Oxygen Extraction and Mortality in Patients Undergoing Chronic Haemodialysis Treatment: A Multicentre Study.

Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypoxic parenchymal stress during HD sessions. The oxygen extraction ratio (OER), an estimate of the oxygen claimed by peripheral tissues, might represent a new prognostic factor in HD patients. This study evaluated whether the intradialytic change in OER (ΔOER) identified patients with higher mortality risks. We enrolled chronic HD patients with permanent central venous catheters with available central venous oxygen saturation (ScvO2) measurements; the arterial oxygen saturation was measured with peripheral oximeters (SpO2). We measured OER before and after HD at enrolment; deaths were recorded during two-years of follow-up. In 101 patients (age: 72.9 ± 13.6 years, HD vintage: 9.6 ± 16.6 years), 44 deaths were recorded during 11.6 ± 7.5 months of follow-up. Patients were divided into two groups according to a 40% ΔOER threshold (ΔOER < 40%, n = 56; ΔOER ≥ 40%, n = 45). The ΔOER ≥ 40% group showed a higher incidence of death (60% vs. 30%; p = 0.005). The survival curve (log-rank-test: p = 0.0001) and multivariate analysis (p = 0.0002) confirmed a ΔOER ≥ 40% as a mortality risk factor. This study showed the intradialytic ΔOER ≥ 40% was a mortality risk factor able to highlight critical hypoxic damage. Using a ΔOER ≥ 40% could be clinically applicable to characterise the most fragile patients.

Effect of Organic Fertilizers on Selected Health Beneficial Bioactive Compounds and Aroma Profile of Red Topepo Sweet Pepper.

Phytochemicals and antioxidant properties of red sweet pepper cv Topepo grown in soil amended with different organic fertilizers were compared with that grown in unamended soil. Organic fertilizers are an environmentally friendly alternative to recovery infertile soils that resulted from the intensified agricultural practices in red Topepo production. The aim was to discriminate the effects of organic fertilizers one from each other on the quality of red Topepo to find out the better sustainable fertilization practice for its cultivation. Results showed that compost from vegetable residues (CV) enhanced the synthesis of total phenols, flavonoids, ascorbic acid, vitamin E, carotenoids, anthocyanins, as well as carbohydrates, antioxidant activities, and aroma profiling, compared to horse manure (HD), compost from olive pomace (CO), and control (CTR). The results indicated a specificity between the quality of red Topepo and compost composition, highlighting that vegetable residues increased the synthesis of secondary metabolites, enhancing sustainably, the nutraceutical, sensorial, and economic value of red Topepo. The fertilizer composition resulted largely responsible for the synthesis of bioactive compounds, flavor, and aroma of this fruit.

Sulfur bentonite-organic-based fertilizers as tool for improving bio-compounds with antioxidant activities in red onion.

BACKGROUND: Red onion is popular in cuisines worldwide and is valued for its potential medicinal properties. Red onion is an important source of several phytonutrients such as flavonoids, thiosulfinates and other sulfur compounds, recognized as important elements of the diet. Nowadays, there is the need of producing food enriched in health benefit compounds. In this study, pads of sulfur bentonite (SB) with the addition of orange residue (OR) or olive pomace (OP) were used to improve the quality of red onion. The experiment was conducted for 3 months in the field to evaluate the phytochemicals of differently amended red onion. RESULTS: Treated plants were better in quality than controls. Antioxidant activity, detected as DPPH, ORAC and ABTS, was highest in plants grown in the presence of SB enriched with agricultural wastes, particularly SB-OR. Polyphenols increased in all treated plants. The volatile fraction was clearly dominated by sulfur compounds that are strictly related to the concentration of the aroma precursors S-alkenyl cysteine sulfoxides. The greater amount of thiosulfinates in treated compared with untreated onion evidenced that SB pelletized with agricultural wastes can represent a new formulation of organic fertilizer able to improve the beneficial properties of onion. The results highlighted that the best red onion quality was obtained using SB-OR pads. CONCLUSION: The use of SB bound with agricultural wastes represents a novel strategy to increase bio-compounds with beneficial effects on human health, to enhance the medical and economic values of sulfur-loving crops, with important consequences on the bio and green economy. © 2019 Society of Chemical Industry.

Impact of Different Storage Methods on Bioactive Compounds in Arthrospira platensis Biomass.

Arthrospira platensis (spirulina) is considered a source of natural molecules with nutritional and health benefits. As the different storage forms can affect the quantity and quality of bioactive ingredients, the aim of the present work was to evaluate the effects of freezing, oven-drying and freeze-drying on chemical composition of spirulina biomass. Total proteins, photosynthetic pigments and antioxidants, were analyzed and compared to respective quantities in fresh biomass. The frozen sample exhibited the highest content of phycocyanin-C, phenols, and ascorbic acid, also respect to the fresh biomass. The highest total flavonoid amount was in the freeze-dried biomass. HPLC-DAD analysis of phenolic acids revealed the presence of the isoflavone genistein, known for its therapeutic role, in all the spirulina samples. The phosphomolybdenum method (TAC) and DPPH scavenging activity were applied to determine the antioxidant activity of different samples. The highest DPPH scavenging activity was detected in fresh and freeze-dried biomass and it was positively related to carotenoid content. A positive correlation indicated that carotenoids, chlorophyll, ascorbic acid and all phenolic compounds were the major contributors to the TAC activity in spirulina biomass. The results highlighted a different functional value of spirulina biomass, depending on the processing methods used for its storage.

Three different methods for turning olive pomace in resource: Benefits of the end products for agricultural purpose.

In Mediterranean countries the olive oil industry produces, yearly, a huge quantity of pollutant wastes in a short time that are phytotoxic for their high content of phenols and wax that affect soil and groundwater quality. With the use of biological processes, we can transform these wastes into fertilizers for a sustainable agriculture. We used three different methods anaerobic digestion, aerobic digestion, and crude agricultural waste management system to produce organic fertilizers. The obtained compounds were chemically analysed to verify if their characteristics fell into the marketability limits permitted by the current Italian regulation. Their effects on soil were subsequently assessed. Results evidenced that all the by-products obtained were suitable as fertilizers. They were able to increase soil organic matter, microbial biomass, and nutrients with beneficial effects on soil fertility, but at different extent. The best effects were in the order: compost, olive pomace-sulphur-bentonite pelletized and digestate. Considering that the three different methodologies dispose different amounts of olive pomace (90% in aerobic digestion, 12% in anaerobic digestion and 5% in sulphur bentonite pelletized) in different time (4months for compost, 1month for anaerobic digestion and 1day for sulphur-bentonite pelletized) and processing set-up, each method can be differently competitive for environment and/or agriculture. Aerobic digestion has economic advantage over other alternatives and has the greatest fertilizer effect even if the production time is longer than the other two. Digestate, coming from anaerobic digestion, reduces the environmental impact of greenhouse gas emissions it is rich in nutrients and can be obtained in a shorter time than compost. Olive pomace-sulphur-bentonite pelletized represents a crude waste management systems that reduce greenhouse gas emission in the atmosphere producing fertilizers able to generate, mainly in alkaline soils, a soluble zone of nutrients while minimizing leaching losses to the environment.

Localization-controlled two-color luminescence imaging via environmental modulation of energy transfer in a multichromophoric species.

We prepared a bichromophoric species 1, made of two different bodipy dyes bridged by a d-galactose unit. 1 exhibits different emission spectra when located in different compartments of biological systems, independently of its concentration. This is an unprecedented feature for a single multicomponent molecule and is due to the dependence on the environment of the photoinduced energy transfer process occurring between its bodipy subunits. Therefore, 1 can give useful information about cell composition and ultimately anomalies without requiring the simultaneous use of several different compounds, paving the way for the use of environment-controlled inter-component energy transfer to gain cell information based on luminescence imaging.

Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas) Grown in Southern Italy.

Jatropha (Jatropha curcas L.) is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C-glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products.

Anaerobic co-digestion of recalcitrant agricultural wastes: Characterizing of biochemical parameters of digestate and its impacts on soil ecosystem.

Anaerobic digestion (AD) of organic wastes is a promising alternative to landfilling for reducing Greenhouse Gas Emission (GHG) and it is encouraged by current regulation in Europe. Biogas-AD produced, represents a useful source of green energy, while its by-product (digestate) is a waste, that needs to be safely disposal. The sustainability of anaerobic digestion plants partly depends on the management of their digestion residues. This study has been focused on the environmental and economic benefits of co-digest recalcitrant agricultural wastes such olive wastes and citrus pulp, in combination with livestock wastes, straw and cheese whey for biogas production. The aim of this work was to investigate the effects of two different bioenergy by-products on soil carbon stock, enzymes involved in nutrient cycling and microbial content. The two digestates were obtained from two plants differently fed: the first plant (Uliva) was powered with 60% of recalcitrant agricultural wastes, and 40% of livestock manure milk serum and maize silage. The second one (Fattoria) was fed with 40% of recalcitrant agricultural wastes and 60% of livestock manure, milk serum and maize silage. Each digestate, separated in liquid and solid fractions, was added to the soil at different concentrations. Our results evidenced that mixing and type of input feedstock affected the composition of digestates. Three months after treatments, our results showed that changes in soil chemical and biochemical characteristics depended on the source of digestate, the type of fraction and the concentration used. The mainly affected soil parameters were: Soil Organic Matter (SOM), Microbial Biomass Carbon (MBC), Fluorescein Diacetate Hydrolysis (FDA), Water Soluble Phenol (WSP) and Catalase (CAT) that can be used to assess the digestate agronomical feasibility. These results show that the agronomic quality of a digestate is strictly dependent on percentage and type of feedstocks that will be used to power the digester.

Sequestering ability to Cu2+ of a new bodipy-based dye and its behavior as in vitro fluorescent sensor.

A Bodipy (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) derivative has been conceived and synthesized starting from l-aspartic acid, as a selective turn-off sensor of Cu2+ ions. Its acid-base properties were determined to study the formation of metal/sensor complex species by titration of solutions each containing a different metal ion, such as Cu2+, Ca2+, Zn2+, Pb2+ and Hg2+ and different metal/sensor ratios. The speciation models allowed us to simulate the distribution of the metal/sensor complex species at the normal concentrations of the corresponding metals present in biological fluids. The distribution diagrams, obtained by varying the concentration of sensor 1, clearly indicate that sensor 1 responds selectively to Cu2+ at micromolar concentrations, even in the presence of other more abundant metal cations Ca2+. Finally, we analyzed the cellular uptake of sensor 1 on human erythrocytes and its ability to chelate Cu2+ in the cellular environment. Results indicate that it crosses the plasmatic membrane and colors the cells of a bright fluorescent red. Exposing the fluorescent cells to Cu2+ results in a complete cellular photobleaching of the red fluorescence, indicating that sensor 1 is able to detect metal changes in the cytosolic environment.

Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.

BACKGROUND: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. METHODS: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. RESULTS: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. CONCLUSION: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

Antioxidant Properties and Flavonoid Profile in Leaves of Calabrian Lavandula multifida L., an Autochthon Plant of Mediterranean Southern Regions.

Lavandula multifida is a rare short-lived plant characteristic of Mediterranean basin able to survive in hot and arid climatic conditions on poorly evolved limestone soils. In this work, we characterize the enzymatic antioxidant system and phenolic composition, as well as the antioxidant properties of L. multifida fresh leaves. Enzymatic patterns show high level of peroxidases, ascorbate peroxidase, and dehydroascorbate reductase activities, when compared with L. angustifolia. The same trend is evident in total carotenoids, ascorbic acid, and reduced glutathione, and in the total antioxidant capacity assay. Moreover, RP-DAD-HPLC analyses of EtOH extract, obtained from fresh leaves, reveal main components, carvacrol, vitexin, and 7- or 8-glucoside derivatives of hypolaetin, scutellarein, luteolin, isoscutellarein, apigenin, and chrysoeriol. The analysis of this autochthon plant depicted a series of strategies adopted by L. multifida to survive in its stressful natural habitat and richness in health-promoting compounds that can be a resource for the preservation of this variety in dangerous of extinction.

Early subclinical rejection treated with low dose i.v. steroids is not associated to graft survival impairment: 13-years' experience at a single center.

Subclinical rejection (SCR) has been variably associated with reduced graft survival, development and progression of interstitial fibrosis/tubular atrophy and chronic allograft nephropathy, but data are controversial concerning SCR treatment in terms of graft survival improvement. In this single-center retrospective study, we enrolled 174 adult kidney transplant recipients with a protocol biopsy performed at 30 days after transplantation to evaluate the incidence rate and risk factors for early SCR and its impact on 10-year graft survival. Five patients showed primary non function and were excluded. Among 159/169 (94.08 %) patients with stable graft function who underwent protocol biopsy, 17 (10.7 %) showed signs of SCR and were treated with low-dose intravenous (i.v.) steroids. Ten patients showed functional impairment, 8 (4.73 %) resulting as acute rejection. At multivariate analysis, donor age [odds ratio (OR) 1.04, 95 % confidence interval (CI) 1.01-1.09], and delayed graft function (DGF) (OR 1.08, 95 % CI 1.03-1.12) were significantly associated with SCR. The 10-year graft survival rate in the SCR group was similar to that in the normal-findings group (76.5 vs. 74.9 % respectively; p = 0.61). At multivariate Cox regression, acute [hazard ratio (HR) 5.22, 95 % CI 1.70-16.01], but not sub-clinical, rejection was independently associated with long-term graft failure. In conclusion, early protocol biopsy is a useful and safe tool to detect early SCR which seems not to affect the long-term survival. We suggest that this could be, probably, linked to early SCR treatment with low dose i.v. steroids.

Oligo(phenylene ethynylene) glucosides: modulation of cellular uptake capacity preserving light ON.

A new family of oligo(phenylene ethynylene) (OPE) glucosides has been prepared and characterized. Our results demonstrate that fine-tuning of their photophysical properties can be obtained by acting on the electronics of the core and molecular skeleton. Modulation of the hydrophobic chain length and substituents on the central moieties influences the bioaffinity too. In particular, introducing a NMe2 group on the aromatic central core affords a highly efficient biocompatible fluorescent probe that can be taken up in cytoplasmic vesicles of HEp-2 cells (cells from epidermoid carcinoma larynx tissue). The photophysical behavior, high quantum yield, and stability open the way to the use of the OPE family as stains for cellular imaging analysis by fluorescence microscopy.

Soluble Klotho levels in adult renal transplant recipients are modulated by recombinant human erythropoietin.

BACKGROUND: Data on serum soluble Klotho levels in chronic kidney disease are contradictory and even less is known after renal transplantation. Experimental studies demonstrated that recombinant human erythropoietin (rhEPO) treatment mitigates Klotho reduction caused by renal damage. Therefore, this study aimed to determine serum Klotho levels in a cohort of kidney transplant recipients (KTR) and to evaluate whether rhEPO treatment can modulate, in vivo and in vitro, soluble Klotho. METHODS: 117 KTR and 22 healthy subjects (HS) were enrolled. In 17 KTR, rhEPO was discontinued for 5 weeks and Klotho levels were compared to 34 propensity score-matched controls. Moreover, we evaluated Klotho mRNA expression and protein secretion in HK-2 tubular cells treated with cyclosporin A (CyA) and rhEPO, alone or in combination. RESULTS: Serum Klotho levels in KTR were significantly higher than in HS (0.68 vs. 0.37, p = 0.002) and significantly associated with estimated glomerular filtration rate (r = -0.378, p = 0.003) and fibroblast growth factor 23 (r = -0.307, p < 0.0001). After 5 weeks of rhEPO discontinuation, treated KTR showed a sharper reduction of Klotho levels than controls (-0.56 vs. -0.11 ng/ml, p < 0.0001). In HK-2 cells CyA treatment induced a Klotho down-regulation that was mitigated by rhEPO pre-treatment. In the same experimental conditions, our results revealed that cells treated with CyA + rhEPO secreted higher soluble Klotho levels than those exposed to CyA or rhEPO alone. CONCLUSIONS: Our results demonstrate that KTR have higher serum Klotho levels than HS and that rhEPO treatment modulates these concentrations, suggesting a link between rhEPO and soluble Klotho in KTR.

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives.

A new class of molecules with a triptycene rigid core surrounded by six monosaccharide residues was synthesized. Hexakis(bromomethyl) substituted triptycene was converted into a six-armed triptycene azide (2,3,6,7,14,15-hexakis(azidomethyl)-9,10-dihydro-9,10-[1',2']benzenoanthracene). The key step of the synthesis was the cycloaddition of the azide to 2-propyn-1-yl ß-D-gluco- or galactopyranosides. All products were isolated in good yields and were fully characterized.

Exposure to nerve growth factor worsens nephrotoxic effect induced by Cyclosporine A in HK-2 cells.

Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkA(NTR) and p75(NTR). Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 (NTR) and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75(NTR) down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.

Adiponectin is expressed and secreted by renal tubular epithelial cells.

BACKGROUND: Adiponectin (ADPN) is predominantly produced by adipose tissue, and high ADPN levels have been detected in patients affected by proteinuric glomerulonephritis. In this study we investigate whether human tubular epithelial cells express and secrete ADPN. METHODS: In human proximal tubular epithelial cells, HK-2, ADPN mRNA was evaluated by real-time PCR assay, while protein expression levels were measured by Western blot analysis and immunofluorescence assay. Moreover, renal ADPN distribution was assessed by immunohistochemical analysis of kidney biopsy samples from healthy patients. Finally, by ELISA, we measured ADPN concentrations in culture media of HK-2 cells treated with 10 µg/mL lipopolysaccharide (LPS). RESULTS: Our analyses revealed that HK-2 cells express ADPN both in terms of mRNA and protein. These results were confirmed by the observed cytoplasmatic HK-2 intense immunoreactivity for ADPN antibody and by immunohistochemical analysis showing a diffuse ADPN distribution in normal kidney tissue. Furthermore, we observed that tubular cells secrete ADPN in the basal condition and, more interestingly, that this secretion significantly increases (p<0.05) upon LPS treatment in a time-dependent manner. Finally, immunohistochemical analysis of kidney biopsy samples obtained from patients affected by membranous and rapidly progressive glomerulonephritis showed a similar pattern of ADPN staining to that observed in healthy controls. CONCLUSIONS: Our study demonstrates for the first time that renal tubular cells express and secrete ADPN, and their concentration increases upon inflammatory stimulus. These results suggest that in renal inflammatory diseases, tubular cells may contribute to the increase in circulating ADPN levels, triggering a feedback response in order to self-mitigate the inflammatory process.

Anthropometric measures can better predict high blood pressure in adolescents.

BACKGROUND: Among children, obesity and overweight may be predictors of cardiovascular (CV) risk. The purpose of this study was to examine whether body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR) were related to blood pressure (BP) among healthy southern Italian students enrolled in 3 different secondary schools. METHODS: Weight, height, BP and WC were measured; BMI and WHtR were calculated for 872 Italian students. Based on percentiles of BMI, the subjects were classified as underweight, normal weight, overweight or obese. Systolic BP or diastolic BP >95th percentile were considered as high BP values (according to the 2004 guidelines of the US National Heart, Lung, and Blood Institute). Central obesity was defined as WC >75th percentile or WHtR =0.5. RESULTS: Of the students, 8.7% were obese, 29% with WC >75th percentile and 29.5% with WHtR >0.5, while 4.6% showed high BP. Logistic regression showed a strong correlation between BMI and high BP (odds ratio [OR] = 1.030, p<0.0001), between WC and high BP (OR = 1.029, p<0.0001). Also WHtR (OR = 3.403, p<0.0001) was shown to be a predictor of high BP. In the male group, all of the variables considered showed a good capability to predict high BP, while in the females, only BMI (OR = 1.019, p<0.05) and WHtR (OR = 2.685, p<0.05) were associated with high BP. CONCLUSIONS: In this study, we found a different correlation between BMI, WC and BP in the 2 subgroups: males and females. Only WHtR showed a significant ability to predict high BP in both groups. WHtR might represent an easily measurable anthropometric index and a better predictor of CV risk in adolescents.

Artificial light-harvesting antenna systems grafted on a carbohydrate platform.

An enantiopure α-D-glucopyranoside derivative has been used as a platform to prepare artificial antenna systems based on bodipy subunits. Efficient and ultrafast energy transfer (in the fs and ps time regimes) takes place in the multibodipy systems.