SGLT2 Inhibitors and the Diabetic Kidney

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether SGLT2 inhibitors, in addition to their glycemic and blood pressure benefits, may provide nephroprotective effects

Evaluation of vegetation post-fire resilience in the Alpine region using descriptors derived from MODIS spectral index time series

In this study a method based on the analysis of MODerate-resolution Imaging Spectroradiometer (MODIS) time series is proposed to estimate the post-fire resilience of mountain vegetation (broadleaf forest and prairies) in the Italian Alps. Resilience is defined herewith as the ability of a dynamical system to counteract disturbances. It can be quantified by the amount of time the disturbed system takes to resume, in statistical terms, an ecological functionality comparable with its undisturbed behavior. Satellite images of the Normalized Difference Vegetation Index (NDVI) and of the Enhanced Vegetation Index (EVI) with spatial resolution of 250m and temporal resolution of 16 days in the 2000-2012 time period were used. Wildfire affected areas in the Lombardy region between the years 2000 and 2010 were analysed. Only large fires (affected area >40ha) were selected. For each burned area, an undisturbed adjacent control site was located. Data pre-processing consisted in the smoothing of MODIS time series for noise removal and then a double logistic function was fitted. Land surface phenology descriptors (proxies for growing season start/end/length and green biomass) were extracted in order to characterize the time evolution of the vegetation. Descriptors from a burned area were compared to those extracted from the respective control site by means of the one-way analysis of variance. According to the number of subsequent years which exhibit statistically meaningful difference between burned and control site, five classes of resilience were identified and a set of thematic maps was created for each descriptor. The same method was applied to all 84 aggregated events and to events aggregated by main land cover. EVI index results more sensitive to fire impact than NDVI index. Analysis shows that fire causes both a reduction of the biomass and a variation in the phenology of the Alpine vegetation. Results suggest an average ecosystem resilience of 6-7 years. Moreover, broadleaf forest and prairies show different post-fire behavior in terms of land surface phenology descriptors. In addition to the above analysis, another method is proposed, which derives from the qualitative theory of dynamical systems. The (time dependent) spectral index of a burned area over the period of one year was plotted against its counterpart from the control site. Yearly plots (or scattergrams) before and after the fire were obtained. Each plot is a sequence of points on the plane, which are the vertices of a generally self-intersecting polygonal chain. Some geometrical descriptors were obtained from the yearly chains of each fire. Principal Components Analysis (PCA) of geometrical descriptors was applied to a set of case studies and the obtained results provide a system dynamics interpretation of the natural process.JRC.H.3 - Forest Resources and Climat

Modeling Gross Primary Production of Agro-Forestry Ecosystems by Assimilation of Satellite-Derived Information in a Process-Based Model

In this paper we present the results obtained in the framework of a regional-scale analysis of the carbon budget of poplar plantations in the northern Italy. We explored the ability of the processbased model BIOME-BGC to estimate the gross primary production (GPP) of these agro-forestry ecosystems exploiting eddy covariance and satellite data using an inverse modeling approach. We present a modified version of BIOME-BGC (named PROSAILH-BGC) which was coupled with the radiative transfer models PROSPECT and SAILH with the aims of i) improving the BIOME-BGC description of the radiative transfer regime within the canopy and ii) allowing the assimilation of remotely-sensed vegetation indexes time series, such as MODIS NDVI, into the BIOME-BGC. In summary, this study showed that assimilation of eddy covariance and remote sensing data in a process model can provide important information for estimating the carbon budget at regional scale.JRC.H.2 - Climate chang

Discriminating irrigated and rainfed maize with diurnal fluorescence and canopy temperature airborne maps

This study evaluates the potential of airborne remote sensing images to detect water stress in maize. Visible and near infrared CASI (Itres Research Ltd., Canada) and thermal AHS-160 (Sensytech Inc., USA) data were acquired at three different times during the day on a maize field (Zea mays L.) grown with three different irrigation treatments. An intensive field campaign was also conducted concurrently with image acquisition to measure leaf ecophysiological parameters and the Leaf Area Index (LAI). The analysis of the field data showed that maize plants were experiencing moderate to severe water stress in rainfed plots and a weaker stress condition in the plots with water deficit imposed between stem elongation and flowering. Vegetation indices including the normalized difference vegetation index (NDVI) and the photochemical reflectance index (PRI) computed from the CASI images, sun-induced chlorophyll fluorescence and canopy temperature (Tc) showed different performances in describing the water stress during the day. During the morning overpasses NDVI was the index with the highest discriminant power. As the day progressed, processes related to heat dissipation through plant transpiration became more and more important and at midday Tc showed the best performances. Furthermore, Tc retrieved from the midday image was the only index able to distinguish all the three classes of water status. Finally, during the afternoon PRI and F760 showed the best performances. These results demonstrate the feasibility to detect water stress using thermal and optical airborne data, pointing out the importance of a careful planning of the airborne surveys as a function of the specific aims of the study.JRC.H.4 - Monitoring Agricultural Resource

Remote sensing-based estimation of gross primary production in a subalpine grassland

This study investigates the performances in a terrestrial ecosystem of gross primary production (GPP) estimation of a suite of spectral vegetation indexes (VIs) that can be computed from currently orbiting platforms. Vegetation indexes were computed from near-surface field spectroscopy measurements collected using an automatic system designed for high temporal frequency acquisition of spectral measurements in the visible near-infrared region. Spectral observations were collected for two consecutive years in Italy in a subalpine grassland equipped with an eddy covariance (EC) flux tower that provides continuous measurements of net ecosystem carbon dioxide (CO2) exchange (NEE) and the derived GPP. Different VIs were calculated based on ESA-MERIS and NASA-MODIS spectral bands and correlated with biophysical (Leaf area index, LAI; fraction of photosynthetically active radiation intercepted by green vegetation, f IPARg), biochemical (chlorophyll concentration) and ecophysiological (green light-use efficiency, LUEg) canopy variables. In this study, the normalized difference vegetation index (NDVI) was the index best correlated with LAI and f IPARg (r = 0.90 and 0.95, respectively), the MERIS terrestrial chlorophyll index (MTCI) with leaf chlorophyll content (r = 0.91) and the photochemical reflectance index (PRI551), computed as (R531 −R551)/(R531 +R551) with LUEg (r = 0.64). Subsequently, these VIs were used to estimate GPP using different modelling solutions based on Monteith’s lightuse efficiency model describing the GPP as driven by the photosynthetically active radiation absorbed by green vegetation (APARg) and by the efficiency (") with which plants use the absorbed radiation to fix carbon via photosynthesis. Results show that GPP can be successfully modelled with a combination of VIs and meteorological data or VIs only. Vegetation indexes designed to be more sensitive to chlorophyll content explained most of the variability in GPP in the ecosystem investigated, characterised by a strong seasonal dynamic of GPP. Accuracy in GPP estimation slightly improves when taking into account high frequency modulations of GPP driven by incident PAR or modelling LUEg with the PRI in model formulation. Similar results were obtained for both measured daily VIs and VIs obtained as 16-day composite time series and then downscaled from the compositing period to daily scale (resampled data). However, the use of resampled data rather than measured daily input data decreases the accuracy of the total GPP estimation on an annual basis.JRC.H.4-Monitoring Agricultural Resource

Obesity management: at the forefront against disease stigma and therapeutic inertia

Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible "persuading" the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out ("eat less and move more") creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence

Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance

Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed.In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy.Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSApT2) and upgrading (GS≥7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage>pT2 and predominant Gleason score 4. Total testosterone was measured before surgery.Low serum testosterone levels (<300 ng/dL) were significantly associated with upgrading, upstaging, unfavorable disease and positive surgical margins. The addition of testosterone to a base model, including age, PSA, PSA density, clinical stage and positive cancer involvement in cores, showed a significant independent influence of this variable on upstaging, upgrading and unfavorable disease.In conclusion, our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor when a close AS program is considered as treatment option

Obesity, Male Reproductive Function and Bariatric Surgery

Overweight and obesity are associated with several chronic complications, such as type 2 diabetes, arterial hypertension and atherosclerotic cardiovascular diseases, with relevant consequences for patients and public health systems. Reproductive function abnormalities, such as obesity-related secondary hypogonadism, erectile dysfunction and infertility, represent other abnormalities negatively affecting the quality of life of men suffering from obesity but, despite their high prevalence, these are often understated because of a general lack of awareness in clinical practice. Obesity and gonadal function are closely related, with obesity being associated with hypogonadism that is reversed by body weight reduction thus ameliorating reproductive and sexual health. Clinical studies specifically evaluating the impact of non-surgical weight loss on testosterone levels sometimes showed conflicting results, whereas extensive literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in testosterone levels greater than that obtained with only lifestyle interventions, suggesting the role of surgery also for the treatment of hypogonadism in obese male. However, studies concerning the consequences of bariatric surgery on overall reproductive function in the male, including also sexual activity and fertility, are limited and data regarding long-term effects are lacking. Here we present a brief review summarizing the evidence regarding the interplay between obesity and reproductive abnormalities in the obese male, together with the role of bariatric surgery for the treatment of these complications, describing both the positive effects and the limitations of this procedure