Methylation marks in blood DNA reveal breast cancer risk in patients fulfilling hereditary disease criteria.

Less than 15-20% of patients who meet the criteria for hereditary breast and ovarian cancer (HBOC) carry pathogenic coding genetic mutations, implying that other molecular mechanisms may contribute to the increased risk of this condition. DNA methylation in peripheral blood has been suggested as a potential epigenetic marker for the risk of breast cancer (BC). We aimed to discover methylation marks in peripheral blood associated with BC in 231 pre-treatment BC patients meeting HBOC criteria, testing negative for coding pathogenic variants, and 156 healthy controls, through methylation analysis by targeted bisulfite sequencing on 18 tumor suppressor gene promoters (330 CpG sites). We found i) hypermethylation in EPCAM (17 CpG sites; p = 0.017) and RAD51C (27 CpG sites; p = 0.048); ii) hypermethylation in 36 CpG-specific sites (FDR q < 0.05) in the BC patients; iii) four specific CpG sites were associated with a higher risk of BC (FDR q < 0.01, Bonferroni p < 0.001): cg89786999-FANCI (OR = 1.65; 95% CI:1.2-2.2), cg23652916-PALB2 (OR = 2.83; 95% CI:1.7-4.7), cg47630224-MSH2 (OR = 4.17; 95% CI:2.1-8.5), and cg47596828-EPCAM (OR = 1.84; 95% CI:1.5-2.3). Validation of cg47630224-MSH2 methylation in one Australian cohort showed an association with 3-fold increased BC risk (AUC: 0.929; 95% CI: 0.904-0.955). Our findings suggest that four DNA methylation CpG sites may be associated with a higher risk of BC, potentially serving as biomarkers in patients without detectable coding mutations.

[Translated article] Pharmaceutical care in respiratory diseases: Current situation and opportunities for hospital pharmacy in Spain.

OBJECTIVE: Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current situation of hospital pharmacy in the field of respiratory diseases. METHOD: Observational, cross-sectional study, with a national scope, divided into 2 parts. In an initial phase, the activity and level of pharmaceutical care in respiratory diseases was evaluated through an online questionnaire using REDCap. The survey was addressed to department chiefs and consisted of 17 items, divided into 2 modules: general data and general activity. The second phase was open to hospital pharmacists, with the aim of exploring their opinion on care, training, and improvement needs. The number of items in this phase was 19, divided into 5 modules: general data, pharmaceutical care, competencies, training, and degree of satisfaction. RESULTS: In the first phase, 23 hospitals were included. Most of them (n=20) had a pharmacist in charge of respiratory diseases. However, a large proportion of them dedicated less than 40% of their working day to this activity. The pharmacist's activity occurred at the level of external patients (n=21), hospitalised patients (n=16), and secondarily in management (n=8). Integration is greater in pathologies such as asthma, IPF, pulmonary hypertension, and bronchiectasis. Participation in committees was present in 15 hospitals, with variability in pathologies and degree of involvement. In the second phase, 164 pharmacists participated, who considered pharmaceutical care in cystic fibrosis, asthma, and lung transplant as a priority. 51% considered integration to be adequate and 91% considered it necessary to implement prioritisation criteria. Professional competencies ranged from 6.5 to 6.9 out of 10 points. Only 45% of participants had received specific training in the last 4 years, indicating greater priority for asthma, pulmonary hypertension, and IPF. CONCLUSIONS: Most centers have pharmacists specialised in respiratory diseases. However, there is room for improvement in terms of subspecialisation, participation in multidisciplinary committees, implementation of prioritisation criteria, diversification in pathologies treated, as well as greater specific training in this area.

Pharmaceutical care in respiratory diseases: Current situation and opportunities for Hospital Pharmacy in Spain. / Atención farmacéutica en enfermedades respiratorias: situación y oportunidades de la farmacia hospitalaria en España.

OBJECTIVE: Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current situation of hospital pharmacy in the field of respiratory diseases. METHOD: Observational, cross-sectional study, with a national scope, divided into 2 parts. In an initial phase, the activity and level of pharmaceutical care in respiratory diseases was evaluated through an online questionnaire using REDCap. The survey was addressed to department chiefs and consisted of 17 items, divided into 2 modules: general data and general activity. The second phase was open to hospital pharmacists, with the aim of exploring their opinion on care, training, and improvement needs. The number of items in this phase was 19, divided into 5 modules: general data, pharmaceutical care, competencies, training and degree of satisfaction. RESULTS: In the first phase, 23 hospitals were included. Most of them (n=20) had a pharmacist in charge of respiratory diseases. However, a large proportion of them dedicated less than 40% of their working day to this activity. The pharmacist's activity occurred at the level of external patients (n=20), hospitalized patients (n=16), and secondarily in management (n=8). Integration is greater in pathologies such as asthma, IPF, pulmonary hypertension, and bronchiectasis. Participation in committees was present in 15 hospitals, with variability in pathologies and degree of involvement. In the second phase, 164 pharmacists participated, who considered pharmaceutical care in cystic fibrosis, asthma and lung transplant as a priority. Fifty-one percent considered integration to be adequate and 91% considered it necessary to implement prioritization criteria. Professional competencies ranged from 6.5-6.9 out of 10 points. Only 45% of participants had received specific training in the last four years, indicating greater priority for asthma, pulmonary hypertension and IPF. CONCLUSIONS: Most centers have pharmacists specialized in respiratory diseases. However, there is room for improvement in terms of sub specialization, participation in multidisciplinary committees, implementation of prioritization criteria, diversification in pathologies treated, as well as greater specific training in this area.

Exploring the intersection of gender identity and homoparental family structure: Implications for educational, family and personal well-being in Spanish students.

This study explores the relationship among self-perceived gender, family type (heteroparental or homoparental) and socioeconomic factors concerning various educational, family and personal well-being domains. The data are derived from a large sample of 69,088 students from 465 schools (65% public; 35% private or semi-private) in Spain. Five separate multi-level generalized mixed (logistic or linear) regression models were calculated. Key findings include that non-binary students from homoparental families reported lower evaluations in multiple dimensions, suggesting the need for additional support. Likewise, students from homoparental families exhibited lower personal well-being and family relationship assessments, possibly due to perceived social stigmatization and peer bullying. This study sheds light on the complexities of gender identity and family type in educational settings, emphasizing the importance of addressing these issues for students' well-being and academic success.

A Hybrid Metal-Organic Framework-Reduced Graphene Oxide Nanomaterial for Selective Removal of Chromate from Water in an Electrochemical Process.

Hexavalent chromium Cr(VI) is a highly toxic groundwater contaminant. In this study, we demonstrate a selective electrochemical process tailored for removal of Cr(VI) using a hybrid MOF@rGO nanomaterial synthesized by in situ growth of a nanocrystalline, mixed ligand octahedral metal-organic framework with cobalt metal centers, [Co2(btec)(bipy)(DMF)2]n (Co-MOF), on the surface of reduced graphene oxide (rGO). The rGO provides the electric conductivity necessary for an electrode, while the Co-MOF endows highly selective adsorption sites for CrO42-. When used as an anode in the treatment cycles, the MOF@rGO electrode exhibits strong selectivity for adsorption of CrO42- over competing anions including Cl-, SO42-, and As(III) and achieves charge efficiency (CE) >100% due to the strong physisorption of CrO42- by Co-MOF; both electro- and physisorption capacities are regenerated with the reversal of the applied voltage, when highly toxic Cr(VI) is reduced to less toxic reduced Cr species and subsequently released into brine. This approach allows easy regeneration of the nonconducting Co-MOF without any chemical addition while simultaneously transforming Cr(VI), inspiring a novel electrochemical method for highly selective degradation of toxic contaminants using tailor-designed electrodes with high affinity adsorbents.

Radioterapia estreotáxica corporal y cirugía mínimamente invasiva en el manejo de las metástasis espinales: un cambio de paradigma / Stereotactic body radiation therapy and minimally invasive surgery in the management of spinal metastases: a change in the paradigm

El objetivo principal del tratamiento en las metástasis espinales es el control local de la enfermedad, el alivio del dolor y el mantenimiento de la deambulación. Clásicamente, se ha recomendado una resección quirúrgica del tumor lo más amplia posible seguida de radioterapia o quimioterapia adyuvante. En la actualidad, la radioterapia estereotáxica corporal (SBRT) en dosis única o hipofraccionada proporciona tasas globales de control local al año superiores al 95% con mínima morbilidad, incluso en histologías que suelen considerarse radiorresistentes. Por otro lado, mediante cirugía de descompresión circunferencial posterolateral y estabilización de la columna es factible crear un espacio de 2-3 mm entre el borde tumoral y la duramadre (separation surgery) suficiente para permitir administrar de forma segura SBRT a dosis ablativas. Dado que con frecuencia se trata de pacientes frágiles, dicha cirugía puede realizarse mediante técnicas mínimamente invasivas, que reducen la agresividad quirúrgica y ayudan a minimizar el retraso de eventuales tratamientos sistémicos

The main goal of treatment in spinal metastatic patients is local control of the disease, pain relief and the maintenance of ambulation. Traditionally, wide surgical resection of the tumour followed by adjuvant radiation and/or chemotherapy has been recommended. Currently, single-fraction or hypofractionated stereotactic body radiation therapy (SBRT) yields a one-year local control rate of over 95% with minimum morbidity, even for tumours previously considered radioresistant. In addition, by posterolateral and circumferential decompression and stabilisation of the spinal cord, it is feasible to create a 2 to 3 mm epidural margin between the dura mater and the tumour (separation surgery), enough to deliver safe and ablative doses of SBRT to the vertebrae. As these patients tend to be frail, such interventions should ideally be minimally invasive, thereby reducing surgical aggressiveness and helping to minimise the delay of any systemic therapies

In vitro Conversion into CD4+CD25+Foxp3+ Induced Regulatory T Cells Is Reduced in Atopic Dermatitis Patients.

BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, with an increasing incidence in clinical practice. AD models have demonstrated that TGF-ß signaling is compromised in regulatory T cells (Tregs). OBJECTIVES: This study aimed to investigate the TGF-ß-dependent in vitro conversion of CD4+CD25- T cells derived from AD-patients into CD4+CD25+Foxp3+ induced Tregs (iTregs) in comparison to healthy controls. METHODS: To analyze in vitro iTreg conversion, human CD4+CD25- T cells were cultured on anti-CD3-coated plates in the presence of TGF-ß and IL-2 for up to 3 days. Consequently, the underlying mechanism of impaired CD4+CD25+Foxp3+ iTreg generation was explored by focusing on TGF-ß signaling. Finally, the functionality of iTregs was investigated. RESULTS: Conversion of CD4+CD25-Foxp3- into CD4+CD25+Foxp3+ iTregs was diminished in AD individuals. Impaired iTreg generation was accompanied by a reduced surface expression of GARP (glycoprotein A repetitions predominant), a marker for activated Tregs. A reduced expression of Smad3 mRNA was revealed in CD4+CD25- T cells. Interestingly, the suppressive quality of iTregs was found to be equal in cells derived from AD and healthy donors. CONCLUSION: The signaling effect of TGF-ß receptors on the suppressor quality of iTreg conversion is conserved. Impaired iTreg generation might be a reason for the lack of immune suppression in AD patients and contributes to the chronicity of the disease.

Stereotactic body radiation therapy and minimally invasive surgery in the management of spinal metastases: a change in the paradigm. / Radioterapia estreotáxica corporal y cirugía mínimamente invasiva en el manejo de las metástasis espinales: un cambio de paradigma.

The main goal of treatment in spinal metastatic patients is local control of the disease, pain relief and the maintenance of ambulation. Traditionally, wide surgical resection of the tumour followed by adjuvant radiation and/or chemotherapy has been recommended. Currently, single-fraction or hypofractionated stereotactic body radiation therapy (SBRT) yields a one-year local control rate of over 95% with minimum morbidity, even for tumours previously considered radioresistant. In addition, by posterolateral and circumferential decompression and stabilisation of the spinal cord, it is feasible to create a 2 to 3 mm epidural margin between the dura mater and the tumour (separation surgery), enough to deliver safe and ablative doses of SBRT to the vertebrae. As these patients tend to be frail, such interventions should ideally be minimally invasive, thereby reducing surgical aggressiveness and helping to minimise the delay of any systemic therapies.

Grado de conocimiento y aceptación de una serie de recomendaciones «No hacer» por parte de médicos de Atención Primaria del área de salud de Elche - Hospital General / No disponible

OBJETIVO: Describir el grado de conocimiento y aceptación de médicos de Atención Primaria respecto a una serie de recomendaciones de prevención cuaternaria. Describir la utilidad y barreras percibidas en su implementación en la práctica clínica. MÉTODOS: Estudio descriptivo transversal, mediante encuesta, incluyéndose una selección de 20 recomendaciones de práctica clínica. La población diana fueron médicos de Atención Primaria del área de salud de Elche - Hospital General. RESULTADOS: La tasa de respuesta fue 68,9%. Cuatro recomendaciones resultaron ser conocidas por la totalidad (100%) de encuestados. Los porcentajes de acuerdo superaron el 70% en todos los casos excepto dos. Éstas fueron percibidas como útiles (27,5%) y muy útiles (64,7%) por los encuestados. La principal barrera aducida en su puesta en práctica fue el tiempo por consulta médica. CONCLUSIONES: Existe alto grado de conocimiento y aceptación de estas recomendaciones, que fueron percibidas como útiles y muy útiles por los facultativos del estudio

OBJECTIVE: To describe the level of knowledge and acceptance among Primary Care physicians regarding a series of quaternary prevention recommendations. To describe the utility and perceived barriers in its implementation in clinical practice. METHODS: Cross-sectional descriptive study, by survey, including a selection of 20 clinical practice recommendations. The target population were Primary Care physicians from the health area of Elche - General Hospital. RESULTS: The response rate was 68.9%. Four recommendations were known by all the respondents (100%). The agreement percentages exceeded 70% except for two cases. These recommendations were perceived as useful (27.5%) and very useful (64.7%) by respondents. The main barrier adduced for its implementation was the time per medical visit. CONCLUSIONS: There is a high degree of knowledge and acceptance of these recommendations, which were perceived as useful and very useful among the studied physicians

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach.

Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.

A revisit of the interaction of gaseous ozone with aqueous iodide. Estimating the contributions of the surface and bulk reactions.

The main source of atmospheric iodine is the heterogeneous reaction of aqueous iodide (I-) with ozone (O3), which takes place in surface seawater and probably in sea-salt aerosols. However, there are seemingly contradictory conclusions about whether this heterogeneous reaction occurs in the bulk of the aqueous phase, via O3 dissolution, or at the aqueous surface, via O3 adsorption. In this work, the ozone uptake coefficient has been calculated as a function of the concentration of aqueous iodide ([I-]aq) and gaseous ozone near the aqueous surface ([O3]gs) by estimating parameters of the resistor model using results of previous studies. The calculated uptake coefficients suggest that the aqueous-phase reaction dominates at low I- concentrations (about <10-4 mol L-1), regardless of [O3]gs, and also at sufficiently high [O3]gs (about >80 ppm), regardless of [I-]aq. In contrast, the surface reaction dominates at high [I-]aq (about >10-4 mol L-1) as long as [O3]gs is low enough (about <80 ppm). This trend is able to reconcile previous studies of this reaction, and is a consequence of several factors, including the high surface excess of both reactants ozone and iodide. Given the typical O3 concentrations in the troposphere and the possible I- concentrations and O3 solubilities in sea-salt aerosols, the surface reaction may compete with the aqueous-phase reaction in accumulation-mode aerosols, unlike in surface seawater, where the aqueous-phase reaction probably prevails. The rate constant of the surface reaction has been estimated as (3-40) × 10-13 cm2 molecule-1 s-1.

Medidas de protección radiológica: implicaciones en el diseño de quirófanos de neurocirugía / Radiation protection measures: Implications on the design of neurosurgery operating rooms

Objetivo: Describir pros y contras de diversas medidas de protección radiológica y sus implicaciones en el diseño de un quirófano de neurocirugía. Material y métodos: Se realizó una reforma estructural del quirófano de neurocirugía a propósito de la adquisición y uso de un O-arm. Se ampliaron las medidas y blindajes del quirófano, y se instaló una mampara blindada y abatible en su interior. Se midieron dosis de radiación delante y detrás de la mampara. Resultados: La mampara proporciona una radioprotección integral para todo el personal de quirófano (dosis < 5μSv a 2,5 m del gantry por cada exploración con O-arm; 0,0μSv tras la mampara por cada exploración de O-arm; dosis acumulada anual tras la mampara, indetectable), obvia la necesidad de delantales plomados y dosímetros personales y minimiza la circulación de personal. El aumento del tamaño del quirófano permite almacenar los equipos dentro y minimiza el riesgo de colisión o contaminación. Los quirófanos rectangulares permiten aumentar la distancia al foco emisor de radiación. Conclusiones: El blindaje de paredes, techos y suelos, la forma rectangular y la superficie lo más amplia posible, la presencia de una mampara plomada y abatible, y los sistemas de seguridad que impiden una irrupción inesperada en el quirófano mientras se está irradiando son cuestiones relevantes a tener en cuenta en el diseño del quirófano de neurocirugía

Objective: To describe pros and cons of some radiation protection measures and the implications on the design of a neurosurgery operating room. Material and methods: Concurring with the acquisition and use of an O-arm device, a structural remodeling of our neurosurgery operating room was carried out. The theater was enlarged, the shielding was reinforced and a foldable leaded screen was installed inside the operating room. Radiation doses were measured in front of and behind the screen. Results: The screen provides whole-body radiation protection for all the personnel inside the theater (effective dose <5μSv at 2,5 m from the gantry per O-arm exploration; 0,0μSv received behind the screen per O-arm exploration; and undetectable cumulative annual radiation dose behind the screen), obviates the need for leaded aprons and personal dosimeters, and minimizes the circulation of personnel. Enlarging the size of the operating room allows storing the equipment inside and minimizes the risk of collision and contamination. Rectangular rooms provide greater distance from the source of radiation. Conclusion: Floor, ceiling and walls shielding, a rectangular-shaped and large enough theater, the presence of a foldable leaded screen, and the security systems precluding an unexpected irruption into the operating room during irradiation are relevant issues to consider when designing a neurosurgery operating theater

Influence of Internet and Social Media in the Promotion of Alternative Oncology, Cancer Quackery, and the Predatory Publishing Phenomenon.

In the last decade, electronic media has irrupted physician's clinical practice. Patients increasingly use Internet and social media to obtain enormous amounts of unsupervised data about cancer. Blogs, social networking sites, online support groups and forums are useful channels for medical education and experience sharing but also perfect environments for misinformation, quackery, violation of privacy and lack of professionalism. The widespread availability of such electronic resources allows some followers of the alternative oncology to spread useless irrational and controversial remedies for cancer, like false medicaments, miraculous diets, electronic devices, and even psychic therapies, as did charlatans in the past, providing false expectations about cancer treatments. Moreover, so-called predatory journals have introduced confusion and malpractice within the academic biomedical publishing system. This is a rising editorial phenomenon affecting all fields of biomedicine, including oncology that jeopardizes the quality of scientific contribution and damages the image of open access publication.

[Radiation protection measures: Implications on the design of neurosurgery operating rooms]. / Medidas de protección radiológica: implicaciones en el diseño de quirófanos de neurocirugía.

OBJECTIVE: To describe pros and cons of some radiation protection measures and the implications on the design of a neurosurgery operating room. MATERIAL AND METHODS: Concurring with the acquisition and use of an O-arm device, a structural remodeling of our neurosurgery operating room was carried out. The theater was enlarged, the shielding was reinforced and a foldable leaded screen was installed inside the operating room. Radiation doses were measured in front of and behind the screen. RESULTS: The screen provides whole-body radiation protection for all the personnel inside the theater (effective dose <5µSv at 2,5 m from the gantry per O-arm exploration; 0,0µSv received behind the screen per O-arm exploration; and undetectable cumulative annual radiation dose behind the screen), obviates the need for leaded aprons and personal dosimeters, and minimizes the circulation of personnel. Enlarging the size of the operating room allows storing the equipment inside and minimizes the risk of collision and contamination. Rectangular rooms provide greater distance from the source of radiation. CONCLUSION: Floor, ceiling and walls shielding, a rectangular-shaped and large enough theater, the presence of a foldable leaded screen, and the security systems precluding an unexpected irruption into the operating room during irradiation are relevant issues to consider when designing a neurosurgery operating theater.

Predatory journals: una amenaza emergente para autores y editores de publicaciones biomédicas / Predatory journals: An emerging threat to authors and editors of biomedical publications

El denominado predatory publishing es un fenómeno reciente y en alza que supone un fraude intelectual, pues pone en peligro la calidad de la contribución científica, compromete a autores, revisores y editores de revistas legítimas, deteriora la imagen de la publicación tipo open access y supone un negocio muy lucrativo para algunos. En este artículo revisamos el concepto y relevancia de las predatory journals y las características que las diferencian de las publicaciones legítimas. Las revistas neuroquirúrgicas y de neurociencia en general no están al margen de este problema. Las instituciones académicas y los comités éticos deberían dar a conocer este fenómeno y proporcionar información y apoyo a los autores y a la comunidad científica en general para evitar su propagación y eventual control del ámbito de la publicación biomédica

So-called predatory publishing is a new and rising phenomenon presenting as an intellectual fraud that jeopardises the quality of scientific contribution, compromises the activity of authors, reviewers and editors of legitimate journals, damages the image of open access publications and is a very profitable business. In this paper, we review the concept and relevance of predatory journals and the characteristics that differentiate them from legitimate publications. Neurosurgical and general neuroscience journals are not immune to this problem. Academic institutions and ethics committees have a duty to raise awareness of this phenomenon and provide information and support to authors and the whole scientific community to avoid its propagation and potential control of biomedical publishing

Predatory journals: una amenaza emergente para autores y editores de publicaciones biomédicas.

So-called predatory publishing is a new and rising phenomenon presenting as an intellectual fraud that jeopardises the quality of scientific contribution, compromises the activity of authors, reviewers and editors of legitimate journals, damages the image of open access publications and is a very profitable business. In this paper, we review the concept and relevance of predatory journals and the characteristics that differentiate them from legitimate publications. Neurosurgical and general neuroscience journals are not immune to this problem. Academic institutions and ethics committees have a duty to raise awareness of this phenomenon and provide information and support to authors and the whole scientific community to avoid its propagation and potential control of biomedical publishing.

Metabolites involved in cellular communication among human cumulus-oocyte-complex and sperm during in vitro fertilization.

BACKGROUND: Fertilization is a key physiological process for the preservation of the species. Consequently, different mechanisms affecting the sperm and the oocyte have been developed to ensure a successful fertilization. Thus, sperm acrosome reaction is necessary for the egg coat penetration and sperm-oolema fusion. Several molecules are able to induce the sperm acrosome reaction; however, this process should be produced coordinately in time and in the space to allow the success of fertilization between gametes. The goal of this study was to analyze the metabolites secreted by cumulus-oocyte-complex (COC) to find out new components that could contribute to the induction of the human sperm acrosome reaction and other physiological processes at the time of gamete interaction and fertilization. METHODS: For the metabolomic analysis, eighteen aliquots of medium were used in each group, containing: a) only COC before insemination and after 3 h of incubation; b) COC and capacitated spermatozoa after insemination and incubated for 16-20 hours; c) only capacitated sperm after 16-20 h in culture and d) only fertilization medium as control. Six patients undergoing assisted reproduction whose male partners provided normozoospermic samples were included in the study. Seventy-two COC were inseminated. RESULTS: The metabolites identified were monoacylglycerol (MAG), lysophosphatidylcholine (LPC) and phytosphingosine (PHS). Analysis by PCR and in silico of the gene expression strongly suggests that the cumulus cells contribute to the formation of the PHS and LPC. CONCLUSIONS: LPC and PHS are secreted by cumulus cells during in vitro fertilization and they could be involved in the induction of human acrosome reaction (AR). The identification of new molecules with a paracrine effect on oocytes, cumulus cells and spermatozoa will provide a better understanding of gamete interaction.

Hepatitis aguda secundaria a mesalazina / Mesalazine-induced acute hepatitis

No disponible

Estudio de los daños estructurales tras la inmovilización espermática previa a la microinyección intracitoplasmática de espermatozoides en sujetos teratozoospérmicos / Study of structural damage after sperm immobilisation prior to intracytoplasmic sperm injection in teratozoospermic males

Objetivo: Describir y comparar las alteraciones ultraestructurales que puede provocar la inmovilización espermática previa a la microinyección intracitoplasmática de espermatozoides, así como los daños en el ADN y el estado del acrosoma en espermatozoides de sujetos teratozoospérmicos y normozoospérmicos. Material y métodos: Se utilizaron 15 muestras seminales procedentes de donantes normozoospérmicos y 20 muestras de pacientes teratozoospérmicos del Instituto Bernabeu de Alicante. Para el estudio con microscopia electrónica de transmisión se utilizaron ovocitos humanos como receptáculo de los espermatozoides. La fragmentación del ADN se valoró mediante la técnica TUNEL, y el estado del acrosoma, utilizando la lectina Pisum sativum conjugada con FITC. El análisis estadístico entre los diferentes grupos se realizó mediante un test ANOVA. Resultados: Los resultados mostraron que, tras la inmovilización, los espermatozoides procedentes tanto de sujetos normozoospérmicos como de teratozoospérmicos sufrieron las mismas alteraciones ultraestructurales a nivel de la membrana plasmática y acrosomal. Tras valorar la fragmentación de ADN mediante TUNEL observamos que en los espermatozoides inmovilizados el porcentaje de espermatozoides con ADN fragmentado era similar en ambos grupos (normozoospérmicos vs. teratozoospérmicos). En cambio, el porcentaje de espermatozoides con reacción acrosómica fue significativamente más elevado en los inmovilizados que en el grupo control, tanto en los sujetos normozoospérmicos como teratozoospérmicos. Conclusión: Los resultados de este estudio evidencian que los da˜nos estructurales provocados por la inmovilización, en espermatozoides procedentes de sujetos normozoospérmicos y teratozoospérmicos, son independientes de la morfología espermática. Y además, dicho proceso no provoca fragmentación del ADN. Sin embargo, la inmovilización tanto en el grupo de los sujetos normozoospérmicos como teratozoospérmicos provoca una inducción mecánica de la reacción acrosómica (AU)

Objective: To describe and compare the ultrastructural alterations, DNA fragmentation and acrosome status that could cause sperm immobilisation prior to intracytoplasmic sperm injection, in samples from normozoospermic and teratozoospermic males. Material and methods: For this study we used 15 sperm samples from consenting normozoospermic donors and 20 samples from teratozoospermic males, submitted for assisted reproduction at Instituto Bernabeu of Alicante. To assess the ultrastructural alterations induced by immobilisation, human oocytes were used as containers for spermatozoa and then observed by transmission electron microscopy. DNA fragmentation was assessed using TUNEL and acrosome status using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin. The control group consisted of sperm without manipulation. Statistical analysis between groups was performed by ANOVA. Results: The results showed that immobilised spermatozoa presented the same damage in plasma and acrosomal membranes in the samples from both normozoospermic and teratozoospermic subjects. After assessing DNA fragmentation in the cells from normozoospermic and teratozoospermic patients by the TUNEL technique, we observed that the percentage of spermatozoa with DNA fragmentation did not increase in the immobilised group compared with the control group. However, the percentage of acrosome-reacted sperm was significantly greater in immobilised spermatozoa than in the control group in both normozoospermic and teratozoospermic males. Conclusion: The results of this study show that the structural damage caused by immobilization in spermatozoa from teratozoospermic and normozoospermic males is independent of sperm morphology. In addition, the immobilisation does not cause DNA fragmentation. However, the percentage of acrosome-reacted sperm was greater in the immobilised group than in the control group, in both normozoospermic and teratozoospermic subjects (AU)