Effects of erythropoietin therapy on the lipid profile in end-stage renal failure

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure. To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 ± 0.3 (mean ± SEM) months later and 53 patients underwent a further assessment 13.1 ± 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 ± 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 ± 0.1 vs. 9.9 ± 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 ± 99 vs. 399 ± 69 µg/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 ± 0.1 vs. 5.4 ± 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 ± 0.04 vs. 1.04 ± 0.06; P < 0.05) and serum triglycerides (2.26 ± 0.14 vs. 1.99 ± 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement. These changes correlated with the increase in Hb (P < 0.001 in each case), and the reduction in ferritin for total cholesterol (P < 0.02), LDL cholesterol (P < 0.03), and to a lesser extent apoprotein B (P < 0.07). No difference was observed in patients using maintenance HD or CAPD, and similar trends were observed in male and female patients. Improvements in the lipid profile occurred independently of the time on dialysis prior to the commencement of EPO. We conclude that EPO treatment is associated with alterations in the lipid profile which may suggest a long-term improvement in the vascular morbidity of chronic renal failure. The causes of the improved lipids are not addressed by this study and may be equally due to a direct or secondary benefit of EPO therapy

Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals

<p>Abstract</p> <p>Background</p> <p>Notch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways.</p> <p>Results</p> <p>We show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells (by the insulin pathway), in T-cells (via TCR activation) or in neurons (via TrKB activation) potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals.</p> <p>Conclusion</p> <p>The PI3K-Akt pathway acts as a "gain control" for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses.</p

Innovation in Diabetes - Ideas and Initiatives

A collection of multiple reports on MyDiabetesMyWay (MDMW). Included reports are: MyDiabetesMyWay Patient Portal; MyDiabetesMyWay e-learning hub (Moodle) ; SCI-diabetes/ MDMW Communication Portal- Tools for Remote Communication/ Consultation; Risk Modelling for Care Planning- integration into Informatics Dashboard for Clinical Use; Access to Chronic Medication Service (CMS) and Pharmaceutical Care Planning Medication and Lifestyle Coaching; Multi-media Diabetes Resources; Promoting Diabetes Education; Tele-Pharmacy; Understanding my diabetes medication; Pharmaceutical Industry and Medical Technology (PIMTs); An on-line and interactive education system for young people with type 1 diabetes to understand self-management for their lifestyle; Proof of Concept study to deliver personalised use of information to support diabetes management and behaviour change; right information; right time; right way; Virtual promotion of physical activity for people with type 2 diabetes; Remote foot ulcer management: RAPID (Reducing Amputation in People with Diabetes); Diabetic foot screening – development of technology; Portable capillary HbA1c testing for diagnosis and self-monitoring of diabetes; Possibility of mobile phone adaption for testing; Web app for decision support for patients with type 1 diabetes undertaking sport or exercise; Online level 3 structured education for type 1 diabetes; My Diabetes My Way electronic personal health record – uptake at scale; TeleClinics for diabetes; Develop a diabetes sim / game in which the main character has diabetes. Young people need to keep the sim / character alive as they face the various challenges of life or the game; Development of meaningful automated glucose data to in-patient clinical areas; In-patient Care: Integrated eHealth solutions to improve patient care, safety and outcomes; Innovative model of care to address the 'process of care' in managing people with long term conditions; Young Persons Remote Clinic Consultation; Maximise use of the data to support self-management of patients with co-morbidities; Virtual practice outreach and education in primary care

Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy

Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5′ AMP-activated protein kinase (AMPKα1/α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment

Prevalence of new variants of Chlamydia trachomatis escaping detection by the Aptima Combo 2 assay, England, June to August 2019

At the end of April 2019, Public Health England (PHE) was alerted, via an international Epidemic Intelligence System-Sexually Transmitted Infections (EPIS-STI) post from Finland, of false-negative Chlamydia trachomatis (CT) test results using the Aptima Combo 2 (AC2) assay (Hologic Inc., San Diego, California, United States (US)), a nucleic acid amplification test (NAAT) for CT (target: 23S rRNA) and Neisseria gonorrhoeae (GC) (target: 16S rRNA). Discrepant results between the AC2 assay and the Aptima Chlamydia trachomatis assay (ACT) (target: 16S rRNA) were reported to have occurred primarily in specimens that had AC2 relative light units (RLU) from 20 to 84 [1]. These false-negative AC2 results [2,3] were attributed to a C1515T mutation in the CT 23S rRNA gene. In early June 2019, Hologic Inc. issued a Field Safety Notice (FSN) to AC2-using laboratories, recommending ACT reflex retesting of AC2 CT-negative with RLU ≥ 15, CT-equivocal, or GC-equivocal/-positive (if CT-negative/equivocal) specimens to ensure detection of the Finnish new variant CT strain (F-nvCT) [3]. A European Centre for Disease Prevention and Control (ECDC) rapid risk assessment recommended countries estimate the spread of F-nvCT to inform the need for patient recall and retesting [4]. Here we report results from an investigation coordinated by a multiagency incident management team (IMT) to ascertain the prevalence of new variants of Chlamydia trachomatis escaping detection by the Aptima Combo 2 assay in England

Disorders of sex development : insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. Results: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46, XY DSD and 48 with 46, XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46, XY DSD. In patients with 46, XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Conclusions: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes