Neutropenia is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with esti-mated glomerular filtration rate (eGFR) 60–89 ml/min/1.73m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophy-laxis of FN. The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of cre-atinine assessment enabled the use of the newly recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration. Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR<60ml/min/1.73m2, while 15 (62.5%) eGFR< 90ml/min/1.73m2. The relative risk of neutro-penia in patients with impaired eGFR was over six times higher than in patients with eGFR>90 ml/min/1.73m2 (RR=6.08; 95%CI:1.45–27.29; p< 0.01). Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.

Background: Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) is a natural antagonist of the CXC chemokine receptor 4 (CXCR4). EPI-X4 is a 16-mer peptide that is released from human serum albumin (HSA) by acidic aspartic proteases such as Cathepsin D and E. Since human serum albumin (HSA) is an important medicinal substance we asked whether different pharmaceutical HSA products contain EPI-X4 which could have been generated during manufacturing and whether HSA can serve as a substrate for cathepsins despite of the presence of stabilizers like caprylate. Methods: Eight pharmaceutical HSA preparations representing all currently used fractionation technologies were analyzed. The previously described specific EPI-X4 ELISA was used for quantification; in vitro EPI-X4 generation by acidification in the presence or absence of cathepsins was followed by quantification with ELISA. Results: None of the pharmaceutical HSA preparations tested contained EPI-X4. Acidification of HSA did not generate EPI-X4. Addition of cathepsins D and E to acidified HSA yielded high concentrations of EPI-X4 in all HSA preparations, indistinguishable between individual products. Conclusion: Medicinal HSA preparations per se do not contain EPI-X4, but will replenish its precursor which can be cleaved to EPI-X4 in vivo, environmental conditions permitting.

Erythropoiesis is a complex process driving the production of red blood cells. During homeostasis, adult erythropoiesis takes place in the bone marrow and is tightly controlled by erythropoietin (EPO), a central hormone mainly produced in renal EPO-producing cells. The expression of EPO is strictly regulated by local changes in oxygen partial pressure (pO₂) as under deprived oxygen (hypoxia) the transcription factor Hypoxia Inducible Factor-2 induces EPO. However, erythropoiesis regulation extends beyond the well-established HIF-EPO axis, and involves processes modulated by other hypoxia pathway proteins (HPPs), including proteins involved in iron metabolism. The importance of a number of these factors is evident as their altered expression has been associated with various anemia-related disorders, including chronic kidney disease. Eventually, our emerging understanding of HPPs and their regulatory feedback will be instrumental in developing specific therapies for anemic patients and beyond.

In December 2019, an animal human coronavirus transmission occurred in Wuhan, China. A state of global pandemic was shortly declared, among a very rapid contagious spread of the virus. The causative virus was identified as SARS CoV 2 virus and is genetically related to the previous SARS outbreak in 2003. The virus causes wide clinical spectrum from mild flu like symptoms to adult respiratory distress syndrome. Kidney involvement has been reported in several reports in patients with various degrees of severity of SARS CoV2 infection. As knowledge is evolving, the accurate incidence of AKI is not known. Many questions are yet to be answered as regards the effect of epidemiological variables and comorbidities on the occurrence of AKI. Some reports have observed the occurrence of hematuria and proteinuria in a percentage of infected patients. Moreover, chronic kidney disease has not been found in some reports to add to the adverse outcomes, an aspect that merits further exploration. Patients on regular hemodialysis may be vulnerable to contagion due to lower status of immunity and need for frequent attendance to healthcare facilities. Due to the previous factors, prevention and mitigation of SARS CoV2 virus in this vulnerable population constitutes a major challenge.

Advanced derivatives of the CXCR4 antagonist EPI-X4 have shown therapeutic efficacy upon topical administration in animal models of asthma and dermatitis. Here, we studied plasma stability of the EPI-X4 lead compounds WSC02 and JM#21, using mass spectrometry to monitor the chemical integrity of the peptides and a functional fluorescence-based assay that determines peptide function in a CXCR4-antibody competition assay. Although mass spectrometry revealed a very rapid disappearance of both peptides in human plasma within seconds, the functional assay revealed a significantly higher half-life of 9 minutes for WSC02 and 6 minutes for JM#21, respectively. Further analyses demonstrated that WSC02 and JM#21 interact with low molecular weight plasma components and serum albumin. Albumin binding is mediated by the formation of a disulfide bridge between Cys10 in the EPI-X4 peptides and Cys34 in albumin. These covalently linked albumin-peptide complexes have a higher stability in plasma as compared to the non-bound peptides and retain the ability to bind and antagonize CXCR4. Remarkably, chemically synthesized albumin-EPI-X4 conjugates coupled by non-breakable bonds have a drastically increased plasma stability of over 2 hours. Thus, covalent coupling of EPI-X4 to albumin in vitro before administration or in vivo post administration may significantly increase the pharmacokinetic properties of the new class of CXCR4 antagonists.

One of creators of quantum mechanics P. Jordan in his work on quantum biology claimed that life's missing laws were the rules of chance and probability of the quantum world. The article presents author’s results of studying frequencies (or probabilities) of nucleotides on so-called epi-chains of long DNA sequences of various eukaryotic and prokaryotic genomes. DNA epi-chains are algorithmically constructed subsequencies of DNA nucleotide sequences. According to the algorithm of construction of any epi-chain of the order n, the epi-chain is such nucleotide subsequence, in which the numerations of adjacent nucleotides differ by natural number n (n = 1, 2, 3, 4,…). Correspondingly each epi-chain of order n ≥ 2 contains n times less nucleotides than the original DNA sequence. The presented results unexpectedly discover that in long single-stranded and double-stranded DNA of any tested genome its DNA epi-chains of different orders n (values n are not too large) have practically identical frequencies (or probabilities) of each kind of nucleotides. These data allow considering DNA as a regular rich set of epi-chains, which can play a certain role in genetic and epigenetic phenomena as the author belives. Appropriate rules of nucleotide frequencies on epi-chains of long DNA sequences are formulated for further their tests on a wider set of genomes. These results testify on existence of long-range coherence in long DNA and remind the Fröhlich's theory of long-range coherence in biological systems. The phenomenological data are discussed from different standpoints: the DNA double helices and helical antennas with circular polarizations of electromagnetic waves; relations with the Fröhlich's theory; numerical analysis of DNA epi-chains under binary representations of nucleotides. Results are useful for developing quantum and algebraic biology.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.

Hyperkalemia burden in non-dialysis CKD under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalemia (sK≥5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of ESKD and death after visit 2. Age was 65±15 y, eGFR 35±17 mL/min/1.73 m2, proteinuria 0.40 (0.14-1.21) g/24h. In the two visits sK was 4.8±0.6 and levels ≥6 mEq/L were observed in  4%. Hyperkalemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis [sub-hazard ratio-sHR, 95%Confidence Interval-CI] evidenced that new onset [sHR 1.34, 95%CI 1.05-1.72] and persistent [sHR 1.27, 95%CI 1.02-1.58] hyperkalemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalemia status is common (37%) and predicts per se higher ESKD risk but not mortality.

Chronic Kidney Disease (CKD) is one of the worldwide health threats, kidneys may be affected by internal pathologies and environmental factors as well as a number of genes are also involved in the kidney dysfunctioning, so UMOD is one of these genes which has significant effect in regulating urea and creatinine level in blood and decreased excretion of uric acid which causes interstitial damages in kidney and may result CKD. Hence, the present study is envisaged to observe the association of this gene locus (r.1264T>C) with CKD in Pakistani population using ARMS-PCR genotyping, for the purpose, a total of 75 samples were investigated, out of which 45 were found homozygous wild-type, 21 heterozygous and 09 homozygous mutants. PLINK data analysis toolset showed that our sampled population does not obeys Hardy-Weinberg Equilibrium by χ² (2, N = 75) = 18.87, p = and Chi-square statistics with p = 1.40×10^-005 showing a significant genotypic association with the subject phenotype with an alternative allele frequency of 0.15 and 0.48 within cases & controls respectively. Furthermore, an odds-ratio of 0.2 predicts that the risk of wild-type allele (A) is 0.8 times higher in patient as compared to controls and mutant allele is 0.2 times preventive in patients. Additionally, a few bioinformatics tools e.g., ProtParam, PsiPred, TMHMM-2.0, Motif Scan, ScanProsite, NetPhos3.1, GPS PAIL2.0, NetOGlyc4.0, PRmePRed, PDB-RCSB and STRING were applied to predict different characteristics of Uromodulin protein including physicochemical properties, secondary/transmembrane structures, protein conserved domains and posttranslational modifications respectively. This pilot scale study provided a comprehensive insight of the association of aforementioned genetic variant with CKD to identify and evaluate the genetic risk factors along with functional effects of the subject variant which may be used as CKD prevention by adopting DNA screening and genetic counselling recommendations.

Expression levels of Cav3.2, BKCa, and anoctamin 1 were previously found to be significantly elevated in patients with chronic kidney disease–associated pruritus (CKD-aP). On the other hand, the expression of TRPV1 was significantly reduced. We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels in the skin, including in peripheral nerve endings。Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative real-time polymerase chain reaction to measure the skin expression levels of the following ion channels in the skin: Nav1.7, Kv7.2, TREK1, HCN2, TrkA, and Piezo2.　RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.

Chronic kidney disease (CKD) affects worldwide 8-16% of the population. In developed countries, the most important risk factors for CKD are diabetes, hypertension and obesity, calling into question the importance of educating and acting on lifestyles and nutrition. A balanced nutrition and supplementation can indeed support the maintenance of a general health status, including preservation of renal function, and help to manage and curb the main risk factors for renal damage. While the concepts of protein and salt restriction in nephrology are historically acknowledged, the role of some nutrients on renal health and the importance of nutrition as a preventative measure for renal care are less known. In this review, we provide an overview of the demonstrated and potential actions of some selected nutrients, nutraceuticals and xenobiotics on renal health and function. The effects on kidney of fibres, proteins, fatty acids, curcumin, steviol glycosides, green tea, coffee, nitrates, nitrites, and alcohol, both direct and indirect, in CKD and non-CKD condition, are reviewed here. In a view of a functional and personalized nutrition, understanding the renal and systemic effects of dietary components is essential since many chronic conditions and CKD are related to systemic dysfunctions such as chronic low-grade inflammation.

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative and antineoplastic activities. Recently, different studies have shown that flavonoid have the potential to inhibit BET bromodomains. Previous reports suggest that flavonoids are putative inhibitors of the ZA channel due to their orientation and interactions with P86, V87, L92, L94 and N140. Herein, a comprehensive characterization of the binding mode of the biflavonoid amentoflavone and fisetin is discussed. To this end, both compounds were docked with BRD4 using four docking programs. Results were post-processed with protein-ligand interaction fingerprints. To gain further insights into the binding mode of the two natural products, docking results were further analyzed with molecular dynamics. Results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as basis for scaffold optimization and further characterization of flavonoids as BET inhibitors.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i act by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy is scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy defibrillator (CRT-D) is preferred in patients that meet the established criteria. The need for cardiac pacing is 3-fold higher in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

Cannabis Sativa L. has been used for a long time to obtain food, fiber and as a medicinal and psychoactive plant. Today the nutraceutical potential of C. Sativa is being increasingly reappraised; however, C. Sativa roots remain poorly studied, despite citations in the scientific literature. In this direction, we identified and quantified the presence of valuable bioactives (namely β-sitosterol, stigmasterol, campesterol, friedelin and epi-friedelanol) in the root extracts of C. Sativa, a finding which might pave the way to the exploitation of the therapeutic potential of C. Sativa in all its parts. To facilitate roots harvesting and processing, aeroponic (AP) and aeroponic elicited cultures (AEP), have been set up and compared to soil-cultivated plant (SP): interestingly a considerable overgrowth of the plants - particularly of roots - and a significant increase (up to 20 fold in the case of β-sitosterol) in the total content of the above roots’ bioactive molecules have been observed in AP and AEP. In conclusion aeroponics, an easy, standardised, free of contaminant cultivation tecchnique, allows an ease harvesting/processing of roots along with a greater production of their secondary bioactive metabolites which could be utilized in the formulation of health promoting and health care products.

Background: Recommended CKD first-line diagnostics is based on GFR-determination by Creatinine. Cystatin C-use may provide better assessment. Methods: We compared creatinine- and cystatin C-derived eGFR determination in first-line di-agnostic of 112 hospital patients aged >60 years (median=76 years). Patients were judged kid-ney-sane according to first-line diagnostic recommendations (N=61, eGFR (CKD-EPI) ≥60ml/min/m2, total urine protein <150mg/g creatinine, urinary red and white blood cells not increased) or classified at-risk for kidney insufficiency due to aortic valve dysfunction (N=51). Plausibility of eGFR-values was evaluated retrospectively by final case diagnoses. Results: eGFR (CAPA) was found linearly correlated to eGFR (CKD-EPI) (R2=0.5, slope=0.69, p<0.0001). In 93/112 (>80%) cases, eGFR (CAPA) yielded lower values (on average ≈20%). In 55/112 (49%) cases CKD-stage decreased. CKD-reclassification from kidney-sane to kid-ney-insufficient state (i.e. CKD1/2 to CKD3a/b or 4) or reclassification to more severe kidney in-sufficiency (i.e. CKD3a3b/4 or 3b4) was found in 41/112 (37%) cases. Worsening of CKD-classification (kidney-sanekidney-insufficient) based on eGFR (CAPA) was in 30% of cases plausible in the light of final case-diagnoses. Conclusion: In elderly patients (>60 years), renal function appears systematically overestimated by creatinine-based eGFR (CKD-EPI) heralding for this group employment of cystatin C-based eGFR (CAPA) as first-line diagnostic.

(+)-epi-Epoformin (1), is a fungal cyclohexene epoxide isolated together with diplopimarane and sphaeropsidins A and C, a nor-ent-pimarane and two pimaranes, from the culture filtrates of Diplodia quercivora, a fungal pathogen for cork oak in Sardinia, Italy. Compound 1 possesses a plethora of biological activities including: antifungal, zootoxic and phytotoxic activity. The last activity and the peculiar structural feature of 1 suggested to carry out a structure activity relationship study, preparing eight key hemisynthetic derivatives and their phytotoxicity was assayed. The complete spectroscopic characterization and the activity in the etiolated wheat coleoptile bioassay of all the compounds is reported. Most of the compounds inhibited growth and some of them had comparable or higher activity than the natural product and the reference herbicide Logran. As regards the structure-activity relationship, the carbonyl proved to be essential for their activity of 1, as well as the conjugated double bond, while the epoxide could be altered with no significant loss.

This in-depth review navigates the intricate relationship between gender, hormonal influences, and the progression of autosomal dominant polycystic kidney disease (ADPKD), highlighting the limited literature on this crucial topic. The study explores the impact of female sex hormones on liver and renal manifestations, uncovering gender-specific differences in disease progression. Actually hormonal therapy in women with ADPKD remains a challenging issue and is a source of concern regarding its potential impact on disease outcomes, particularly at the hepatic level. Notably, women with ADPKD exhibit a slower renal disease progression compared to men, attributed to hormonal dynamics. The review sheds light on the role of estrogen in regulating pathways of the renin-angiotensin-aldosterone system, revealing its complex interplay and implications for cardiovascular and renal health. Therapeutic considerations for fertile women with ADPKD, including contraception options, are discussed, emphasizing the necessity for personalized approaches. In the postmenopausal phase, the review evaluates the role of hormonal replacement therapy, considering its potential benefits and risks in the context of ADPKD. The review concludes by underscoring the imperative need for tailored treatment approaches for ADPKD patients, considering individual risks and benefits. The scarcity of literature underlines the call for further research to enhance our understanding of optimal hormonal therapies in the context of ADPKD, ultimately paving the way for innovative and personalized therapeutic interventions.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Tomato (Solanum lycopersicum), an important vegetable crop, is a host for numerous pests and pathogens. Consequently, tomato breeders are striving to improve pest resistance. Many acces-sions of the wild relative S. habrochaites display high resistance towards arthropod pests such as spider mites and whiteflies and the presence of the sesquiterpene hydrocarbon 7-epi zingiberene in its trichomes has been associated with arthropod resistance. Consequently, tomato breeders are attempting to introgress 7-epi zingiberene from wild to cultivated tomato, which requires the ability to quantify zingiberene. 7-Epi zingiberene has conjugated double bonds causing it to ab-sorb uv light. In fact, de Freitas, et al. [1] have claimed that measurement of absorbance at 270 nm of tomato leaflet washes can be used to quantify zingiberene. However, this claim has never been critically evaluated. We initially evaluated the use of uv absorbance to estimate zingiberene content of leaflet washes from an interspecific hybrid tomato BC4F2 generation that was segre-gating widely for presence and abundance of zingiberene. When absorbances at 270 nm were compared with zingiberene measured by gas chromatography the resulting relationship did not obey the Beer-Lambert law. Consequently, we examined in detail aspects of the uv-absorbance of zingiberenoids by: 1) obtaining uv absorbance spectra for three isolated zingiberenoids and de-termining the relationship between the abundance of each isolated compound and absorbance at single wavelengths; 2) obtaining uv absorbance spectra of leaflet washes of relevant wild acces-sions and parents; 3) obtaining average absorbance spectra for interspecific generations of tomato that were segregating for abundance of zingiberenoids and determining their λmax values in the 250-280 nm region; 4) evaluating by regression the relationship between absorbance at a single wavelength and the concentration of zingiberene and when present, its derivatives, as measured by gas chromatography in several interspecific hybrid generations; and 5) exploring the potential use of absorbances at multiple wavelengths to improve estimates of concentrations of zingi-berenoids. Results indicated that isolated zingiberenoids as well as leaflet washes of wild tomatoes that contain zingiberenoids have broad absorbance spectra in the uv region with a λmax of 264 nm. The relationship between abundance of isolated zingiberenoids and absorbance at a single wavelength of 264 nm did obey the Beer-Lambert Law. Average absorbance spectra for leaflet washes from BC3F5 generation plants sampled by two methods, as well as from a BC5F1 and a BC3F3 generation showed subtle shifts in the λmax away from 264 nm. Furthermore, the rela-tionship between absorbance at 264 nm and zingiberenoid content of these generations did not obey the Beer-Lambert Law in that in each case regression of absorbance on zingiberenoid content of the leaflet washes resulted in non-zero intercept estimates that varied considerably among generations and sampling methods. Use of multiple wavelengths for estimation zingiberenoids in these breeding generations was explored and inclusion of additional absorbances at one or two wavelengths identified by stepwise regression always improved estimates of zingiberenoid content from absorbance data. However, the identified wavelength(s) differed among generations. Taken together the results indicate that measurement of absorbance of tomato leaflet washes at a single wavelength is not a reliable quantitative estimate of zingiberenoids in the leaflet wash. These estimates can be improved by utilizing absorbance at multiple wavelengths, but the par-ticular wavelengths will likely vary among generations. Lastly, measurement of absorbance may be a useful tool in identifying those relatively rare individuals in a generation that is widely segregating for zingiberenoid content. However, even in this situation the determination of the actual zingiberene content e.g., for comparison with the donor parent, would need to be back-stopped by a valid quantitative method such as gas chromatography.

Naturally occurring small molecules include a large variety of natural products from different sources that have confirmed activity against epigenetic targets. In this work we review chemoinformatic, molecular modeling and other computational approaches that have been used to uncover natural products as inhibitors of DNA metiltransferases, a major family of epigenetic targets with significant potential for the treatment of cancer and several other diseases. Examples of these computational approaches include docking, similarity-based virtual screening, and pharmacophore modeling. It is also commented the chemoinformatic-based exploration of the chemical space of naturally occurring compounds as epigenetic modulators which may have significant implications in epigenetic drug discovery and nutriepigenetics.

In this work we discuss the insights from activity landscape, docking and molecular dynamics towards the understanding of the structure-activity relationships of dual inhibitors of major epigenetic targets: lysine metiltransferase (G9a) and DNA metiltranferase 1 (DNMT1). The study was based on a novel data set of 50 published compounds with reported experimental activity for both targets. The activity landscape analysis revealed the presence of activity cliffs, e.g., pairs of compounds with high structure similarity but large activity difference. Activity cliffs were further rationalized at the molecular level by means of molecular docking and dynamics simulations that led to the identification of interactions with key residues involved in the dual activity or selectivity with the epigenetic targets.

Polymorphism of vitamin D3 receptor (VDR), has been associated with low bone mineral density and other immune and metabolic disorders; however, its impact on mortality of female dialysis patients is not well studied. This study aimed to identify bone mass-related factors, VDR gene polymorphism, and their interaction with morbid conditions that could influence all-cause mortality. In 246 female dialysis patients, age 43±11 years on continuous ambulatory dialysis peritoneal; 48%, haemodialysis; 23% and automated peritoneal dialysis; 29%. Tscore, Ca, PO4, albumin, hs-CRP, osteoprotegerin, fetuin, osteocalcin, iPTH, PINP and β-CTx were measured. PCR products were digested with Bsml to analyze VDR polymorphisms. Patients n=229; were followed for a median of 17 (15-31) months; 42 patients died. Bsml polymorphism, bb=64% and BB+Bb=36%. Hs-CRP was the risk of death in multivariate Cox Analysis. Patients with bb and inflammation had a higher risk of death (HR 2.48, 95% CI 1.08-5.68) persisted after adjustment for age, diabetes and iPTH (HR 2.33; 95% CI, 1.01-8.33) and after further adjustment for vintage, albumin, osteoprotegerin and vitamin D therapy (HR 3.49; 95% CI, 1.20-10.9). We may conclude that the presences of the bb genotype of VDR and inflammation have additive effects on all cause-mortality in females in CAPD, APD, and HD patients.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in ADL. Fractures in the elderly people are associated with bone fragility. Diabetes and chronic kidney disease are associated with bone fragility. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Background and purpose: Chronic kidney disease (CKD) is a common chronic disease usually associated with cardiovascular disease (CVD), and premature death and millions of people are at increased risk for CKD. As this disease is extremely complex, multidisciplinary care (MDC) is needed to provide complete and continuous care. Usually, the nephrology units need coopera-tion from several other Healthcare Professionals (HCPs) such as cardiologists, nutritionists, ob-stetricians, and so forth. All modalities of treatments, peritoneal dialysis (PD) and Hemodialysis (HD) require HCPs and patients to develop a variety of skills to effectively deliver and manage dialysis tasks in the center or at home. Information and Communication Technology (ICT) in-terventions can offer tools that provide HCPs and patients with tools that facilitate the manage-ment of kidney patients in centers or at home. ICT interventions can allow to automate registra-tions, videoconferencing, minimize the geographic burden and resource cost savings. ICT can be the best way to promote cost saving on health spending and ensure the sustainability of the health system and, the environment as well. In the Iberian Peninsula, kidney patients consume about 3% of the total cost of healthcare. The cost of kidney transplants and dialysis is around 1.8 billion euros annually, and 75 % of this amount goes to dialysis treatment. Objective: This study aimed to evaluate and analyze the opinion of Healthcare Professionals (HCP) in Nephrology units about the Intervention of ICT in nephrology care and the Clinical benefits results from the use of ICT in Nephrology Services and dialysis Units in Portugal and Spain. Thus we collected the opinion of Health care professionals concerning the role of ICT intervention in nephrology. Understanding HCPs' feelings and attitudes is essential to understand if such technologies are correctly adjusted to the workflow and really bring huge benefits for the clinical practice of nephrology and also what features need improvement and what should be implemented in the future. ICT intervention has been implemented to promote better healthcare in nephrology units and improve patient outcomes. In the Survey, we intended to evaluate nephrology HCPs' opinions concerning the ICT interventions, in nephrology, represented by several tools that al-low the HCPs to implement solutions such as Remote Patient Monitoring(RPM); Remote Moni-toring of Treatment (RMT); Tele homecare; Telehealth (Tele-nephrology); Home Dialysis; mHealth; mobile App; Web Portal, Telemedicine, and so forth. Key Points: In many countries particularly in the Iberian Peninsula (Portugal and Spain) the incidence of CKD is substantially high. The “treatments” for kidney disease have not improved substantially over the past 50 years, leaving too many kidney patients with a poor quality of life and reduced life expectancy. This situation is associated with staggering aggregate annual costs amounting to €140 billion per year in Europe, more than the annual healthcare costs of cancer or diabetes [1]. The increased daily use of information and communication technologies may lead to the need for healthcare professionals to incorporate technology use competencies into practice.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p&lt;0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p&lt;0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p&lt;0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.