A History of Navajo Nation Education: Disentangling Our
Sovereign Body unravels the tangle of federal and state
education programs that have been imposed on Navajo people and
illuminates the ongoing ...efforts by tribal communities to transfer
state authority over Diné education to the Navajo Nation. On the
heels of the fiftieth anniversary of the founding of the Department
of Diné Education, this important education history explains how
the current Navajo educational system is a complex terrain of power
relationships, competing agendas, and jurisdictional battles
influenced by colonial pressures and tribal resistance. An iron
grip of colonial domination over Navajo education remains, thus
inhibiting a unified path toward educational sovereignty. In
providing the historical roots to today's challenges, Wendy Shelly
Greyeyes clears the path and provides a go-to reference to move
discussions forward.
Hypertension is the primary risk factor for cardiovascular disease that constitutes a serious worldwide health concern and a significant healthcare burden. As the majority of hypertension has an ...unknown etiology, considerable research efforts in both experimental models and human cohorts has focused on the premise that alterations in the fetal and perinatal environment are key factors in the development of hypertension in children and adults. The exact mechanisms of how fetal programming events increase the risk of hypertension and cardiovascular disease are not fully elaborated; however, the focus on alterations in the biochemical components and functional aspects of the renin-angiotensin (Ang) system (RAS) has predominated, particularly activation of the Ang-converting enzyme (ACE)-Ang II-Ang type 1 receptor (AT
R) axis. The emerging view of alternative pathways within the RAS that may functionally antagonize the Ang II axis raise the possibility that programming events also target the non-classical components of the RAS as an additional mechanism contributing to the development and progression of hypertension. In the current review, we evaluate the potential role of the ACE2-Ang-(1-7)-Mas receptor (MasR) axis of the RAS in fetal programming events and cardiovascular and renal dysfunction. Specifically, the review examines the impact of fetal programming on the Ang-(1-7) axis within the circulation, kidney, and brain such that the loss of Ang-(1-7) expression or tone, contributes to the chronic dysregulation of blood pressure (BP) and cardiometabolic disease in the offspring, as well as the influence of sex on potential programming of this pathway.
Differences in defining acute kidney injury (AKI) may impact incidence ascertainment. We assessed the effects of different AKI definition interpretation methods on epidemiology ascertainment.
Two ...groups were studied at Texas Children's Hospital, Houston, Texas: 150 critically ill children (prospective) and 254 noncritically ill, hospitalized children receiving aminoglycosides (retrospective). SCr was collected for 14 d in the prospective study and 21 d in the retrospective study. Children with known baseline serum creatinine (bSCr) were classified by the pediatric Risk, Injury, Failure, Loss, End-Stage Kidney Disease (pRIFLE) AKI definition using SCr change (pRIFLE(DeltaSCr)), estimated creatinine clearance (eCCl) change (pRIFLE(DeltaCCl)), and the Acute Kidney Injury Network (AKIN) definition. In subjects without known bSCr, bSCR was estimated as eCCl = 100 (eCCl(100)) and 120 ml/min per 1.73 m(2) (eCCl(120)), admission SCr (AdmSCr) and lower/upper normative values (NormsMin, NormsMax). The differential impact of each AKI definition interpretation on incidence estimation and severity distribution was evaluated.
pRIFLE(DeltaSCr) and AKIN led to identical AKI distributions. pRIFLE(DeltaCCl) resulted in 14.5% (critically ill) and 11% (noncritical) more patients diagnosed with AKI compared to other methods (P 0.05). Different bSCr estimates led to differences in AKI incidence, from 12% (AdmSCr) to 87.8% (NormsMin) (P 0.05) in the critically ill group and from 4.6% (eCCl(100)) to 43.1% (NormsMin) (P 0.05) in the noncritical group.
AKI definition variation causes interstudy heterogeneity. AKI definition should be standardized so that results can be compared across studies.
A classification system has been proposed to standardize the definition of acute kidney injury in adults. These criteria of risk, injury, failure, loss, and end-stage renal disease were given the ...acronym of RIFLE. We have modified the criteria based on 150 critically ill pediatric RIFLE (pRIFLE) patients to assess acute kidney injury incidence and course along with renal and/or non-renal comorbidities. Of these children, 11 required dialysis and 24 died. Patients without acute kidney injury in the first week of intensive care admission were less likely to subsequently develop renal Injury or Failure; however, 82% of acute kidney injury occurred in this initial week. Within this group of 123 children, 60 reached pRIFLEmax for Risk, 32 reached Injury, and 31 reached Failure. Acute kidney injury during admission was an independent predictor of intensive care; hospital length of stay and an increased risk of death independent of the Pediatric Risk of Mortality (PRISM II) score (odds ratio 3.0). Our results show that a majority of critically ill children develop acute kidney injury by pRIFLE criteria and do so early in the course of intensive care. Acute kidney injury is associated with mortality and may lead to increased hospital costs. We suggest that the pRIFLE criteria serves to characterize the pattern of acute kidney injury in critically ill children.
Patients with hepatocellular carcinoma (HCC) within Milan criteria receive priority on the liver transplant waiting list (WL) and compete with non‐HCC patients. Dropout from the WL is an indirect ...measure of transplant access. Competing risks (CR) evaluation of dropout for HCC and non‐HCC patients has not previously been reported. Patients listed between 16 March 2005 and 30 June 2008 were included. Probability of dropout was estimated using a CR technique as well as a Cox model for time to dropout. Overall, non‐HCC patients had a higher dropout rate from the WL than HCC patients (p < 0.0001). This was reproducible throughout all regions. In Cox regression, tumor size, model for end‐stage liver disease (MELD) score and alpha fetoprotein (AFP) were associated with increased dropout risk. Multivariable analysis with CR showed that MELD score and AFP, were most influential in predicting dropout for HCC patients. The index of concordance for predicting dropout with the CR was 0.70. HCC patients appear to be advantaged in the current allocation scheme based on lower dropout rates without regard to geography. A continuous score incorporating MELD, AFP and tumor size may help to prioritize HCC patients to better equate dropout rates with non‐HCC patients and equalize access.
Candidates for liver transplantation with HCC MELD exception scores drop off the waiting list at lower rates than non‐HCC candidates indicating that these patients continue to maintain too much priority in the current allocation system for cadaveric liver allografts. See editorial by Volk on page 1507.
We observe the movement of water over time between pores of differing sizes in Castlegate sandstone. To achieve this, we perform an NMR transverse relaxation exchange experiment for several mixing ...times. The resulting data are converted to 2D T2 distributions using a 2D inverse Laplace transform (ILT). We show for the first time that quantitative analysis of ILT distributions enables one to extract characteristic times for different pores sizes. This information is potentially useful for permeability determination as well as better understanding of exchange between specific pore subpopulations.
Neuronal activity enhances the elaboration of newborn neurons as they integrate into the synaptic circuitry of the adult brain. The role microRNAs play in the transduction of neuronal activity into ...growth and synapse formation is largely unknown. MicroRNAs can influence the expression of hundreds of genes and thus could regulate gene assemblies during processes like activity-dependent integration. Here, we developed viral-based methods for the in vivo detection and manipulation of the activity-dependent microRNA, miR-132, in the mouse hippocampus. We find, using lentiviral and retroviral reporters of miR-132 activity, that miR-132 is expressed at the right place and right time to influence the integration of newborn neurons. Retroviral knockdown of miR-132 using a specific 'sponge' containing multiple target sequences impaired the integration of newborn neurons into the excitatory synaptic circuitry of the adult brain. To assess potential miR-132 targets, we used a whole-genome microarray in PC12 cells, which have been used as a model of neuronal differentiation. miR-132 knockdown in PC12 cells resulted in the increased expression of hundreds of genes. Functional grouping indicated that genes involved in inflammatory/immune signaling were the most enriched class of genes induced by miR-132 knockdown. The correlation of miR-132 knockdown to increased proinflammatory molecular expression may indicate a mechanistic link whereby miR-132 functions as an endogenous mediator of activity-dependent integration in vivo.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Serum creatinine is a late marker of acute kidney injury (AKI). Urine neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of AKI, where the timing of kidney injury is known. It is ...unknown whether uNGAL predicts AKI in the general critical care setting. We assessed the ability of uNGAL to predict AKI development and severity in critically ill children.
This was a prospective cohort study of critically ill children. Children aged between 1 month and 21 years who were mechanically ventilated and had a bladder catheter inserted were eligible. Patients with end-stage renal disease or who had just undergone kidney transplantation were excluded. Patients were enrolled within 24 to 48 hours of initiation of mechanical ventilation. Clinical data and serum creatinine were collected daily for up to 14 days from enrollment, and urine was collected once daily for up to 4 days for uNGAL measurement. AKI was graded using pRIFLE (pediatric modified Risk, Injury, Failure, Loss, End Stage Kidney Disease) criteria. Day 0 was defined as the day on which the AKI initially occurred, and pRIFLEmax was defined as the worst pRIFLE AKI grade recorded during the study period. The chi2 test was used to compare associations between categorical variables. Mann-Whitney and Kruskal-Wallis tests were used to compare continuous variables between groups. Diagnostic characteristics were evaluated by calculating sensitivity and specificity, and constructing receiver operating characteristic curves.
A total of 140 patients (54% boys, mean +/- standard deviation Pediatric Risk of Mortality II score 15.0 +/- 8.0, 23% sepsis) were included. Mean and peak uNGAL concentrations increased with worsening pRIFLEmax status (P < 0.05). uNGAL concentrations rose (at least sixfold higher than in controls) in AKI, 2 days before and after a 50% or greater rise in serum creatinine, without change in control uNGAL. The parameter uNGAL was a good diagnostic marker for AKI development (area under the receiver operating characteristic curve AUC 0.78, 95% confidence interval CI 0.62 to 0.95) and persistent AKI for 48 hours or longer (AUC 0.79, 95% CI 0.61 to 0.98), but not for AKI severity, when it was recorded after a rise in serum creatinine had occurred (AUC 0.63, 95% CI 0.44 to 0.82).
We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury.
Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate ...system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, high resolution lineage tracing method and 3D culture system to analyse ADM in human cells. In this system, well-known mouse ADM inducers did not promote ADM in human cells. In contrast, TGF-β1 efficiently converted human acinar cells to duct-like cells (AD) in a SMAD-dependent manner, highlighting fundamental differences between the species. Functionally, AD cells gained transient proliferative capacity. Furthermore, oncogenic KRAS did not induce acinar cell proliferation, but did sustain the proliferation of AD cells, suggesting that oncogenic KRAS requires ADM-associated-changes to promote PDAC initiation. This ADM model provides a novel platform to explore the mechanisms involved in the development of human pancreatic diseases.
Background. Urinary interleukin-18 (uIL-18) is an earlier acute kidney injury (AKI) biomarker than serum creatinine (SCr) in specific populations. In the present study, the relationship between ...uIL-18 and AKI was determined in a heterogeneous group of critically ill children. Methods. We studied critically ill children to determine whether uIL-18 was an early predictor of AKI. SCr was determined daily for up to 14 days from mechanical ventilation initiation and up to four serial urine specimens were collected for the uIL-18 measurement. AKI was graded by paediatric modified risk, injury, failure, loss, end-stage kidney disease (pRIFLE) criteria. Day 0 was defined as the day of attaining pRIFLE AKI. Results. One hundred thirty-seven children aged 6.5 ± 6.4 years (53% male) were studied. The peak levels of IL-18 correlated with the severity of AKI by pRIFLE classification (P < 0.05). In non-septic AKI patients, uIL-18 rose to a level higher than control levels 2 days prior to a significant rise in SCr. Urinary IL-18 concentration from the first urine specimen was associated with AKI development within 48 h (odds ratio = 3.5, P < 0.05) independent of the paediatric risk of mortality (PRISM II) score. Urinary IL-18 concentration ≥100 pg/ml had a specificity and negative predictive value of 81 and 83% to predict AKI development within 24 h. Urinary IL-18 ≥200 pg/ml collected within 24 h of Day 0 had a specificity and positive predictive value of 93 and 88% respectively to predict the AKI duration ≥48 h. Urinary IL-18 was associated with mortality (odds ratio = 1.29, P < 0.05), independent of the PRISM II score. Conclusions. Urinary IL-18 rises prior to SCr in non-septic critically ill children, predicts severity of AKI and is an independent predictor of mortality.
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