Bone as a Possible Target of Chemical Toxicity of Natural Uranium in Drinking Water

Uranium accumulates in bone, affects bone metabolism in laboratory animals, and when ingested in drinking water increases urinary excretion of calcium and phosphate, important components in the bone structure. However, little is known about bone effects of ingested natural uranium in humans. We studied 146 men and 142 women 26–83 years of age who for an average of 13 years had used drinking water originating from wells drilled in bedrock, in areas with naturally high uranium content. Biochemical indicators of bone formation were serum osteocalcin and amino-terminal propeptide of type I procollagen, and a marker for bone resorption was serum type I collagen carboxy-terminal telopeptide (CTx). The primary measure of uranium exposure was uranium concentration in drinking water, with additional information on uranium intake and uranium concentration in urine. The data were analyzed separately for men and women with robust regression (which suppresses contributions of potential influential observations) models with adjustment for age, smoking, and estrogen use. The median uranium concentration in drinking water was 27 μg/L (interquartile range, 6–116 μg/L). The median of daily uranium intake was 36 μg (7–207 μg) and of cumulative intake 0.12 g (0.02–0.66 g). There was some suggestion that elevation of CTx (p = 0.05) as well as osteocalcin (p = 0.19) could be associated with increased uranium exposure (uranium in water and intakes) in men, but no similar relationship was found in women. Accordingly, bone may be a target of chemical toxicity of uranium in humans, and more detailed evaluation of bone effects of natural uranium is warranted

Asbestos-related pleural and lung fibrosis in patients with retroperitoneal fibrosis

<p>Abstract</p> <p>Background</p> <p>Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disease that leads to hydronephrosis and renal failure. In a case-control study, we have recently shown that asbestos exposure was the most important risk factor for RPF in the Finnish population. The aim of this study was to evaluate the relation of asbestos exposure to radiologically confirmed lung and pleural fibrosis among patients with RPF.</p> <p>Methods</p> <p>Chest high-resolution computed tomography (HRCT) was performed on 16 unexposed and 22 asbestos-exposed RPF patients and 18 asbestos-exposed controls. Parietal pleural plaques (PPP), diffuse pleural thickening (DPT) and parenchymal fibrosis were scored separately.</p> <p>Results</p> <p>Most of the asbestos-exposed RPF patients and half of the asbestos-exposed controls had bilateral PPP, but only a few had lung fibrosis. Minor bilateral plaques were detected in two of the unexposed RPF patients, and none had lung fibrosis. DPT was most frequent and thickest in the asbestos-exposed RPF-patients. In three asbestos-exposed patients with RPF we observed exceptionally large pleural masses that were located anteriorly in the pleural space and continued into the anterior mediastinum.</p> <p>Asbestos exposure was associated with DPT in comparisons between RPF patients and controls (case-control analysis) as well as among RPF patients (case-case analysis).</p> <p>Conclusion</p> <p>The most distinctive feature of the asbestos-exposed RPF patients was a thick DPT. An asbestos-related pleural finding was common in the asbestos-exposed RPF patients, but only a few of these patients had parenchymal lung fibrosis. RPF without asbestos exposure was not associated with pleural or lung fibrosis. The findings suggest a shared etiology for RPF and pleural fibrosis and furthermore possibly a similar pathogenetic mechanisms.</p

Mixed-Monolayer-Protected Au 25

Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Some Methods to Improve Life Cycle Manageability of Low-Volume Mobile Processing Platforms

The life cycles of mobile control electronics are significantly longer than in the mainstream electronics. The low production quantities and high number of product variants together with long life cycles has led to scattered production volumes. Producing low quantities is expensive and inefficient and component obsolescence causes high maintenance costs during the life cycle of each control product. Increasing use of distributed sensors and actuators has improved the functional re-use, but has not solved the maintenance of the application processing platforms. Moreover increased use of networking has pointed out some constraints of the current field buses. AD-interfaces in the application processing platforms form another challenge due to the different application requirements. Hubs and switches have been widely used in computer networks to solve the network constraints. The use of the same principles has been investigated with the standard high-speed physical layer of CAN. Due to the different bus access scheme, a thorough behavioral physical layer analysis was required. The problematic occurrences found in the theoretical analysis were proved with prototypes and real networks. The same tasks were performed for LIN to find out the effect of the different bus systems. The problem of the AD-interfaces has been solved by implementing and evaluating reconfigurable ADC implemented with the combination of FPGA and FPAA. To get a proper view of the possibilities, two main platforms and two conversion principles were evaluated. Active CAN hub and switch can significantly move the constraints of current CAN networks. More flexible topologies can be implemented without baudrate restrictions and violating the standard physical layer. Advanced condition monitoring and fault isolation features are provided by both active hub and switch. Because of the differences between CAN and LIN, the physical layer constraints of LIN can be reduced only with a multiport interface embedded into the master node. According to the case implementations, reconfigurable hardware is required to support all the alternative structures. Mobile processing platforms interface with the analog world and most of the analog outputs are pulse width modulated, which can be supported by reconfigurable digital hardware, CPLDs and FPGAs. The flexibility of the mixed-signal platforms can also be spread to cover the analog inputs by utilizing the reconfigurable mixed-signal hardware, FPAAs. The concept of reconfigurable ADC has been proved in this thesis with two different AD conversion principles implemented into two existing hardware platforms. Despite the hardware differences, generic ADC-functions were successfully implemented. Fully customizable standard hardware expects full reconfigurability from the platform. CPLDs and FPGAs have already supported the approach in the digital systems, including network hubs and switches. Using FPAAs together with FPGAs provides the same flexibility to the mixed-signal platforms needed in the mobile control systems. The hardware flexibility enables efficient higher volume production of the control electronics, because the same platforms can be adapted to any application of any system integrator without physical hardware modifications. Furthermore, the flexible hardware can be shared with multiple platform generations

Some Methods to Improve Life Cycle Manageability of Low-Volume Mobile Processing Platforms

The life cycles of mobile control electronics are significantly longer than in the mainstream electronics. The low production quantities and high number of product variants together with long life cycles has led to scattered production volumes. Producing low quantities is expensive and inefficient and component obsolescence causes high maintenance costs during the life cycle of each control product. Increasing use of distributed sensors and actuators has improved the functional re-use, but has not solved the maintenance of the application processing platforms. Moreover increased use of networking has pointed out some constraints of the current field buses. AD-interfaces in the application processing platforms form another challenge due to the different application requirements. Hubs and switches have been widely used in computer networks to solve the network constraints. The use of the same principles has been investigated with the standard high-speed physical layer of CAN. Due to the different bus access scheme, a thorough behavioral physical layer analysis was required. The problematic occurrences found in the theoretical analysis were proved with prototypes and real networks. The same tasks were performed for LIN to find out the effect of the different bus systems. The problem of the AD-interfaces has been solved by implementing and evaluating reconfigurable ADC implemented with the combination of FPGA and FPAA. To get a proper view of the possibilities, two main platforms and two conversion principles were evaluated. Active CAN hub and switch can significantly move the constraints of current CAN networks. More flexible topologies can be implemented without baudrate restrictions and violating the standard physical layer. Advanced condition monitoring and fault isolation features are provided by both active hub and switch. Because of the differences between CAN and LIN, the physical layer constraints of LIN can be reduced only with a multiport interface embedded into the master node. According to the case implementations, reconfigurable hardware is required to support all the alternative structures. Mobile processing platforms interface with the analog world and most of the analog outputs are pulse width modulated, which can be supported by reconfigurable digital hardware, CPLDs and FPGAs. The flexibility of the mixed-signal platforms can also be spread to cover the analog inputs by utilizing the reconfigurable mixed-signal hardware, FPAAs. The concept of reconfigurable ADC has been proved in this thesis with two different AD conversion principles implemented into two existing hardware platforms. Despite the hardware differences, generic ADC-functions were successfully implemented. Fully customizable standard hardware expects full reconfigurability from the platform. CPLDs and FPGAs have already supported the approach in the digital systems, including network hubs and switches. Using FPAAs together with FPGAs provides the same flexibility to the mixed-signal platforms needed in the mobile control systems. The hardware flexibility enables efficient higher volume production of the control electronics, because the same platforms can be adapted to any application of any system integrator without physical hardware modifications. Furthermore, the flexible hardware can be shared with multiple platform generations