Sets compactos, ¿facilitan el sondaje vesical intermitente femenino? / Compact sets, do they make female intermittent catheterization easier?

Objetivo: El objetivo fundamental es evaluar la facilidad de uso y comodidad de Actreen® Mini Set para el cateterismo vesical intermitente femenino, siguiendo el número de cateterismos prescritos por el especialista. Adicionalmente, se analiza si la utilización de un set compacto puede facilitar el seguimiento del tratamiento y si este tipo de dispositivo es un producto considerado seguro, de fácil manejo y adecuado, en relación a la edad o el nivel de destreza de las usuarias. Método: Evaluación sobre el manejo del set compacto, teniendo en cuenta la experiencia de uso de mujeres que deben realizar el sondaje vesical intermitente (SVI) como parte del tratamiento en la disfunción vesical. Para ello, se ha contado con la colaboración de profesionales de enfermería urológica de diferentes centros hospitalarios españoles. Se utilizó un cuestionario de elaboración propia. Resultados: El análisis de los resultados muestra un elevado nivel de satisfacción de las usuarias, tanto con las características del producto como con la facilidad de uso para seguir el tratamiento, así como la sensación de que es un producto seguro y adecuado. (AU)

Objective: The main objective is to evaluate the ease of use and comfort of the Actreen® Mini Set for female intermittent bladder catheterization, following the number of catheterizations prescribed by the specialist. Additionally, it is analyzed whether the use of a compact set can facilitate the follow-up of the treatment and whether this type of device is considered a safe, easy to use and appropriate product, in relation to the age or skill level of the users. Method: Method: Evaluation of the management of the compact set, taking intoaccount the experience of use by women who have to perform intermittentbladder catheterization as part of the treatment of bladder dysfunction. Forthis purpose, urological nursing professionals from different Spanish hospitals collaborated in the study. An own designed questionnaire was used. Results: Analysis of the results shows a high level of satisfaction among users, both with the characteristics of the product and the ease of use in following the treatment, as well as the feeling that it is a safe and appropriate product. (AU)

Acidosis induces RIPK1-dependent death of glioblastoma stem cells via acid-sensing ion channel 1a.

Eliciting regulated cell death, like necroptosis, is a potential cancer treatment. However, pathways eliciting necroptosis are poorly understood. It has been reported that prolonged activation of acid-sensing ion channel 1a (ASIC1a) induces necroptosis in mouse neurons. Glioblastoma stem cells (GSCs) also express functional ASIC1a, but whether prolonged activation of ASIC1a induces necroptosis in GSCs is unknown. Here we used a tumorsphere formation assay to show that slight acidosis (pH 6.6) induces necrotic cell death in a manner that was sensitive to the necroptosis inhibitor Nec-1 and to the ASIC1a antagonist PcTx1. In addition, genetic knockout of ASIC1a rendered GSCs resistant to acid-induced reduction in tumorsphere formation, while the ASIC1 agonist MitTx1 reduced tumorsphere formation also at neutral pH. Finally, a 20 amino acid fragment of the ASIC1 C-terminus, thought to interact with the necroptosis kinase RIPK1, was sufficient to reduce the formation of tumorspheres. Meanwhile, the genetic knockout of MLKL, the executive protein in the necroptosis cascade, did not prevent a reduction in tumor sphere formation, suggesting that ASIC1a induced an alternative cell death pathway. These findings demonstrate that ASIC1a is a death receptor on GSCs that induces cell death during prolonged acidosis. We propose that this pathway shapes the evolution of a tumor in its acidic microenvironment and that pharmacological activation of ASIC1a might be a potential new strategy in tumor therapy.

The Cell Adhesion Molecule L1 Interacts with Methyl CpG Binding Protein 2 via Its Intracellular Domain.

Cell adhesion molecule L1 regulates multiple cell functions, and L1 deficiency is linked to several neural diseases. Recently, we have identified methyl CpG binding protein 2 (MeCP2) as a potential binding partner of the intracellular L1 domain. By ELISA we show here that L1's intracellular domain binds directly to MeCP2 via the sequence motif KDET. Proximity ligation assay with cultured cerebellar and cortical neurons suggests a close association between L1 and MeCP2 in nuclei of neurons. Immunoprecipitation using MeCP2 antibodies and nuclear mouse brain extracts indicates that MeCP2 interacts with an L1 fragment of ~55 kDa (L1-55). Proximity ligation assay indicates that metalloproteases, ß-site of amyloid precursor protein cleaving enzyme (BACE1) and É£-secretase, are involved in the generation of L1-55. Reduction in MeCP2 expression by siRNA decreases L1-dependent neurite outgrowth from cultured cortical neurons as well as the migration of L1-expressing HEK293 cells. Moreover, L1 siRNA, MeCP2 siRNA, or a cell-penetrating KDET-containing L1 peptide leads to reduced levels of myocyte enhancer factor 2C (Mef2c) mRNA and protein in cortical neurons, suggesting that the MeCP2/L1 interaction regulates Mef2c expression. Altogether, the present findings indicate that the interaction of the novel fragment L1-55 with MeCP2 affects L1-dependent functions, such as neurite outgrowth and neuronal migration.

New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) is an iron metabolism disease clinically characterized by excessive iron deposition in parenchymal organs such as liver, heart, pancreas, and joints. It is caused by mutations in at least five different genes. HFE hemochromatosis is the most common type of hemochromatosis, while non-HFE related hemochromatosis are rare cases. Here, we describe six new patients of non-HFE related HH from five different families. Two families (Family 1 and 2) have novel nonsense mutations in the HFE2 gene have novel nonsense mutations (p.Arg63Ter and Asp36ThrfsTer96). Three families have mutations in the TFR2 gene, one case has one previously unreported mutation (Family A-p.Asp680Tyr) and two cases have known pathogenic mutations (Family B and D-p.Trp781Ter and p.Gln672Ter respectively). Clinical, biochemical, and genetic data are discussed in all these cases. These rare cases of non-HFE related hereditary hemochromatosis highlight the importance of an earlier molecular diagnosis in a specialized center to prevent serious clinical complications.

An opportunity to emphasize the relevance of laboratory medicine.

Objectives: Clinical practice guidelines (CPGs) are recommendations based on a systematic review of scientific evidence that are intended to help healthcare professionals and patients make the best clinical decisions. CPGs must be evidence-based and are designed by multidisciplinary teams. The purpose of this study is to assess the topics related to the clinical laboratory addressed in CPGs and evaluate the involvement of laboratory professionals in the CPG development process. Methods: A total of 16 CPGs recommended by the Spanish Society of Laboratory Medicine and/or retrieved from PubMed-Medline were included. A review of the information provided in CPGs about 80 topics related to the clinical laboratory was performed. The authorship of laboratory professionals was assessed. Results: On average, the 16 CPGs addressed 49% (standard deviation [SD]: 11%) of the topics evaluated in relation to the clinical laboratory. By order of frequency, CPGs contained information about 69% of postanalytical variables (SD: 20%); 52% of preanalytical variables (SD: 11%); and 43% of the analytical variables studied (SD: 18%). Finally, half the CPGs included a laboratory professional among its authors. Conclusions: CPGs frequently failed to provide relevant laboratory-related information. Laboratory professionals were co-authors in only half the CPGs. There is scope for improvement, and laboratory professionals should be included in multidisciplinary teams involved in the development of CPGs.

The cell adhesion molecule L1 interacts with nuclear proteins via its intracellular domain.

Proteolytic cleavage of the cell adhesion molecule L1 (L1) in brain tissue and in cultured cerebellar neurons results in the generation and nuclear import of a 30 kDa fragment comprising most of L1's C-terminal, intracellular domain. In search of molecules that interact with this domain, we performed affinity chromatography with the recombinant intracellular L1 domain and a nuclear extract from mouse brains, and identified potential nuclear L1 binding partners involved in transcriptional regulation, RNA processing and transport, DNA repair, chromatin remodeling, and nucleocytoplasmic transport. By co-immunoprecipitation and enzyme-linked immunosorbent assay using recombinant proteins, we verified the direct interaction between L1 and the nuclear binding partners non-POU domain containing octamer-binding protein and splicing factor proline/glutamine-rich. The proximity ligation assay confirmed this close interaction in cultures of cerebellar granule cells. Our findings suggest that L1 fragments regulate multiple nuclear functions in the nervous system. We discuss possible physiological and pathological roles of these interactions in regulation of chromatin structure, gene expression, RNA processing, and DNA repair.

Isolation and Analysis of Fasciola hepatica Extracellular Vesicles.

The finding of extracellular vesicles (EVs) as important players in parasite-parasite and host-parasite communications has led to an increasing number of reports in the literature. Different protocols have been developed for isolation and further characterization of EVs from parasitic helminths. In this chapter, we describe step by step procedures to isolate EVs secreted by Fasciola hepatica adults in culture, which could be also applied for other developmental stages of the parasite, as well as EVs present in plasma and urine. Along with classical isolation methods like differential ultracentrifugation, and more recent techniques like size exclusion chromatography (SEC), here we also refer to the storage of EVs for further functional assays. In addition, characterization of F. hepatica by electron microscopy techniques like immuno-gold staining, as well as labeling techniques useful for functional assays, like in vitro uptake of fluorescent EVs by cells in culture are also described.

Characteristics and Evolution of Renal Transplant Recipients Infected by Carbapenemase-Producing Klebsiella pneumoniae.

BACKGROUND: Renal transplant (RT) recipients are especially susceptible to carbapenem-resistant Klebsiella pneumoniae carbapenemase (KPC) infections. However, published experience is limited. OBJECTIVE: To analyze the characteristics and evolution of RT recipients with KPC infection in our hospital. METHODS: We performed a retrospective cohort study of all RT recipients with KPC infection in our hospital from December 1, 2017 (first case), to July 31, 2019. For each RT recipient infected with KPC, 3 controls were selected. RESULTS: During the study period, 8 RT recipients presented KPC infection. Seven were detected in the first year post-RT. The most common site of infection was urine. In 2 cases the germ was isolated in blood. The number of patients with diabetes was significantly higher in the group with KPC infection (P = .023), and urologic interventions were more frequent in those patients (P = .039). No differences were found in the immunosuppressive treatment. A total of 62.5 % of patients required readmission after the KPC infection. One patient died of septicemia by KPC. In all these cases, the clone of KPC isolated was KPC ST512. CONCLUSION: KPC infection is more frequent in the first months after the RT and causes an important number of hospital admissions. It can be cause of death in RT recipients, especially in those with isolation of the germ in blood. Diabetes and urologic interventions were more frequent in this population. The analysis by molecular typing suggests exposure to a common source, highlighting the importance of preventive isolation measures and surveillance for limiting the transmission of this bacteria.

Recursos y fuentes de infomación útiles en la práctica de la medicina de laboratorio basado en la evidencia / Resources and sources useful in evidence-based laboratory medicine practice

No disponible

Characterization and serotype distribution of Aggregatibacter actinomycetemcomitans isolated from a population of periodontitis patients in Spain.

OBJECTIVE: There is no study characterizing the variability of Aggregatibacter actinomycetemcomitans isolates in periodontitis patients in Spain. It is therefore the aim of this investigation to study the serotype distribution of A. actinomycetemcomitans strains isolated from periodontitis patients in Spain. The polymorphism of the genes that codifies the leukotoxin and the operon of the cytolethal-distending toxin (cdt) will also be investigated. DESIGN: From a total of 701 patients samples, 40 A. actinomycetemcomitans-positive periodontitis patients were included in the study (mean age 45.3, 62.5% females) and their clinical periodontal status was assessed. On average, 1-3 isolates from each patient were sub-cultured and characterized by PCR. RESULTS: Using culture the prevalence of A. actinomycetemcomitans was 5.7%. The most frequent serotype was "b", being 30 patients infected by a unique serotype, while 7 patients showed co-colonization, mostly with serotypes "a" and "b". From the 79 pure isolates obtained, 24 were from serotype "a", 30 from serotype "b", 12 from serotype "c" and 4 from serotype "d". Further characterization of these samples showed that none of these 79 isolates demonstrated the 530-bp deletion in the leukotoxin's promoter region that characterizes the JP2 strain. Conversely 65.8% of the isolates were cdt+. CONCLUSIONS: The most common serotypes were "a" and "b", being serotype "b" the most prevalent in mono-colonization, while serotypes "e" and "f" were not detected. In the majority of samples, operon that codifies the cdt (65.8%) and the genes responsible for the codification of leukotoxin (100%) were found. None of the isolates were JP2 strains.

Analysis of energetic and exergetic efficiency, and environmental benefits of biomass integrated gasification combined cycle technology.

The problem of the high carbon dioxide emissions linked to power generation makes necessary active research on the use of biofuels in gas turbine systems as a promising alternative to fossil fuels. Gasification of biomass waste is particularly of interest in obtaining a fuel to be run in gas turbines, as it is an efficient biomass-to-biofuel conversion process, and an integration into a combined cycle power plant leads to a high performance with regard to energetic efficiency. The goal of this study was to carry out an energetic, exergetic and environmental analysis of the behaviour of an integrated gasification combined cycle (IGCC) plant fuelled with different kinds of biomass waste by means of simulations. A preliminary economic study is also included. Although a technological development in gasification technology is necessary, the results of simulations indicate a high technical and environmental interest in the use of biomass integrated gasification combined cycle (BioIGCC) systems for large-scale power generation from biomass waste.

Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells.

The study of host-parasite interactions has increased considerably in the last decades, with many studies focusing on the identification of parasite molecules (i.e. surface or excretory/secretory proteins (ESP)) as potential targets for new specific treatments and/or diagnostic tools. In parallel, in the last few years there have been significant advances in the field of extracellular vesicles research. Among these vesicles, exosomes of endocytic origin, with a characteristic size ranging from 30-100 nm, carry several atypical secreted proteins in different organisms, including parasitic protozoa. Here, we present experimental evidence for the existence of exosome-like vesicles in parasitic helminths, specifically the trematodes Echinostoma caproni and Fasciola hepatica. These microvesicles are actively released by the parasites and are taken up by host cells. Trematode extracellular vesicles contain most of the proteins previously identified as components of ESP, as confirmed by proteomic, immunogold labeling and electron microscopy studies. In addition to parasitic proteins, we also identify host proteins in these structures. The existence of extracellular vesicles explains the secretion of atypical proteins in trematodes, and the demonstration of their uptake by host cells suggests an important role for these structures in host-parasite communication, as described for other infectious agents.

Diabetes como factor de riesgo de Periodontitis / Diabetes as a risk factor for Perodontitis

La periodontitis en una enfermedad de etiología infecciosa que presenta como síntomas el sangradode encías, movilidad del diente, recesiones gingivales o hipersensibilidad dentaria, y en la quediversas enfermedades sistémicas pueden favorecer su progresión, entre ellas la diabetes mellitus.Se presenta el caso de un varón que acude a consulta por sangrado e infl amación de encías, quepresenta un historial de diabetes insulinodependiente de 35 años de evolución. El paciente es diagnosticadode una periodontitis generalizada en fase moderada, aunque algunas piezas dentalespresentan un estado avanzado con pérdida de cresta alveolar superior al 50%. El plan de tratamientoincluye: instrucción en higiene oral, raspados y alisados radiculares de todos los dientes, cirugíasperiodontales y mantenimiento periodontal periódico. Dada la importancia de la detección precozde la periodontitis, el médico de familia juega un papel muy importante a la hora de derivar a estospacientes al dentista para su diagnóstico y control

Periodontitis is an infection which causes symptoms such as bleeding gums, loose or separatingteeth and receding or tender gums. It can also advance the progression of some diseases amongstthem diabetes mellitus. We report a case of a man who came to the doctor’s consultancy due tobleeding, swollen gums. He had had insulin dependent diabetes for the last 35 years. The patient wasdiagnosed with generalised, moderate periodontitis, although some teeth were at an advanced stagewith over 50% loss of the alveolar crest. Treatment included: instruction in oral hygiene, scaling androot planing of all teeth, periodontal surgery and periodic periodontal check ups. Early detection ofperiodontitis is very important and the family doctor can play a very important role in referring these patients to the dentist for diagnosis and control (AU)

Sobrecrecimiento gingival tras la toma de Nifedipino / Gingival over growth after takin gnifedipine

El nifedipino es un agente antagonista del calcio que por sus efectos antihipertensivos es utilizado en el control de la hipertensión arterial. Se ha descrito en la literatura científica la aparición de sobrecrecimientos gingivales tras su toma, que suelen aparecer tras varios meses del inicio de la medicación. Estas alteraciones se caracterizan por un aumento de la encía a nivel de la papila interdental, que puede cubrir parcial o totalmente la corona del diente, y se ve agravada ante la presencia de placa bacteriana en personas con higiene oral deficiente. Su tratamiento incluye la remoción correcta de la placa bacteriana con un cepillado meticuloso, la eliminación de los depósitos de sarro, la realización de curetajes gingivales, y, finalmente, la realización de gingivectomías para eliminar el tejido gingival sobrante. Aunque se trata de una alteración de carácter benigno, puede ocasionar problemas estéticos y funcionales, y puede plantear, en ocasiones, la sustitución del nifedipino por otros agentes de acción similar, cuando sea posible (AU)

Nifedipine is a calcium channel blocking which, because of its antihypertensive effects, is used to control high blood pressure. There are reports in the literature of gingival overgrowth that usually appear several months after first taking this medication. These changes are characterised by increased gum around the interdental papilla that can partially or totally cover the tooth crown, which is exacerbated by the presence of bacterial plaque in patients with poor dental hygiene. Treatment includes removal of dental plaque with meticulous brushing, removal of tartar, gingival curettage, and gingivectomies to remove excess gum tissue. Although this is a benign alteration, it can produce aesthetic and functional complications, and can occasionally lead, where possible, to nifedipine being replaced by other agents of similar action (AU)

High proportion of large genomic rearrangements in hMSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families of the Basque Country.

Hereditary nonpolyposis colorectal cancer (HNPCC), which represents the most common form of inherited colorectal cancer, results from germline alterations of the mismatch repair genes MSH2, MLH1 and MSH6. Rearrangements of MSH2 and MLH1 are involved in at least 10% and 4.3%, respectively, of the HNPCC families fulfilling the Amsterdam (AMS) criteria. We applied a recently developed method, multiplex ligation-dependent probe amplification (MLPA), to study MLH1/MSH2 copy number changes in 29 unrelated Basque Country HNPCC families. We detected six different genomic rearrangements in total (6/29=20.69%), four in MSH2 gene (13.79%), and two in MLH1 gene. All of the MSH2 rearrangements were genomic deletions involving several exons. The MLH1 rearrangements were initially detected as one deletion of exon 18 and one deletion of exon 19, but after sequencing analysis, these deletions were not confirmed and corresponded to base pair mutations. We conclude that MLPA is an excellent tool for detecting exon copy number changes in MLH1 and MSH2 in the DNA from HNPCC patients, although all detected rearrangements should be confirmed by an independent molecular methodology. Furthermore, our results in the Basque Country show higher percentages of rearrangements than previously published by other authors.

Quantifier variables of the back surface deformity obtained with a noninvasive structured light method: evaluation of their usefulness in idiopathic scoliosis diagnosis.

New noninvasive techniques, amongst them structured light methods, have been applied to study rachis deformities, providing a way to evaluate external back deformities in the three planes of space. These methods are aimed at reducing the number of radiographic examinations necessary to diagnose and follow-up patients with scoliosis. By projecting a grid over the patient's back, the corresponding software for image treatment provides a topography of the back in a color or gray scale. Visual inspection of back topographic images using this method immediately provides information about back deformity, but it is important to determine quantifier variables of the deformity to establish diagnostic criteria. In this paper, two topographic variables [deformity in the axial plane index (DAPI) and posterior trunk symmetry index (POTSI)] that quantify deformity in two different planes are analyzed. Although other authors have reported the POTSI variable, the DAPI variable proposed in this paper is innovative. The upper normality limit of these variables in a nonpathological group was determined. These two variables have different and complementary diagnostic characteristics, therefore we devised a combined diagnostic criterion: cases with normal DAPI and POTSI (DAPI < or = 3.9% and POTSI < or = 27.5%) were diagnosed as nonpathologic, but cases with high DAPI or POTSI were diagnosed as pathologic. When we used this criterion to analyze all the cases in the sample (56 nonpathologic and 30 with idiopathic scoliosis), we obtained 76.6% sensitivity, 91% specificity, and a positive predictive value of 82%. The interobserver, intraobserver, and interassay variability were studied by determining the variation coefficient. There was good correlation between topographic variables (DAPI and POTSI) and clinical variables (Cobb's angle and vertebral rotation angle).