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Chronic heart failure (CHF) represents a challenge for the healthy system due to its high prevalence, high burden of morbidity and mortality, and high consumption of health resources. To address this problem, it is necessary to develop efficient management strategies that include both hospital care and outpatient care. The primary objective is to stabilize the patient and prevent decompensation, with the consequent improvement in quality of life, reduction in hospital admissions and emergency department care, and, consequently, reduction in healthcare costs. In this context, the heart failure and atrial fibrilation working group of the Spanish Society of Internal Medicine has developed a protocol for the management of outpatient CHF, that addresses, from the perspective of Internal medicine, all the problems suffered by the patient with CHF. This protocol aims to optimize pharmacological treatment, control cardiovascular risk factors and various comorbidities, educate the patient and their environment about the disease, promote adherence to treatment and stablish follow-up adapted to their condition., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas with a poor survival rate, presenting either sporadically or in the context of neurofibromatosis type 1 (NF1). The histological diagnosis of MPNSTs can be challenging, with different tumors exhibiting great histological and marker expression overlap. This heterogeneity could be partly responsible for the observed disparity in treatment response due to the inherent diversity of the preclinical models used. For several years, our group has been generating a large patient-derived orthotopic xenograft (PDOX) MPNST platform for identifying new precision medicine treatments. Herein, we describe the expansion of this platform using six primary tumors clinically diagnosed as MPNSTs, from which we obtained six additional PDOX mouse models and three cell lines, thus generating three pairs of in vitro-in vivo models. We extensively characterized these tumors and derived preclinical models, including genomic, epigenomic, and histological analyses. Tumors were reclassified after these analyses: three remained as MPNSTs (two being classic MPNSTs), one was a melanoma, another was a neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, and, finally, the last was an unclassifiable tumor bearing neurofibromin-2 (NF2) inactivation, a neuroblastoma RAS viral oncogene homolog (NRAS) oncogenic mutation, and a SWI/SNF-related matrix-associated actin-dependent regulator of chromatin (SMARCA4) heterozygous truncated variant. New cell lines and PDOXs faithfully recapitulated histology, marker expression, and genomic characteristics of the primary tumors. The diversity in tumor identity and their specific associated genomic alterations impacted treatment responses obtained when we used the new cell lines for testing compounds against known altered pathways in MPNSTs. In summary, we present here an extension of our MPNST precision medicine platform, with new PDOXs and cell lines, including tumor entities confounded as MPNSTs in a real clinical scenario. This platform may constitute a useful tool for obtaining correct preclinical information to guide MPNST clinical trials., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) Upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease. (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response. (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors. (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

In this paper, the mesophilic Biochemical Methane Potential of several fabrics was assessed at different Total Solid concentrations (1-4%TS). Physico-chemical techniques were applied to explore the arising structural changes on fibers during the anaerobic digestion process. Additionally, the modified Gompertz model was used to assess and compare the AD performance of the fabrics. In cellulose-based fibers the production of biogas was enhanced thanks to the easy solubilization of acetate, which is generated upon partial breakage of cellulose bonds. The crystallinity of vegetal fibers decreased significantly from day 19. The highest methane yields were attained for silk and wool fabrics at the lowest TS concentrations. Conformational changes in fibroin and keratin were detected. The highest degrees of degradation were observed in solid samples with lower solid concentrations. Accordingly, the maximum methane yields were reported in the reactors operating with lower TS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGFβ coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs., Experimental Design: ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis, were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models., Results: ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma-circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis., Conclusions: Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease., (©2023 American Association for Cancer Research.)

Neurofibromas are benign peripheral nervous system tumors associated with neurofibromatosis type 1, which originate from NF1(-/-) Schwann cell precursors. We describe a protocol to generate neurofibromaspheres by differentiating NF1(-/-) Schwann cells from induced pluripotent stem cells and combining them with neurofibroma primary fibroblasts. We also describe the development of neurofibroma-like tumors when neurofibromaspheres are engrafted in the sciatic nerve of nude mice. This model constitutes a versatile platform for drug screening and the study of neurofibroma biology. For complete details on the use and execution of this protocol, please refer to Mazuelas et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The local waste co-digestion is an interesting option to tackle in reduced and isolated areas like the islands. The islands have limited territory and scarce fuel production. Moreover, organic waste can create serious environmental problems in soil, water and air. Anaerobic co-digestion (AcoD) is a technology fulfilling the concept of waste-to-energy (WtE) based on local resources. The valorisation of organic waste through AcoD on an island would prevent environmental impacts, while being a source of renewable energy. In this study, cow manure (outdoor and indoor), pig slurry, bird manure, kitchen waste, sewage sludge and oily lacteous waste produced on Island Terceira (Portugal) were tested in mesophilic -35 °C- Biochemical Methane Potential (BMP) co-digestion assays. The goals were to analyse the recalcitrant and high potential produced waste and to estimate the energetic supply source on the island. The cow manure and pig slurry were used as inocula and specific methanogenic activities (SMAs) were carried out. The results showed that both substrates have a significant methanogenic activity-SMA 0.11 g-COD/(g-VSS.d) and 0.085 g-COD/(g-VSS.d), respectively. All the studied combinations were feasible in AcoD, showing TS removals in the range of 19-37%; COD removals in the range 67-78% and specific methane yields from 0.14 to 0.22 L/gCOD removed, but some differences were found. The modified Gompertz model fitted the AcoD assays (R 2 0.982-0.998). The maximum biogas production rate, Rmax. was highest in the AcoD of Cow+Pig+Oily and in the Cow+Pig+Sludge with 0.017 and 0.014 L/g-VS added .day, respectively, and the lowest in Cow+Pig+Bird with 0.010 L/g-VS added . In our AcoD studies, the bird manure limited the performance of the process, since it was recalcitrant to anaerobic degradation. On the other hand, the oily lacteous waste showed a great potential in the anaerobic digestion. The estimated biogas production, from the best-studied condition, could cover the 11.4% of the energy supply of the inhabitants. These preliminary results would prevent the environmental impact of organic waste on the island and promote the use of local waste in a circular economy scenario.

Collagen-based polymers and their blends have attracted considerable interest for new materials development due to their unique combination of biocompatibility, physical and mechanical properties and durability. Leather, a modified natural biopolymer made from animal rawhide and the first synthetic collagen-based polymer known since the dawn of civilization, combines all these features. Rawhide is transformed into leather by tanning, a process in which the collagen is cross-linked with different agents to make it stronger and more durable and to prevent its decay. Research on the development of environmentally friendly procedures and sustainable materials with higher efficiency and lower costs is a rapidly growing field, and leather industry is not an exemption. Chrome-tanned and vegetable-tanned (chromium-free) shavings from the leather industry present a high content of organic matter, yet they are considered recalcitrant waste to be degraded by microbiological processes like anaerobic digestion (AD), a solid technology to treat organic waste in a circular economy framework. In this technology however, the solubilisation of organic solid substrates is a significant challenge to improving the efficiency of the process. In this context, we have investigated the process of microbial decomposition of leather wastes from the tannery industry to search for the conditions that produce optimal solubilisation of organic matter. Chrome-tanned and chromium-free leather shavings were pre-treated and anaerobically digested under different temperature ranges (thermophilic-55 °C-, intermediate-42 °C- and mesophilic-35 °C) to evaluate the effect on the solubilisation of the organic matter of the wastes. The results showed that the presence of chromium significantly inhibited the solubilization (up to 60%) in the mesophilic and intermediate ranges; this is the fastest and most efficient solubilization reached under thermophilic conditions using the chromium-free leather shaving as substrates. The most suitable temperature for the solubilization was the thermophilic regime (55 °C) for both chromium-free and chrome-tanned shavings. No significant differences were observed in the thermophilic anaerobic digestion of chromium-free shavings when a pre-treatment was applied, since the solubilisation was already high without pre-treatment. However, the pre-treatments significantly improved the solubilisation in the mesophilic and intermediate configurations; the former pre-treatment was better suited in terms of performance and cost-effectiveness compared to the thermophilic range. Thus, the solubilisation of chromium-free tannery solid wastes can be significantly improved by applying appropriate pre-treatments at lower temperature ranges; this is of utter importance when optimizing anaerobic processes of recalcitrant organic wastes, with the added benefit of substantial energy savings in the scaling up of the process in an optimised circular economy scenario.

Malignant peripheral nerve sheath tumors (MPNST) are soft-tissue sarcomas that are the leading cause of mortality in patients with Neurofibromatosis type 1 (NF1). Single chemotherapeutic agents have shown response rates ranging from 18% to 44% in clinical trials, so there is still a high medical need to identify chemotherapeutic combination treatments that improve clinical prognosis and outcome. We screened a collection of compounds from the NCATS Mechanism Interrogation PlatE (MIPE) library in three MPNST cell lines, using cell viability and apoptosis assays. We then tested whether compounds that were active as single agents were synergistic when screened as pairwise combinations. Synergistic combinations in vitro were further evaluated in patient-derived orthotopic xenograft/orthoxenograft (PDOX) athymic models engrafted with primary MPNST matching with their paired primary-derived cell line where synergism was observed. The high-throughput screening identified 21 synergistic combinations, from which four exhibited potent synergies in a broad panel of MPNST cell lines. One of the combinations, MK-1775 with Doxorubicin, significantly reduced tumor growth in a sporadic PDOX model (MPNST-SP-01; sevenfold) and in an NF1-PDOX model (MPNST-NF1-09; fourfold) and presented greater effects in TP53 mutated MPNST cell lines. The other three combinations, all involving Panobinostat (combined with NVP-BGT226, Torin 2, or Carfilzomib), did not reduce the tumor volume in vivo at noncytotoxic doses. Our results support the utility of our screening platform of in vitro and in vivo models to explore new therapeutic approaches for MPNSTs and identified that combination MK-1775 with Doxorubicin could be a good pharmacologic option for the treatment of these tumors., (©2022 American Association for Cancer Research.)

Plexiform neurofibromas (pNFs) are developmental tumors that appear in neurofibromatosis type 1 individuals, constituting a major source of morbidity and potentially transforming into a highly metastatic sarcoma (MPNST). pNFs arise after NF1 inactivation in a cell of the neural crest (NC)-Schwann cell (SC) lineage. Here, we develop an iPSC-based NC-SC in vitro differentiation system and construct a lineage expression roadmap for the analysis of different 2D and 3D NF models. The best model consists of generating heterotypic spheroids (neurofibromaspheres) composed of iPSC-derived differentiating NF1(-/-) SCs and NF1(+/-) pNF-derived fibroblasts (Fbs). Neurofibromaspheres form by maintaining highly proliferative NF1(-/-) cells committed to the NC-SC axis due to SC-SC and SC-Fb interactions, resulting in SC linage cells at different maturation points. Upon engraftment on the mouse sciatic nerve, neurofibromaspheres consistently generate human NF-like tumors. Analysis of expression roadmap genes in human pNF single-cell RNA-seq data uncovers the presence of SC subpopulations at distinct differentiation states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas with poor prognosis, developing either sporadically or in persons with neurofibromatosis type 1 (NF1). Loss of CDKN2A/B is an important early event in MPNST progression. However, many reported MPNSTs exhibit partial or no inactivation of CDKN2A/B, raising the question of whether there is more than one molecular path for MPNST initiation. We present here a comprehensive genomic analysis of MPNST cell lines and tumors to explore in depth the status of CDKN2A. After accounting for CDKN2A deletions and point mutations, we uncovered a previously unnoticed high frequency of chromosomal translocations involving CDKN2A in both MPNST cell lines and primary tumors. Most identified translocation breakpoints were validated by PCR amplification and Sanger sequencing. Many breakpoints clustered in an intronic 500 bp hotspot region adjacent to CDKN2A exon 2. We demonstrate the bi-allelic inactivation of CDKN2A in all tumors (n = 15) and cell lines (n = 8) analyzed, supporting a single molecular path for MPNST initiation in both sporadic and NF1-related MPNSTs. This general CDKN2A inactivation in MPNSTs has implications for MPNST diagnostics and treatment. Our findings might be relevant for other tumor types with high frequencies of CDKN2A inactivation.

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45 years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65 years in Spain, a quarter of whom die within 1 year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30 days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: 1) At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. 2) During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. 3) To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers and aldosterone antagonists). 4) At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65years in Spain, a quarter of whom die within 1year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: (1)At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. (2)During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. (3)To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensinII receptor blockers, beta blockers and aldosterone antagonists). (4)At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Bacteria from the same species can differ widely in their gene content. In Escherichia coli, the set of genes shared by all strains, known as the core genome, represents about half the number of genes present in any strain. Although recent advances in bacterial genomics have unravelled genes required for fitness in various experimental conditions, most studies have focused on single model strains. As a result, the impact of the species' genetic diversity on core processes of the bacterial cell remains largely under-investigated. Here, we have developed a CRISPR interference platform for high-throughput gene repression that is compatible with most E. coli isolates and closely related species. We have applied it to assess the importance of ~3,400 nearly ubiquitous genes in three growth conditions in 18 representative E. coli strains spanning most common phylogroups and lifestyles of the species. Our screens revealed extensive variations in gene essentiality between strains and conditions. Investigation of the genetic determinants for these variations highlighted the importance of epistatic interactions with mobile genetic elements. In particular, we have shown how prophage-encoded defence systems against phage infection can trigger the essentiality of persistent genes that are usually non-essential. This study provides broad insights into the evolvability of gene essentiality and argues for the importance of studying various isolates from the same species under diverse conditions.

Type 2 diabetes is a big health concern due to its high prevalence and morbi-mortality. Medical treatment has a growing complexity which is focus on patients' clinical situations. This article contains a consensus statement about recommendations on medical treatment of type-2 diabetes from the Working Group of Diabetes, Obesity and Nutrition of Spanish Society of Internal Medicine. The aim of this consensus is to facilitate therapeutic decision-making to improve the diabetes patients care. The document prioritizes treatments with cardiovascular, especially heart failure, and real benefits., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Type 2 diabetes mellitus is a major health problem with high prevalence, morbidity and mortality, and its medical treatment is growing in complexity due to patients' diverse clinical conditions. This article presents a consensus document by the Diabetes, Obesity and Nutrition Group of the Spanish Society of Internal Medicine, with recommendations for the medical treatment of type 2 diabetes mellitus. The main objective of this article is to facilitate the therapeutic decision-making process to improve the care of patients with diabetes. The document prioritises treatments with cardiovascular benefits, especially those that benefit patients with heart and renal failure., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background: The aim of this study was to test the feasibility and utility of developing patient-derived orthotopic xenograft (PDOX) models for patients with malignant peripheral nerve sheath tumors (MPNSTs) to aid therapeutic interventions in real time., Patient & Methods: A sporadic relapsed MPNST developed in a 14-year-old boy was engrafted in mice, generating a PDOX model for use in co-clinical trials after informed consent. SNP-array and exome sequencing was performed on the relapsed tumor. Genomics, drug availability, and published literature guided PDOX treatments., Results: A MPNST PDOX model was generated and expanded. Analysis of the patient's relapsed tumor revealed mutations in the MAPK1, EED , and CDK2NA/B genes. First, the PDOX model was treated with the same therapeutic regimen as received by the patient (everolimus and trametinib); after observing partial response, tumors were left to regrow. Regrown tumors were treated based on mutations (palbociclib and JQ1), drug availability, and published literature (nab-paclitaxel; bevacizumab; sorafenib plus doxorubicin; and gemcitabine plus docetaxel). The patient had a lung metastatic relapse and was treated according to PDOX results, first with nab-paclitaxel, second with sorafenib plus doxorubicin after progression, although a complete response was not achieved and multiple metastasectomies were performed. The patient is currently disease free 46 months after first relapse., Conclusion: Our results indicate the feasibility of generating MPNST-PDOX and genomic characterization to guide treatment in real time. Although the treatment responses observed in our model did not fully recapitulate the patient's response, this pilot study identify key aspects to improve our co-clinical testing approach in real time., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2020.)

Background: Malignant peripheral nerve sheath tumor (MPNST) constitutes the leading cause of neurofibromatosis type 1-related mortality. MPNSTs contain highly rearranged hyperploid genomes and exhibit a high division rate and aggressiveness. We have studied in vitro whether the mitotic kinesins KIF11, KIF15, and KIF23 have a functional role in maintaining MPNST cell survival and can represent potential therapeutic vulnerabilities., Methods: We studied the expression of kinesin mRNAs and proteins in tumors and cell lines and used several in vitro functional assays to analyze the impact of kinesin genetic suppression (KIF15, KIF23) and drug inhibition (KIF11) in MPNST cells. We also performed in vitro combined treatments targeting KIF11 together with other described MPNST targets., Results: The studied kinesins were overexpressed in MPNST samples. KIF15 and KIF23 were required for the survival of MPNST cell lines, which were also more sensitive than benign control fibroblasts to the KIF11 inhibitors ispinesib and ARRY-520. Co-targeting KIF11 and BRD4 with ARRY-520 and JQ1 reduced MPNST cell viability, synergistically killing a much higher proportion of MPNST cells than control fibroblasts. In addition, genetic suppression of KIF15 conferred an increased sensitivity to KIF11 inhibitors alone or in combination with JQ1., Conclusions: The mitotic spindle kinesins KIF11 and KIF15 and the cytokinetic kinesin KIF23 play a clear role in maintaining MPNST cell survival and may represent potential therapeutic vulnerabilities. Although further in vivo evidences are still mandatory, we propose a simultaneous suppression of KIF11, KIF15, and BRD4 as a potential therapy for MPNSTs., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Microbial dynamics in an upgrading biogas reactor system undergoing a more than two years-period at stable operating conditions were explored. The carbon dioxide generated during biomass degradation in the first reactor of the system was converted to methane into the secondary reactor by addition of external hydrogen. Considering the overall efficiency, the long-term operation period resulted in an improved biogas upgrading performance (99% methane content). However, a remarkable accumulation of acetate was revealed, indicating the enhancement of homoacetogenic activity. For this reason, a shift in the anaerobic digestion microbiome was expected and evaluated by 16S rRNA amplicon analysis. Results demonstrated that the most abundant archaeal species identified in the first time point, Candidatus Methanoculleus thermohydrogenotrophicum, was replaced by Methanothermobacter thermautotrophicus, becoming dominant after the community adaptation. The most interesting taxonomic units were clustered by relative abundance and six main long-term adaptation trends were found, characterizing functionally related microbes (e.g. homoacetogens)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

These data and analyses support the research article "Production of cellulose nanoparticles from blue agave waste treated with environmentally friendly processes" Robles et al. [1]. The data and analyses presented here include fitted curves for selected carbons of the 13 C CP-MAS NMR analysis; SEM images of the raw and bleached fibers, graphics with chemical composition and visual images of the fibers throughout the process.

Tequila elaboration leaves two main byproducts that are undervalued (bagasse and leaves). Organosolv pulping and Total Chlorine Free bleaching were integrated to obtain cellulose fibers from agricultural waste which consisted of blue agave bagasse and leaf fibers; together they represent a green process which valorizes biomass waste. The obtained celluloses were characterized by FT-IR, colorimetry, and SEM and their extraction yields were evaluated. These celluloses were used to produce cellulose nanocrystals and cellulose nanofibers. First, an acid hydrolysis was performed in a sonication bath to induce cavitation during the reaction to produce cellulose nanocrystals. Then a high-pressure homogenization was selected to produce cellulose nanofibers. These nanocelluloses were characterized by powder XRD, Nanosizer, zeta potential, NMR, and electronic microscopy. Results showed that cellulose from organosolv pulps bleached with TCF bleaching is suitable for nanocellulose production. Moreover, the use of a new step to separate cellulose nanocrystals resulted in yields almost doubling traditional yields, while the rest of the properties remained within the expected., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To estimate the prevalence of obesity in patients treated by departments of Internal Medicine and to classify the patients according to the Edmonton Obesity Staging System (EOSS)., Material and Methods: An observational, descriptive cross-sectional study included outpatients older than 18 years, with a body mass index (BMI)>30, from 38 hospitals between the 1st and 14th of February, 2016. We classified the patients according to the EOSS and analysed their clinical, laboratory and demographic variables. A value of P<.05 was considered statistically significant., Results: Of the 1,262 patients treated in consultations, we recruited 298 and analysed 265. The prevalence of obesity was 23.6%, the mean age was 62.47±15.27 years, and the mean BMI was 36.1±5.3kg/m 2 . According to EOSS stage (0, 1, 2, 3 and 4), the prevalence was 4.9, 14.7, 62.3, 15.5 and 2.64%, respectively. Those patients with EOSS>2 were significantly older and had significantly more comorbidities. The multivariate analysis related age (OR 1.06; P<.0003), blood glucose (OR 1.04; P<.0006), total cholesterol (OR 0.98; P<.02) and uric acid (OR 1.32; P<.02) levels with an EOSS>2. An analysis of correspondence grouped, with an explanatory percentage of 78.2%, the patients according to their EOSS, comorbidity, education level, employment status and functional capacity., Conclusions: The prevalence of obesity in the patients treated by Internal Medicine departments is similar to that of the general population, although the patients are older and have a higher BMI. EOSS is useful for implementing a comprehensive approach for patients with obesity, regardless of the BMI, which can help achieve better health and quality-of-life results., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Purpose: Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders., Methods: We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect., Results: We found seven JMJD1C variants that were not present in any control sample (~ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity., Conclusions: Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.Genet Med 18 1, 378-385.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas that can arise either sporadically or in association with neurofibromatosis type 1 (NF1). These aggressive malignancies confer poor survival, with no effective therapy available. We present the generation and characterization of five distinct MPNST orthoxenograft models for preclinical testing and personalized medicine. Four of the models are patient-derived tumor xenografts (PDTX), two independent MPNSTs from the same NF1 patient and two from different sporadic patients. The fifth model is an orthoxenograft derived from an NF1-related MPNST cell line. All MPNST orthoxenografts were generated by tumor implantation, or cell line injection, next to the sciatic nerve of nude mice, and were perpetuated by 7-10 mouse-to-mouse passages. The models reliably recapitulate the histopathological properties of their parental primary tumors. They also mimic distal dissemination properties in mice. Human stroma was rapidly lost after MPNST engraftment and replaced by murine stroma, which facilitated genomic tumor characterization. Compatible with an origin in a catastrophic event and subsequent genome stabilization, MPNST contained highly altered genomes that remained remarkably stable in orthoxenograft establishment and along passages. Mutational frequency and type of somatic point mutations were highly variable among the different MPNSTs modeled, but very consistent when comparing primary tumors with matched orthoxenografts generated. Unsupervised cluster analysis and principal component analysis (PCA) using an MPNST expression signature of ~1,000 genes grouped together all primary tumor-orthoxenograft pairs. Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines. Following standardization and extensive characterization and validation, the orthoxenograft models were used for initial preclinical drug testing. Sorafenib (a BRAF inhibitor), in combination with doxorubicin or rapamycin, was found to be the most effective treatment for reducing MPNST growth. The development of genomically well-characterized preclinical models for MPNST allowed the evaluation of novel therapeutic strategies for personalized medicine., (© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)

Spent sulfite liquor is a lignocellulosic waste obtained after the sulfite pulping process. It is mainly formed by sugars and lignosulfonates which are isolated from the pulp during the cooking process. The current work investigates the kinetic modeling of the sulfite process from a biorefinery point of view since monosaccharides present in the spent liquor can be used as a raw material in further biorefinery processes to produce other value-added products. Kinetic parameters of carbohydrate degradation have been determined following sugar and inhibitors from wood to spent liquor, using laboratory scale reactors and different temperatures, 130, 140 and 150 °C. Three types of reaction schemes were developed. Kinetic parameters were obtained for each one using first and n order reactions, using Aspen Custom Modeler. Results show that the best temperature to be used in the process is 130 °C, giving the maximum sugar conversion, 33.91 mol% and obtaining 13.81 mol% of decomposition products., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

To analyze the effects of an intervention focused on increasing the time and intensity of Physical Education (PE), on adolescents' cognitive performance and academic achievement. A 4-month group-randomized controlled trial was conducted in 67 adolescents from South-East Spain, 2007. Three classes were randomly allocated into control group (CG), experimental group 1 (EG1) and experimental group 2 (EG2). CG received usual PE (two sessions/week), EG1 received four PE sessions/week and EG2 received four PE sessions/week of high intensity. Cognitive performance (non-verbal and verbal ability, abstract reasoning, spatial ability, verbal reasoning and numerical ability) was assessed by the Spanish Overall and Factorial Intelligence Test, and academic achievement by school grades. All the cognitive performance variables, except verbal reasoning, increased more in EG2 than in CG (all P < 0.05). Average school grades (e.g., mathematics) increased more in EG2 than in CG. Overall, EG2 improved more than EG1, without differences between EG1 and CG. Increased PE can benefit cognitive performance and academic achievement. This study contributes to the current knowledge by suggesting that the intensity of PE sessions might play a role in the positive effect of physical activity on cognition and academic success. Future studies involving larger sample sizes should confirm or contrast these preliminary findings., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent investigations suggest that, despite lack of lethality in validated bioassays, micropollutants in surface waters could induce sublethal toxicity in sensitive taxa, jeopardizing their biological performance and eventually leading to populations' extinction. A broader array of testing species, the miniaturization of bioassays and the development of reliable biomarkers of damage are sought in order to improve ecological relevance and cost efficiency of environmental monitoring. Our aim is to assess the different sensitivity of validated bioassays and new approaches using biomarkers as sensitive endpoints of toxicity in spores of Polystichum setiferum and Danio rerio embryos. Six water samples were collected in Tagus basin in summer and winter. Samples tested induce no acute toxicity in validated methods (algae growth inhibition and daphnia mobility inhibition). Summer water samples induced acute membrane damage (lipid peroxidation) in Danio rerio embryos and hormetic increases in fern spore mitochondrial activity. One of the samples dramatically reduced mitochondrial activity indicating severe acute sublethal phytotoxicity. All the winter samples induced significant decreases in fern spore mitochondrial activity and membrane damage increases in Danio rerio embryo. Furthermore, three samples induced lethal phytotoxicity in fern spores. We conclude that the new microbioassays show a better sensitivity to fluvial water micropollution and confirm the necessity to test critical life stages such as development and provide cost-efficient methods for environmental monitoring., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Germline inactivating mutations in BRCA1 and BRCA2 genes are responsible for Hereditary Breast and Ovarian Cancer Syndrome (HBOCS). Genetic testing of these genes is available, although approximately 15% of tests identify variants of uncertain significance (VUS). Classification of these variants into pathogenic or non-pathogenic type is an important challenge in genetic diagnosis and counseling. The aim of the present study is to functionally assess a set of 7 missense VUS (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L and G1770V) located in the C-terminal region of BRCA1 by combining in silico prediction tools and structural analysis with a transcription activation (TA) assay. The in silico prediction programs gave discrepant results making its interpretation difficult. Structural analysis of the three variants located in the BRCT domains (Y1703S, W1718L and G1770V) reveals significant alterations of BRCT structure. The TA assay shows that variants Y1703S, W1718L and G1770V dramatically compromise the transcriptional activity of BRCA1, while variants Q1409L, S1473P, E1586G and R1589H behave like wild-type BRCA1. In conclusion, our results suggest that variants Y1703S, W1718L and G1770V can be classified as likely pathogenic BRCA1 mutations.

Comprehensive genetic testing of the breast cancer susceptibility genes BRCA1 and BRCA2 identified approximately 16% of variants of unknown significance (VUS), a significant proportion of which could affect the correct splicing of the genes. Our aim is to establish a workflow for classifying VUS in these complex genes, the first stage of which is splicing analysis. We used a combined approach consisting of five in silico splicing prediction programs and RT-PCR analysis for a set of 26 variants not previously studied at the mRNA level and six variants that had already been studied, four of which were used as positive controls as they were found to affect the splicing of these genes and the other two were used as negative controls. We identified a splicing defect in 8 of the 26 newly studied variants and ruled out splicing alteration in the remaining 18 variants. The results for the four positive and the two negative control variants were consistent with results presented in the literature. Our results strongly suggest that the combination of RNA analysis and in silico programs is an important step towards the classification of VUS. The results revealed a very high correlation between experimental data and in silico programs when using tools for predicting acceptor/donor sites but a lower correlation in the case of tools for identifying ESE elements.

Background: Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4 in German or Byelorussian familial cases of breast cancer without detected mutations in BRCA1 or BRCA2 has been completed, with globally negative results., Methods: The genomic region of SLX4, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of BRCA1 or BRCA2 mutations., Results: This mutational analysis revealed extensive genetic variation of SLX4, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them., Conclusions: Overall, while the results of this study do not identify clearly pathogenic mutations of SLX4 contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.

The aim of this study was to review all cases of recovery of renal function in chronic haemodialysis patients, observed in the last ten years. During the study period, 218 chronic renal failure patients were managed on haemodialysis for a minimum of 90 days. In 17 cases (8%), it was possible to interrupt dialysis after 95 to 529 days. The probability of renal function recovery was higher in patients with chronic interstitial nephritis (P=.04) or autoimmune diseases (P=.07), as well as in those starting haemodialysis treatment at a frequency of two sessions per week (P=.02). No significant differences in age, gender, glomerular filtration rate at the beginning of haemodialysis treatment, or comorbidity rate were observed. Seven patients returned to haemodialysis treatment after a dialysis-free period of 11 +/- 7 months. Two patients died for reasons unrelated to renal failure treatment, and another patient was moved to another hospital following 35 months without dialysis. The other 14 patients are alive and 8 are dialysis-free, with a monitoring period of 13 to 106 months. The conclusion reached is that there is no reason why residual kidney function should inexorably worsen after the start of haemodialysis treatment, and that functional recovery is possible in some patients.

Here we analyze the genetic and molecular basis responsible for a very benign phenotype observed in an NF1 patient. Quantification of cells carrying the NF1 mutation in different samples derived from the three embryonic layers revealed mosaicism. Furthermore, the construction of a minigene with patient's mutation (c.3198 - 314G>A) confirmed its benign nature due to the leakiness of the splicing mechanism that generated a proportion of correctly spliced transcripts. Hence, we concluded that the mild phenotype observed in this patient is the result of the presence of mosaicism together with the benign nature of a leaky NF1-splice mutation. Finally, with the aim of developing a personalized therapeutic approach for this patient, we demonstrated correction of the splicing defect by using specific antisense morpholino oligomers. Our results provide an example of the molecular complexity behind disease phenotypes and highlight the importance of using comprehensive genetic approaches to better assess phenotype-genotype correlations., (© 2011 Wiley-Liss, Inc.)

Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens., Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk., Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively., Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.

Dermal neurofibromas (dNFs) are benign tumors of the peripheral nervous system typically associated with Neurofibromatosis type 1 (NF1) patients. Genes controlling the integrity of the DNA are likely to influence the number of neurofibromas developed because dNFs are caused by somatic mutational inactivation of the NF1 gene, frequently evidenced by loss of heterozygosity (LOH). We performed a comprehensive analysis of the prevalence and mechanisms of LOH in dNFs. Our study included 518 dNFs from 113 patients. LOH was detected in 25% of the dNFs (N = 129). The most frequent mechanism causing LOH was mitotic recombination, which was observed in 62% of LOH-tumors (N = 80), and which does not reduce the number of NF1 gene copies. All events were generated by a single crossover located between the centromere and the NF1 gene, resulting in isodisomy of 17q. LOH due to the loss of the NF1 gene accounted for a 38% of dNFs with LOH (N = 49), with deletions ranging in size from ∼80 kb to ∼8 Mb within 17q. In one tumor we identified the first example of a neurofibroma-associated second-hit type-2 NF1 deletion. Analysis of the prevalence of mechanisms causing LOH in dNFs in individual patients (possibly under genetic control) will elucidate whether there exist interindividual variation., (© 2010 Wiley-Liss, Inc.)

Neurofibromatosis type 1 is one of the most common neurocutaneous autosomal dominant disorders. It is caused by mutations in the neurofibromatosis type 1 (NF1) gene and approximately 30-40% of them affect the correct splicing of NF1 pre-mRNA. In this report, we evaluate the effect of five different drugs, previously found to modify splicing in several genetic disorders, on the splicing of mutated NF1 alleles. For this purpose, cell lines derived from patients bearing 19 different NF1-splicing defects were used. Our results showed that kinetin partially corrects the splicing defect in four of the studied mutations (c.910C>T, c.3113G>A, c.6724C>T and c.6791dupA). Our study is a valuable contribution to the field because it identifies new exon-skipping events that can be reversed by kinetin treatment and provides new information about kinetin splicing modulation. However, owing to the nature of mutations in our patients, kinetin treatment could not be used as a therapeutic agent in these cases.

A systematic analysis of resonant x-ray Bragg diffraction data for UPd(3), with signal enhancement at the U M(IV) edge, including possible structural phase transitions leads to a new determination of the space groups of the material in the phases between T(0)=7.8 K and T(+1)=6.9 K, as P 222(1), and between T(-1)=6.7 K and T(2)=4.4 K, as P2(1). In addition, the quadrupolar order parameters, {Q(ab)}, inferred from diffraction data for the phase between T(-1) and T(2), are {Q(xz)} and {Q(yz)} at the (103) Bragg reflection and {Q(xy)} at the (104) reflection., (© 2010 IOP Publishing Ltd)

The dependences on energy of the resonant soft x-ray Bragg diffraction intensities in DyB(2)C(2) for the (00½) reflection at the Dy M(4,5) edges have been calculated with an atomic multiplet Hamiltonian including the effect of the crystal field and introducing an intra-atomic quadrupolar interaction between the 3d core and 4f valence shell. These calculations are compared with experimental results (Mulders et al 2006 J. Phys.: Condens. Matter 18 11195) for the antiferroquadrupolar and antiferromagnetic phases of DyB(2)C(2). We reproduce all the features appearing in the (00½) reflection energy profile in the antiferroquadrupolar ordered phase, and we reproduce the behaviour of the resonant x-ray scattering intensity at different energies in the vicinity of the Dy M(5) edge when the temperature is lowered within the antiferromagnetic phase. These calculations show that a detailed description of the energy dependences of resonant x-ray scattering signals at the M edges in 4f and 5f systems with multipolar ordering may require the inclusion of an aspherical intra-atomic Coulomb interaction.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1:3,500 individuals. Disease expression is highly variable and complications are diverse. However, currently there is no specific treatment for the disease. NF1 is caused by mutations in the NF1 gene, approximately 2.1% of constitutional mutations identified in our population are deep intronic mutations producing the insertion of a cryptic exon into the mature mRNA. We used antisense morpholino oligomers (AMOs) to restore normal splicing in primary fibroblast and lymphocyte cell lines derived from six NF1 patients bearing three deep intronic mutations in the NF1 gene (c.288+2025T>G, c.5749+332A>G, and c.7908-321C>G). AMOs were designed to target the newly created 5' splice sites to prevent the incorporation of cryptic exons. Our results demonstrate that AMO treatment effectively restored normal NF1 splicing at the mRNA level for the three mutations studied in the different cell lines analyzed. We also found that AMOs had a rapid effect that lasted for several days, acting in a sequence-specific manner and interfering with the splicing mechanism. Finally, to test whether the correction of aberrant NF1 splicing also restored neurofibromin function to wild-type levels, we measured the amount of Ras-GTP after AMO treatment in primary fibroblasts. The results clearly show an AMO-dependent decrease in Ras-GTP levels, which is consistent with the restoration of neurofibromin function. To our knowledge this is the first time that an antisense technique has been used successfully to correct NF1 mutations opening the possibility of a therapeutic strategy for this type of mutation not only for NF1 but for other genetic disorders., (2009 Wiley-Liss, Inc.)

This study aimed to investigate the influence of prophylactic ankle taping on two balance tests (static and dynamic balance) and one jump test, in the push off and the landing phase. Fifteen active young subjects (age: 21.0 ± 4.4 years) without previous ankle injuries volunteered for the study. Each participant performed three tests in two different situations: with taping and without taping. The tests were a counter movement jump, static balance, and a dynamic posturography test. The tests and conditions were randomly performed. The path of the center of pressures was measured in the balance tests, and the vertical ground reaction forces were recorded during the push-off and landing phases of the counter movement jump. Ankle taping had no influence on balance performance or in the push off phase of the jump. However, the second peak vertical force value during the landing phase of the jump was 12% greater with ankle taping (0.66 BW, 95% CI -0.64 to 1.96). The use of prophylactic ankle taping had no influence on the balance or jump performance of healthy young subjects. In contrast, the taped ankle increased the second peak vertical force value, which could be related to a greater risk of injury produced by the accumulation of repeated impacts in sports where jumps are frequently performed. Key pointsAnkle taping has no influence on balance performance.Ankle taping does not impair performance during the push-off phase of the jump.Ankle taping could increase the risk of injury during landings by increasing peak forces.

Objectives: The purpose of this study was to assess the value of the serum levels of alpha-L-fucosidase activity in the diagnosis of patients with colorectal cancer., Methods: Using a fluorometric method we analyzed the alpha-L-fucosidase activity in preoperative sera from 137 colorectal cancer patients and in sera from 232 donors., Results: The enzymatic activity of alpha-L-fucosidase was significantly lower (p <0.001) in patients (4.8+/-3.09 U/ml) than in donors (10.5+/-5.46 U/ml). Using the ROC curve, the ideal cut-off for the diagnostic value of alpha-L-fucosidase activity was determined to be 5.6 U/ml. The diagnostic efficiency for colorectal cancer of alpha-L-fucosidase activity was higher than that observed for carcinoembryonic antigen (cut-off 5.0 ng/ml), especially for tumors at an early stage., Conclusions: Our results suggest that preoperative serum alpha-L-fucosidase activity may be used as a cheap and easy complementary test, in addition to standard clinical procedures routinely used for the diagnosis of colorectal cancer., (Copyright 2000 S. Karger AG, Basel.)

The expression of different sialoglycoconjugates and fucoglycoconjugates in normal mucosa and adenocarcinoma samples from 43 colorectal cancer patients was investigated by using specific lectins and applying a semiquantitative analysis. A pronounced decrease in the intracellular binding of the Maackia amurensis lectin, which recognizes alpha(2,3)-linked sialic acid residues, was found in the tumoral tissue. In contrast, a significant increase in the staining with the Sambucus nigra lectin (SNA I), which binds to alpha(2,6)-linked sialic acid residues, was detected in the epithelial cells as well as in the mucins from tumors. No significant differences in the reactivity with the Aleuria aurantia lectin, which recognizes the sequence Fuc(alpha1,6)GlcNAc, between normal and malignant colorectal tissues were detected. Furthermore, the correlation between lectin-binding profiles and the prognosis of colorectal cancer patients was examined. After an average postoperative follow-up period of 31 months, patients with tumors showing a strong SNA I staining presented a greater probability of disease recurrence. This result suggests that the intensity of staining with SNA I could be a valid parameter for predicting recurrence in colorectal cancer., (Copyright 2000 S. Karger AG, Basel)

The aim of this study was to examine the prognostic value of the alpha-L-fucosidase enzyme to determine whether it can help in the early recognition of colorectal cancer cases at high risk of tumor recurrence. One hundred and twenty-three colorectal carcinoma patients treated by curative surgery were studied. The alpha-L-fucosidase activity was assayed in the tumor and in normal mucosa from each patient using a fluorometric method. Seven other clinical and pathologic features were also studied. To evaluate the impact of each variable over the disease-free interval, a postoperative 30-month follow-up of patients was performed, and a statistical survival analysis was carried out. The recurrence appearance was higher when the relative decrease of alpha-L-fucosidase activity was more than 52% (log-rank test, P = .0261). The results of this work indicate that alpha-L-fucosidase activity appears to be a good independent prognostic factor of tumoral recurrence in colorectal carcinoma.

Objectives: To review the up-dated classification of limb girdle muscular dystrophies (LGMDs) in relation to the defective protein and the genetic abnormality. To explain how these proteins are related to dystrophin and to the proteins of the extracellular matrix. To show that an accurate diagnosis is necessary and that it can be adequately made in neuromuscular pathology laboratories., Development: We present a study of the different types of LGMDs, dystrophinopathies and congenital muscular dystrophy. We emphasize the recent events which concluded in the identification of these disorders, the genetic alteration, the defective proteins and, briefly, the clinical features., Conclusions: The recent identification of numerous skeletal muscle proteins and of the codifying genes made possible a new classification of a large group of muscular dystrophies. The possibility to study these proteins on the muscle biopsy with immunohistochemistry and Western blot techniques indicates the need of an accurate diagnosis in specialized neuromuscular laboratories. Since there is a great number of genes discovered and of mutations within the same gene, and the clinical picture of different diseases can be similar, a previous study of the protein is advisable as a guide for a further genetic study.

Introduction: Limb Girdle Muscular Dystrophy type 2C (LGMD2C) is an autosomal recessive dystrophy due to the deficit of gamma-sarcoglycan, one of the proteins of the dystrophin-associated proteins complex (DAP). A new mutation in the gamma-sarcoglycan gene, 13q12, has been described recently and is exclusive of the gypsy community., Objective: To describe the clinicopathological and the genetic findings of eleven cases from a Spanish gypsy family with LGMD2C and the mutation C283Y., Material and Methods: We describe a large gypsy family with the C283Y mutation and eleven affected patients. We have performed an extensive clinical and pathological study with immunohistochemistry and Western blot analyses in the eleven patients and a genetic study of a total of twenty-seven members of the family., Results: The patients presented a severe muscular dystrophy with a dystrophic pattern in the muscle biopsy, normal immunolabeling for dystrophin, very weak for alpha-, beta- and delta-sarcoglycan and absent for gamma-sarcoglycan. These eleven patients were found to be homozygous for the mutation and twelve other members of the family, heterozygous., Conclusions: The clinical picture and the evolution of the disease herein described is similar to that observed in DMD. Two fundamental differences were found: the autosomal recessive mode of inheritance, and the normal immunohistochemistry and immunoblot for dystrophin in the skeletal muscle.

Fucose levels were determined in normal and tumour-derived tissues from patients with colorectal adenocarcinoma. Total, free and bound fucose were significantly higher (P < 0.001) in the tumoral tissue. Comparison of serum fucose levels between patients with colorectal cancer and control subjects indicated no statistically significant differences in total, free and bound fucose expressed as nmol/ml serum. However, when total and bound fucose were normalized to total protein (nmol/mg protein), an elevation in both parameters was found in colorectal cancer patients, although only that for total fucose was statistically significant (P < 0.001). A clear association between fucose content and clinical stage of patients according to the Dukes' classification can not be established, although patients at stage C showed higher levels of fucose both in serum and tissue. The current investigation provides direct evidence of a relationship between the elevation of fucose and the presence of tumour in colorectal cancer patients.

Background: A healthy diet and adequate personal hygiene are essential factors for good health. Adolescents gradually achieve a degree of autonomy in these areas. The aim of the study is to find out the diet and hygiene habits of adolescents in Navalcarnero, a rural town in the Autonomous Region of Madrid (Spain)., Methods: A descriptive study of a cross section of the relevant population, by previously validated, self-completed and anonymous questionnaire, filled in by adolescents (3 degrees BUP/ESO/FP) in by 13- and 14-year old school children (EGB.) The diet survey assessed the weekly consumption frequency of different foodstuffs., Results: The respondents normally had milk and cocoa for breakfast, with toast or a bun. Lunch was more abundant than the evening meal, and more fruit was consumed more often in the former. Most of the children drank milk every day, usually in its natural state, but in two out of three cases, the consumption of dairy products was not as recommended, vegetable consumption was low. Among the children of BUP/ESO/FP, the girls consumed greens, salad, fruit and sliced bread more often, this difference being particularly marked in the case of the bread, and the boys consumed considerably more meat and bread of the French-stick kind. With respect to personal hygiene, most of them have a shower and wash their hair every two or three days and brush their teeth and change their underwear on a daily basis; the girls proved to be much more assiduous in having a shower, brushing their teeth and changing their underwear., Conclusions: In some areas, behaviour as regards diet and hygiene shows differences depending on the sex of the individual, certain habits ought to be improved upon.