THE EFFECT OF ALUMINUM ON HEPATIC BILIARY TRANSPORTERS AS A CONTRIBUTING FACTOR TO PARENTERAL NUTRITION INDUCED INTRAHEPATIC CHOLESTASIS

Intravenous feeding of patients with essential and balanced nutrition is required when enteral feeding is not tolerated, therefore indicating the need for Total Parenteral Nutrition (TPN). This life-saving therapy is also associated with the increase risk of intrahepatic cholestasis. The incidence of TPN-related hepatobiliary complications is common in both adults and infants on TPN. Previous work in in vivo models suggested that one of the potential contributing factors is the aluminum contamination of TPN solutions. The mechanism by which aluminum contributes to the PNAC development, though, was unknown. Aluminum as a risk factor may influence a number of hepatocellular functions to lead to cholestasis but one possible mechanism is the potential for aluminum to cause dysfunction of those transporters responsible in the maintenance of bile flow. To provide some initial information regarding the role of aluminum as a contributing factor to cholestasis and the possible underlying mechanism, cytotoxicity studies were conducted to determine whether aluminum causes direct toxicity of HepG2 cells. Furthermore, the influence of aluminum on the mRNA expression of hepatic biliary transporters (BSEP, MRP2, MATE1, NTCP) and nuclear transcription factor (FXR) in HepG2 cells using real-time RT-PCR analysis was assessed. Since inflammation is a component of cholestasis, these investigations also involved the use of an inflammatory stimulus, lipopolysaccharide (LPS), to determine whether the effects of aluminum were exacerbated by underlying inflammation. My data suggest that for the canalicular hepatic transporters MATE1 and BSEP, aluminum at higher concentration alone as well as with LPS caused increased mRNA expression levels. In addition to this, BSEP mRNA expression was preserved and that of MATE1 was increased on LPS exposure. Given the particular importance of BSEP in the maintenance of bile flow and reported effects of drug-induced inhibition of BSEP to cause hepatic cholestasis, the influence of aluminum on BSEP (and MATE1) protein expression and activity warrant investigation. Further studies may identify that inhibition of BSEP function (and possibly MATE1) by aluminum contamination of total parenteral nutrition formulations may explain, in part, the intrahepatic cholestasis associated with parenteral nutrition

Synthesis and investigation of highly conductive Cu-Cr-MWCNT composites

There is great demand for contact materials with superior electrical and thermal conductivities and mechanical strength, for use in Vacuum Circuit Breakers (VCB). Copper (Cu) and chromium (Cr) alloy, developed in the 1970’s [1] has been the most common contact material in VCBs. Although Cu-Cr alloys possess good conductivity and mechanical properties, 50% of Cr (a strategic metal) in the alloy is resource prohibitive. A reduction in Cr usage without compromising desired properties is desirable. Previous researchers focused on developing Cu-Cr alloys with fine and uniform microstructure to enhance their physical properties. This investigation focused on the development of a Cu-Cr-MWCNT (Multi walled Carbon Nanotubes) composite with enhanced properties as compared with currently used materials. The electrical conductivity of the composite increased up to 18 times that of Cu and there was also an increase in the Vicker’s hardness

Least-Privilege Identity-Based Policies for Lambda Functions in Amazon Web Services (AWS)

We address least-privilege in a particular context of public cloud computing: identity-based policies for callback functions, called Lambda functions, in serverless applications of the Amazon Web Services (AWS) cloud provider. We argue that this is an important context in which to consider the fundamental security design principle of least-privilege, which states that every thread of execution should possess only those privileges it needs. We observe that poor documentation from AWS makes the task of devising least-privilege policies difficult for developers of such applications. We then describe our experimental approach to discovering least-privilege for a method call, and our observations, some of which are alarming, from running it against 171 methods across five different AWS services. We discuss also our assessment of two repositories, and two full-fledged serverless applications, all of which are publicly available, for least-privilege, and find that the vast majority of policies are over-privileged. We conclude with a few recommendations for developers of Lambda functions in AWS. Our work suggests that much work is needed, both from developers and providers, in securing cloud applications from the standpoint of least-privilege

Assessment of Biodegradable Magnesium Alloys for Enhanced Mechanical and Biocompatible Properties

Biomaterials have been used for more than a century in the human body to improve body functions and replace damaged tissues. Currently approved and commonly used metallic biomaterials such as, stainless steel, titanium, cobalt chromium and other alloys have been found to have adverse effects leading in some cases, to mechanical failure and rejection of the implant. The physical or chemical nature of the degradation products of some implants initiates an adverse foreign body reaction in the tissue. Some metallic implants remain as permanent fixtures, whereas others such as plates, screws and pins used to secure serious fractures are removed by a second surgical procedure after the tissue has healed sufficiently. However, repeat surgical procedures increase the cost of health care and the possibility of patient morbidity. This study focuses on the development of magnesium based biodegradable alloys/metal matrix composites (MMCs) for orthopedic and cardiovascular applications. The Mg alloys/MMCs possessed good mechanical properties and biocompatible properties. Nine different compositions of Mg alloys/MMCs were manufactured and surface treated. Their degradation behavior, ion leaching, wettability, morphology, cytotoxicity and mechanical properties were determined. Alloying with Zn, Ca, HA and Gd and surface treatment resulted in improved mechanical properties, corrosion resistance, reduced cytotoxicity, lower pH and hydrogen evolution. Anodization resulted in the formation of a distinct oxide layer (thickness 5-10 μm) as compared with that produced on mechanically polished samples (~20-50 nm) under ambient conditions. It is envisaged that the findings of this research will introduce a new class of Mg based biodegradable alloys/MMCs and the emergence of innovative cardiovascular and orthopedic implant devices

Development of Large Bandgap Materials Using Reactive Growth in Al-SI Eutectic for Optical and RF Applications

Carbon was utilized as reactive element to modify the microstructure using forced mixing during crystallization of the Al-Si alloy by rotation and stirring. We nucleated the material on SiC substrates while the Al-Si melt was rotated with a speed of 30rpm in a graphite crucible. Several experiments were performed and parameters such as time of mixing, soaking temperature, rotation rate of the substrate and rate of cooling during the solidification was changed. We observed dendrite and cell morphologies during the solidification of rotating melt. The microstructure was characterized by optical microscopy and SEM-EDX and compositional spectroscopy. The effect of carbon impurities was studied on the solidifying microstructure. When we used the longer soak time of the melt in presence of carbon impurities we observed the destruction of dendritic morphology and the formation of cellular and colony structures. Similar approach has been used for Ga2O3, a novel large bandgap material also

Electrocardiographic changes in Emphysema

Chronic obstructive lung disease (COPD), predominantly emphysema, causes several thoracic anatomical and hemodynamic changes which may cause changes in various electrocardiographic parameters. A 12-lead electrocardiogram (ECG), which is often a part of routine evaluation in most clinical settings, may serve as a useful screening modality for diagnosis of COPD or emphysema. Our current article aims to provide a comprehensive review of the electrocardiographic changes encountered in COPD/emphysema utilizing published PubMed and Medline literature database. Several important ECG changes are present in COPD/emphysema and may serve as a good diagnostic tool. Verticalization of Pvector, changes in QRS duration, pattern recognition of precordial R-wave progression and axial shifts can be considered some of the most valuable markers among other changes. In conclusion, 12-lead surface electrocardiogram can serve as a valuable tool for the diagnosis of COPD and/or emphysema. An appropriate knowledge of these ECG changes can not only help in the diagnosis but can also immensely help in an appropriate clinical management of these patients

Lung cancer stage-shift following a symptom awareness campaign

Background: Lung cancer outcomes in the UK are worse than in many other developed nations. Symptom awareness campaigns aim to diagnose patients at an earlier stage to improve cancer outcomes. Methods: An early diagnosis campaign for lung cancer commenced in Leeds, UK in 2011 comprising public and primary-care facing components. Rates of community referral for chest X-ray and lung cancer stage (TNM seventh edition) at presentation were collected from 2008 to 2015. Linear trends were assessed by χ2 test for trend in proportions. Headline figures are presented for the 3 years pre-campaign (2008–2010) and the three most recent years for which data are available during the campaign (2013–2015). Findings: Community-ordered chest X-ray rates per year increased from 18 909 in 2008–2010 to 34 194 in 2013–2015 (80.8% increase). A significant stage shift towards earlier stage lung cancer was seen (χ2(1)=32.2, p<0.0001). There was an 8.8 percentage point increase in the proportion of patients diagnosed with stage I/II lung cancer (26.5% pre-campaign vs 35.3% during campaign) and a 9.3% reduction in the absolute number of patients diagnosed with stage III/IV disease (1254 pre-campaign vs 1137 during campaign). Interpretation: This is the largest described lung cancer stage-shift in association with a symptom awareness campaign. A causal link between the campaign and stage-shift cannot be proven but appears plausible. Limitations of the analysis include a lack of contemporary control population

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention