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Background and Aims: Sodium [ 18 F]fluoride (Na [ 18 F]F) positron emission tomography imaging allows detailed visualization of early arterial micro-calcifications. This study aims to investigate atherosclerosis manifested by micro-calcification, macro-calcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria and severely decreased kidney function., Methods: A cohort was stratified in four groups (N = 10 per group), based on KDIGO categories (G1-5 A1-3). G1-2A1 non-diabetic controls (median [IQR] estimated glomerular filtration rate (eGFR) in mL/min/1.73 m 2 91 [81-104]), G1-2A1 with T2DM (eGFR 87 [84-93], and albumin-creatinin-ratio (ACR) in mg/mmol 0.35 [0.25-0.75]), G1-2A3 with T2DM (eGFR 85 [60-103], and ACR 74 [62-122], and G4A3 with T2DM (eGFR 19 [13-27] and ACR 131 [59-304])., Results: Na [ 18 F]F femoral artery grading score differed significantly in the groups with the highest Na [ 18 F]F activity in A3 groups with T2DM (G1-2A3 with T2DM 228 [100-446] and G4A3 with T2DM 198 [113-578]) from the lowest groups of the G1-2A1 with T2DM (33 [0-93]) and in G1-2A1 non-diabetic controls (75 [0-200], p = 0.001). Aortic Na [ 18 F]F activity and femoral artery computed tomography (CT)-assessed macro-calcification was increased in G4A3 with T2DM compared with G1-2A1 with T2DM (47.5 [33.8-73.8] vs. 17.5 [8.8-27.5] (p = 0.006) and 291 [170-511] vs. 12.2 [1.41-44.3] mg (p = 0.032), respectively). Carotid-femoral pulse wave velocity (PWV)-assessed aortic stiffness was significantly higher in both A3 groups with T2DM compared with G1-2A1 with T2DM (11.15 and 12.35 vs. 8.86 m/s, respectively (p = 0.009))., Conclusions: This study indicates that the presence of severely increased albuminuria in patients with T2DM is cross-sectionally associated with subclinical arterial disease in terms of micro-calcification and aortic stiffness. Additional decrease in kidney function was associated with advanced macro-calcifications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP., Methods: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years., Results: Our analyses prioritized myofibroblasts and endothelial cells, among the total of 33 annotated cell type, as specifically involved in BP regulation ( P  < 0.05/33, i.e., 0.001515). Enrichment of heritability for systolic BP (SBP) was observed in myofibroblast cells in mature human kidney cortex, and enrichment of heritability for diastolic BP (DBP) was observed in descending vasa recta and peritubular capillary endothelial cells as well as stromal myofibroblast cells. The new finding of myofibroblast, the significant cell type for both BP traits, was consistent in 8 replication efforts using 7 sets of independent data, including in human fetal kidney, in East-Asian (EAS) ancestry, using mouse single-cell RNA sequencing (scRNA-seq) data, and when using another prioritization method., Conclusion: Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: This study aimed to investigate challenges, competencies, and support in breast and gynecological cancer patients when dealing with information needs and how health literacy as an interplay of these factors might be improved., Methods: Semi-structured interviews were conducted with patients in acute care (n = 19), undergoing rehabilitation (n = 20) or attending self-help groups (n = 16). Interviews were analyzed using content analysis., Results: Challenges: gain information according to own needs, internet as information source, information evaluation and decisions, doctor-patient communication, situationally limited information processing, difficult access to information. Competencies: self-regulation of information needs, media and social competencies, communication skills in the doctor-patient conversation, internet competencies, self-directed decisions according to own needs, interest/self-efficacy, previous knowledge, trust in the doctor., Support: by professionals (e.g., patient-centered communication), relatives (e.g., support during consultations), peers (e.g., exchange), facilities (e.g., clinics)., Conclusions: Our findings provide insight into challenges and competencies relevant to patients' health literacy and the influence of support. The individuality of the interplay highlights the relevance of an active patient role and patient-centered care., Practice Implications: Patients' health literacy should be improved in (psycho)oncological work by both reducing challenges (e.g., by communication skills training, involving relatives) and promoting competencies (e.g., by needs- and competence-oriented information offers)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m 2 and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

There is limited information about long-term effects of permeable pavement parking lots on concentrations of nutrients in infiltrates. A 0.40-ha parking lot that contained three types of permeable pavement including permeable interlocking concrete pavement (PICP), porous asphalt (PA) and pervious concrete (PC) was constructed in 2010 at a U.S. EPA facility in Edison, New Jersey. This study was conducted from October 2010 to August 2017. Water quality samples were collected from the rainfall, parking lot runoff, and infiltrate from these three pavement types. Samples were analyzed for parameters including NH 3 -N, NO 2 -N, NO 3 -N, TN, PO 4 -PO 4 , TOC, ORP and pH. Statistical methods were used to study infiltrate concentration changes with time. Results showed, for all analytes, there were no differences between permeable interlocking concrete pavement and pervious concrete median concentrations. Data showed distribution of species changed and supported nitrification processes. The trend varied with source. Nitrogen species showed slowly increasing trends in rainwater, PC and PICP infiltrate concentrations while phosphate concentration showed a slightly increasing trend in rainwater and porous asphalt infiltrate. It is recommended that communities select PC and PICP when nitrogen species are the pollutants of concern and PA is more suitable for orthophosphate removal., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Little is known about how stormwater exfiltrates from green infrastructure and few efforts have been undertaken to address this question. This study used tensiometers to monitor water exfiltration from an aggregate-filled storage gallery installed under permeable pavement. An 80-space parking lot was built at Seitz elementary school in Fort Riley, KS under an agreement between EPA and US Army during the summer of 2015. A network of twelve tensiometers and twelve monitoring wells was installed under and south of the storage gallery. Tensiometers were installed a various depths and distances to monitor soil moisture tension. The installation was used to monitor subsurface water flow patterns from the storage gallery under the permeable pavement site. The results of the study showed that soil moisture tension is larger at the shallower depths, decreasing with depth from the ground surface. Larger soil tension was associated with increased distance from the permeable pavement storage gallery. The results showed exfiltration from both the sidewalls and the bottom of the gallery while the changes in soil tension were larger for the tensiometer monitoring exfiltration from the side walls. Both the accumulated water depth inside the storage gallery and groundwater level rise were positively correlated with total rainfall depth. The calculated vertical flow rate was larger than the horizontal flow. The soil water tension change associated with storage gallery exfiltration was measured in a radius of <5 m from the storage gallery. Long-term peak groundwater level rise should be considered for design of the storage gallery depth to maintain the effective exfiltration. Understanding the exfiltration pathways aids with the placement and design the storage gallery. Additional research is necessary to understand how specific local parameters and vadose zone characteristics would affect the long-term exfiltration process., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Both a high dietary sodium and high phosphate load are associated with an increased cardiovascular risk in patients with chronic kidney disease (CKD), and possibly also in non-CKD populations. Sodium and phosphate are abundantly present in processed food. We hypothesized that (modulation of) dietary sodium is accompanied by changes in phosphate load across populations with normal and impaired renal function., Methods and Results: We first investigated the association between sodium and phosphate load in 24-h urine samples from healthy controls (n = 252), patients with type 2 diabetes mellitus (DM, n = 255) and renal transplant recipients (RTR, n = 705). Secondly, we assessed the effect of sodium restriction on phosphate excretion in a nondiabetic CKD cohort (ND-CKD: n = 43) and a diabetic CKD cohort (D-CKD: n = 39). Sodium excretion correlated with phosphate excretion in healthy controls (R = 0.386, P < 0.001), DM (R = 0.490, P < 0.001), and RTR (R = 0.519, P < 0.001). This correlation was also present during regular sodium intake in the intervention studies (ND-CKD: R = 0.491, P < 0.001; D-CKD: R = 0.729, P < 0.001). In multivariable regression analysis, sodium excretion remained significantly correlated with phosphate excretion after adjustment for age, gender, BMI, and eGFR in all observational cohorts. In ND-CKD and D-CKD moderate sodium restriction reduced phosphate excretion (31 ± 10 to 28 ± 10 mmol/d; P = 0.04 and 26 ± 11 to 23 ± 9 mmol/d; P = 0.02 respectively)., Conclusions: Dietary exposure to sodium and phosphate are correlated across the spectrum of renal function impairment. The concomitant reduction in phosphate intake accompanying sodium restriction underlines the off-target effects on other nutritional components, which may contribute to the beneficial cardiovascular effects of sodium restriction. (f) Registration numbers: Dutch Trial Register NTR675, NTR2366., (Copyright © 2016. Published by Elsevier B.V.)

Background and Aims: A high circulating fibroblast growth factor 23 (FGF23) level is an independent risk factor for cardiovascular mortality in renal transplant recipients and the general population. N-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) may contribute to cardiovascular risk reduction. We investigated whether fish and EPA-DHA intake are related to FGF23 levels in renal transplant recipients., Methods and Results: We performed a cross-sectional analysis in 619 stable renal transplant recipients (mean age 53 years, 57% male, estimated glomerular filtration rate [eGFR] 53 ± 20 mL/min/1.73 m(2)). Dietary intake was assessed by a 177-item food frequency questionnaire. Serum intact FGF23 was measured by ELISA. We examined differences in FGF23 levels across categories of fish and EPA-DHA intake using analysis of variance models adjusted for age, sex, dietary and lifestyle factors and key determinants of FGF23. Patients consumed on average 15 g of fish and 139 mg EPA-DHA/day. Median FGF23 was 62 pg/mL (IQR 43-98 pg/mL). Higher dietary EPA-DHA and fish intake were associated with lower serum FGF23 levels. Subgroup analyses revealed that particularly in patients with reduced renal function (eGFR <60 mL/min/1.73 m(2)), adjusted FGF23 levels (114, 79, 75 pg/mL, P = 0.0001) were inversely associated with tertiles of EPA-DHA intake. Similarly, we observed an inverse association between fish consumption and serum FGF23 levels in adjusted analyses., Conclusion: A higher intake of fish and dietary n-3 fatty acids (EPA-DHA) is related to lower circulating FGF23 levels in renal transplant recipients. Further research is needed to assess the causality of this association and the clinical implications., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Local renal complement activation by the donor kidney plays an important role in the pathogenesis of renal injury inherent to kidney transplantation. Contradictory results were reported about the protective effects of the donor C3F allotype on renal allograft outcome. We investigated the influence of the donor C3F allotype on renal transplant outcome, taking all different donor types into account. C3 allotypes of 1265 donor-recipient pairs were determined and divided into four genotypic groups according to the C3F allotype of the donor and the recipient. The four genotypic groups were analyzed for association with primary nonfunction (PNF), delayed graft function, acute rejection, death-censored graft survival and patient survival. Considering all donor types, multivariable analysis found no association of the donor C3F allotype with renal allograft outcome. Also, for living and deceased brain-dead donors, no association with allograft outcome was found. Post hoc subgroup analysis within deceased cardiac dead (DCD) donors revealed an independent protective association of donor C3F allotype with PNF. This study shows that the donor C3F allotype is not associated with renal allograft outcome after kidney transplantation. Subgroup analysis within DCD donors revealed an independent protective association of the donor C3F allotype with PNF, which is preliminary and warrants further validation., (© copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In addition to standard therapy with ACE-inhibitors, digitalis and diuretics, beta-adrenergic receptor blockers have become a widely accepted strategy in the treatment of chronic heart failure. The role of calcium antagonists in CHF however remains controversial. To evaluate if a combination therapy of metoprolol and felodipine might improve hemodynamic parameters, a randomized and placebo-controlled study was designed., Methods and Results: Sixty-three patients with DCMP, LVEF 3 months in NYHA II-III on standard medication were prospectively treated with either a) a combination of metoprolol+felodipine (MF group, n=20), b) metoprolol+felodipine-placebo (MP group, n=23), or c) metoprolol-placebo+felodipine-placebo (PP group, n=20). Compared to baseline, LVEF and LVEDD significantly improved after 6 months in the MP group (LVEF: 36+/-2% vs 29+/-2%, p<0.01; LVEDD: 68+/-3 mm vs 64+/-3 mm, p<0.05), whereas in the other treatment groups only minor changes were observed. A significant benefit in hemodynamic parameters as determined by right heart catheterization was noted also only in the MP group with a marked reduction in PAP mean (17 vs 24 mmHg, p<0.01), PCWP (10 vs 15 mmHg, p<0.001) resulting in a significant increase in cardiac and stroke volume index at rest with no marked changes in the MF and PP group., Conclusion: beta-blocker treatment in CHF patients improves left ventricular function and additionally invasive hemodynamic measurements both at rest and during exercise. In contrast, the combined therapy with the long-acting calcium antagonist felodipine neutralizes these beneficial effects of metoprolol therapy to almost placebo level, providing evidence based on hemodynamic measurements that this combination should be avoided in patients with CHF.

Objective: We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia., Study Design: A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis., Results: The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection., Conclusion: Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease.

During the past decade there have been remarkable strides in the understanding of the basic mechanism of cancer. It is now clear that there is a set of genes, known as oncogenes, that can cause cells to become malignant if their expression is altered, either by mutation or overexpression. The products of these genes include growth factors, growth factor receptors, signal tranduction proteins, and DNA binding proteins. The normal cellular counterparts of these genes play very important roles in the regulation of growth and proliferation by normal cells. Another set of genes, anti-oncogenes, also play an important role in preventing abnormal cell proliferation. The remarkable explosion of understanding of the pathophysiology of malignancy has led to a common unifying concept of malignant transformation that applies to all tumors. It is likely that these new insights will lead to improved and more specific treatments for malignant disease in the next decade.

DNA isolation and Southern Blot analysis are two of the many techniques currently being used routinely by molecular biologists to discover genetic defects that affect human health. Together these two techniques have greatly aided in the growing knowledge of genetics on a molecular level. Southern blotting can be used to discern genetic deletions, alterations, or amplifications that are not detectable by cytogenetic methods. Several examples of the clinical applications of these methods are discussed in Table 4. Southern analysis has been recently used: (1) to facilitate prenatal diagnosis of sickle cell hemoglobinopathies, (2) to demonstrate human papillomavirus DNA integration in the genome of cervical cancer cells and (3) to demonstrate that oncogene amplification in the tumors of patients with node positive breast cancer correlates inversely with prognosis. Each of these examples not only have diagnostic value for patient care but also may help begin to understand the very basis of the disease processes themselves.

After an initial 4-wk period, 36 healthy male subjects aged 19-28 y (14 lactoovovegetarians and 22 omnivores) were given a supplement to their usual diet of 27.9 mmol calcium/d for 5 wk. During this period 22 blood pressure measurements were taken and 30 24-h urine specimens and 15 24-h dietary records were obtained. Base-line blood pressures did not differ significantly between vegetarians and omnivores (118.3/59.3 and 119.5/60.7, respectively). At the end of the supplementation period there was a decrease in diastolic blood pressure of 1.4 mm Hg (p less than 0.10) and an unexpected increase in systolic blood pressure of 2.1 mm Hg (p less than 0.01) in the omnivores. Although not significant, the same trends were observed in the vegetarians. In both groups Ca and magnesium excretions increased significantly and phosphorus excretion decreased significantly. Blood pressure of normotensive subjects with high basal Ca intake may not be sensitive to Ca supplementation.