117,192 research outputs found

    What is the importance of sperm subpopulations?

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    .The study of sperm subpopulations spans three decades. The origin, meaning, and practical significance, however, are less clear. Current technology for assessing sperm morphology (CASA-Morph) and motility (CASA-Mot) has enabled the accurate evaluation of these features, and there are many options for data classification. Subpopulations could occur as a result of the stage of development of each spermatozoon in the subpopulation. Spermatogenesis might contribute to the production of these subpopulations. Insights from evolutionary biology and recent molecular research are indicative of the diversity among male gametes that could occur from unequal sharing of transcripts and other elements through cytoplasmic bridges between spermatids. Sperm cohorts exiting the gonads would contain different RNA and protein contents, affecting the spermatozoon physiology and associations with the surrounding environmental milieu. Subsequently, these differences could affect how spermatozoa interact with the environmental milieu (maturation, mixing with seminal plasma, and interacting with the environmental milieu, or female genital tract and female gamete). The emergence of sperm subpopulations as an outcome of evolution, related to the reproductive strategies of the species, genital tract structures, and copulatory and fertilization processes. This kind of approach in determining the importance of sperm subpopulations in fertilization capacity should have a practical impact for conducting reproductive technologies, inspiring and enabling new ways for the more efficient use of spermatozoa in the medical, animal breeding, and conservation fields. This manuscript is a contribution to the Special Issue in memory of Dr. Duane GarnerS

    Interactive Sonic Environments: Sonic artwork via gameplay experience

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    The purpose of this study is to investigate the use of video-game technology in the design and implementation of interactive sonic centric artworks, the purpose of which is to create and contribute to the discourse and understanding of its effectiveness in electro-acoustic composition highlighting the creative process. Key research questions include: How can the language of electro-acoustic music be placed in a new framework derived from videogame aesthetics and technology? What new creative processes need to be considered when using this medium? Moreover, what aspects of 'play' should be considered when designing the systems? The findings of this study assert that composers and sonic art practitioners need little or no coding knowledge to create exciting applications and the myriad of options available to the composer when using video-game technology is limited only by imagination. Through a cyclic process of planning, building, testing and playing these applications the project revealed advantages and unique sonic opportunities in comparison to other sonic art installations. A portfolio of selected original compositions, both fixed and open are presented by the author to complement this study. The commentary serves to place the work in context with other practitioners in the field and to provide compositional approaches that have been taken

    P469 Infliximab for induction of medically-induced remission in Crohn’s disease: a Cochrane systematic review

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    Background Infliximab is a monoclonal antibody that binds and neutralizes tumour necrosis factor-alpha, which is present in high levels in the blood serum, mucosa and stool of patients with Crohn‚Äôs disease (CD). We sought to determine the effectiveness and safety of infliximab in inducing remission in patients with CD. Methods On 31 August 2021, we searched CENTRAL, CINAHL, ClinicalTrials.gov, Embase, MEDLINE, and WHO ICTRP with no language, date, publication status, or document type limitations. We included randomized controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator in adult (18 and over) patients with active CD. The review authors independently conducted data extraction and ‚ÄėRisk of bias‚Äô assessment of the included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE methodology. The primary outcome was the proportion of patients who achieved clinical remission. Results We included 9 RCTs (1130 participants). Three studies compared multiple arms with different infliximab doses (between 5mg and 20mg/kg) to placebo. Two studies each with three arms compared azathioprine and placebo, infliximab and placebo, or infliximab and azathioprine combined. One study compared infliximab with biosimilar CT-P13. One study compared infliximab and azathioprine with steroids and azathioprine and only infliximab if no response. The final study compared a single dose (5mg/kg) of infliximab to placebo. In all trials that didn‚Äôt require a purine analogue to be given to both study groups, they allowed such concomitant use in both groups. There is evidence that infliximab combined with azathioprine is superior to azathioprine combined with placebo in inducing clinical remission for CD (RR 1.97, 95% CI 1.60‚Äď2.42, moderate certainty evidence downgraded due to risk of bias, NNT = 3). Sensitivity analysis considering a fixed effects model and then removing a study where most received azathioprine in both groups instead of all, had no impact on the result, which remained significant. There is evidence that there may be no difference in withdrawals from adverse events between infliximab combined with azathioprine and azathioprine combined with placebo when inducing clinical remission for CD (RR 0.74, 95% CI 0.29‚Äď1.86, low certainty evidence downgraded due to serious imprecision). The evidence is uncertain for all other comparisons and outcomes due to imprecision from small sample sizes. Conclusion There is evidence that infliximab with azathioprine is probably better than azathioprine, however the remaining data is based on limited total patient numbers and offers limited scope for meta-analysis

    Medicina personalizada en lactantes con cáncer: Estudio farmacogenético de polimorfismos relacionados con toxicidad y respuesta a la quimioterapia

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    Introducci√≥n La farmacogen√©tica es una herramienta de la ‚ÄúMedicina personalizada‚ÄĚ que contribuye a optimizar los tratamientos antineopl√°sicos, adapt√°ndolos a las caracter√≠sticas gen√©ticas particulares de cada individuo, maximizando su eficacia y minimizando su toxicidad. El lactante con c√°ncer es un paciente de particular vulnerabilidad y sus comorbilidades tiene una especial repercusi√≥n vital. El estudio farmacogen√©tico en esta poblaci√≥n resulta pionero y novedoso en nuestro medio. La identificaci√≥n de marcadores predictivos espec√≠ficos permitir√° individualizar m√°s la terap√©utica en esta poblaci√≥n tan fr√°gil y mejorar en consecuencia su calidad de vida y su pron√≥stico vital. Material y m√©todos Estudio de cohortes ambispectivo de pacientes oncol√≥gicos entre 1 y 18 meses de edad, receptores de quimioterapia en el Hospital La Fe de Valencia, en el periodo comprendido entre enero 2007 y agosto 2019. La parte retrospectiva comprende hasta diciembre 2015, el estudio prospectivo desde enero 2016 hasta agosto 2019. En primer lugar, se realiza un an√°lisis descriptivo de variables epidemiol√≥gicas, cl√≠nico/biol√≥gicas, terap√©uticas y pron√≥sticas de 72 pacientes con dichas caracter√≠sticas. Se describe la toxicidad derivada de sus 578 ciclos de quimioterapia (37 variables cl√≠nicas), el tiempo de seguimiento y su supervivencia (meses). En segundo lugar, se realiza un estudio anal√≠tico cuyo objetivo es correlacionar los polimorfismos gen√©ticos relacionados con la quimioterapia de 64 de los pacientes, la toxicidad grave secundaria al tratamiento (‚Č• grado 3 seg√ļn CTAE 4.0) y su supervivencia. El genotipado se realiza en el Centro Nacional de Genotipado (CEGEN) mediante la tecnolog√≠a MassArray (AgenaBioscience), previa configuraci√≥n de un panel farmacogen√©tico pedi√°trico en base a las evidencias recogidas en la base de datos PharmGKB, fichas t√©cnicas de los medicamentos y consorcios internacionales expertos. El an√°lisis estad√≠stico descriptivo se realiza con los programas Excel 2016 y R: las variables cualitativas con el recuento num√©rico (porcentaje) y las variables cuantitativas como mediana +/- rango intercuart√≠lico ante ausencia de normalidad en la distribuci√≥n de los datos (p <0,05, prueba de Kolmogorov-Smirnov). En el an√°lisis de supervivencia se utiliza el estimador Kaplan-Meier. El an√°lisis estad√≠stico anal√≠tico de correlaci√≥n entre polimorfismos y toxicidad se realiza mediante regresi√≥n log√≠stica penalizada por Elastic Net empleando R. El an√°lisis estad√≠stico anal√≠tico de correlaci√≥n entre polimorfismos y reca√≠da/muerte se realiza mediante regresi√≥n de Cox penalizada por Elastic Net. Resultados Las variables epidemiol√≥gicas, cl√≠nico/biol√≥gicas y terap√©uticas de los pacientes de la muestra son consecuentes con las descritas en la literatura del lactante con c√°ncer. Las neoplasias con mayor impacto negativo en la supervivencia son la leucemia mielobl√°stica aguda y los tumores del sistema nervioso central. La toxicidad m√°s prevalente es hematol√≥gica, digestiva e infecciosa. Existe correlaci√≥n entre la toxicidad grave secundaria a los quimioter√°picos en forma de anemia, neutropenia y/o trombopenia y 46 polimorfismos gen√©ticos diferentes. As√≠ mismo se encuentra asociaci√≥n estad√≠sticamente significativa entre la supervivencia global y la supervivencia libre de enfermedad y ciertos polimorfismos gen√©ticos (26 y 13 respectivamente). Los polimorfismos obtenidos pertenecen a genes encargados del transporte (6 genes) y metabolismo (17 genes) de los f√°rmacos, de la reparaci√≥n del material gen√©tico y la supresi√≥n tumoral (5 genes) y de otras funciones biol√≥gicas (4 genes). Conclusi√≥n Los resultados del presente estudio muestran correlaci√≥n estad√≠stica entre 46 polimorfismos de genes implicados en la cin√©tica farmacol√≥gica y la reparaci√≥n del material gen√©tico y la variabilidad en la toxicidad quimioter√°pica y supervivencia de pacientes lactantes con c√°ncer. En definitiva, aportaciones de la farmacogen√©tica que pueden contribuir a la optimizaci√≥n del tratamiento antineopl√°sico en esta poblaci√≥n particular y a la predicci√≥n de sus riesgos, de especial impacto en los supervivientes del c√°ncer infantil

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock séptico

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    La sepsis es una afecci√≥n potencialmente mortal causada por una respuesta anormal del hu√©sped a una infecci√≥n, produciendo respuestas fisiol√≥gicas alteradas que da√Īan los propios tejidos del paciente y pueden provocar disfunci√≥n org√°nica e incluso la muerte. Asimismo, algunos pacientes s√©pticos progresan a shock s√©ptico, caracterizado por alteraciones circulatorias, celulares y metab√≥licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol√≥gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi√≥n, la alta complejidad de la fisiopatolog√≠a de la sepsis requiere una mayor investigaci√≥n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot√≥xicos en la sepsis, ya que act√ļan como patrones moleculares asociados a da√Īo, que inducen estr√©s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci√≥n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci√≥n mediante la expresi√≥n de IL-18, IL-1ő≤ and IL-1őĪ. Sin embargo, a pesar de la evidencia de activaci√≥n del inflamasoma en las c√©lulas inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activaci√≥n del inflamasoma NLRP3 y la piroptosis en las c√©lulas endoteliales, contribuyendo a la disfunci√≥n endotelial y la desregulaci√≥n de la respuesta inmune mediada por el endotelio. Asimismo, tambi√©n demostramos c√≥mo la acetilaci√≥n de histonas disminuye la activaci√≥n de la piroptosis. Adem√°s, demostramos que la piroptosis se produce en pacientes con shock s√©ptico y los niveles de histonas circulantes se correlacionan con la expresi√≥n de citoquinas proinflamatorias y citoquinas piropt√≥ticas, la liberaci√≥n de factores de adhesi√≥n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl√≠nicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes cr√≠ticamente enfermos no s√©pticos, s√©pticos y de shock s√©ptico. Nuestro enfoque ayudar√° a caracterizar r√°pidamente las respuestas inmunes alteradas en pacientes s√©pticos y de shock s√©ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci√≥n del ADN en el control del sistema inmune s√©ptico. Nuestros resultados demostraron el papel central de la metilaci√≥n del ADN modulando la respuesta molecular en los pacientes de shock s√©ptico y contribuyendo a la inmunosupresi√≥n, a trav√©s de la alteraci√≥n de los patrones de metilaci√≥n de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1ő≤ and IL-1őĪ. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters

    Propuesta de mejoramiento en los pasos del proceso de selecci√≥n de personal para la empresa de alimentos McDonald¬īs.

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    Cantidad entre g√©nero de personas entrevistadas, Lista de gr√°ficas. De la p√°g. 17 a la 26Este trabajo tiene como fin dar a conocer, principalmente, por supuesto a los lectores de todo tipo de inter√©s, pero sobre todo a los tutores y compa√Īeros, el proyecto de investigaci√≥n que se ha trabajado en un lapso de tiempo, en observaci√≥n a los procesos de selecci√≥n de personal en la empresa McDonald¬īs: El cual se enfoca en la reclutamiento de personal y sus falencias, con el que se busca mejorar los procesos de contrataci√≥n para los nuevos trabajadores en la organizaci√≥n, logrando de esta forma cumplir con el objetivo de minimizar cualquier tipo de problema que se pueda presentar al momento de hacer la selecci√≥n del mismo y la asignaci√≥n del cargo . Con base en una correcta planeaci√≥n, la direcci√≥n de personas dentro de la organizaci√≥n se convierte en el c√≠rculo perfecto entre necesidades de la empresa, de los empleados y viceversa de esta manera se adquiere una retroalimentaci√≥n donde el planeamiento da la correcta vinculaci√≥n y contrataci√≥n cubriendo dichas necesidades empresariales solucionando problem√°ticas como las falencias que se encuentran en el proceso, el cual es el objetivo del presente trabajo. As√≠ pues, la inducci√≥n y la capacitaci√≥n se convierten en la optimizaci√≥n del clima organizacional, donde el que no siempre ser√° el cliente si no todos los individuos que participen en el mismo y finalmente promover, premiar y motivar al practicante con pr√°cticas de evaluaci√≥n, de manera justificable, razonable y fundamental.The purpose of this work is to make known, mainly, of course, to readers of all kinds of interest, but above all to tutors and colleagues, the research project that has been worked on over a period of time, in observation of the processes of personnel selection in the McDonald's company: Which focuses on the hiring of personnel and their shortcomings, with which it seeks to improve the hiring processes for new workers in the organization, thus achieving the objective to minimize any type of problem that may arise at the time of making the selection of the same and the design of the position. Based on proper planning, the direction of people within the organization becomes the perfect circle between the needs of the company, the employees and vice versa, in this way a feedback is acquired where planning gives the correct connection and hiring covering said needs. necessary needs solving problems such as the shortcomings that are found in the process, which is the objective of this work. Thus, the induction and training will be perfected in the optimization of the organizational climate, where the one that will not always be the client but all the individuals that participate in it and finally promote, reward and motivate when practicing with evaluation practices, justifiable, reasonable and fundamental manner

    The company she keeps : The social and interpersonal construction of girls same sex friendships

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    This thesis begins a critical analysis of girls' 'private' interpersonal and social relations as they are enacted within two school settings. It is the study of these marginal subordinated worlds productivity of forms of femininity which provides the main narrative of this project. I seek to understand these processes of (best) friendship construction through a feminist multi-disciplinary frame, drawing upon cultural studies, psychoanalysis and accounts of gender politics. I argue that the investments girls bring to their homosocial alliances and boundary drawing narry a psychological compulsion which is complexly connected to their own experiences within the mother/daughter bond as well as reflecting positively an immense social debt to the permissions girls have to be nurturant and ; negatively their own reproduction of oppressive exclusionary practices. Best friendship in particular gives girls therefore, the experience of 'monogamy' continuous of maternal/daughter identification, reminiscent of their positioning inside monopolistic forms of heterosexuality. But these subcultures also represent a subversive discontinuity to the public dominance of boys/teachers/adults in schools and to the ideologies and practices of heterosociality and heterosexuality. By taking seriously their transmission of the values of friendship in their chosen form of notes and diaries for example, I was able to access the means whereby they were able to resist their surveillance and control by those in power over them. I conclude by arguing that it is through a recognition of the valency of these indivisiblly positive and negative aspects to girls cultures that Equal Opportunities practitioners must begin if they are serious about their ambitions. Methods have to be made which enable girls to transfer their 'private' solidarities into the 'public' realm, which unquestionably demands contesting with them the causes and consequences of their implication in the divisions which also contaminate their lives and weaken them

    Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder.

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    Despite the progress in characterising the pharmacological profile of drugs of abuse, their precise biochemical impact remains unclear. The metabolome reflects the multifaceted biochemical processes occurring within a biological system. This includes those encoded in the genome but also those arising from environmental/exogenous exposures and interactions between the two. Using metabolomics, the biochemical derangements associated with substance abuse can be determined as the individual transitions from recreational drug to chronic use (dependence). By understanding the biomolecular perturbations along this time course and how they vary across individuals, metabolomics can elucidate biochemical mechanisms of the addiction cycle (dependence/withdrawal/relapse) and predict prognosis (recovery/relapse). In this review, we summarise human and animal metabolomic studies in the field of opioid and psychostimulant addiction. We highlight the importance of metabolomics as a powerful approach for biomarker discovery and its potential to guide personalised pharmacotherapeutic strategies for addiction targeted towards the individual's metabolome
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