Epigenetic therapies for heart failure: Current insights and future potential

Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy (“epidrugs”) is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF

Corticosteroid-Sparing Effect of Chromoglycate Sodium and Nedocromil

The most appropiate management for bronchial asthma is the control of airway inflammation. Corticosteroids are the most effective anti-inflammatory drugs available, but they have a number of side effects; most of these are dose-dependent. In children, asthma control should be accomplished with low steroid doses possibly given by inhalation. In a double-bind placebo-controlled crossover study a group of children with mild to moderate asthma received NED 16 mg/day or BDP 400 μg/day. Values for FEV1, PEF, symptoms use ofbronchodilators overlapped, whereas bronchial hyper-responsiveness assessed by histamine bronchoprovocation challenge was better with BDP than NED. In another case, one boy with high bronchial hyper-reactivity assessed by provocation test with hypertonic solution, experienced a significant improvement only after 2 weeks of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on combined treatment with NED (16 mg/day) and BDP (300 μ/day). Authors conclude that NED could have a steroidsparing effect over long-term use

Impact of radar data assimilation for the simulation of a heavy rainfall case in central Italy using WRF–3DVAR

Abstract. The aim of this study is to investigate the role of the assimilation of Doppler weather radar (DWR) data in a mesoscale model for the forecast of a heavy rainfall event that occurred in Italy in the urban area of Rome from 19 to 22 May 2008. For this purpose, radar reflectivity and radial velocity acquired from Monte Midia Doppler radar are assimilated into the Weather Research Forecasting (WRF) model, version 3.4.1. The general goal is to improve the quantitative precipitation forecasts (QPF): with this aim, several experiments are performed using the three-dimensional variational (3DVAR) technique. Moreover, sensitivity tests to outer loops are performed to include non-linearity in the observation operators. In order to identify the best initial conditions (ICs), statistical indicators such as forecast accuracy, frequency bias, false alarm rate and equitable threat score for the accumulated precipitation are used. The results show that the assimilation of DWR data has a large impact on both the position of convective cells and on the rainfall forecast of the analyzed event. A positive impact is also found if they are ingested together with conventional observations. Sensitivity to the use of two or three outer loops is also found if DWR data are assimilated together with conventional data

Net gain: Low-cost, trawl-associated eDNA samplers upscale ecological assessment of marine demersal communities

Marine biodiversity stewardship requires costly and time-consuming capture-based monitoring techniques, which limit our understanding of the distribution and status of marine populations. Here, we reconstruct catch and demersal community compo- sition in a set of 24 fishing sites in the central Tyrrhenian Sea by gathering environ- mental DNA (eDNA) aboard commercial bottom-trawl fishing vessels. We collected genetic material from two sources: the water draining from the net after the end of hauling operations (“slush”), and custom-made rolls of gauze tied to a hollow perfo- rated sphere placed inside the fishing net (“metaprobe”). Species inventories were generated using a combination of fish-specific (Tele02 12S) and universal metazoan (COI) molecular markers. DNA metabarcoding data recovered over 90% of the caught taxa and accurately reconstructed the overall structure of the assemblages of the examined sites, reflecting expected differences linked to major drivers of community structure in Mediterranean demersal ecosystems, such as depth, distance from the coast, and fishing effort. eDNA also returned a “biodiversity bonus” mostly consisting of pelagic species not catchable by bottom trawl but present in the surrounding en- vironment. Overall, the “metaprobe” gauzes showed a greater biodiversity detection power as compared to “slush” water, both qualitatively and quantitatively, strengthen- ing the idea that these low-cost sampling devices can play a major role in upscaling the gathering of data on both catch composition and the broader ecological charac- teristics of marine communities sustaining trawling activities. This approach has the potential to drastically expand the reach of ecological monitoring, whereby fishing vessels operating across the oceans may serve as opportunistic scientific platforms to increase the strength and granularity of marine biodiversity data

487 Left atrial strain/strain rate analysis in patients with dilated cardiomyopathy. correlation with clinical, electrocardiographic and echocardiographic findings

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