Search

Next generation sequencing (NGS) is transforming the diagnostic approach for neurological disorders, since it allows simultaneous analysis of hundreds of genes, even based on just a broad, syndromic patient categorization. However, such an approach bears a high risk of incidental and uncertain genetic findings. We report a patient with spastic paraplegia whose comprehensive neurological and imaging examination raised a high clinical suspicion of SPG11. Thus, although our NGS pipeline for this group of disorders includes gene panel and exome sequencing, in this sample only the spatacsin gene region was captured and subsequently searched for mutations. Two probably pathogenic variants were quickly and clearly identified, confirming the diagnosis of SPG11. This case illustrates how combination of expert clinical characterization with highly oriented NGS protocols leads to a fast, cost-efficient diagnosis, minimizing the risk of findings with unclear significance. [ABSTRACT FROM AUTHOR]

Development of automatic retinal disease diagnosis systems based on retinal image computer analysis can provide remarkably quicker screening programs for early detection. Such systems are mainly focused on the detection of the earliest ophthalmic signs of illness and require previous identification of fundal landmark features such as optic disc (OD), fovea or blood vessels. A methodology for accurate center-position location and OD retinal region segmentation on digital fundus images is presented in this paper. The methodology performs a set of iterative opening–closing morphological operations on the original retinography intensity channel to produce a bright region-enhanced image. Taking blood vessel confluence at the OD into account, a 2-step automatic thresholding procedure is then applied to obtain a reduced region of interest, where the center and the OD pixel region are finally obtained by performing the circular Hough transform on a set of OD boundary candidates generated through the application of the Prewitt edge detector. The methodology was evaluated on 1200 and 1748 fundus images from the publicly available MESSIDOR and MESSIDOR-2 databases, acquired from diabetic patients and thus being clinical cases of interest within the framework of automated diagnosis of retinal diseases associated to diabetes mellitus. This methodology proved highly accurate in OD-center location: average Euclidean distance between the methodology-provided and actual OD-center position was 6.08, 9.22 and 9.72 pixels for retinas of 910, 1380 and 1455 pixels in size, respectively. On the other hand, OD segmentation evaluation was performed in terms of Jaccard and Dice coefficients, as well as the mean average distance between estimated and actual OD boundaries. Comparison with the results reported by other reviewed OD segmentation methodologies shows our proposal renders better overall performance. Its effectiveness and robustness make this proposed automated OD location and segmentation method a suitable tool to be integrated into a complete prescreening system for early diagnosis of retinal diseases. [ABSTRACT FROM AUTHOR]

Abstract: Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects. [Copyright &y& Elsevier]

• Biological invasions of animals and pathogens threat biodiversity. • Early detection of biological invasions is critical for effective management. • Artificial intelligence enables massive processing of camera-trapping photographs. • Combining AI, camera traps, and remote sensing can be used for real-time detection. [ABSTRACT FROM AUTHOR]

Abstract: The primary advantages of electrospun membranes include the ability to obtain very thin fibers that are on the order of magnitude of several nanometers with a considerable superficial area and the possibility for these membranes to be manipulated and processed for many different applications. The purpose of this study is to evaluate and quantify the transport mechanisms that control the release of drugs from polymer-based sandwich membranes produced using the electrospinning processes. These electrospun membranes were composed of poly(lactic acid) (PLA) because it is one of the most promising biodegradable polymers due to its mechanical properties, thermoplastic processability and biological properties, such as its biocompatibility and biodegradability. The transport mechanism that controls the drug delivery was evaluated via the release kinetics of a bioactive agent in physiological serum, which was used as a corporal fluid simulation. To describe the delivery process, mathematical models, such as the Power Law, the classical Higuchi equation and an approach to Fick's Second Law were used. Using the applied mathematical models, it is possible to conclude that control over the release of the drug is significantly dependent on the thickness of the membrane rather than the concentration of the drug. [Copyright &y& Elsevier]

Highlights: [•] A methodology for detecting the fovea center position in fundus images is presented. [•] The methodology was evaluated on 1200 fundus images of the MESSIDOR database. [•] Evaluation criterion: methodology-provided and actual fovea center distance. [•] In 93% of analyzed images, the distance remained below 1/4 of one optic disc radius. [•] These results outperform all the reviewed methodologies available in literature. [Copyright &y& Elsevier]

Abstract: Solid-organ transplant recipients are at increased risk of developing cancer compared with the general population. Tumours can arise de novo, as a recurrence of a preexisting malignancy, or from the donated organ. The ATOS (Aula sobre Trasplantes de Órganos Sólidos; the Solid-Organ Transplantation Working Group) group, integrated by Spanish transplant experts, meets annually to discuss current advances in the field. In 2011, the 11th edition covered a range of new topics on cancer and transplantation. In this review we have highlighted the new concepts and best practices for managing cancer in the pre-transplant and post-transplant settings that were presented at the ATOS meeting. Immunosuppression plays a major role in oncogenesis in the transplant recipient, both through impaired immunosurveillance and through direct oncogenic activity. It is possible to transplant organs obtained from donors with a history of cancer as long as an effective minimization of malignancy transmission strategy is followed. Tumour-specific wait-periods have been proposed for the increased number of transplantation candidates with a history of malignancy; however, the patient''s individual risk of death from organ failure must be taken into consideration. It is important to actively prevent tumour recurrence, especially the recurrence of hepatocellular carcinoma in liver transplant recipients. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients, with long-term intensive screening programs showing a reduced incidence of cancer post-transplantation. Proposed management strategies for post-transplantation malignancies include viral monitoring and prophylaxis to decrease infection-related cancer, immunosuppression modulation with lower doses of calcineurin inhibitors, and addition of or conversion to inhibitors of the mammalian target of rapamycin. [Copyright &y& Elsevier]

Abstract: The design of axial compressors is dictated by the maximisation of flow efficiency at on design conditions whereas at part speed the requirement for operation stability prevails. Among other stability aids, compressor variable geometry is employed to rise the surge line for the provision of an adequate surge margin. The schedule of the variable vanes is in turn typically obtained from expensive and time consuming rig tests that go through a vast combination of possible settings. The present paper explores the suitability of stochastic approaches to derive the most flow efficient schedule of an axial compressor for a minimum variable user defined value of the surge margin. A genetic algorithm has been purposely developed and its satisfactory performance validated against four representative benchmark functions. The work carries on with the necessary thorough investigation of the impact of the different genetic operators employed on the ability of the algorithm to find the global extremities in an effective and efficient manner. This deems fundamental to guarantee that the algorithm is not trapped in local extremities. The algorithm is then coupled with a compressor performance prediction tool that evaluates each individualʼs performance through a user defined fitness function. The most flow efficient schedule that conforms to a prescribed surge margin can be obtained thereby fast and inexpensively. Results are produced for a modern eight stage high bypass ratio compressor and compared with experimental data available to the research. The study concludes with the analysis of the existent relationship between surge margin and flow efficiency for the particular compressor under scrutiny. The study concludes with the analysis of the existent relationship between surge margin and flow efficiency for the particular compressor under scrutiny. [Copyright &y& Elsevier]

Abstract: The relationships between climate variability and canopy dynamics (monthly litter production), chemical composition of the litter, secondary growth and female-cone production were studied in an old growth Scots pine (Pinus sylvestris) forest over the 1993–2003 period. The forest was located at a Mediterranean mountain site (Valsaín, Segovia, central Spain). The temporally explicit relationships between the mentioned variables were explored by chronological cluster of their time series. Mean air temperature significantly influenced litter production and its seasonal and intradecadal patterns. Seasonal patterns of litter N and P content were negatively correlated with litter production, exhibiting minima of 5.3gkg−1 (N) and 0.5gkg−1 (P) by the end of the summer and maxima of 15gkg−1 (N) and 1.2gkg−1 (P) during winter; these results are interpreted as retranslocation before needle shedding in summer and loss of green needles in winter respectively. In general the driest and hottest years (1994 and 1995) were associated with significantly decreased secondary growth in the next year, an increased cone production, and an increased nutrient loss due to the combined effect of an increased litter production and an increased nutrient concentration of the litter. Climatic changes during the early stages of cone formation that take place during the spring led to alterations in masting and in the tri-annual process of cone production. Since each parameter studied was differentially affected by climatic variability, the overall effect of the short-term climatic changes experienced by the Scots pine forest studied was an uncoupling of litter production, secondary growth, and reproduction. [Copyright &y& Elsevier]

Abstract: Although serum creatinine has traditionally been used as the preferred marker of kidney function in the follow-up of renal transplant patients, there are several problems that make it inadvisable to use. Criterion standard measurements of glomerular filtration rate (GFR) using an exogenous agent allow a very precise estimation of kidney function; but they are cumbersome, expensive, and time consuming, and not all centers have them available. A simpler option is to estimate GFR from creatinine- or cystatin C–derived equations. These formulas have been compared in several reports in kidney transplant recipients. These reports have found discordant results about what equation is the best to use in kidney transplant recipients. Every equation performs better in the group or subgroup of patients in which it was developed or in populations with similar characteristics. In general, equations derived from the “Modification of Diet in Renal Disease” study have shown better accuracy, higher grade of correlation, and lower bias to estimate GFR in renal transplant patients than the other equations. Although cystatin C–derived equations seem to perform better than creatinine-derived equations, further studies will be necessary to know their role in the kidney transplant field. [Copyright &y& Elsevier]

Abstract: In this work the content of seven heavy metals (Cd, Cr, Cu, Hg, Ni, Pb and Zn) and other parameters (the pH, organic matter, carbonates and granulometric fraction) in agricultural topsoil in the Ebro basin are quantified, based on 624 samples collected according to an 8 by 8km square mesh. The average concentrations (mg/kg) obtained were: Cd 0.415±0.163, Cr 20.27±13.21, Cu 17.33±14.97, Ni 20.50±22.71, Pb 17.54±10.41, Zn 17.53±24.19 and Hg 35.6±42.05μg/kg. The concentration levels are relatively low in areas of high pH and low organic matter content concentration. The results of factor analysis group Cd, Cu, Hg, Pb and Zn in F1 and Cr y Ni in F2. The spatial heavy metals component maps based on geostatistical analysis, show definite association of these factors with the soil parent material. The local anomalies (found in Cu, Zn and Pb) are attributed to anthropogenic influence. [Copyright &y& Elsevier]

Abstract: Desminopathies represent a subtype of myofibrillar myopathy caused by mutations in the DES gene, which cause myofibril disruption and intracellular inclusions containing desmin and other protein components. Desminopathy mainly involves skeletal and cardiac muscle, separately or together. Both autosomal dominant and autosomal recessive inheritance have been reported. Here, we describe the second family identified to date with an L370P desmin mutation. The disease in this family shows autosomal dominant inheritance with a particular phenotype, where males suffer from sudden death of cardiac origin while females exhibit a more benign myopathy of distal onset and slower progression. Because the only family previously identified with this mutation was limited to one studied patient, the present kindred represents the largest clinical investigation of the phenotype associated with the L370P mutation. [Copyright &y& Elsevier]

Abstract: Renal allograft survival has substantially increased during the last 2 decades. Nonetheless, death with a functioning graft is still the most common cause of renal graft loss after the first year, with cardiovascular disease (CVD) being the most common cause of patient death. Cardiovascular morbidity and mortality in patients who undergo renal transplantation are dramatically increased compared with the general population. Despite the description of new CVD risk factors and markers, modification of conventional risk factors for CVD may still be important in the care of patients who undergo renal transplantation. The objective of this review is to analyze traditional risk factors for CVD and define clinical markers for high-risk recipients. Clinical markers include unmodifiable risk factors such as male sex and old age. Presence of CVD before transplantation represents an important risk factor in these patients. Similarly, nephrosclerosis as cause of primary renal disease implies a worse pretransplant vascular state and a high-risk of cardiovascular events. Modifiable risk factors include hyperlipemia and hypertension, which have a high prevalence after transplantation. Posttransplant diabetes may have a role in the development of CVD, although it is difficult to obtain a reliable estimate of the incidence of diabetes because of the lack of standardized definition. Development of persistent proteinuria is an independent risk factor for increased mortality and especially cardiovascular morbidity and mortality, as it is the general population with essential hypertension or diabetes mellitus. Early renal dysfunction is also a marker not only of worse graft survival but also worse patient survival. Despite recent advances in the prolongation of patient and graft survival, patients who undergo transplantation die prematurely from accelerated CVD. Widespread adoption of simple clinical markers could help prolong graft and patient survival through prevention of CVD. [Copyright &y& Elsevier]

Background. Chronic allograft nephropathy is the main cause of late graft loss. It has been suggested that both alloantigen-dependent and alloantigen-independent factors influence the development of progressive transplant failure. The present study analyzed the importance of non-immunologic factors in the progression of kidney disease in transplant patients, with the emphasis on well-established risk factors for progression in native kidneys. Methods. A retrospective analysis was performed on 485 renal transplant patients who had functioning kidneys for at least 1 year. We investigated whether the initial presence and subsequent maintenance of proteinuria, hypertension, anemia, hyperlipidemia, and hyperparathyroidism influenced the progression of transplant failure. To analyze the relative effects of these factors, patients were categorized into two groups: group A had a baseline serum creatinine concentration of less than 1.5 mg/dL, and group B had a baseline serum creatinine concentration of 1.5 to 3 mg/dL. Results. High urine protein excretion was a significant independent risk factor for progression of renal failure (group A: relative risk, 3.73; 95% confidence interval [CI], 2.24–6.21; group B: relative risk, 4.01; 95% CI, 2.51–6.39). Hypertension was also a significant independent risk factor for progression, but the risk was lower than for proteinuria (group A: relative risk, 1.2; 95% CI, 1.04–1.75; group B: relative risk, 1.20; 95% CI, 1.02–2.1). Anemia, hyperlipidemia, and hyperparathyroidism had no influence on the progression of renal failure. Conclusion. Our results show strong independent relationships between high blood pressure, urine protein excretion, and the relative risk of chronic progression of renal failure, as described for native kidney disease. These factors are potentially modifiable and are therefore attractive targets for therapeutic targets. [ABSTRACT FROM AUTHOR]

Return to dialysis after renal transplantation. Which would be the best way? The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hispital admissions during the first year after initiation of dialysis were considereably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss. [ABSTRACT FROM AUTHOR]

Ovum Pick Up (OPU) is a minimally invasive technique widely used in cattle and mares for oocyte retrieval, involving ultrasound-guided puncture of ovarian follicles. It has been demonstrated that this technique is safe for its repeated use in the same female without affecting her reproductive health, allowing for the retrieval of oocytes in individuals regardless of their reproductive status. The oocytes obtained through OPU can subsequently be used for in vitro embryo production (IVP) using assisted reproductive techniques (ARTs) or be cryopreserved in biobanks for their future use. Traditionally, the minimally invasive technique of choice performed in vivo in domestic and wild felines was LOPU (laparoscopic-guided ovum pick up). The present study was designed to explore if ultrasound-guided OPU in the domestic cat is safe and effective. In an initial series of ex vivo experiments (n = 92 ovaries, n = 434 oocytes), the effect of different aspiration pressures for oocyte collection was explored. These experiments identified 43 mmHg as the optimal aspiration pressure, resulting in the highest recovery rate and a favorable maturation and blastocyst rate. Subsequently, 16 grade I and II oocytes were retrieved by OPU and 101 oocytes were retrieved following ovariectomy and slicing. Sixteen oocytes obtained with each technique were subjected to in vitro maturation (IVM) and in vitro fertilization (IVF). A total of 14 presumptive zygotes were selected for in vitro culture (IVC) from each group (OPU and slicing), obtaining a cleavage rate of 57.1 % and 64.2 %, a morula rate of 28.5 % in both groups, and a blastocyst rate of 7.14 % and 14.2 % respectively. The hormonal stimulation protocol was well-tolerated, with no adverse effects observed. Moreover, no complications arose during the ovariectomy performed post-OPU. The use of this technique in domestic cats represents a significant step forward in terms of safety, replicability, and invasiveness, serving as a valuable model for its application in wild felids species. Additional research involving a greater number of animals is required to validate these encouraging findings. • This study presents the first successful ultrasound-guided ovum pick-up (OPU) in the domestic cat. • OPU is a minimally invasive technique that offers advantages in terms of invasiveness and safety compared to LOPU. • In vitro embryo production from OPU and slicing showed comparable cleavage, morula, and blastocyst rates. • This research provides a replicable model for potential application in wild felid species. [ABSTRACT FROM AUTHOR]

Lava caves are the result of a geological process related to the cooling of basaltic lava flows. On the Moon, this process may lead to caves several kilometers long and diameters of hundreds of meters. Access to lava tubes can be granted through skylights, a vertical pit between the lava tube and the lunar surface. This represents an outstanding opportunity for long-term missions, for future permanent human settlements, and for accessing pristine samples of lava, secondary minerals and volatiles. Given this, the ESA launched a campaign through the Open Space Innovation Platform calling for ideas that would tackle the many challenges of exploring lava pits. Five projects, including Robocrane, were selected. Solar light and direct line of sight (for communications) with the lunar surface are not available inside lava tubes. This is a problem for any robot (or swarm of robots) exploring the lava tubes. Robocrane tackles both problems by deploying an element (called the Charging head, or CH) at the bottom of the skylight by means of a crane. This CH behaves as a battery charger and a communication relay for the exploring robots. The required energy is extracted from the crane's solar panel (on the surface) and driven to the bottom of the skylight through an electrical wire running in parallel to the crane hoisting wire. Using a crane allows the system to deal with unstable terrain around the skylight rim and protect the wires from abrasion from the rocky surface and the pit rim. The charger in the CH is wireless so that the charging process can begin as soon as any of the robots get close enough to the CH. This avoids complex and time-consuming docking operations, aggravated by the skylight floor orography. The crane infrastructure can also be used to deploy the exploring robots inside the pit, reducing their design constraints and mass budget, as the robots do not need to implement their own self-deployment system. Finally, RoboCrane includes all the sensors and actuators for remote operation from a ground station. RoboCrane has been designed in a parametric tool so it can be dynamically and rapidly adjusted to input-variable changes, such as the number of exploring robots, their electrical characteristics, and crane reach, etc. • The use of a crane for deploying robots inside the skylight alleviates their design. • The reach of the crane, for robots of several kilograms, may be as high as 25 m. • The use of a power wireless charger simplifies the charging operation and time. • A wired communication link between bottom and surface results in excessive weight. • A Rover-crane joint design is preferred given the similar mass between both. [ABSTRACT FROM AUTHOR]

Effector (TEM) and central memory (TCM) T cells have been recently described as the main memory T-cell subsets generated after primary immune response, with a potential role in graft rejection after rechallenge with alloantigen. Because of their effector function, they could be involved in driving the response against the allograft, leading to rejection. In this study, we sought to investigate the different memory T-cell subpopulations in peripheral blood from a cohort of 90 patients who underwent consecutive renal transplant, and their association with acute rejection (AR) episodes and induction therapy. Twenty-one of them were monitored in the short term during the first 2 months after transplantation. Three of them suffered an AR but no changes in the circulating levels of either CD4+ or CD8+ TEM were observed as compared with rejection-free renal transplant patients. In total, 69 patients out of 90 were monitored in the long term. Even 2 years after transplantation, maintained increased numbers of peripheral blood CD4+ TEM were observed in patients suffering with AR. Interestingly, induction therapy with thymoglobulin, but not with basiliximab, produced an increase in circulating CD4+ TEM cells at 6 months after transplantation. In conclusion, our data suggest that AR episodes favor the induction of TEM cells in the periphery of renal transplant patients in the long term. It remains to be determined whether such an effect has any impact on long-term renal transplantation. [ABSTRACT FROM AUTHOR]

To evaluate cardiovascular disease (CVD) after renal transplantation we established a CVD database (no-intervention) including all patients transplanted among 2000–2002 in 14 hospitals from Spain (Renal Forum Group) (n=2600). They were prospective followed annually thereafter and we present herein the most important results concerning survival figures and CVD at four years. Mean recipient age was 49.7±13.7 years: 16% retransplanted and 12.5% hyperimmunized. Tacrolimus, mycophenolate mofetil, and steroids was used in 63%. Acute rejection (AR) rate at 1 year was 14.8%. Graft and patient survival at 48 months were 85.6% (death censored) and 91.7% respectively. The first cause of graft loss was vascular in the first year, death with function during the 2–3 years, and chronic allograft nephropathy at the 4th year. Donor age, time on dialysis, acute tubular necrosis (ATN), AR, SCr at 6 months, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in the first year, and systolic blood pressure at 24 months were independent risk factors for graft loss at 4th year. The first cause of death was CVD (predominantly ischemic heart disease (IHD) in the first year). Recipient age, ATN, and SCr at 6 months were independent predictors of mortality. Despite worsening of donor age, comorbidity, and advanced age of recipients, survival figures at four years are considered good in our Spanish non-selected population. Cardiovascular mortality is the most important cause of death and graft loss particularly, IHD in the first year. Therefore, to decrease post-transplant mortality a careful cardiovascular evaluation and treatment in the waiting list and a close follow-up of patients after transplantation is mandatory.Kidney International (2008) 74, S94–S99. doi:10.1038/ki.2008.547 [ABSTRACT FROM AUTHOR]

Maintenance of target hemoglobin (Hb) values in hemodialysis patients treated with erythropoiesis-stimulating agents (ESAs) remains difficult. We examined Hb variability in the clinical setting in hemodialysis patients. Hemodialysis patients treated with ESAs who maintained the recommended Hb range of 11–13 g per 100 ml over 3 months and were not admitted to hospital, did not require transfusion, and did not experience any major clinical event during this period were followed prospectively for 1 year. Anemia events, Hb variation events (any value out of ±1.5 g per 100 ml of the median Hb level in the total follow-up period for the individual patient), risk factors for anemia, and Hb variation events were assessed. We studied 420 patients (63% males, mean age 61 years), 222 received short-acting erythropoietin (EPO) and 198 long-acting darbepoetin. A total of 4654 blood samples (mean 11.1 per patient-year) were analyzed. Only 3.8% of patients were maintained within the target Hb levels (11–13 g per 100 ml) during 1 year. Hb variation events occurred in 20.8% of laboratory values and anemia events in 14.7%, with a median time to the first event of 3 months. Treatment with short-acting EPO (vs long-acting darbepoetin), change of ESA dose in the previous visit, resistance index, and hospitalization were significant risk factors for both anemia events and Hb variation events. Our results show that Hb values are rarely maintained within the recommended guidelines even in more stable hemodialysis patients. Hb variability is frequently associated with clinical events or ESA dose changes. Long-acting darbepoetin achieved better Hb stability than short-acting EPO.Kidney International (2008) 74, S82–S87. doi:10.1038/ki.2008.524 [ABSTRACT FROM AUTHOR]

This study characterized and mapped the spatial variability patterns of seven topsoil heavy metals (Cr, Ni, Pb, Cu, Zn, Hg and Cd) within the Ebro river basin (9.3 million ha) by Multivariate Factorial Kriging. The variograms and cross-variograms of heavy metal concentrations showed the presence of multiscale variation that was modeled using three variogram models with ranges of 20km (short-range), 100km (medium-range) and 225km (long-range). Our results indicate that the heavy metal concentration is influenced by bedrock composition and dynamics at all the spatial scales, while human activities have a notorious effect only at the short- and medium-range scale of variation. Sources of Cu, Pb and Zn (and secondary Cd) are associated with agricultural practices (at the short-range scale of variation), whereas Hg variation at the short- and medium-range scale of variation is related to atmospheric deposition. [Copyright &y& Elsevier]

Over the next decade, the number of patients with end-stage renal disease requiring treatment by dialysis may double, and even developed nations will have difficulty coping with this alarming increase. There is an urgent need to highlight the importance of modifiable risk factors as a basis for treatment strategies to prevent the development and progression of chronic kidney disease (CKD). This should include active extension of our current understanding of a healthy lifestyle. [ABSTRACT FROM AUTHOR]

Abstract: There is increased evidence about the deleterious effect of delayed graft function (DGF) in both short- and long-term kidney graft outcome. Among the mechanisms involved in the production of DGF, immune factors play a role, especially in the level of hypersensitization. From the 1389 patients transplanted at our hospital until November 2004, it has been found that the presence of moderate and high levels of sensitization, as measured by panel-reactive antibodies, is a risk factor for suffering from DGF. Further, DGF was associated with poor graft survival, and the risk was even higher when DGF was combined with moderate/high panel-reactive antibodies. Recent data demonstrate the usefulness of intravenous immunoglobulins in the management of hypersensitized patients in terms of short-term outcome. It remains to be demonstrated whether this therapy is able to ameliorate the higher ischemic injury that kidneys undergo from these immunologically high-risk patients. [Copyright &y& Elsevier]

Bone disease in long-term adult kidney transplant patients with normal renal function. Background. In successful renal transplantation, the degree of renal function recovery is usually incomplete and information is scarce about the abnormalities of mineral metabolism in long-term adult renal recipients with normal renal function. This study was designed to investigate bone mineral metabolism in patients with a long-term normal functioning kidney. Methods. Twenty-nine adult asymptomatic renal transplant (RT) recipients with stable graft function for more than 10 years and serum creatinine <2 mg/dL were studied. They were classified into two groups according to glomerular filtration rate: Group A (N = 12; nine men, three women)>70 mL/min (x: 126 ± 55 mL/min) and Group B (N = 17; nine men, eight women) <70 mL/min (x: 56 ± 11 mL/min). Circulating biochemical markers of bone remodelling, bone histomorphometry, and densitometry (lumbar spine and hip) were obtained to investigate bone disease in these patients. Results. Serum PTH was slightly elevated in 10 patients (83%) in group A. Serum PTH levels were positively related to serum calcium, osteocalcin, BAP, telopeptide, OH-proline, and creatinine. There was no histologic data to support overactivity on bone in this group of patients, with only one showing high bone turnover. Mineralization was prolonged in 34% of patients. Twenty-two patients (75%) exhibited normal bone turnover. In the group with GFR>70 mL/min the prevalence of mineralization defect in the presence of normal serum levels of calcitriol suggested vitamin D resistance. Lumbar and femoral neck osteoporosis was present in 25% and 33% of patients in group A, and 23% and 53% in group B, respectively. T-score at lumbar spine was negatively correlated with months since transplantation. Patients under treatment with cyclosporine (CsA) showed increased concentrations of osteocalcin and D-pyr and higher lumbar bone mineral density (BMD), but bone... [ABSTRACT FROM AUTHOR]

Measurement of renal function in pre-ESRD patients. The measurement of renal function in pre-dialysis patients is important in order to determine the appropriate time to begin renal replacement therapy, to forecast the start, and to compare, in groups of patients, the efficiency of different treatments that limit renal disease progression. The most reliable methods, such as inulin clearance or measurement by radioisotopes, are too awkward for the usual clinical follow-up of patients. Although much simpler and almost as reliable, the use of iohexol radiologic contrast does not allow the frequent monitoring of the patient either. The determinations of the plasmatic creatinine and its clearance or the estimate of the glomerular filtration rate by means of equations derived from the creatinine are the methods most often used in order to measure renal function, although not without problems in pre-dialysis. In order to try to overcome such problems, more precise equations and procedures, including the measurement of averaged urea-creatinine clearance or creatinine clearance with cimetidine, have been designed that better estimate the glomerular filtration rate. However, none of these methods is totally reliable in pre-dialysis. A new endogen marker, cystatin C, has advantages over creatinine, though more studies are needed in pre-dialysis in order to ascertain its use. The initial proposal of the National Kidney Foundation's Kidney Disease Outcome Quality Initiative (DOQI) guidelines to use weekly Kt/V and nutritional parameters to determine the time for starting renal replacement therapy has widened the prospects of the debate on the measurement of renal function in pre-dialysis, but further work is required to define their role in pre-dialysis patients' follow-up. [ABSTRACT FROM AUTHOR]

Examines the importance of hemodiafiltration with online regeneration of ultrafiltrate in the United States. Changes of the post-cartridge ultrafiltrate-stimulated cytokine release; Use of ultrafiltrate for sorbent application; Release of tumor necrosis factor and interleukin-1.

Effect of serum phosphate on parathyroid hormone secretion during hemodialysis. Background . Recent studies have demonstrated that a high concentration of phosphate directly stimulates parathyroid hormone (PTH) secretion. High serum levels of phosphate are usually observed in patients with end-stage renal disease. The aim of the present study was to evaluate whether serum phosphate concentration had an acute effect on PTH secretion in hemodialysis patients. The levels of serum phosphate were manipulated during the hemodialysis session by using a phosphate free dialysate or a dialysate with a high content of phosphate. Methods . Ten stable hemodialysis patients with PTH values above 300 pg/ml were included in the study. A PTH-calcium curve was obtained during both high phosphate and phosphate free hemodialysis. Results . The serum phosphate concentration remained high (2.17 ± 0.18 mM) throughout the high phosphate hemodialysis and decreased progressively to normal levels (1.02 ± 0.06 mM) during the phosphate free hemodialysis. The serum PTH levels at maximal inhibition by hypercalcemia (minimal PTH) were greater during the high phosphate than the phosphate free hemodialysis (413 ± 79 vs. 318 ± 76 pg/ml, P < 0.003). In all patients the values of minimum PTH were greater during the high phosphorus than the phosphorus free hemodialysis. The values of maximally stimulated PTH during hypocalcemia and the set point of the PTH-calcium curve were similar during the high phosphate and the phosphate free hemodialysis. Conclusion . The maintenance of high serum phosphorus levels during hemodialysis prevented, in part, the inhibition of PTH secretion by calcium, which strongly suggests that in hemodialysis patients high serum phosphate contributes directly to the elevation of PTH levels despite normal or high serum calcium concentration. [ABSTRACT FROM AUTHOR]