Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome

Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1-19) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet-Biedl syndrome-related renal disease attending the United Kingdom national Bardet-Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4-5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations in BBS10, mutations in BBS1 associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b-5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet-Biedl syndrome and identifies risk factors to be considered in genetic counseling

Validity and worth in the science curriculum: learning school science outside the laboratory

It is widely acknowledged that there are problems with school science in many developed countries of the world. Such problems manifest themselves in a progressive decline in pupil enthusiasm for school science across the secondary age range and the fact that fewer students are choosing to study the physical sciences at higher levels and as careers. Responses to these developments have included proposals to reform the curriculum, pedagogy and the nature of pupil discussion in science lessons. We support such changes but argue from a consideration of the aims of science education that secondary school science is too rooted in the science laboratory; substantially greater use needs to be made of out-of-school sites for the teaching of science. Such usage should result in a school science education that is more valid and more motivating and is better at fulfilling defensible aims of school science education. Our contention is that laboratory-based school science teaching needs to be complemented by out-of-school science learning that draws on the actual world (e.g. through fieldtrips), the presented world (e.g. in science centres, botanic gardens, zoos and science museums) and the virtual worlds that are increasingly available through information and communications technologies (ICT)

Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease

Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated. Methods 140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively. Results The median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74 with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71, TG 76, TT 73, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively). Conclusions eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses. © 2015 Chand et al

To what extent can online mapping be decolonial? A journey throughout Indigenous cartography in Canada

In this paper, we describe and reflect upon our journey through Indigenous online mapping in Canada. This journey has been planned according to an academic goal: assessing the potential of online cartography for decolonial purposes. To reach this goal, we have followed methodological directions provided by Indigenous scholar Linda Tuhiwai Smith to review 18 Indigenous web-mapping sites across Canada. Supported by a series of ten interviews, this content analysis enabled us to sketch some of the contours of contemporary Indigenous cartography. On one hand, Indigenous communities largely control the data that are shared on these websites. They also partially control the way these data are represented through the mobilization of digital storytelling technologies that are better aligned with Indigenous ways of envisioning relationships to places than conventional maps. On the other hand, they do not have much control over the technological aspects of these projects, for which they remain heavily dependent on non-Indigenous partners. Throughout this journey, we noticed that women’s voices remained marginal in most of these mapping projects, but we also identified evidence supporting the idea that these voices are starting to play a vital role in the on-going effort of decolonizing mapping processes

Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis

BACKGROUND: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. METHODS: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. RESULTS: Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. CONCLUSION: NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH

The associations of endotoxemia with systemic inflammation, endothelial activation, and cardiovascular outcome in kidney transplantation

Objective: Cardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored. Design and Methods: This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs. Main Outcome Measures: Demographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected. Results: Endotoxemia (P = .03), reduced 25-hydroxyvitamin D (P = .04), high fructose intake (P < .001), decreased fiber intake (P < .001), and abdominal obesity (P = .002) were independently associated with elevated hsCRP. In turn, endotoxemia (P = .007) and increasing hsCRP (P = .02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P = .02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P < .001), hypertriglyceridemia (P < .001), increased fructose intake (P = .01), and abdominal obesity (P = .01). Conclusions: Endotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets

Extra-Activism: Counter-Mapping and Data Justice

Neither big data, nor data justice are particularly new. Data collection, in the form of land surveys and mapping, was key to successive projects of European imperialist and then capitalist extraction of natural resources. Geo-spatial instruments have been used since the fifteenth century to highlight potential sites of mineral, oil, and gas extraction, and inscribe European economic, cultural and political control across indigenous territories. Although indigenous groups consistently challenged maintained their territorial sovereignty, and resisted corporate and state surveillance practices, they were largely unable to withstand the combined onslaught of surveyors, armed personnel, missionaries and government bureaucrats. This article examines the use of counter-mapping by indigenous nations in Canada, one of the globe’s hubs of extractivism, as part of the exercise of indigenous territorial sovereignty. After a brief review of the colonial period, I then compare the use of counter-mapping during two cycles of indigenous mobilization. During the 1970s, counter-mapping projects were part of a larger repertoire of negotiations with the state over land claims, and served to re-inscribe first nation’s long-standing history of economic, social and cultural relations in their territories, and contribute to new collective imaginaries and identities. In the current cycle of contests over extractivism and indigenous sovereignty, the use, scope and geographic scale of counter-mapping has shifted; maps are used as part of larger trans-media campaigns of Indigenous sovereignty. During both cycles, counter-mapping as data justice required fusion within larger projects of redistributive, transformative and restorative justice

Risk factors of post renal transplant anaemia among Sudanese patients, a study in three renal transplant centres

<p>Abstract</p> <p>Background</p> <p>There is a relative lack of recent information about late post kidney transplantation anaemia (PTA), especially in the developing countries; data are scarce about the prevalence and risk factors of PTA. Sudan was a leading country in Africa and Arab world in kidney transplantation. The first kidney transplantation in Sudan was in 1973.</p> <p>Methods</p> <p>This is a cross-sectional hospital analytic study enrolling all kidney transplanted recipients following in the transplant referral clinics at Ahmed Gassim, Selma and Ibn Sina Hospitals, Khartoum/Sudan, in the period from 1/8/2010 to 1/9/2010, clinical and laboratory data were obtained from 114 patients, anaemia was defined as Hb levels of < 13 g/dl for male patients and < 12 g/dl for female patients, exclusion criteria were pregnancy, below 18 years old patients, multiple organ transplantation, and patients with less than one year from the transplantation.</p> <p>Results</p> <p>The study showed that 39.5% of the patients were anaemic. Univariate analysis showed that late PTA is significantly associated with not using Erythropoietin (EPO) in the pre-transplant period (p = < 0.001), history of rejection (p = 0.003), longer time from transplantation (p = 0.015), and eGFR (p < 0.0001). Multivariate analysis showed that eGFR (p = < 0.001) and not use of EPO in the pre transplant period (p < 0.001) are strong predictors of PTA. The use of Angiotensin converting enzyme inhibitors/Angiotensin receptors blockers (ACEI/ARB), immunosuppressive treatments, presence or absence of co-morbidities, donor type and donor age are not significantly associated with late PTA.</p> <p>Conclusion</p> <p>The study concluded that late PTA is common and under recognized. Risk factors for late PTA include renal dysfunction, history of rejection, longer duration of transplantation and not using EPO in the pre-transplant period. Renal dysfunction and not using EPO in the pre-transplant period are major predictors of late PTA.</p