A multi-objective optimisation approach for the linear modelling of cerebral autoregulation system.

OBJECTIVE: Dynamic cerebral autoregulation (dCA) has been addressed through different approaches for discriminating between normal and impaired conditions based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CF). This work presents a novel multi-objective optimisation (MO) approach for finding good configurations of a cerebrovascular resistance-compliance model. METHODS: Data from twenty-nine subjects under normo and hypercapnic (5% CO2 in air) conditions was used. Cerebrovascular resistance and vessel compliance models with ABP as input and CF velocity as output were fitted using a MO approach, considering fitting Pearson's correlation and error. RESULTS: MO approach finds better model configurations than the single-objective (SO) approach, especially for hypercapnic conditions. In addition, the Pareto-optimal front from the multi-objective approach enables new information on dCA, reflecting a higher contribution of myogenic mechanism for explaining dCA impairment.

Single nucleotide polymorphisms associated with wine fermentation and adaptation to nitrogen limitation in wild and domesticated yeast strains.

For more than 20 years, Saccharomyces cerevisiae has served as a model organism for genetic studies and molecular biology, as well as a platform for biotechnology (e.g., wine production). One of the important ecological niches of this yeast that has been extensively studied is wine fermentation, a complex microbiological process in which S. cerevisiae faces various stresses such as limited availability of nitrogen. Nitrogen deficiencies in grape juice impair fermentation rate and yeast biomass production, leading to sluggish or stuck fermentations, resulting in considerable economic losses for the wine industry. In the present work, we took advantage of the "1002 Yeast Genomes Project" population, the most complete catalogue of the genetic variation in the species and a powerful resource for genotype-phenotype correlations, to study the adaptation to nitrogen limitation in wild and domesticated yeast strains in the context of wine fermentation. We found that wild and domesticated yeast strains have different adaptations to nitrogen limitation, corroborating their different evolutionary trajectories. Using a combination of state-of-the-art bioinformatic (GWAS) and molecular biology (CRISPR-Cas9) methodologies, we validated that PNP1, RRT5 and PDR12 are implicated in wine fermentation, where RRT5 and PDR12 are also involved in yeast adaptation to nitrogen limitation. In addition, we validated SNPs in these genes leading to differences in fermentative capacities and adaptation to nitrogen limitation. Altogether, the mapped genetic variants have potential applications for the genetic improvement of industrial yeast strains.

Integrating Social Assistive Robots, IoT, Virtual Communities and Smart Objects to Assist at-Home Independently Living Elders: the MoveCare Project.

The integration of Ambient Assisted Living (AAL) frameworks with Socially Assistive Robots (SARs) has proven useful for monitoring and assisting older adults in their own home. However, the difficulties associated with long-term deployments in real-world complex environments are still highly under-explored. In this work, we first present the MoveCare system, an unobtrusive platform that, through the integration of a SAR into an AAL framework, aimed to monitor, assist and provide social, cognitive, and physical stimulation in the own houses of elders living alone and at risk of falling into frailty. We then focus on the evaluation and analysis of a long-term pilot campaign of more than 300 weeks of usages. We evaluated the system's acceptability and feasibility through various questionnaires and empirically assessed the impact of the presence of an assistive robot by deploying the system with and without it. Our results provide strong empirical evidence that Socially Assistive Robots integrated with monitoring and stimulation platforms can be successfully used for long-term support to older adults. We describe how the robot's presence significantly incentivised the use of the system, but slightly lowered the system's overall acceptability. Finally, we emphasise that real-world long-term deployment of SARs introduces a significant technical, organisational, and logistical overhead that should not be neglected nor underestimated in the pursuit of long-term robust systems. We hope that the findings and lessons learned from our work can bring value towards future long-term real-world and widespread use of SARs.

A multi-modal algorithm based on an NSGA-II scheme for phylogenetic tree inference.

The analysis of evolutionary data allows uncovering information about the organisms and how they have adapted and evolved. This information could provide us with new insights about the specialisation of organisms (or part of them), how they adapt, how similar they are with other species, among others. Unfortunately, this evolutionary history can only be estimated, and for that, several computational methods exist. Among the methods, optimisation methods are one of the main approaches to deal with this problem, with multiobjective optimisation producing promising results. In this paper, we deal with multiobjective phylogenetic inference, using a multi-modal metaheuristic approach that exploits the decision space in the multiobjective formulation of the problem. In particular, we incorporate a new metric based on a topological tree distance. We compare the method with state of the art algorithms in terms of performance. Additionally, we perform a thorough analysis of a study case on a yeast Saccharomyces cerevisiae dataset. Results show that our proposal is able to improve the diversity of solutions while improving or keeping the quality of solutions in terms of hypervolume.

Processed animal manure improves morpho-physiological and biochemical characteristics of Brassica napus L. under nickel and salinity stress.

Soil contamination with readily soluble salts and heavy metals is a major challenge concerning sustainable crop production. The use of organic wastes in agriculture not only helps in waste reduction but also acts as a soil conditioner and bio-stimulant for enhancing crop growth. In this regard, a pot experiment was conducted to investigate the effect of raw and processed animal manure (AM) on the growth, yield, and physicochemical parameters of Brassica napus L. developed under salinity and Ni stress. The experiment comprised two salinity levels (1.05 and 8 dS m-1), two Ni levels (0 and 50 mg kg-1), and two types of AMs (raw and processed at a rate of 2% w/w). A control treatment without AM incorporation was also included. In results, the application of AM markedly increased the growth and yield of B. napus under Ni and salinity stress; at the same time, it improved the physiological and chemical parameters of the said crop. Similarly, incorporation of processed AM significantly improved nutrient uptake and decreased Na/K ratios in the shoot and grain under the different stress conditions, as compared to the control. Likewise, Ni uptake in the grain, shoot, and root samples was also significantly reduced under the AM treatment. Also, the application of AM significantly reduced the daily intake of metal (DIM) index and the health risk index (HRI) values under the different stress conditions, as compared to the control. In conclusion, the application of processed AM constitutes an effective agricultural strategy to alleviate the adverse effects of Ni and salinity stress on growth, physiology, and yield of B. napus, thus resulting in enhanced productivity, as well as reduced risks associated with human health.

SARS-CoV-2 and other pathogens could be determined in liquid samples from soils.

In the current COVID-19 pandemic, SARS-CoV-2 has been quantified in wastewater in various countries, and wastewater based epidemiology has been proposed as a potential early warning tool for new outbreaks. However, even taking into account that poorly treated wastewater and sewage sludge may be spread on soils, there is no published paper dealing with the quantification of the virus in soil-related liquid samples, as could be runoff, leachates, or soil solution. To fill this gap, the authors of this piece propose reflections on the development of a methodological approach for the quantification of SARS-CoV-2 (and eventually other pathogens) in soil-related liquid samples.

Foliar application of Zn reduces Cd accumulation in grains of late rice by regulating the antioxidant system, enhancing Cd chelation onto cell wall of leaves, and inhibiting Cd translocation in rice.

Paddy soil contaminated by cadmium (Cd) has attracted worldwide attention, while foliar spraying of zinc (Zn) could be considered a cost-effective and practical agronomic measure for reducing Cd accumulation in rice grain. However, the effects due to foliar spraying of Zn on different cultivars, as well as the mechanism of subsequent processes taking place are not fully understood up to now. To go a step ahead, a field experiment was conducted with the aim of studying the capability of foliar application of Zn (0.4% ZnSO4) to reduce Cd concentration in grain in five late rice cultivars (here named JLYHZ, FYY272, JY284, CLY7 and LXY130), and the antioxidant activities and subcellular distribution of Cd in the leaves. The results indicate that foliar Zn application significantly decreased grain yield in JY284, CLY7 and JLYHZ, compared to controls. In addition, foliar application of Zn significantly decreased Cd concentration in grain of the five rice cultivars, while increased Zn concentration. The effect of foliar application of Zn on transport coefficients of Cd varied greatly for the different rice cultivars. Foliar application of Zn significantly decreased the malondialdehyde (MDA) concentration in rice leaves, and increased peroxidase (POD) activity. Also, it changed the distribution of Cd in the soluble fraction in leaves (expressed as proportion), which was significantly decreased, and the proportion of Cd in the cell wall increased. The structural equation model (SEM) revealed the positive effects of flag leaf Cd, first node Cd, old leaf Cd, and root Cd concentration on grain Cd concentration. Flag leaf Cd had the highest standardized total effects on grain Cd concentration, followed by old leaf Cd. These results indicated that foliar application of Zn was effective in reducing grain Cd concentration of late rice by enhancing antioxidant activities and Cd chelation onto cell wall of leaves, and reducing Cd concentrations in leaves.

How to study SARS-CoV-2 in soils?

Wastewater based epidemiology is increasingly being considered as a potentially useful tool for early warning about eventual new COVID-19 outbreaks. In addition, some authors are investigating on the detection and quantification of SARS-CoV-2 in sewage sludge. However, no paper has been published up to date indicating how this virus could be quantified in soil samples. In view of that, we review available data searching for methodological approaches that could guide on the quantification of SARS-CoV-2 (and even other pathogenic microorganisms) in soils.

Total evidence or taxonomic congruence? A comparison of methods for combining biological evidence.

Phylogenetic inference proposes an evolutionary hypothesis for a group of taxa which is usually represented as a phylogenetic tree. The use of several distinct biological evidence has shown to produce more resolved phylogenies than single evidence approaches. Currently, two conflicting paradigms are applied to combine biological evidence: taxonomic congruence (TC) and total evidence (TE). Although the literature recommends the application of these paradigms depending on the congruence of the input data, the resultant evolutionary hypotheses could vary according to the strategy used to combine the biological evidence biasing the resultant topologies of the trees. In this work, we evaluate the ability of different strategies associated with both paradigms to produce integrated evolutionary hypotheses by considering different features of the data: missing biological evidence, diversity among sequences, complexity, and congruence. Using datasets from the literature, we compare the resultant trees with reference hypotheses obtained by applying two inference criteria: maximum parsimony and likelihood. The results show that methods associated with TE paradigm are more robust compared to TC methods, obtaining trees with more similar topologies in relation to reference trees. These results are obtained regardless of (1) the features of the data, (2) the estimated evolutionary rates, and (3) the criteria used to infer the reference evolutionary hypotheses.

Competitive adsorption and desorption of three tetracycline antibiotics on bio-sorbent materials in binary systems.

Batch-type experiments were used to study competitive adsorption/desorption for the antibiotics tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC), onto by-products from forest and food industries (oak ash, pine bark, and mussel shell). These antibiotics are frequently present in manures and slurries spread on agrosystems. Binary competitive systems were performed by setting the dose of one antibiotic to 200 µmol L-1, and varying the concentration of a second antibiotic from 50 to 600 µmol L-1. In the cases where a concentration of 200 µmol L-1 was used for each antibiotic, the results of the binary experiments were also compared with those obtained in parallel tests corresponding to simple and ternary systems using the same concentration. The results indicated that pine bark can adsorb most of the antibiotics added, with desorption being less than 5% in most cases. Oak ash showed high adsorption for all three antibiotics in the simple systems (100% of CTC, 90% of TC, and 80% of OTC), but clearly decreased in the binary systems (up to values below 40%), especially for higher antibiotics concentrations, although desorption was generally less than 5%. Mussel shell showed adsorption results lesser than 25% for OTC and CT in simple systems, while increased up to 65% in binary systems in which CTC was present at high concentrations, but desorption was generally very high. CTC was the antibiotic with the highest adsorption onto all three by-products, and the one showing less decrease for its adsorption in the binary systems. Overall, the smallest differences among the various competitive systems were obtained when the adsorbent used was pine bark, and especially for the CTC antibiotic. These results could aid to develop management practices, based on the use of low-cost bio-sorbents, which would decrease risks of pollution due to tetracycline antibiotics spread in agroecosystems and affecting the environment.

Adsorption/desorption of three tetracycline antibiotics on different soils in binary competitive systems.

Taking into account environmental and public health issues due to emerging pollutants, and specifically to antibiotics spread into environmental compartments, this work focused on the competition among three tetracycline antibiotics (tetracycline, CT; oxytetracycline, OTC; and chlortetracycline, CTC) for adsorption sites in six different soils. Batch-type adsorption/desorption tests were carried out, with 24 h as contact time. The six soils were from two different farming areas, and were selected according to pH values and organic matter contents. Binary systems (pairs of antibiotics present simultaneously) were used to study competition, setting the dose of one antibiotic at 200 µmol L-1, and varying the concentration of another from 50 to 600 µmol L-1. In the case of the concentration of 200 µmol L-1, the results of the binary systems were also compared with those obtained in simple and ternary systems. The results showed that those soils with the highest organic matter content (soils 50AL and 71S) adsorbed 100% of the three antibiotics, with desorption being <10% in all cases. The other four soils showed some degree of competition for adsorption sites in binary systems, with adsorption decreasing between 25 and 47% compared to simple systems, and with desorption increasing, especially in soils with higher pH and less organic matter. This competition was even more pronounced in ternary systems, affecting to these same soils, while the effects were very scarce in soils with higher organic matter content. The results indicate that most of the studied soils have high adsorption capacity for tetracycline antibiotics, retaining them with high energy even in the case of multiple systems. It was also shown that hysteresis affected adsorption/desorption processes. These results have relevance at environmental and social levels, given the growing concern regarding antibiotics pollution, and the need of promoting their retention and inactivation when spread in environmental compartments.

Comparison of Phylogenetic Tree Topologies for Nitrogen Associated Genes Partially Reconstruct the Evolutionary History of Saccharomyces cerevisiae.

Massive sequencing projects executed in Saccharomyces cerevisiae have revealed in detail its population structure. The recent "1002 yeast genomes project" has become the most complete catalogue of yeast genetic diversity and a powerful resource to analyse the evolutionary history of genes affecting specific phenotypes. In this work, we selected 22 nitrogen associated genes and analysed the sequence information from the 1011 strains of the "1002 yeast genomes project". We constructed a total evidence (TE) phylogenetic tree using concatenated information, which showed a 27% topology similarity with the reference (REF) tree of the "1002 yeast genomes project". We also generated individual phylogenetic trees for each gene and compared their topologies, identifying genes with similar topologies (suggesting a shared evolutionary history). Furthermore, we pruned the constructed phylogenetic trees to compare the REF tree topology versus the TE tree and the individual genes trees, considering each phylogenetic cluster/subcluster within the population, observing genes with cluster/subcluster topologies of high similarity to the REF tree. Finally, we used the pruned versions of the phylogenetic trees to compare four strains considered as representatives of S. cerevisiae clean lineages, observing for 15 genes that its cluster topologies match 100% the REF tree, supporting that these strains represent main lineages of yeast population. Altogether, our results showed the potential of tree topologies comparison for exploring the evolutionary history of a specific group of genes.

Competitive adsorption/desorption of tetracycline, oxytetracycline and chlortetracycline on pine bark, oak ash and mussel shell.

We studied competitive adsorption for the tetracycline antibiotics (TCs) tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC) on three bio-adsorbents (mussel shell, oak wood ash, and pine bark). The results were compared for individual systems (with antibiotics added separately) and ternary systems (with all three antibiotics added simultaneously). In all cases batch-type experiments were carried out, with 24 h of contact time. In the individual systems, concentrations of 200 µmol L-1 were used for each of the three antibiotics, separately. In the ternary system, all three TCs were added simultaneously, using the following total concentrations: 50, 100, 200, 400, 600 µmol L-1, each antibiotic being 1/3 of the total. Taking into account that ionic strength of a solution is related to a measure of the concentration of ions in that solution, the use of individual and ternary systems allows to compare, for each antibiotic, systems having equal concentrations and similar ionic strength (concentrations of 200 µmol L-1), and systems having different concentrations and ionic strength (200 µmol L-1 in the individual systems, and 600 µmol L-1 in the ternary systems, resulting from the sum of 200 µmol L-1 corresponding to each of the three antibiotics). Adsorption/desorption results indicated that these processes were in all cases closely related to pH values, and to carbon and non-crystalline minerals contents in the bio-adsorbents. Both oak ash and pine bark adsorbed close to 100% of TCs in individual and ternary systems, with desorption <4% for oak ash, and <12% for pine bark. However, mussel shell gave clearly poorer results, only relatively acceptable for CTC, with adsorption <56% and desorption even >30% for TC and OTC. In view of the results, oak ash and pine bark can be recommended as effective bio-adsorbents for the three TCs studied, and could be useful to retain/inactive them in wastes, and soil or liquid media receiving these emerging pollutants, thus reducing risks of damage for public health and the environment.

Retention of propiconazole and terbutryn on acid sandy-loam soils with different organic matter and Cu concentrations.

Equilibrium propiconazole and terbutryn adsorption characteristics were evaluated in ten acid vineyard soils with a wide range of organic matter and copper concentrations using batch experiments. Adsorption data from equilibrium adsorption experiments were generally well described by linear and Freundlich models. Parameters from these models showed that soil organic matter played a key role of propiconazole adsorption processes, but also the amorphous Fe oxides content in soils. Soil organic matter positively influenced terbutryn adsorption, whereas increases in exchangeable copper decreased terbutryn adsorption. Desorption experiments showed that both, propiconazole and terbutryn adsorption in soils was quite irreversible, i.e. the amount of pesticides desorbed after its adsorption was always less than 50%.

Competitive adsorption of tetracycline, oxytetracycline and chlortetracycline on soils with different pH value and organic matter content.

Antibiotics spread into the environment can cause soil and water degradation. Specifically, tetracycline antibiotics (TCs) are among those most consumed in veterinary medicine, and near 90% of the doses administered to animals are excreted as original compounds, due to poor absorption. In this study we investigated competitive soil adsorption/desorption for three tetracycline antibiotics (tetracycline: TC, oxytetracycline: OTC, and chlortetracycline: CTC), usually spread on soils by slurry fertilization, affecting to soil degradation due to chemical pollution. The study was carried out on six soils selected according to their pH values (4.49-7.06), and organic matter contents (1.07-10.92%). The competitive experiments were performed in ternary systems (adding all three TCs simultaneously, using five equal and increasing concentrations, from 17 to 200 µmol L-1). The results were compared with those obtained in simple systems (adding individual antibiotics separately), for the same final concentration (in this case, 200 µmol L-1) and for different concentrations (200 µmol L-1 in the simple systems, versus 600 µmol L-1 in the ternary systems, resulting from the sum of 200 µmol L-1 of each of the three antibiotics). In all cases, batch-type adsorption/desorption experiments were carried out, with 24 h as contact time. Those soils with higher organic matter content adsorbed 100% of the TCs, with desorption being always lower than 3%. In soils with less organic matter, adsorption decreased as the dose of added antibiotic increased, due to competition for adsorption sites. CTC was the most retained among the three TCs (up to 20% more than the other when high doses of antibiotic were added). In the simple systems, percentage adsorption was always high (>85%) for the three TCs; however, percentage adsorption decreased in the ternary systems, reaching just 65% and 40% (for equal and different ionic strength, respectively) in soils with low organic matter contents. These results show the environmental and public health relevance of competition among the three TCs. In fact, the highest risk of entering the food chain takes place when these antibiotics are spread together on soils with low organic matter content, especially in the case of TC and CTC, which are the least adsorbed and the most desorbed molecules.

Expression of several cytokines in prostate cancer: Correlation with clinical variables of patients. Relationship with biochemical progression of the malignance.

BACKGROUND: This work is focused on finding new markers that complement or diagnoses currently used towards improving knowledge histological and statistical aspects that allow us to predict the local stage carcinomas and to identify and understand all the factors related to the progression of this disease. MATERIALS AND METHODS: Prostates were obtained from: normal prostates from 20 men, diagnosis of BPH (Benign Prostatic Hyperplasia) from 35 men and prostate cancer from 86 men. We studied the behavior of cytokines that have been implicated in inflammatory processes: TNF-alfa, IL-6, IL-1, EGF and TGF-B. Expression of these cytokines and its receptors was analyzed by immunohistochemistry. Spearman's test, Kaplan-Meier curves, univariate and multivariate Cox proportional hazard regression analyses were performed. RESULTS: Spearman's analysis showed that there was at least one correlation between TGFB-B, IL-6, gp-130, IL-1B, IL-1R, IL-1RII and clinic pathological feature (preoperative serum PSA, clinical t stage, pathological t stage, positive surgical margins, biochemical progression, survival). Immunostaining score was correlated with some of the clinicopathological feature. In Cox multivariate analysis between the prognostic variables (pathological T stage, Gleason score and lymph node) and immunohistochemical parameters (TGF-B, IL-1a, intensity TGFBRI and intensity TGFBRII) only the expression of IL-1a was retained as independent predictors of biochemical progression after radical prostatectomy. CONCLUSIONS: Our results suggest a role for prostatic expression of TGF-B, IL-1a, TGFBRI and TGFBRII as prognostic markers for prostate cancer. The rational combination of novel agents directed toward the inactivation of TGF-B, IL-1a, TGFBRI and TGFBRII could disrupt complementary tumor cell proliferation pathways.

As(V)/Cr(VI) retention on un-amended and waste-amended soil samples: competitive experiments.

Focusing on simultaneous arsenic and chromium pollution, we used batch-type experiments to study As(V)/Cr (VI) competitive sorption on soil samples, pyritic material, mussel shell, oak ash, pine bark and hemp waste, as well as on binary mixtures (50 % mussel shell and 50 % another material-oak ash, pine bark, or hemp waste), and on forest and vineyard soil samples and pyritic material amended with 48 t ha-1 of mussel shell, oak ash, pine bark, or hemp waste. Equal As(V) and Cr(VI) concentrations (0 to 6 mmol L-1) were added to the individual materials, binary mixtures, and 48 t ha-1 amended materials. The individual forest soil sample, pyritic material, and oak ash showed clearly higher As(V) sorption, whereas Cr(VI) sorption was higher on pine bark. Sorption was up to 50 % higher for As(V) than for Cr(VI) on the forest soil sample, oak ash, and pyritic material, while pine bark sorbed 95 % more Cr(VI). Regarding binary mixtures, the presence of mussel shell increased As(V) sorption on pine bark and Cr(VI) sorption on hemp waste. As regards the amendments, in the case of the forest soil sample, the amendments with oak ash and mussel shell increased As(V) sorption, while pine bark amendment increased Cr(VI) sorption; in the vineyard soil sample, the mussel shell amendment increased As(V) sorption; in the pyritic material, pine bark amendment increased Cr(VI) sorption. These results could be useful to appropriately manage the soils and individual or mixed by-products assayed when As(V) and Cr(VI) pollution occurs.

A New Strategy to Evaluate Technical Efficiency in Hospitals Using Homogeneous Groups of Casemix : How to Evaluate When There is Not DRGs?

The public health system has restricted economic resources. Because of that, it is necessary to know how the resources are being used and if they are properly distributed. Several works have applied classical approaches based in Data Envelopment Analysis (DEA) and Stochastic Frontier Analysis (SFA) for this purpose. However, if we have hospitals with different casemix, this is not the best approach. In order to avoid biases in the comparisons, other works have recommended the use of hospital production data corrected by the weights from Diagnosis Related Groups (DRGs), to adjust the casemix of hospitals. However, not all countries have this tool fully implemented, which limits the efficiency evaluation. This paper proposes a new approach for evaluating the efficiency of hospitals. It uses a graph-based clustering algorithm to find groups of hospitals that have similar production profiles. Then, DEA is used to evaluate the technical efficiency of each group. The proposed approach is tested using the production data from 2014 of 193 Chilean public hospitals. The results allowed to identify different performance profiles of each group, that differs from other studies that employs data from partially implemented DRGs. Our results are able to deliver a better description of the resource management of the different groups of hospitals. We have created a website with the results ( bioinformatic.diinf.usach.cl/publichealth ). Data can be requested to the authors.

Prognostic value of inhibitors of apoptosis proteins (IAPs) and caspases in prostate cancer: caspase-3 forms and XIAP predict biochemical progression after radical prostatectomy.

BACKGROUND: The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer--clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival--and evaluated its capability to predict biochemical progression after radical prostatectomy. METHODS: Protein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3, caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry in radical prostatectomy samples from 84 prostate cancer patients. Spearman's test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analysis were performed. RESULTS: cIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors of biochemical progression independent of Gleason score and pathological T stage. CONCLUSIONS: Our results indicate that alterations in the expression of IAPs and caspases contribute to the malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved caspase-3 may help to identify prostate cancer patients at risk of progression.

Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata.

Multiple cutaneous and uterine leiomyomata syndrome (MCL) is an autosomal dominant disease characterized by the presence of concurrent benign tumors of smooth muscle origin (leiomyoma) in the skin and uterus of affected females, and in the skin of affected males. MCL can also be associated with type II papillary renal cell cancer (HLRCC). The genetic locus for MCL and HLRCC was recently mapped to chromosome 1q42.3-43 and subsequently, dominantly inherited mutations in the fumarate hydratase gene ( FH ) were identified. Importantly, analysis of the FH gene in tumors of MCL patients revealed a second mutation inactivating the wild-type allele in some tumors. Based on these findings, it has been suggested that FH may function as a tumor suppressor gene in MCL. Here, we report the analysis of the FH gene in a group of 11 MCL families, with the identification of 8 different mutations accounting for the disease in all families. One of the mutations, 905-1G>A, has been identified in 4 families of Iranian origin. The analysis of highly polymorphic markers in the vicinity of the FH gene showed a shared haplotype in these 4 families, suggesting that 905-1G>A represents a founder mutation. Collectively, identification of 5 novel and 3 recurrent mutations further supports the role of FH in the pathogenesis of MCL.