The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI.

Left ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure.This study was supported by a grant from the Seneca Foundation-Agency of Science and Technology of the Region of Murcia (20652/JLI/18) and a grant from the Instituto de Salud Carlos III (PI19/00519) which is cofinanced through the European Union's European Regional Development Fund (FEDER). Dr. Lax is a Ramon and Cajal researcher at the Department of Medicine, University of Murcia.S

Improvement of diabetic retinopathy screening of diabetic patients seen at the Internal Medicine Clinic​​

Diabetic retinopathy (DR) is a leading cause of vision loss globally. The International Diabetes Federation (IDF) estimated the global population with diabetes to be 463 million in 2019 and 700 million in 2045. Retinopathy is a highly specific neurovascular complication of both type 1 and types 2 diabetes, and the prevalence strongly correlates to both the duration of diabetes and the level of glycemic control. Regular follow-up with early detection and treatment of vision-threatening retinopathy enables the prevention of up to 98% of visual loss due to diabetic retinopathy

Potentially inappropriate prescriptions according to explicit and implicit criteria in patients with multimorbidity and polypharmacy. MULTIPAP : a cross-sectional study

Background Multimorbidity is a global health challenge that is associated with polypharmacy, increasing the risk of potentially inappropriate prescribing (PIP). There are tools to improve prescription, such as implicit and explicit criteria. Objective To estimate the prevalence of PIP in a population aged 65 to 74 years with multimorbidity and polypharmacy, according to American Geriatrics Society Beers Criteria® (2015, 2019), the Screening Tool of Older Person’s Prescription -STOPP- criteria (2008, 2014), and the Medication Appropriateness Index -MAI- criteria in primary care. Methods This was an observational, descriptive, cross-sectional study. The sample included 593 community-dwelling elderly aged 65 to 74 years, with multimorbidity and polypharmacy, who participated in the MULTIPAP trial. Socio-demographic, clinical, professional, and pharmacological-treatment variables were recorded. Potentially inappropriate prescribing was detected by computerized prescription assistance system, and family doctors evaluated the MAI. The MAI-associated factors were analysed using a logistic regression model. Results A total of 4,386 prescriptions were evaluated. The mean number of drugs was 7.4 (2.4 SD). A total of 94.1% of the patients in the study had at least one criterion for drug inappropriateness according to the MAI. Potentially inappropriate prescribing was detected in 57.7%, 43.6%, 68.8% and 71% of 50 patients according to the explicit criteria STOPP 2014, STOPP 2008, Beers 2019 and Beers 2015 respectively. For every new drug taken by a patient, the MAI score increased by 2.41 (95% CI 1.46; 3.35) points. Diabetes, ischaemic heart disease and asthma were independently associated with lower summated MAI scores.   Conclusions The prevalence of potentially inappropriate prescribing detected in the sample was high and in agreement with previous literature for populations with multimorbidity and polypharmacy. The MAI criteria detected greater inappropriateness than did the explicit criteria, but their application was more complex and difficult to automate.Publisher PDFPeer reviewe

Role of light chain clearance in the recovery of renal function in multiple myeloma: another point of view

Lay Summary This is a retrospective multicenter study that evaluated the effectiveness of intensive haemodialysis (IHD) vs standards dialysis on renal recovery in patients with acute kidney injury (AKI) associated with myeloma multiple (MM). In this paper, we demonstrated that IHD for early light chain reduction was associated with a better renal prognosis. Another finding is the importance of maintenance diuresis as a marker of good prognosis of renal function. To our knowledge few studies have been focused in the comparison between IHD vs standard dialysis in MM patients with AKI. We consider that if we manage to recover the renal function, we achieve a great clinical impact since the patient with chronic kidney disease and especially in hemodialysis, an increased risk of mortality as well as poorer quality of life. Background Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). Methods This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. Results A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9% vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P = .024). Conclusion Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery

Primary systemic therapy in HER2-positive operable breast cancer using trastuzumab and chemotherapy: efficacy data, cardiotoxicity and long-term follow-up in 142 patients diagnosed from 2005 to 2016 at a single institution

Objective: The aim of this study was to evaluate the efficacy, cardiotoxicity profile and long-term benefits of neoadjuvant therapy in human epidermal growth factor receptor 2-positive operable breast cancer patients. Patients and methods: A total of 142 patients diagnosed from 2005 to 2016 were included in the study. The treatment consisted of a sequential regimen of taxanes and anthracyclines plus trastuzumab. The clinical and pathological responses were evaluated and correlated with clinical and biological factors. The cardiotoxicity profile and long-term benefits were analyzed. Results: The median age was 49 years, and 4%, 69% and 27% of patients had stage I, II and III breast cancer, respectively, while 10% had inflammatory breast cancer at diagnosis. Hormone receptor (HR) status was negative in 43%, and 62% had grade III breast cancer. The clinical complete response rate was 49% and 63% as assessed using ultrasound and magnetic resonance imaging, respectively, and this allowed a high rate of conservative surgery (66%). The pathological complete response (pCR) rate was 52%, and it was higher in HR-negative (64%) patients than in HR-positive (41%) patients and in grade III breast cancer (53%) patients than in grade I-II breast cancer (45%) patients. Patients who achieved pCR had longer disease-free survival and a trend toward improved overall survival. A total of 2% of patients showed a 10% decrease in left ventricular ejection fraction to <50% during treatment. All patients except one recovered after discontinuation of trastuzumab. Conclusion: A sequential regimen of taxanes and anthracyclines plus trastuzumab was effective, with high pCR rates and long-term benefit, and had a very good cardiotoxicity profile

Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established. This review summarizes the current available data concerning copy number variants in sudden cardiac death-related diseases

Using online adverts to increase the uptake of cervical screening amongst "real Eastenders": an opportunistic controlled trial.

BACKGROUND: Cervical screening uptake has increased as a result of occurrences of cervical cancer in TV 'soap operas' and in real life celebrities such as Jade Goody. Media analysis at the time of Jade Goody's death suggested the NHS did not take sufficient advantage of this opportunity to improve cervical screening rates. Google AdWords has been used to recruit and raise awareness of health but we were not aware of its use to supplement media events. METHODS: This was an opportunistic service evaluation to accompany a cervical cancer storyline in Eastenders (a TV 'soap opera'). We ran an AdWords campaign based on keywords such as 'Eastenders', and 'cervical cancer' in a one mile radius in East London, linked to one webpage giving details of 10 practices and other links on cervical cancer. We recorded costs of adverts and setting up the webpage. We used routine statistics from Tower Hamlets, City and Hackney, and Newham Primary Care Trusts (PCTs) of the number of smears, eligible populations, and coverage by practice by month from September 2010 to January 2012 to compare the ten intervention practices with controls. RESULTS: Eight people per day in the target area viewed the project webpage. The cost of setting up the website and running Google AdWords was £1320 or £1.88 per person viewing the webpage. Unlike Jade Goody's death, there was no major impact from the Eastenders' storyline on Google searches for cervical cancer. There was considerable monthly variation in the number of smear tests in the 3 PCTs. The AdWords campaign may have had some effect on smear rates but this showed, at best, a marginal statistical difference. Assuming a 'real' effect, the intervention may have resulted in 110 'extra' women being screened but there was no change in coverage. CONCLUSIONS: Although the Eastenders storyline seemed to have no effect on interest in cervical cancer or screening, the AdWords campaign may have had some effect. Given the small scale exploratory nature of the study this was not statistically significant but the relatively modest cost of advertising suggests a larger study may be worthwhile. An outline of a possible study is described

Sub-micrometric reflectometry for localized label-free biosensing

In this work we present an optical technique for characterizing sub-micrometric areas based on reflectivity of the light as a function of angle of incidence for the two pure polarizations s and p, covering a range of angles of incidence from -71.80 degrees to 71.80 degrees with a resolution of 0.1 degrees. Circular areas with a diameter in the order of 600 nm can be characterized, and the spectra for the two polarizations can be obtained with a single measurement. For biosensing purposes, we have fabricated several Bio Photonic Sensing Cells (BICELLs) consisting of interferometers of 1240 nm of SU-8 polymer over silicon. An indirect immunoassay is performed over these BICELLs and compared experimentally with FT-VIS-NIR spectrometry and theoretical calculations. The Limit of Detection (LoD) achieved is comparable with standard high resolution spectrometry, but with the capability of analyzing sub-micrometric domains for immunoassays reactions onto a sensing surface. (C) 2015 Optical Society of AmericaThis work has been partially funded under the projects under the projects PLATON (Ref: TEC2012-31145) and INNBIOD (Ref: IPT-2011-1429-01000) from the Ministerio de Economia y Competitividad (MINECO) of Spain. We acknowledge Nightingale-EOS and Stephen Morris for his contribution to the development of this optical tool.Casquel, R.; Soler, JA.; Holgado, M.; Lopez, A.; Lavin, A.; De Vicente, J.; Sanza, FJ.... (2015). Sub-micrometric reflectometry for localized label-free biosensing. Optics Express. 23(10):12544-12554. doi:10.1364/OE.23.012544S12544125542310Fan, X., White, I. M., Shopova, S. I., Zhu, H., Suter, J. D., & Sun, Y. (2008). Sensitive optical biosensors for unlabeled targets: A review. Analytica Chimica Acta, 620(1-2), 8-26. doi:10.1016/j.aca.2008.05.022Homola, J. (2008). Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species. Chemical Reviews, 108(2), 462-493. doi:10.1021/cr068107dBarrios, C. A., Bañuls, M. J., González-Pedro, V., Gylfason, K. B., Sánchez, B., Griol, A., … Casquel, R. (2008). Label-free optical biosensing with slot-waveguides. Optics Letters, 33(7), 708. doi:10.1364/ol.33.000708Estevez, M. C., Alvarez, M., & Lechuga, L. M. (2011). Integrated optical devices for lab-on-a-chip biosensing applications. Laser & Photonics Reviews, 6(4), 463-487. doi:10.1002/lpor.201100025Haes, A. J., & Van Duyne, R. P. (2002). A Nanoscale Optical Biosensor:  Sensitivity and Selectivity of an Approach Based on the Localized Surface Plasmon Resonance Spectroscopy of Triangular Silver Nanoparticles. Journal of the American Chemical Society, 124(35), 10596-10604. doi:10.1021/ja020393xKugel, V., & Ji, H.-F. (2014). Nanopillars for Sensing. Journal of Nanoscience and Nanotechnology, 14(9), 6469-6477. doi:10.1166/jnn.2014.9346Holgado, M., Barrios, C. A., Ortega, F. J., Sanza, F. J., Casquel, R., Laguna, M. F., … Maquieira, A. (2010). Label-free biosensing by means of periodic lattices of high aspect ratio SU-8 nano-pillars. Biosensors and Bioelectronics, 25(12), 2553-2558. doi:10.1016/j.bios.2010.04.042Holgado, M., Casquel, R., Sánchez, B., Molpeceres, C., Morales, M., & Ocaña, J. L. (2007). Optical characterization of extremely small volumes of liquid in sub-micro-holes by simultaneous reflectivity, ellipsometry and spectrometry. Optics Express, 15(20), 13318. doi:10.1364/oe.15.013318Rosencwaig, A., Opsal, J., Willenborg, D. L., Kelso, S. M., & Fanton, J. T. (1992). Beam profile reflectometry: A new technique for dielectric film measurements. Applied Physics Letters, 60(11), 1301-1303. doi:10.1063/1.107323Fanton, J. T., Opsal, J., Willenborg, D. L., Kelso, S. M., & Rosencwaig, A. (1993). Multiparameter measurements of thin films using beam‐profile reflectometry. Journal of Applied Physics, 73(11), 7035-7040. doi:10.1063/1.352421Leng, J. M., Chen, J., Fanton, J., Senko, M., Ritz, K., & Opsal, J. (1998). Characterization of titanium nitride (TiN) films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry. Thin Solid Films, 313-314, 308-313. doi:10.1016/s0040-6090(97)00838-9Sanza, F. J., Laguna, M. F., Casquel, R., Holgado, M., Barrios, C. A., Ortega, F. J., … Puchades, R. (2011). Cost-effective SU-8 micro-structures by DUV excimer laser lithography for label-free biosensing. Applied Surface Science, 257(12), 5403-5407. doi:10.1016/j.apsusc.2010.10.010Ho, H. P., Law, W. C., Wu, S. Y., Lin, C., & Kong, S. K. (2005). Real-time optical biosensor based on differential phase measurement of surface plasmon resonance. Biosensors and Bioelectronics, 20(10), 2177-2180. doi:10.1016/j.bios.2004.09.01