Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Leisure-time physical activity, sedentary behavior, and risk of breast cancer: Results from the SUN ('Seguimiento Universidad De Navarra') project.

Evidence is still limited on the influence of sedentary lifestyles on breast cancer (BC) risk. Also, prospective information on the combined effects of both sedentariness and leisure-time physical activity (LTPA) is scarce. We aimed to assess the association of higher sedentary behavior and LTPA (separately and in combination) with the risk of BC in a middle-aged cohort of university graduates. The SUN Project is a follow-up study initiated in 1999 with recruitment permanently open. Baseline assessments included a validated questionnaire on LTPA and sedentary habits. Subsequently, participants completed biennial follow-up questionnaires. Multivariable adjusted Cox models were used to estimate the hazard ratios (HR) for incident BC according to LTPA, TV-watching, the joint classification of both, and a combined 8-item multidimensional active lifestyle score. We included 10,812 women, with 11.8 years of median follow-up of. Among 115,802 women-years of follow-up, we confirmed 101 incident cases of BC. Women in the highest category of LTPA (>16.5 MET-h/week) showed a significantly lower risk of BC (HR = 0.55; 95% CI: 0.34-0.90) compared to women in the lowest category (≤6 MET/h-week). Women watching >2 h/d of TV sh owed a higher risk (HR = 1.67; 95% CI:1.03-2.72) than those who watched TV <1 h/d. Women in the highest category (6-8 points) of the multidimensional combined 8-item score showed a lower BC risk (HR = 0.35; 95% CI: 0.15-0.79) than those in the lowest category (<2 points) group. There was no significant supra-multiplicative interaction between TV-watching and LTPA. Both low LTPA and TV-watching >2 h/d may substantially increase BC risk, independently of each other.

Hydrochemical characterization of a river affected by acid mine drainage in the Iberian Pyrite Belt.

This paper addresses the modelling of the processes associated with acid mine drainage affecting the Trimpancho River basin, chosen for this purpose because of its location and paradigmatic hydrological, geological, mining and environmental contexts. By using physical-chemical indicators it is possible to define the contamination degree of the system from the perspective of an entire river basin, due to its reduced dimension. This allows an exhaustive monitoring of the study area, considering the particularity that the stream flows directly into a water dam used for human supply. With such a perspective, and in order to find global solutions, the present study seeks to develop methodologies and tools for expeditious and accurate diagnosis of the pollution level of the affected stream that feeds the water reservoir. The implemented methodology can be applied to other water systems affected by similar problems, while the results will contribute to the development of the state of the art in a representative basin of the Iberian Pyrite Belt, whose pollutants' contributions are incorporated into the reservoir.

Relationships between sources of acid mine drainage and the hydrochemistry of acid effluents during rainy season in the Iberian Pyrite Belt.

In the Iberian Pyrite Belt (IPB), southwest Spain, a prolonged and intense mining activity of more than 4,500 years has resulted in almost a hundred mines scattered through the region. After years of inactivity, these mines are still causing high levels of hydrochemical degradation in the fluvial network. This situation represents a unique scenario in the world, taking into consideration its magnitude and intensity of the contamination processes. In order to obtain a benchmark regarding the degree of acid mine drainage (AMD) pollution in the aquatic environment, the relationship between the areas occupied by the sulfide mines and the characteristics of the respective effluents after rainfall was analysed. The methodology developed, which includes the design of a sampling network, analytical treatment and cluster analysis, is a useful tool for diagnosing the contamination level by AMD in an entire metallogenic province, at the scale of each mining group. The results presented the relationship between sulfate, total dissolved solids and electrical conductivity, as well as other parameters that are typically associated with AMD and the major elements that compose the polymetallic sulfides of IPB. This analysis also indicates the low level of proximity between the affectation area and the other variables.

Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response.

Ire1 (Ern1) is an unusual transmembrane protein kinase essential for the endoplasmic reticulum (ER) unfolded protein response (UPR). Activation of Ire1 by association of its N-terminal ER luminal domains promotes autophosphorylation by its cytoplasmic kinase domain, leading to activation of the C-terminal ribonuclease domain, which splices Xbp1 mRNA generating an active Xbp1s transcriptional activator. We have determined the crystal structure of the cytoplasmic portion of dephosphorylated human Ire1α bound to ADP, revealing the 'phosphoryl-transfer' competent dimeric face-to-face complex, which precedes and is distinct from the back-to-back RNase 'active' conformation described for yeast Ire1. We show that the Xbp1-specific ribonuclease activity depends on autophosphorylation, and that ATP-competitive inhibitors staurosporin and sunitinib, which inhibit autophosphorylation in vitro, also inhibit Xbp1 splicing in vivo. Furthermore, we demonstrate that activated Ire1α is a competent protein kinase, able to phosphorylate a heterologous peptide substrate. These studies identify human Ire1α as a target for development of ATP-competitive inhibitors that will modulate the UPR in human cells, which has particular relevance for myeloma and other secretory malignancies.

Stratification of Metal and Sulphate Loads in Acid Mine Drainage Receiving Water Dams - Variables Regionalization by Cluster Analysis.

The Sancho Reservoir (Iberian Pyrite Belt, SW Spain) is nourished by the waters of the river Meca, which is affected by acid mine drainage (AMD) processes from the abandoned Tharsis mine. The aim of the present work is to study the hydrochemical variations in this reservoir, in order to define potential stratification processes in metal load and sulphates. A stratified sampling from the surface, with one meter deep intervals to the bottom of the dam, was performed. The results show a clear stratification of temperature, pH, electric conductivity, dissolved oxygen, metal and sulphate loads associated with depth. There is an increase of metal loads at the bottom of the reservoir, though previous studies only detect iron. The proximity between pH and aluminium suggests that water chemistry is strongly influenced by aluminium precipitation processes. This indicates the buffer effect that aluminium exercises, which precipitates as amorphous or low crystalline phases, introducing hydrogen ions to the system, while alkalinity input tends to raise pH.

Economic impact of managing invasive mold disease with isavuconazole compared with liposomal amphotericin B followed by posaconazole in Spain.

BACKGROUND: Invasive fungal infections (IFI) are associated with significant morbidity and mortality. The objective of this work was to compare the costs per adult patient, associated with intravenous isavuconazole (ISAV) followed by oral ISAV versus the regimen of liposomal amphotericin B followed by posaconazole (L-AMB→POSA) in the treatment of IFI. The comparison was conducted from the perspective of the Spanish National Health System (SNS). METHODS: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration, hospitalization, laboratory tests and adverse events costs were evaluated from SNS perspective. Deterministic and probabilistic sensitivity analyzes were performed. RESULTS: Total costs per-patient were €24,715.54 with ISAV versus €29,753.53 with L-AMB→POSA, resulting in cost-savings per patient treated with ISAV of €5,037.99 (-16.9%). Treatment costs of IFI remained lower for ISAV than for L-AMB→POSA across all sensitivity analyses (-7,968.89€ to -326.59€), being treatment duration the most influential parameter. CONCLUSION: According to the present model, the treatment of IFIs with ISAV would generate savings for the SNS compared to L-AMB→POSA. These savings are attributed to the shorter duration of IV treatment, reduced use of healthcare resources and lower costs associated with managing adverse effects when ISAV was employed.

Benzimidazole inhibitors of the protein kinase CHK2: clarification of the binding mode by flexible side chain docking and protein-ligand crystallography.

Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR. Unconstrained rigid docking of benzimidazole ligands into representative CHK2 protein crystal structures reveals an alternative binding mode involving a water-mediated interaction with the hinge region; docking which incorporates protein side chain flexibility for selected residues in the ATP binding site resulted in a refinement of the water-mediated hinge binding mode that is consistent with observed SAR. The flexible docking results are in good agreement with the crystal structures of four exemplar benzimidazole ligands bound to CHK2 which unambiguously confirmed the binding mode of these inhibitors, including the water-mediated interaction with the hinge region, and which is significantly different from binding modes previously postulated in the literature.

A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study.

PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

The Negro River (Ancash-Peru): A unique case of water pollution, three environmental scenarios and an unresolved issue.

This paper is focused on the hydrogeochemical characterization of the Negro River along its course, as well as in the proposal of a functioning model for the contamination processes in order to establish potential cause-effect relationships between water quality, geology (ARD), mining activities (AMD) and the tectonic framework as transmission vector of acidity, metals and sulphates. The scenario shows a heavily-contaminated river compared to the unaffected regional background. By graphical and statistical treatments of physico-chemical data of Negro River and the unaffected values of regional background and other AMD/ARD representative rivers' it is possible to conclude that Antamina Mine, is not the cause of the Negro River contamination, without the need of isotopic tracers, but just through the inexistent concentrations of Cu, Bi and Mo found in the waters. In the proposed contamination model, climatic factors (glacial retreat) activate geological (ARD) processes. The tectonic scenario (faults) intervenes as a transport medium of the contamination flux from the sulphide oxidation surface in upper altitudes until the spring in lower altitudes. At the end, it is concluded that this contamination comes from the recent glacial retreat in areas near the Cordillera Blanca that has left massive amounts of sulphide materials exposed to weathering conditions, oxidizing naturally (ARD processes) and finally contributing to the contamination of the Negro River through faults. In this case, we would face an ARD process in the strict sense, which is the direct oxidation of sulphides outcropping in the upper part of the mountain with the generation of sulphates, the release of hydrogen ions and the consequent generation of acid and the dissolution of the metals. This ARD process would come from the glacial retreat, which, through the faults, transports contaminated water until the spring.

[Vancomycin dosing in hemodialysis patients]. / Dosificación de vancomicina en pacientes en hemodiálisis.

UNLABELLED: Vancomycin is widely used in haemodialysis (HD) patients for treating infections of vascular access due to St. Aureus. To avoid subtherapeutic levels it is important to know the adequate dosing in patients undergoing haemodialysis with high flux membranes. OBJECTIVE: The aim of this study was to evaluate whether HD patients treated with 1 g intravenous (IV) vancomycin reached optimum plasma levels. MATERIAL AND METHODS: In a crossover design we studied 28 chronic HD patients, 3 times a week, treated with vancomycin between 15/2/2006 and 14/2/2007. Antibiotic was given at dose of 1 g during the last hour of dialysis session. Plasma levels of vancomycin were measured immediately before next HD (preHD1) and after (postHD1), and prior to the beginning of the second next session (preHD2). We evaluated age, sex, dry height, week Kt/V and the type of membrane used. RESULTS: Of 28 patients, 5 were analysed 3 times, 2 were analysed twice and 9 were analysed once . There were 43 samples, 19 men (44,2%) and 24 women (55,8%), with a mean age of 70 +/- 8,4 years. 1 g dose is equivalent to > 15 mg/kg in 31 patients (72,1%) and < 15 mg/kg in 12 (27,9%). The type of membrane used was high flux polyetersulfone (PES-AP) (44,2%), eval (7%), medium-low polyetersulfone (PES-BP) (32,5%) and polyacrylonitrile (16,3%). PreHD1 mean concentration results for the total population was 7,06 mg/ml, being 16,3% bellow optimum levels. There were not difference between patients treated with dose > 15 mg/kg (7,5 mg/ml) and < 15 mg/kg (6 m/ml). When the dose administered was > 15 mg/kg, 6,45% results were subtherapeutic, whereas if the dose was < 15 mg/kg, 41,67% values were bellow optimum levels (p<0,05). With regard to the dialyzers used, the lowest concentrations were observed with PES-AP (5,95 mg/ml) and the highest values were observed with PES-BP (7,27 mg/ml) (p no significance). No patient using PES-BP versus 31,58% patients using PES-AP showed suboptimum values (p> or =0,07). All postHD1 and preHD2 results were in subtherapeutic range (mean values, dose > and < 15 mg/kg and all types of membrane). CONCLUSIONS: Based on the above results, the vancomycin dosing schedule of 1 g IV every 5-7 days is not recommended for patients undergoing haemodialysis with high flux membranes. Since there are not guidelines for handling this antibiotic in these patients our findings suggest that it may be necessary to monitorize predialysis plasma levels to avoid subtherapeutic values.

Oxaliplatin plus gemcitabine as a salvage schedule for hormone-refractory prostate adenocarcinoma.

We report a case of hormone-refractory prostate cancer (HRPC) treated with oxaliplatin plus gemcitabine in a third-line schedule after liver progression, with an excellent clinical, biochemical and radiological response and with an acceptable tolerance. Prior chemotherapy regimens included docetaxel plus estramustine and oral etoposide. To our knowledge, this is the first report that shows this approach in an HRPC patient.

[Hormonal therapy in breast cancer]. / Tratamiento hormonal del cáncer de mama.

Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications.

Map of impact by acid mine drainage in the river network of The Iberian Pyrite Belt (Sw Spain).

The Iberian Pyrite Belt (IPB), in the southwest of Europe, is characterized by high levels of contamination by acid mine drainage (AMD) in a large extent of its river network. In this scenario, it is necessary to characterize the degree of pollution of the mining leachates in the AMD-generating sources as well as of the main receiving watercourses. A map of impact of each basin was developed, based on the model proposed by Grande (2011) and the European Directive 98/83/EC that defines the quality standards for drinking water. The results indicate that practically all the mining leachates exceeded the maximum concentrations established by Directive 98/83/CE for Fe and Cd, almost 90% exceeded the limit for Mn and 82% for Al. Likewise, Fe, Cd, and Mn caused 'extremely high' degradation in most sampled leachates. Similarly, these metals, in addition to Pb, produced more pollution in watercourses located downstream of exploitations.

Application of fuzzy logic tools for the biogeochemical characterisation of (un)contaminated waters from Aljustrel mining area (South Portugal).

Aljustrel mining area (South Portugal) belongs to the Iberian Pyrite Belt (IPB). It is classified of high environmental risk due to its large tailings and to the Acid Mine Drainage (AMD) affected waters, generated by sulphides' oxidation. Integrating biological parameters (for the first time) in the input data matrix of the software PreFuRGe, allowed a better discrimination of the diatoms' responses to the stimuli caused by the hydrochemical changes imposed by the processes affecting water quality. Each hydrochemical scenario, was modeled by imposing maximum and minimum limits for each antecedent, according to the conditions imposed by the consequent, which in this case were the number of diatom species and pH. Thus, PreFuRGe evidenced some qualitative aspects that could not be achieved by classic statistics. pH appeared as the main discriminator of diversity and diatom species composition, nevertheless and due to the complex environment under study other chemical interactions must be considered: (a) AMD waters, with extremely low pH values, but also with extremely high hydrogeochemical complexity, represented by a mixture of metals, do not allow to associate, unequivocally, the reduction in diatom diversity to pH, but also to high metal (loid)s concentrations; (b) in the most alkaline waters, with higher abundance of diatom species, average to high concentrations of Na and Cl (due to Cenozoic sediments) do not seem to affect diatom diversity. This methodology proved to be an efficient tool to establish, for the first time, cause-effect relationships, improving the comprehension between biological (diatoms) and hydrochemical parameters.

Histone-histone interactions and centromere function.

Cse4p is a structural component of the core centromere of Saccharomyces cerevisiae and is a member of the conserved CENP-A family of specialized histone H3 variants. The histone H4 allele hhf1-20 confers defects in core centromere chromatin structure and mitotic chromosome transmission. We have proposed that Cse4p and histone H4 interact through their respective histone fold domains to assemble a nucleosome-like structure at centromeric DNA. To test this model, we targeted random mutations to the Cse4p histone fold domain and isolated three temperature-sensitive cse4 alleles in an unbiased genetic screen. Two of the cse4 alleles contain mutations at the Cse4p-H4 interface. One of these requires two widely separated mutations demonstrating long-range cooperative interactions in the structure. The third cse4 allele is mutated at its helix 2-helix 3 interface, a region required for homotypic H3 fold dimerization. Overexpression of wild-type Cse4p and histone H4 confer reciprocal allele-specific suppression of cse4 and hhf1 mutations, providing strong evidence for Cse4p-H4 protein interaction. Overexpression of histone H3 is dosage lethal in cse4 mutants, suggesting that histone H3 competes with Cse4p for histone H4 binding. However, the relative resistance of the Cse4p-H4 pathway to H3 interference argues that centromere chromatin assembly must be highly regulated.

A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission.

The histone proteins are essential for the assembly and function of th e eukaryotic chromosome. Here we report the first isolation of a temperature-sensitive lethal histone H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae. The mutant requires two amino acid substitutions in histone H4: a lethal Thr-to-Ile change at position 82, which lies within one of the DNA-binding surfaces of the protein, and a substitution of Ala to Val at position 89 that is an intragenic suppressor. Genetic and biochemical evidence shows that the mutant histone H4 is temperature sensitive for function but not for synthesis, deposition, or stability. The chromatin structure of 2 micrometer circle minichromosomes is temperature sensitive in vivo, consistent with a defect in H4-DNA interactions. The mutant also has defects in transcription, displaying weak Spt- phenotypes. At the restrictive temperature, mutant cells arrest in the cell cycle at nuclear division, with a large bud, a single nucleus with 2C DNA content, and a short bipolar spindle. At semipermissive temperatures, the frequency of chromosome loss is elevated 60-fold in the mutant while DNA recombination frequencies are unaffected. High-copy CSE4, encoding an H3 variant related to the mammalian CENP-A kinetochore antigen, was found to suppress the temperature sensitivity of the mutant without suppressing the Spt- transcription defect. These genetic, biochemical, and phenotypic results indicate that this novel histone H4 mutant defines one or more chromatin-dependent steps in chromosome segregation.

Primary central nervous system lymphoma treated with rituximab plus temozolomide in a second line schedule.

We report a case of primary CNS lymphoma treated with high-dose methotrexate in the first line. After disease progression the patient received cranial radiotherapy with concomitant temozolomide, followed by rituximab plus temozolomide, with complete remission of the disease maintained for at least two years and without major toxicity.

Definition of redox and pH influence in the AMD mine system using a fuzzy qualitative tool (Iberian Pyrite Belt, SW Spain).

Poderosa Mine is an abandoned pyrite mine, located in the Iberian Pyrite Belt which pours its acid mine drainage (AMD) waters into the Odiel river (South-West Spain). This work focuses on establishing possible reasons for interdependence between the potential redox and pH, with the load of metals and sulfates, as well as a set of variables that define the physical chemistry of the water-conductivity, temperature, TDS, and dissolved oxygen-transported by a channel from Poderosa mine affected by acid mine drainage, through the use of techniques of artificial intelligence: fuzzy logic and data mining. The sampling campaign was carried out in May of 2012. There were a total of 16 sites, the first inside the tunnel and the last at the mouth of the river Odiel, with a distance of approximately 10 m between each pair of measuring stations. While the tools of classical statistics, which are widely used in this context, prove useful for defining proximity ratios between variables based on Pearson's correlations, in addition to making it easier to handle large volumes of data and producing easier-to-understand graphs, the use of fuzzy logic tools and data mining results in better definition of the variations produced by external stimuli on the set of variables. This tool is adaptable and can be extrapolated to any system polluted by acid mine drainage using simple, intuitive reasoning.

Polonium behaviour in reservoirs potentially affected by acid mine drainage (AMD) in the Iberian Pyrite Belt (SW of Spain).

The province of Huelva is one of the areas most affected by acid mine drainage (AMD) in the world, which can produce big enhancements and fractionations in the waters affected by AMD. There are very few studies on this issue, and none on polonium-210. Twenty-two water reservoirs were sampled, and the (210)Po was measured in both dissolution and particulate phases. The (210)Po concentrations in the waters were in the same order of magnitude to those ones for unperturbed systems, although the data published to particulate matter are very scarce. A mean value and standard uncertainty for (210)Po of 0.25 ± 0.03 mBq L(-1) in the dissolved matter, and 62 ± 9 mBq g(-1) in the particulate matter can be established as base line for the reservoirs of the Huelva area. The distribution coefficients (kd) range from 10(4) to 10(6) L kg(-1), in agreement to the found ones by other authors for the case of neutral waters, but being the lowest values for the more acidic reservoirs. It has been also found that (210)Po has a high tendency to be associated to the particulate matter for neutral-alkaline waters, however, under extreme acid conditions (pH < 3), increases the Po tendency to be associated to the dissolved phase. Therefore, the main conclusion obtained in this work is that AMD has no a significant influence on the total activity concentration of (210)Po in the waters of reservoirs, but the acidity has a clear influence on its distribution between both dissolved and the particulate phases.