Diagnostic accuracy of biomarkers and imaging for bone turnover in renal osteodystrophy

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.MethodsWe obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.ResultsLevels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.ConclusionsThe biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX

Climate Change and Water Scarcity: The Case of Saudi Arabia

Background: Climate change is expected to bring increases in average global temperatures (1.4°C–5.8°C [34.52°F–42.44°F] by 2100) and precipitation levels to varying degrees around the globe. The availability and quality of water will be severely affected, and public health threats from the lack of this valuable resource will be great unless water-scarce nations are able to adapt. Saudi Arabia provides a good example of how the climate and unsustainable human activity go hand in hand in creating stress on and depleting water resources, and an example for adaptation and mitigation. Method: A search of the English literature addressing climate change, water scarcity, human health, and related topics was conducted using online resources and databases accessed through the University at Albany, State University of New York library web page. Results: Water scarcity, which encompasses both water availability and water quality, is an important indicator of health. Beyond drinking, water supply is intimately linked to food security, sanitation, and hygiene, which are primary contributors to the global burden of disease. Poor and disadvantaged populations are the ones who will suffer most from the negative effects of climate change on water supply and associated human health issues. Examples of adaptation and mitigation measures that can help reduce the strain on conventional water resources (surface waters and fossil aquifers or groundwater) include desalination, wastewater recycling and reuse, and outsourcing food items or “virtual water trade.” These are strategies being used by Saudi Arabia, a country that is water poor primarily due to decades of irresponsible irrigation practices. The human and environmental health risks associated with these adaptation measures are examined. Finally, strategies to protect human health through international collaboration and the importance of these efforts are discussed. Conclusion: International, multidisciplinary cooperation and collaboration will be needed to promote global water security and to protect human health, particularly in low-income countries that do not have the resources necessary to adapt on their own

HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate

Acute myeloid leukemia (AML) is a poor prognosis hematopoietic malignance characterized by abnormal proliferation and differentiation of hematopoietic stem cells (HSCs). Although advances in treatment have greatly improved survival rates in young patients, in the elderly population, ~70% of patients present poor prognosis. A pan-cancer analysis on the TCGA cohort showed that AML has the second higher HUWE1 expression in tumor samples among all cancer types. In addition, pathway enrichment analysis pointed to RAS signaling cascade as one of the most important pathways associated to HUWE1 expression in this particular AML cohort. In silico analysis for biological processes enrichment also revealed that HUWE1 expression is correlated with 13 genes involved in myeloid differentiation. Therefore, to understand the role of HUWE1 in human hematopoietic stem and progenitor cells (HSPC) we constitutively expressed KRASG12V oncogene concomitantly to HUWE1 knockdown in stromal co-cultures. The results showed that, in the context of KRASG12V, HUWE1 significantly reduces cell cumulative growth and changes myeloid differentiation profile of HSPCs. Overall, these observations suggest that HUWE1 might contribute to leukemic cell proliferation and impact myeloid differentiation of human HSCs, thus providing new venues for RAS-driven leukemia targeted therapy approach

Optimality and distortionary lobbying: regulating tobacco consumption

We examine policies directed at regulating tobacco consumption through three types of instruments: (i) an excise tax hindering consumption by increasing the price of cigarettes, (ii) prevention programs helping consumers to make choices that are more time consistent when trading-off the current pleasure from smoking and its future health harms, and (iii) smoking bans directly restricting consumption. First, on normative grounds, we focus on the optimal design of public policies maximizing the economy’s surplus. Second, in a positive perspective, we investigate how the lobbying activities of the tobacco industry, of smokers, and of anti-tobacco organizations may distort government intervention

Creating a Gold Medal Olympic and Paralympics Health Care Team: A Satisfaction Survey of the Mobile Medical Unit/Polyclinic Team Training for the Vancouver 2010 Winter Games

BACKGROUND: The mobile medical unit/polyclinic (MMU/PC) was an essential part of the medical services to support ill or injured Olympic or Paralympics family during the 2010 Olympic and Paralympics winter games. The objective of this study was to survey the satisfaction of the clinical staff that completed the training programs prior to deployment to the MMU. METHODS: Medical personnel who participated in at least one of the four training programs, including (1) week-end sessions; (2) web-based modules; (3) just-in-time training; and (4) daily simulation exercises were invited to participate in a web-based survey and comment on their level of satisfaction with training program. RESULTS: A total of 64 (out of 94 who were invited) physicians, nurses and respiratory therapists completed the survey. All participants reported favorably that the MMU/PC training positively impacted their knowledge, skills and team functions while deployed at the MMU/PC during the 2010 Olympic Games. However, components of the training program were valued differently depending on clinical job title, years of experience, and prior experience in large scale events. Respondents with little or no experience working in large scale events (45%) rated daily simulations as the most valuable component of the training program for strengthening competencies and knowledge in clinical skills for working in large scale events. CONCLUSION: The multi-phase MMU/PC training was found to be beneficial for preparing the medical team for the 2010 Winter Games. In particular this survey demonstrates the effectiveness of simulation training programs on teamwork competencies in ad hoc groups

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities