Comparison of glucose tolerance in renal transplant recipients and hemodialysis patients

BACKGROUND: Impaired glucose tolerance is a risk factor for atherosclerosis in hemodialysis patients and renal transplant recipients. METHODS: To check the relationship of impaired glucose tolerance with the other atherosclerotic risk factors, fasting blood sugar and the standard two hour glucose tolerance test, serum tryglyceride, serum cholesterol, cyclosporine through level (in renal tranpslant recipients) and hemoglobin A1C were measured in 55 stable renal transplant recipients, 55 hemodialysis patients and 55 healthy controls with similar demographic characteristics. Patients with diabetes mellitus and propranolol consumers were excluded. The mean age and female to male ratio were 39 +/- 7 years and 23/22, respectively. RESULTS: Four of the renal transplant recipients and twelve of the hemodialysis patients had impaired glucose tolerance. Significant linear correlation was observed with body mass index and IGT only in hemodialysis patients (r = 0.4, p = 0.05). Glucose tolerance also had a significant correlation with triglyceride levels (217.2 +/- 55 mg/dl in hemodialysis patients vs. 214.3 +/- 13 mg/dl in renal transplant recipients and 100.2 +/- 18 mg/dl in control groups, p = 0.001). The glucose tolerance had significant relationship with higher serum cholesterol levels only in the renal transplant recipients (269.7 +/- 54 in renal transplant recipients vs. 199.2 +/- 36.6 mg/dl in hemodialysis and 190.5 +/- 34 mg/dl in control groups, p = 0.0001). In the renal transplant recipients, a linear correlation was observed with glucose tolerance and both the serum cyclosporine level (r = 0.9, p = 0.001) and the hemoglobin A1C concentration (6.2 +/- 0.9 g/dl). The later correlation was also observed in the hemodialysis patients (6.4 +/- 0.7 g/dl; r = 67, p = 0.001). CONCLUSIONS: We conclude that although fasting blood sugar is normal in non-diabetic renal transplant and hemodialysis patients, impaired glucose tolerance could be associated with the other atherosclerotic risk factors

Application and Effectiveness of Telehealth to Support Severe Mental Illness Management: Systematic Review

Background: It is important that people with SMI receive early interventions to prevent mental health deterioration or relapse. Telecommunications and other technologies are increasingly used to assist healthcare delivery (‘telehealth’) , providing service users with immediate real-time information to improve the management of chronic health conditions. Telehealth has been found to be successful in improving management and symptoms across a number of health conditions, whilst also being acceptable to users. Initial findings suggest technology could improve quality of life in people with SMI. Objectives: This systematic review aimed to identify the variety of uses and efficacy of teleheal th technology for SMI. Methods: We systematically searched electronic databases from inception to March 2016 (MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, AMED, He alth Techno logy Assessment, CINAHL plus and NHS EED ) for randomised controlled trials (RCTs) evaluating telehealth for adults with SMI , published in English. Additional literature was identified by searching reference lists of key articles. The articles meeting the inclusion criteria were systematically reviewed and assessed for quality and risk of bias. Results: The search identified 31 eligible articles, describing 29 trials. The included studies evaluated the use of computers to deliver cognitive rehabilitation (1 5 trials), patient education (3 trials), online self- management interventions (2 trials), and to support consultations (1 trial). Virtual reality (VR) was used to simulate work and social sit uations (2 trials ) and to deliver cognitive training (1 trial). Telephones were used to prompt medication use (3 trials ) and report SMI symptoms to healthcare teams (1 trial ). Remote sensors were used to monitor medication use (1 trial). Telephone support was found effective for improving medication adherence and reducing symptom severity and inpatient days. Computer assisted cognitive rehabilitation was effective in improving cognitive function. The impact of telehealth on other outcomes was inconsistent. Few studies evaluated the 3 use of remote medication telemonitoring, VR, online self-management and computer -mediated consultations, suggesting these are novel technologies for managing SMI, although all were found effective for improving psycho social and behavioural outcomes. The results of this review should be taken in the context of varied quality in study design, with only five studies demonstrating a low risk of bias. Conclusions : A growing variety of telehealth technologies are used to support SMI. Specific types of technology have been found to be effective for som e outcomes, for example telephone prompts for medication adherence, while other types of telehealth had no benefit over traditional methods and were less acceptable to patients. Few studies found benefits for telehealth on quality of life, except for novel technologies with a limited number of trials. Further research is warranted to establish the full potential benefits of telehealth for improving quality of life in SMI, acceptability from the service user perspective, and cost-effectivenes

Manipulating infrared photons using plasmons in transparent graphene superlattices

Superlattices are artificial periodic nanostructures which can control the flow of electrons. Their operation typically relies on the periodic modulation of the electric potential in the direction of electron wave propagation. Here we demonstrate transparent graphene superlattices which can manipulate infrared photons utilizing the collective oscillations of carriers, i.e., plasmons of the ensemble of multiple graphene layers. The superlattice is formed by depositing alternating wafer-scale graphene sheets and thin insulating layers, followed by patterning them all together into 3-dimensional photonic-crystal-like structures. We demonstrate experimentally that the collective oscillation of Dirac fermions in such graphene superlattices is unambiguously nonclassical: compared to doping single layer graphene, distributing carriers into multiple graphene layers strongly enhances the plasmonic resonance frequency and magnitude, which is fundamentally different from that in a conventional semiconductor superlattice. This property allows us to construct widely tunable far-infrared notch filters with 8.2 dB rejection ratio and terahertz linear polarizers with 9.5 dB extinction ratio, using a superlattice with merely five graphene atomic layers. Moreover, an unpatterned superlattice shields up to 97.5% of the electromagnetic radiations below 1.2 terahertz. This demonstration also opens an avenue for the realization of other transparent mid- and far-infrared photonic devices such as detectors, modulators, and 3-dimensional meta-material systems.Comment: under revie

An extended phase Ib study of epertinib, an orally active reversible dual EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours.

BACKGROUND: Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2 inhibitor, has established a recommended daily dose of 800 mg in patients with solid tumours. In this study, we have recruited a larger number of patients to assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour activity. PATIENTS AND METHODS: Patients with solid tumours expressing EGFR or HER2 received a single dose of epertinib at 800 mg on Day 1 to assess PK over 7 days, followed by continuous once-daily dosing from Day 8. RESULTS: We treated 76 patients with breast (n = 27), upper gastrointestinal (GI; n = 30), head and neck (n = 12) or renal cancers (n = 7). Epertinib was well-tolerated with mostly grade I and II adverse events (AEs). The most frequent AE was diarrhoea, which was generally manageable with loperamide. The objective response rate (ORR) in patients with heavily pretreated breast and upper GI cancers was 16.0% (4 PRs) and 8.3% (1CR, 1PR), respectively. All six responding patients had HER2-positive tumours; the ORR for HER2-positive breast and upper GI cancer populations was 19.0% and 20.0%. Partial response in the brain disease of one breast cancer patient lasted 7.5 months. CONCLUSION: Once-daily dosing of epertinib at 800 mg was well-tolerated and demonstrated promising antitumour activity in patients with heavily pretreated HER2-positive breast and upper GI cancer, including those with brain metastases. EUDRACT NUMBER: 2009-017817-31

Artificial intelligence in cancer imaging: Clinical challenges and applications

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care

Pre-surgical radiologic identification of peri-prosthetic osteolytic lesions around TKRs: a pre-clinical investigation of diagnostic accuracy

Background: Emerging longitudinal data appear to demonstrate an alarming trend towards an increasing prevalence of osteolysis-induced mechanical failure, following total knee replacement (TKR). Even with high-quality multi-plane X-rays, accurate pre-surgical evaluation of osteolytic lesions is often difficult. This is likely to have an impact on surgical management and provides reasonable indication for the development of a model allowing more reliable lesion assessment. The aim of this study, using a simulated cadaver model, was to explore the accuracy of rapid spiral computed tomography (CT) examination in the non-invasive evaluation of peri-prosthetic osteolytic lesions, secondary to TKR, and to compare this to conventional X-ray standards. Methods: A series of nine volume-occupying defects, simulating osteolytic lesions, were introduced into three human cadaveric knees, adjacent to the TKR implant components. With implants in situ, each knee was imaged using a two-stage conventional plain X-ray series and rapid-acquisition spiral CT. A beam-hardening artefact removal algorithm was employed to improve CT image quality. After random image sorting, 12 radiologists were independently shown the series of plain X-ray images and asked to note the presence, anatomic location and 'size' of osteolytic lesions observed. The same process was repeated separately for review of the CT images. The corresponding X-ray and CT responses were directly compared to elicit any difference in the ability to demonstrate the presence and size of osteolytic lesions. Results: Access to CT images significantly improved the accuracy of recognition of peri-prosthetic osteolytic lesions when compared to AP and lateral projections alone (P = 0.008) and with the addition of bi-planar oblique X-rays (P = 0.03). No advantage was obtained in accuracy of identification of such lesions through the introduction of the oblique images when compared with the AP and lateral projections alone (P = 0.13) Conclusion: The findings of this study suggest that peri-prosthetic osteolytic lesions can be reliably described non-invasively using a simple, rapid-acquisition CT-based imaging approach. The low sensitivity of conventional X-ray, even with provision of supplementary bi-planar 45° oblique views, suggests a limited role for use in situ for TKR implant screening where peri-prosthetic osteolytic lesions are clinically suspected. In contrast, the accuracy of CT evaluation, linked to its procedural ease and widespread availability, may provide a more accurate way of evaluating osteolysis around TKRs, at routine orthopaedic follow up. These findings have direct clinical relevance, as accurate early recognition and classification of such lesions influences the timing and aggressiveness of surgical and non-operative management strategies, and also the nature and appropriateness of planned implant revision or joint-salvaging osteotomy procedures.Timothy P. Kurmis, Andrew P. Kurmis, David G. Campbell and John P. Slavotine

Tumours and tremors: how PTEN regulation underlies both

Mutations of the tumour suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) are seen in many human cancers. However, dysregulation of PTEN may be involved in other disease states such as Parkinson's disease. This minireview describes recent work examining PTEN regulation and its implications for the development of both cancer and neurodegenerative disease

Is there a role for glucocorticoid receptor beta in asthma?

Glucocorticoids (GCs) are routinely used as anti-inflammatory drugs in the treatment of asthma. They act through binding to glucocorticoid receptor α (GRα), which represses numerous genes encoding pro-inflammatory mediators. A hormone binding deficient GR isoform named GRβ has been isolated in humans. When overexpressed by transfection, GRβ may function as a dominant negative modulator of GRα. However, to act as such, GRβ has to be more abundant than GRα, and conflicting data have been obtained concerning the relative levels of the two isoforms in cell lines and freshly isolated cells. Moreover, the dominant negative effect was not confirmed by independent laboratories. In GC-resistant asthmatics, GRβ was expressed by an increased number of peripheral blood mononuclear cells (PBMCs), airway T cells, and cells found in skin biopsies of tuberculin responses. However, the relative amounts of GRα and GRβ in these cells were not determined. In GC-dependent asthmatics, PBMCs expressed GRα predominantly. No cells containing higher levels of GRβ than GRα have yet been reported in asthmatics. Even if the existence of such cells is demonstrated, the role of GRβ in asthma will remain a matter of controversy because functional studies have given discrepant data

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Establishing a clinical phenotype for cachexia in end stage kidney disease - study protocol.

BACKGROUND: Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. METHODS: A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. DISCUSSION: Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education