagy kizsákmányolás gyökerei lehetnek. Másrészt pedig a kooperatív kutatás alkalmazásával a hallgatók emancipációját szándékoztak előmozdítani, továbbá az üzleti felsőoktatást uraló pozitivista filozófiát és értékrendszert kívánták kihívás elé állítani, s ily módon segíteni egy kritikusabb világnézet kibontakozását. ________ In this paper we present the results of a cooperative inquiry research project undertaken with Master students specialized in Human Resource Management on the employment of disabled people. Unemployment among people with disabilities is very high in Hungary and HR professionals have a key role in maintaining or reducing employment barriers and modifying the present situation. Following the tradition of critical Human Resource Development and critical pedagogy, the aim of the research project was twofold. First, we aimed to reveal the mental patterns, attitudes and beliefs of future HR professionals to the employment of people with disabilities, which might become roots causes of domination, discrimination or exploitation. Secondly, through applying cooperative inquiry, researchers aimed to emancipate students and challenge the positivist philosophy and value system which usually dominate business education and thereby engender a more critical worldview.

Seasonal fish community variation in headwater mangrove creeks in the southwestern Everglades: an examination of their role as dry-down refuges

The connectivity between the fish community of estuarine mangroves and that of freshwater habitats upstream remains poorly understood. In the Florida Everglades, mangrove-lined creeks link freshwater marshes to estuarine habitats downstream and may act as dry-season refuges for freshwater fishes. We examined seasonal dynamics in the fish community of ecotonal creeks in the southwestern region of Everglades National Park, specifically Rookery Branch and the North and watson rivers. Twelve low-order creeks were sampled via electrofishing, gill nets, and minnow traps during the wet season, transition period, and dry season in 2004-2005. Catches were greater in Rookery Branch than in the North and watson rivers, particularly during the transition period. Community composition varied seasonally in Rookery Branch, and to a greater extent for the larger species, reflecting a pulse of freshwater taxa into creeks as marshes upstream dried periodically. The pulse was short-lived, a later sample showed substantial decreases in freshwater fish numbers. No evidence of a similar influx was seen in the North and watson rivers, which drain shorter hydroperiod marshes and exhibit higher salinities. These results suggest that head-water creeks can serve as important dry-season refugia. Increased freshwater flow resulting from Everglades restoration may enhance this connectivity.

A Conceptual Framework to Develop Long-Term Ecological Research and Management Objectives in the Wider Caribbean Region

The Caribbean Sea and its watersheds show signs of environmental degradation. These fragile coastal ecosystems are susceptible to environmental impacts, in part because of their oligotrophic conditions and their critical support of economic development. Tourism is one of the major sources of income in the Caribbean, making the region one of the most ecotourism dependent in the world. Yet there are few explicit, long-term, comprehensive studies describing the structure and function of Caribbean ecosystems. We propose a conceptual framework using the environmental signature hypothesis of tropical coastal settings to develop a series of research questions for the reef–sea-grass–wetland seascape. We applied this approach across 13 sites throughout the region, including ecosystems in a variety of coastal settings with different vulnerabilities to environmental impacts. This approach follows the strategy developed by the Long Term Ecological Research program of the National Science Foundation to establish ecological research questions best studied over decades and large spatial areas.