Letteratura scientifica selezionata sul tema "Ws 11.1 l727m 2001"

Gene flow from imidazolinone (IMI)-resistant domestic sunflower to IMI-susceptible common sunflower and prairie sunflower was studied. Under greenhouse conditions, pollen from IMI-resistant domesticated sunflower was applied to flower heads of IMI-susceptible common and prairie sunflower. In addition, field studies were conducted in 2000 and 2001 near Manhattan, KS, to evaluate IMI-resistant gene flow from IMI-resistant domesticated sunflower to common and prairie sunflower under natural conditions. Common and prairie sunflower were planted in concentric circles at distances of 2.5, 5, 15, and 30 m around a densely planted IMI-resistant domesticated sunflower species. For both greenhouse and field studies, IMI-resistant gene flow was determined by treating the progeny of both wild species with 40 g ai ha−1of imazamox. Greenhouse crosses made by hand showed that 94% of common sunflower and 79% of prairie sunflower were resistant or moderately resistant. The resistant plants were allowed to grow in the greenhouse and were backcrossed with the corresponding susceptible wild parents. Progeny of the backcross showed a 1:1 ratio of resistant to susceptible plants. In the field, gene flow was detected up to 30 m from the pollen source for both species, and it decreased as distance from the pollen source increased. In 2000, 11 to 22% of the progeny were resistant at 2.5 m from the pollen source and 0.3 to 5% were resistant at 30 m. In 2001, the number of resistant progeny did not exceed 7 and 2% at 2.5 and 30 m from the pollen source, respectively. The results of this study showed that IMI-resistant domesticated sunflower outcrosses with common and prairie sunflower over distances typically encountered near production fields. Also, backcrosses of resistant hybrids with wild parents are successful, further increasing the potential for the spread of IMI-resistant feral sunflowers.

ABSTRAK Strategi penghimpunan zakat infaq dan sedekah masa kini harus selaras dengan perkembangan teknologi dan perilaku masyarakat 5.0 (society 5.0), dimana Society 5.0 menciptakan masyarakat yang berbasis teknologi sehingga pembayaran zakat, infaq, dan sedekah non tunai harus memanfaatkan teknologi finansial seperti, mobile banking, ATM, QRIS, dompet digital maupun e-commerce. Tujuan penelitian ini yaitu guna mengetahui besarnya penerimaan dan penggunaan layanan teknologi finansial dalam membayar Zakat, Infaq, dan Sedekah (ZIS) menggunakan ekstensi Technology of Acceptance Model (TAM) dengan motivasi spiritual. Adapun metode penelitian yang digunakan adalah Structural Equation Modeling Partial Least Square (SEM-PLS) dengan sebanyak 129 responden yang berasal dari Kota Bekasi, Bandung, Bogor, Cimahi, Sukabumi, Garut, Majalengka, Tasikmalaya, dan Pangandaran. Penelitian ini menemukan bahwa muzakki dalam menerima dan menggunakan layanan teknologi keuangan untuk membayar ZIS secara non tunai dipengaruhi oleh persepsi kemudahan, persepsi kegunaan, sikap, dan intensi. Implikasi dari penelitian ini adalah agar lembaga zakat dapat mengetahui penerimaan dan penggunaan teknologi muzakki dalam menunaikan zakat non tunai sehingga dapat berinovasi dalam menyediakan layanan bagi muzakki maupun masyarakat yang akan membayar zakat non tunai. Kata Kunci: Zakat Non Tunai, Kesejahteraan Umum, Perilaku Mikroekonomi, Ekonomi Keuangan. ABSTRACT The strategy of collecting zakat infaq and alms today must be in line with technological developments and community behavior 5.0 (society 5.0), where Society 5.0 creates a technology-based society. ATM, QRIS, digital wallet, and e-commerce. The purpose of this study is to determine the amount of acceptance and use of financial technology services in paying Zakat, Infaq, and Alms (ZIS) using the Technology of Acceptance Model (TAM) extension with spiritual motivation. The research method used is Structural Equation Modeling Partial Least Square (SEM-PLS) with 129 respondents taken from Bekasi, Bandung, Bogor, Cimahi, Sukabumi, Garut, Majalengka, Tasikmalaya, and Pangandaran. This study found that muzakki in accepting and using financial technology services to pay ZIS non-cash were influenced by perceived ease of use, perceived usefulness, attitudes, and intentions. However, the perceived usefulness does not affect the attitude of muzakki in paying non-cash ZIS, and indirectly the perceived usefulness does not affect the actual use of muzakki to pay ZIS. 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La comunicación de malas noticias, si bien supone un momento de importante vulnerabilidad para el paciente y sus allegados, es un acto necesario para una atención de calidad. Se trata de una habilidad transversal que, sin embargo, suele carecer de una formación específica en las facultades de Medicina. Existen numerosos protocolos que establecen las bases de una comunicación eficiente. No obstante, lo que marca la diferencia en términos de humanidad es el toque personal que cada médico ofrece. En este artículo ofrecemos una reflexión sobre la visión predominante en el Servicio de Oncología Médica de Fuenlabrada del proceso de comunicación de malas noticias. Exponemos conceptos metafísicos, psicológicos y sociales sobre los cuales impera la necesidad reflexionar para, desde una compresión profunda de la dificultad que la comunicación de malas noticias entraña, ser capaces de mejorar. Así mismo, sugerimos elementos fácilmente incorporables a la práctica clínica diaria. Recibido: Septiembre 7, 2022 Aceptado: Noviembre 2, 2022 Publicado: Diciembre 2, 2022 Editor: Dra. Evelyn Valencia Espinoza Introducción La comunicación de malas noticias es una herramienta fundamental en la práctica clínica, sin embargo, suele constituir una habilidad frecuentemente olvidada por los sistemas formativos en el ámbito de la sanidad. Se trata de una destreza difícil de perfeccionar y no existe una fórmula que garantice una comunicación eficiente y humana. No obstante, existen una serie de directrices que ayudan a sentar las bases del proceso comunicativo y una serie de matices que se pueden potenciar para cuidar el componente humano. El concepto de morir Oncólogos y paliativistas se enfrentan con frecuencia a la comunicación de malas noticias de gran magnitud, que suelen abordar el concepto de morir. La muerte es una noción cada vez más enmascarada en las sociedades occidentales. Paralelamente al desarrollo de la sociedad del bienestar, la muerte ha dejado de ser un recambio generacional natural para convertirse en algo evitable. Esto se encuentra en relación con la amplia aceptación de creencias como la fe en la ciencia y sus avances o la infalibilidad del sistema sanitario y sus profesionales. También se relaciona con la búsqueda continua de la inmediatez, que en el ámbito de la sanidad se traduce como la aspiración a la curación instantánea [1]. En nuestra sociedad, la muerte se siente como un hecho lejano e improbable. En algunas especialidades médicas, como la oncología, el médico es la persona que rompe por primera vez dicha ilusión de inmortalidad tan socialmente extendida. El choque entre la realidad y las expectativas La comunicación de malas noticias comienza siempre con un choque entre la realidad clínica y las expectativas de los pacientes, que engloban tanto las propias expectativas del médico basadas en el proceso terapéutico llevado a cabo, así como las expectativas que el paciente y sus familiares depositan en el personal sanitario y también las expectativas que el propio paciente puede tener sobre su existencia y su porvenir [2]. Quebrantar estas expectativas es doloroso y el médico se convierte en portador momentáneo de la más absoluta desolación. Esta desolación la trasladará al paciente y a sus familiares, entrando en juego emociones que harán que el impacto sea mucho mayor. La comunicación de malas noticias como una oportunidad para cuidar La buena comunicación de malas noticias es un paso necesario para una atención de calidad. Esto se debe a que centrar la situación clínica en la realidad del ahora, aunque inicialmente sea un duro golpe emocional, va a permitir adaptar la atención sanitaria posterior a las necesidades reales del paciente [2]. Además, aunque se trate uno de los momentos de mayor vulnerabilidad de todo el proceso clínico, también es una de las circunstancias donde más se puede poner en práctica el “arte” de cuidar [3]. La adquisición de competencias en este aspecto, más humano y menos técnico de la medicina, debe ser un objetivo fundamental en el desarrollo de cualquier profesional sanitario. Discusión La oncología es una especialidad con una dimensión humana fascinante y se presta a potenciar la capacidad de “cuidar” en aquellos que la ejercen. Desde la experiencia, la acción de “cuidar” muchas veces es algo tan sencillo y a la vez tan complicado como “saber estar”. Si entendemos la comunicación de malas noticias como una “ocasión de cuidar”, deduciremos fácilmente que no es suficiente el mero hecho de transmitir una información (“comunicar”), sino que debemos ser capaces de “estar” (“acompañar”) y recoger las emociones que este proceso genera: los miedos, las frustraciones, las ansiedades, las preguntas, la negación, la culpa, la ira y la tristeza Además, es importante aprender a “regresar”[3], a acompañar insistente y prolongadamente en el tiempo a nuestros pacientes para dar respuesta, si se puede, a la esfera psicológica y metafísica que surge en torno al final de la vida y que es tan importante como la esfera orgánica [4]. En muchas ocasiones, cuando no tenemos respuestas, la simple escucha activa y el hecho de demostrar que nos seguimos preocupando, resultan de gran ayuda tanto para el paciente como para sus familiares. Acompañar en momentos tan delicados, no es solo un deber, es un privilegio. Para aprender a comunicar malas noticias, existen una serie de directrices básicas sistematizadas, entre otros, en el protocolo SPIKES (acrónimo traducido al castellano como EPICEE) que se encuentran ampliamente aceptadas en las práctica clínica [5]. El protocolo EPICEE establece seis pasos fundamentales para una comunicación eficiente de malas noticias. “E”: Entorno, “P”: Percepción, “I”: Invitación, “C”: Conocimiento, “E”: Empatía y emociones “E”: Estrategia [5]. Sin embargo, son los matices que cada médico otorga a este protocolo los que marcan la diferencia en el proceso de comunicación. Por ello, presentamos a continuación, aquellas puntualizaciones que, desde la experiencia clínica, consideramos que pueden resultar de utilidad. Respecto a la “C” de “Conocimiento” Cuando el médico comunica una mala noticia, y más si hay que comunicarla en términos de posibilidades, existe una difícil encrucijada entre la esperanza y que quien nos escucha se sepa con la posibilidad de estar próximo al final de su vida y lograr que se encuentre en paz con ello. No debemos caer ni en el falso optimismo ni en el catastrofismo. Hay que buscar el término medio: medir las palabras, dosificarlas, dar respuestas, respetar los tiempos de cada persona. En este punto del protocolo, es muy importante adecuar el lenguaje y huir de los tecnicismos. Además, se debe dosificar la información y mandar mensajes concisos y claros. Puede parecer que el empleo de circunloquios ayuda a suavizar la mala noticia, pero no sólo no lo hace, sino que además aumenta el riesgo de malentendidos y puede traducirse en una elevación de la ansiedad del paciente si éste siente que se está perdiendo información relevante. Respecto a la “E” de “Empatía y emociones”: Durante la comunicación de malas noticias, se debe promover un ambiente de confianza que favorezca la expresión de emociones. Nos debemos entrenar en el reconocimiento de las mismas, tanto cuando el paciente las expresa directamente como cuando se pueden intuir a través de su lenguaje corporal. Es fundamental empatizar con las emociones y legitimarlas. No está de más tener unas nociones básicas de psicología que ayuden a comprender la emoción y a reconducirla en caso de ser preciso, aunque muchas veces basta con empatizar y dejar la conversación fluir. Entre las principales emociones se encuentran la ansiedad, la tristeza, la culpa y la ira. La ansiedad responde a una valoración de amenaza y pone en marcha mecanismos de anticipación. Se reconduce centrando a la persona en el ahora [6]. La tristeza responde a una valoración de pérdida donde se pone sistemáticamente el foco en lo negativo. Se reconduce ampliando la visión a otras áreas y rompiendo el mecanismo de atención selectiva hacia lo perjudicial [6]. La culpa responde a una valoración de responsabilidad y desencadena mecanismos de rumiación. Frenar la culpa pasa por hacer un análisis de error y responsabilidad, reparar lo modificable y tener un plan de acción alternativo en caso de volverse a dar una situación similar a la que nos ha hecho sentir culpables. Si a pesar de lo previo regresa el sentimiento, hay que evitar entrar nuevamente en el círculo de rumiación [7]. La ira es la emoción más compleja de todas y la que provoca el fenómeno de transferencia más negativo [8]. Traduce una valoración de daño, de la que se hace responsable a otro. Cuando surge la ira, se pone el foco en la intencionalidad del daño recibido y esto desencadena conductas agresivas. Se reconduce redefiniendo los objetivos. Se debe hacer entender que el agravio sufrido no se puede cambiar y, por tanto, el objetivo debe ser “estar bien”, en vez de hacer “justicia” (que es lo que se persigue con la conducta agresiva) [8]. Respecto a la “E” de “Estrategia”: En todas las situaciones clínicas, pero especialmente en las que perdemos la opción de la estrategia terapéutica orientada a la curación o a la cronificación y el objetivo pasa a ser el control de síntomas, se debe tener presente el concepto de “aliviar”. Si bien es cierto que manejar las emociones de manera empática y fijar unos objetivos terapéuticos ya supone alivio para muchos pacientes, se puede ir un paso más allá dando una respuesta humana y cercana a las necesidades metafísicas que indudablemente van a surgir [4]. Es importante entender el final de la vida como algo natural en la historia de todo ser humano, aceptar nuestras limitaciones y nuestra falta de control sobre cuándo llega y a quién le llega, abrir un tiempo de introspección y agradecimiento por lo ya vivido, entender que cada persona deja una huella única y maravillosa en el mundo, contribuir a que los últimos días supongan un tiempo de fortalecimiento de las relaciones humanas con los seres queridos, una oportunidad para cerrar asuntos pendientes, ayudar a encontrar paz. No es un terreno fácil y no es un terreno que todos los pacientes nos vayan a permitir o deseen abordar. Pero con aquellos que nos abran la puerta, si encontramos las palabras adecuadas, estaremos perfeccionando el “arte” de cuidar y nos convertiremos, sin duda, en portadores de alivio. Conclusión Siendo sinceros, los médicos nunca se acostumbra a la comunicación de malas noticias o al sufrimiento que existe en torno a la muerte. Esta falta de acontumbramiento es natural, y así debe ser. El error es evitar que surja la tristeza o el duelo, porque son reacciones intrínsecas al proceso de ruptura de expectativas. Tampoco se debe entender la comunicación de malas noticias como un proceso pasivo en el que se deja fluir la información y las emociones rebotan sin control y nos dañan a todos. El gran acierto es la formación para perfeccionar este proceso buscando no sólo transmitir información sino “cuidar” a través del mismo, siendo capaces de empatizar y, desde ahí, acompañar y aliviar. Estos valores son parte de nuestro compromiso para preservar la dignidad de nuestros pacientes en el proceso de enfermar y también en el proceso de morir, siendo buenos médicos, tan buenos como podamos, pero, ante todo, siendo buenos seres humanos. Abreviaturas EPICEE: “E”: Entorno, “P”: Percepción, “I”: Invitación, “C”: Conocimiento, “E”: Empatía y emociones “E”: Estrategia. Información administrativa Archivos Adicionales Ninguno declarado por los autores. Agradecimientos No declarada. Contribuciones de los autores Irene Solana López: conceptualización, validación, visualización, metodología, administración de proyecto, escritura: revisión y edición. Ignacio Juez Martel: conceptualización, curación de datos, análisis formal, adquisición de fondos, investigación, recursos, software. Elia Martínez Moreno, conceptualización, curación de datos, análisis formal, adquisición de fondos, investigación, recursos, software. Juan Antonio Guerra Martínez, conceptualización, curación de datos, análisis formal, adquisición de fondos, investigación, recursos, software. Todos los autores leyeron y aprobaron la versión final del manuscrito. Fondos Los autores no recibieron ningún tipo de reconocimiento económico por este trabajo de investigación. Disponibilidad de datos y materiales Existe la disponibilidad de datos bajo solicitud al autor de correspondencia. No se reportan otros materiales. Declaraciones Aprobación del comité de ética No aplica a estudios observacionales con revisión de bases de datos o historias clínicas. Consentimiento para publicación No aplica para estudios que no publican imágenes explícitas como tomografías, resonancias, imágenes de exámenes físicos. Conflictos de interés Los autores declaran que ellos no tienen ningún conflicto de competencia o interés. Nota del Editor La Revista Oncología Ecu permanece neutral con respecto a los reclamos jurisdiccionales en mapas publicados y afiliaciones institucionales. Referencias Caycedo Bustos, Martha Ligia. "La muerte en la cultura occidental: antropología de la muerte." Revista Colombiana de psiquiatría 36.2 (2007): 332-339. VandeKieft, Gregg. "Breaking bad news." American family physician 64.12 (2001): 1975. Blackall GF. Stand and wait. J Clin Oncol. 2010 Dec 1;28(34):5124-5. doi: 1200/JCO.2010.32.5324. Epub 2010 Oct 4. PMid:20921470. Puchalski CM, Sbrana A, Ferrell B, Jafari N, King S, Balboni T, Miccinesi G, Vandenhoeck A, Silbermann M, Balducci L, Yong J, Antonuzzo A, Falcone A, Ripamonti CI. Interprofessional spiritual care in oncology: a literature review. ESMO Open. 2019 Feb 16;4(1):e000465. DOI: 1136/esmoopen-2018-000465.PMid:30962955. PMCid:PMC6435249. Baile WF, Buckman R, Lenzi R, Glober G, Beale EA, Kudelka AP. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4):302-11. doi: 1634/theoncologist.5-4-302.PMid:10964998 Dekker J, Karchoud J, Braamse AMJ, Buiting H, Konings IRHM, van Linde ME, Schuurhuizen CSEW, Sprangers MAG, Beekman ATF, Verheul HMW. Clinical management of emotions in patients with cancer: introducing the approach "emotional support and case finding". Transl Behav Med. 2020 Dec 31;10(6):1399-1405. DOI: 1093/tbm/ibaa115. PMid:33200793 PMCid:PMC7796719 Harpham WS. View from the Other Side of the Stethoscope: Patient Handout-If Patients Feel Guilty…. Oncology Times, 2014;36(3):35. 1097/01.COT.0000444048.63798.a4 Howells K, Day A. Readiness for anger management: clinical and theoretical issues. Clin Psychol Rev. 2003 Mar;23(2):319-37. DOI: 1016/s0272-7358(02)00228-3. PMid:12573674.

Introduction Methods Resuts Discussion Conclusions Acknowledgments Authors' contributions Competing interests Ethical approval References Effect of Methotrexate and Omega-3 Combination on Cytogenetic Changes of Bone Marrow and Some Enzymatic Antioxidants: An Experimental Study Inaam N. Ali1, Muthana M. Awad2, Alaa S. Mahmood2,* 1 Water and Environment Directorate, Ministry of Sciences and Technology, Baghdad, Iraq 2 Department of Biology, College of Science, University of Anbar, Anbar, Iraq * Corresponding author: A. S. Mahmood (alaashm91@gmail.com) Abstract: Objective: To assess the effect of methotrexate and omega-3 combination on cytogenetic changes of bone marrow and activities of some enzymatic antioxidants. Methods: Fifty-six mature male Wistar rats were divided into two experimental groups and a control group. The first experimental group was sub-divided into three sub-groups depending on the concentration of methotrexate (MTX): X1 (0.05 mg/kg MTX), X2 (0.125 mg/kg MTX) and X3 (0.250 mg/kg MTX), which were given intraperitoneally on a weekly basis for eight weeks. The second experimental group (MTX and omega-3 group) was also sub-divided into three sub-groups (Y1, Y2 and Y3), which were injected intraperitoneally with 0.05, 0.125 and 0.25 mg/kg MTX, respectively, weekly for eight weeks accompanied by the oral administration of 300 mg/kg omega-3. The rats of the control group were given distilled water. The enzymatic activity of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) were measured in the sera of rats. In addition, the mitotic index (MI) and chromosomal aberrations of bone marrow were also studied. Results: MTX resulted in a significant decrease in the activities of CAT, SOD and GR compared to the controls. It also increased the MI and chromosomal aberrations of rat bone marrows. On the other hand, omega-3 significantly increased the activities of the investigated enzymatic antioxidants and reduced the MI and chromosomal aberrations in treated mice when given in combination with MTX. Conclusions: MTX has a genotoxic effect on the bone marrow by increasing the MI and all types of chromosomal aberrations and decreasing the enzymatic activity of CAT, SOD and GR. The addition of omega-3 can lead to a protective effect by reducing the toxic and mutagenic effects of MTX. Keywords: Methotrexate, Omega-3, Antioxidant, Wistar rat, Chromosomal aberration, Mitotic index 1. Introduction Methotrexate (MTX) is a folic acid antagonist because of their chemical similarity [1]. Vezmar et al. [2] showed that MTX affects the synthesis of nucleic acids deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) by interfering with the biosynthesis of thymine and purines. It also directly affects the rapidly dividing and intact cells, especially those in the mucous membranes of the mouth, intestine and bone marrow [3]. Omega-3 is a type of unsaturated fats, which are classified as essential fatty acids that cannot be manufactured by the body and should be taken with food [4]. Sources of omega-3 include fish oils, such as salmon, sardines and tuna, as well as soybeans, walnuts, raisins and linseed, almonds and olive oils [5]. Omega-3 is used in the prevention of a number of diseases such as rheumatoid arthritis, ulcerative colitis, asthma, atherosclerosis, cancer, and cardiovascular diseases [6]. A large amount of evidence indicates that omega-3 fatty acids have significant health benefits, including anti-inflammatory and antioxidant properties besides their effect on blood cholesterol levels [7]. Antioxidants retard the oxidation process by different mechanisms such as the removal of free radicals [8]. Enzymatic antioxidants include catalase (CAT), which is the first line of defense in the cell that removes hydrogen peroxide formed during biological processes by converting it into an aldehyde, and superoxide dismutase (SOD). There are three major families of SOD enzymes: manganese SOD (Mn-SOD) in the mitochondria and peroxisomes, iron SOD (Fe-SOD) in prokaryote cells and copper/zinc SOD (Cu-Zn SOD) in the cytoplasm of eukaryote cells [9]. Therefore, changes in the metal co-factors (manganese, iron, copper and zinc) can alter the effectiveness of SOD and may lead to diseases as a result of oxidative stress [10]. Glutathione reductase (GR) is also an enzymatic antioxidant that converts the oxidized glutathione to the reduced glutathione in the presence of NADPH, which is oxidized to NADP [11]. Therefore, the aim of the present study was to assess the effects of MTX and omega-3 on the cytogenetic changes of bone marrow as well as the activities of CAT, SOD and GR enzymatic antioxidants in male rats. 2. Method 2.1. Laboratory animals and experimental design Fifty-six mature male Wistar rats (Rattus norvegicus), aged 10–12 weeks old and weighing 250–300 gm, were used in the present study. The rats were kept in separate cages, with natural 13- hour light and 11-hour dark periods in a contamination-free environment with a controlled temperature (28.0 ± 1.0°C). In addition, rats were maintained on a standard diet and tap water ad libitum. The rats were randomly allocated to two experimental groups and a control group. The first experimental group (MTX group) included 24 rats injected intraperitoneally with different MTX dilutions with distilled water [12]. It was sub-divided into three sub-groups (eight rats per sub-group) according to MTX concentration as follows: X1 (0.05 mg/kg MTX), X2 (0.125mg/kg MTX) and X3 (0.25 mg/kg MTX). All rats were given a single dose of the specified MTX concentration weekly for eight weeks. The second experimental group (MTX and omega-3 group) included 24 rats allocated to three sub-groups (Y1, Y2 and Y3), which were injected intraperitoneally with 0.05, 0.125 and 0.25 mg/kg MTX, respectively, weekly for eight weeks accompanied by the oral administration of 300 mg/kg omega-3. The control group included eight rats that were intraperitoneally injected with distilled water and given a single dose of distilled water orally weekly for eight weeks. 2.2. Blood collection and processing After the end of the dosing period, 5 ml of blood were withdrawn from the heart (by cardiac puncture) using a 5 cc disposable syringe. The collected blood was immediately poured into a clean sterile screw-capped tube (plain tube) and left for coagulation in a water bath at 37°C for 15 minutes. After coagulation of blood, the plain tube was centrifuged for 5 minutes at 1500 rpm. Then the samples were stored at -20°C for subsequent analysis. 2.3. Measurement of the activity of antioxidant enzymes The antioxidant activities of CAT, SOD and GR were measured using enzyme-linked immunosorbent assay kits purchased from Kamiya Biomedical Company (Seattle, WA, US), according to the manufacturer's instructions. 2.4. Cytogenetic study of bone marrow Rats were killed by cervical dislocation, and their hip bones were cleaned from surrounding muscles and then dissected by cutting both ends of the bone. Five milliliters of physiological buffered saline were injected inside the bone to withdraw bone marrow into a test tube. Tubes were centrifuged at 2000 rpm/10 minutes. The supernatant was then removed, and 10 ml of KCL solution (0.075 M) were added to the sediment. The mixture was then incubated at 37 °C in a water bath for 30 minutes, with shaking from time to time. The tubes were then centrifuged at 2000rpm/10 minutes to remove the supernatant. However, 5 ml of a freshly prepared fixative solution (methanol: glacial acetic acid 1:3) were added gradually in the form of droplets into the inner wall of the tube with constant mixing. After that, the tubes were placed at 4 °C for half an hour to fix the cells. This process was repeated for three times, and the cells were then suspended in 2 ml of the fixative solution. The tubes were centrifuged at 2000 rpm for 5 minutes, and the supernatant was then removed while the cells were re-suspended in 1-2 ml of cold fixative solution. After shaking the tubes, 4–5 drops were then taken from each tube onto a clean slide from a height of about three feet to provide an opportunity for the cells and nuclei to spread well. The slides were stained with acridine orange solution (0.01%) for 4–5 minutes, incubated in Sorensen’s buffer (0.06M, pH 6.5) for a minute. and then examined using a fluorescence microscope Olympus BX 51 America at a wavelength of 450–500 nm [13, 14]. A total of 1000 cells were examined, and both dividing and non-dividing cells were calculated [13]. Mitotic index (MI) was calculated according to the following formula [13]: MI= No. of dividing cells / 1000 × 100 2.5. Analysis of chromosomal aberrations of bone marrow cells A total of 1000 dividing cells were examined on the stained slides under a fluorescence microscope at a wavelength of 45–500 nm. The examined cells were at the first metaphase of the mitotic division, where chromosomal aberrations are clear and can be easily seen [13]. 2.6. Statistical analysis Data were analyzed using the Statistical Analysis System (SAS®) software, version 9.1 (Cary, NC, USA) [15]. Effects were expressed as mean ± standard error (SE) and statistically compared using a completely randomized design analysis of variance and least significant differences. Differences at P values <5 were considered statistically significant. 3. Results 3.1. Effects of MTX and MTX-omega-3 combination on antioxidant enzymatic activities Table (1) shows significantly lower SOD activities among rats treated with MTX or MTX-omega-3 compared to controls. Moreover, sera of rats receiving relatively high doses of MTX (sub-groups X2 and X3) showed the lowest enzymatic activities of 4.29 ± 0.01 IU and 3.93 ± 0.11 IU, respectively. On the other hand, CAT activity differed significantly between treated and control rats as well as among treated rats themselves, In this respect, the controls showed the highest activity of 39.38 ±0.02 IU, while those receiving the highest MTX concentration, either alone or in combination with omega-3 (sub-groups X3 and Y3), showed the lowest activities of 30.97 ± 0.03 IU and 32.12± 0.06 IU, respectively. Regarding GR activity, control rats showed a higher activity of 53.09± 0.05 IU compared to treated ones; however, the differences in GR activities in rats given low doses of MTX, either alone or in combination with omega-3 (sub-groups X1 and Y1), were not statistically significant. On the other hand, rats in sub-groups X3 and Y3 showed the lowest GR activities of 34.59 ± 0.63 IU and 37.15 ±0.01, respectively, with statistically significant differences from other sub-groups. 3.2. Effects of MTX and MTX-omega-3 combination on mitotic index of bone marrow cells Figure (1) shows a significant decrease in the MI in all treated groups compared to control. In addition, there was a reverse association between MTX concentration and MI, where rats treated with the highest dose of MTX (sub-group X3) showed a significant decrease in MI compared to all other treated rat sub-groups. In addition, rats in sub-groups treated with MTX and omega-3 (sub-groups Y1, Y2 and Y3) showed a significant increase in MI compared to their counterpart rats receiving MTX only. Table 1. Activity of antioxidant enzymes in rats treated with MTX and MTX-omega-3 Group Enzymatic activity (mean± SE) SOD (IU) CAT (IU) GR (µmol) Control 6.41±0.02 a 39.38±0.02 a 53.09±0.05 a X1 (0.05 mg MTX/ kg) 5.33±0.01 b 37.81±0.01 c 51.12±0.06 a Y1 (0.05 mg MTX + 300 mg omega-3/ kg) 6.08±0.04 a 38.40±0.02 b 51.97±0.03 a X2 (0.125 mg MTX/ kg) 4.29±0.01 cd 33.13±0.01 e 42.34±0.03 b Y2 (0.125 mg MTX + 300 mg omega-3/ kg) 4.99±0.40 b 36.68±0.02 d 43.02±3.04 b X3 (0.25 mg MTX/ kg) 3.93±0.11 d 30.97±0.03 g 34.59±0.63 c Y3 (0.25 mg MTX + 300 mg omega-3/ kg) 4.47±0.02 c 32.12±0.06 f 37.15±0.01 c SE, Standard error; IU, international unit; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; *statistically significant at P < 0.05; **statistically significant at P < 0.01. Means with different letters within the same column showed a statistically significant difference. 3.3. Effects of MTX and MTX-omega-3 combination on chromosomal aberrations of bone marrow cells Rats receiving higher concentrations of MTX (sub-group X3) showed a significant increase in all types of chromosomal aberrations, i.e., chromatid gaps, chromosome gaps, chromatid breaks, chromosome breaks, deletions and simple fragments (Figure 2 and Table 2) than those of the control group or other treated sub-groups. All rats treated with MTX-omega-3 combination showed a significant decrease in almost all types of chromosomal aberrations compared to their counterpart rats receiving MTX alone (Table 2). Figure 1. Effect of MTX and MTX-omega-3 on the MI of bone marrow cells of treated rats compared to the controls. The groups X1 (0.05 MTX), X2 (0.125 MTX) and X3 (0.250 MTX) were compared to the control group, while the groups Y1 (0.05 MTX+ omega-3), Y2 (0.125 MTX+ omega-3) and Y3 (0.25 MTX+ omega-3) were compared to X1, X2 and X3, respectively. Figure 2. Effect of MTX and MTX-omega-3 on chromosomal aberration as seen under fluorescence microscope after staining with acridine orange: (1) a simple fragment; (2) a chromatid gap; (3) a chromosomal gap (A) and a chromosomal break (B). 4. Discussion The present experiment reveals that the addition of omega-3 to MTX alleviates its effects on the activities of the antioxidant enzymes CAT, SOD and GR, and decreases the MI as well as all types of chromosomal aberrations in the bone marrow cells. Daham et al. [16] showed that the decline in antioxidants associated with chemotherapy is attributed to the increase in lipid peroxidation caused by these kinds of drugs, which increase the level of free radicals. In addition, Weijl et al. [17] showed that some chemotherapeutic drugs have a negative effect on the antioxidant levels such as GR, whose activity decreases as a result of its involvement in many cellular processes such as cell defenses against the toxicity of some compounds. Al-Dalawy et al. [18] found that the decrease in the level of SOD is an evidence of its increased activity due to the increased release of free radicals. MTX causes an increase in the release of free radicals, including the OH radical that causes direct damage to DNA [16]. Al-Helaly [19] showed that the amount of food taken has an effect on antioxidants, where nutritional deficiency decreases the antioxidant levels, thus increasing free radicals that cause damage to DNA. Table 2. Chromosomal aberrations of bone marrow cells in rats treated with MTX and MTX-omega-3 Group Type of chromosomal aberration(mean ± SE) Chromatid gap Chromosome Gap Chromatid breaks Chromosome breaks Deletion Simple Fragments Chromosomal aberration (%) Control 1.33±0.33 e 0.00±0.00 e 1.67±0.33 c 0.33±0.15 c 0.00±0.00 0.67±0.33 cd 0.04±0.005 f X1 2.75±0.47 cd 1.50±0.28 cd 2.50±0.64 bc 1.00±0.41 bc 0.50±0.28 bc 0.75±0.25 bcd 0.09±0.02 de Y1 1.75±0.47 de 0.75±0.25 de 1.50±0.28 c 1.00±0.00 bc 0.75±0.25 abc 0.75±0.25 abc 0.065±0.005 ef X2 4.67±0.33 b 2.67±0.33 ab 2.67±0.33 bc 1.67±0.33 ab 0.67±0.33 abc 1.67±0.33 ab 0.14±0.006 bc Y2 3.00±0.00 c 2.00±0.00 bc 3.00±0.057 bc 1.33±0.33 b 0.67±0.33 abc 0.33±0.15 d 0.106±0.003 cd X3 6.80±0.37 a 3.00±0.31 a 4.60±0.74 a 2.40±0.24 a 1.40±0.24 a 1.80±0.37 a 0.20±0.017 a Y3 5.60±0.40 ab 2.40±0.24 ab 3.60±0.24 ab 1.80±0.20 ab 1.20±0.20 ab 1.40±0.24 abc 0.16±0.003 b LSD 1.231** 0.814** 0.602** 0.841** 0.774* 0.941** 3.499* SE, Standard error; * statistically significant at P < 0.05; ** statistically significant at P < 0.01. Means with different letters within the same column showed a statistically significant difference. X1 (0.05 mg MTX/ kg); X2 (0.125 mg MTX/ kg); X3 (0.25 mg MTX/ kg); Y1 (0.05 mg MTX + 300 mg omega-3/ kg); Y2 (0.125 mg MTX + 300 mg omega-3/ kg); Y3 (0.25 mg MTX + 300 mg omega-3/ kg). In the present study, the intraperitoneal administration of MTX to rats also caused a decrease in the MI of bone marrow and a significant increase in the rate of abnormal chromosomal aberration compared to the control rats. This finding is consistent with those reported previously [20], [21]. The effect of MTX can be attributed to its ability to interfere with the genetic material, leading to the appearance of toxic and mutagenic consequences. Rushworth et al. [22] reported that MTX leads to a lack of dihydrofolate reductase, which is the key to the growth and cell division processes. This, in turn, leads to a reduction of the nucleotides involved in the building of DNA and, therefore, to a stop or obstruction of the repair mechanisms of the damaged DNA. In addition, Wong and Choi [23] concluded that MTX inhibits the action of enzymes controlling the purine metabolism, which leads to the accumulation of adenosine in addition to the damage of the molecule itself and to the occurrence of chromosomal aberrations. Jafer et al. [24] reported the ability of MTX to induce chromosomal aberration in humans or animals by preventing the repair of DNA and affecting the proteins found in chromosomes. These findings were also confirmed by Hussain et al. [25], who found that MTX causes an increase in chromosomal aberrations. In the present study, the MI showed a significant increase in rat sub-groups treated with MTX-omega-3 combination, but there was a decrease in the rate of chromosomal aberration, which confirms the role of omega-3 unsaturated fatty acids in protecting the cell from the impact of free radicals [26], [27]. Attia and Nasr [28] reported the antioxidant effect of omega-3, which was attributed to the reduction in lipid peroxidation and the increase in SOD and CAT or the stimulation of GR. It is noteworthy that GR leads to the synthesis of reduced glutathione, which is important in the defense of the cell against toxic substances and the prevention of the occurrence of mutations [29]. 5. Conclusions MTX significantly decreases the activity of enzymatic antioxidants, reduce the MI and increase the chromosomal aberrations of all types in bone marrow. This gives further evidence on the genotoxic effects of MTX on the bone marrow. 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Introduction Methods Resuts Discussion Conclusions Acknowledgments Authors' contributions Competing interests Ethical approval References Effect of Methotrexate and Omega-3 Combination on Cytogenetic Changes of Bone Marrow and Some Enzymatic Antioxidants: An Experimental Study Inaam N. Ali1, Muthana M. Awad2, Alaa S. Mahmood2,* 1 Water and Environment Directorate, Ministry of Sciences and Technology, Baghdad, Iraq 2 Department of Biology, College of Science, University of Anbar, Anbar, Iraq * Corresponding author: A. S. Mahmood (alaashm91@gmail.com) Abstract: Objective: To assess the effect of methotrexate and omega-3 combination on cytogenetic changes of bone marrow and activities of some enzymatic antioxidants. Methods: Fifty-six mature male Wistar rats were divided into two experimental groups and a control group. The first experimental group was sub-divided into three sub-groups depending on the concentration of methotrexate (MTX): X1 (0.05 mg/kg MTX), X2 (0.125 mg/kg MTX) and X3 (0.250 mg/kg MTX), which were given intraperitoneally on a weekly basis for eight weeks. The second experimental group (MTX and omega-3 group) was also sub-divided into three sub-groups (Y1, Y2 and Y3), which were injected intraperitoneally with 0.05, 0.125 and 0.25 mg/kg MTX, respectively, weekly for eight weeks accompanied by the oral administration of 300 mg/kg omega-3. The rats of the control group were given distilled water. The enzymatic activity of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) were measured in the sera of rats. In addition, the mitotic index (MI) and chromosomal aberrations of bone marrow were also studied. Results: MTX resulted in a significant decrease in the activities of CAT, SOD and GR compared to the controls. It also increased the MI and chromosomal aberrations of rat bone marrows. On the other hand, omega-3 significantly increased the activities of the investigated enzymatic antioxidants and reduced the MI and chromosomal aberrations in treated mice when given in combination with MTX. Conclusions: MTX has a genotoxic effect on the bone marrow by increasing the MI and all types of chromosomal aberrations and decreasing the enzymatic activity of CAT, SOD and GR. The addition of omega-3 can lead to a protective effect by reducing the toxic and mutagenic effects of MTX. Keywords: Methotrexate, Omega-3, Antioxidant, Wistar rat, Chromosomal aberration, Mitotic index 1. Introduction Methotrexate (MTX) is a folic acid antagonist because of their chemical similarity [1]. Vezmar et al. [2] showed that MTX affects the synthesis of nucleic acids deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) by interfering with the biosynthesis of thymine and purines. It also directly affects the rapidly dividing and intact cells, especially those in the mucous membranes of the mouth, intestine and bone marrow [3]. Omega-3 is a type of unsaturated fats, which are classified as essential fatty acids that cannot be manufactured by the body and should be taken with food [4]. Sources of omega-3 include fish oils, such as salmon, sardines and tuna, as well as soybeans, walnuts, raisins and linseed, almonds and olive oils [5]. Omega-3 is used in the prevention of a number of diseases such as rheumatoid arthritis, ulcerative colitis, asthma, atherosclerosis, cancer, and cardiovascular diseases [6]. A large amount of evidence indicates that omega-3 fatty acids have significant health benefits, including anti-inflammatory and antioxidant properties besides their effect on blood cholesterol levels [7]. Antioxidants retard the oxidation process by different mechanisms such as the removal of free radicals [8]. Enzymatic antioxidants include catalase (CAT), which is the first line of defense in the cell that removes hydrogen peroxide formed during biological processes by converting it into an aldehyde, and superoxide dismutase (SOD). There are three major families of SOD enzymes: manganese SOD (Mn-SOD) in the mitochondria and peroxisomes, iron SOD (Fe-SOD) in prokaryote cells and copper/zinc SOD (Cu-Zn SOD) in the cytoplasm of eukaryote cells [9]. Therefore, changes in the metal co-factors (manganese, iron, copper and zinc) can alter the effectiveness of SOD and may lead to diseases as a result of oxidative stress [10]. Glutathione reductase (GR) is also an enzymatic antioxidant that converts the oxidized glutathione to the reduced glutathione in the presence of NADPH, which is oxidized to NADP [11]. Therefore, the aim of the present study was to assess the effects of MTX and omega-3 on the cytogenetic changes of bone marrow as well as the activities of CAT, SOD and GR enzymatic antioxidants in male rats. 2. Method 2.1. Laboratory animals and experimental design Fifty-six mature male Wistar rats (Rattus norvegicus), aged 10–12 weeks old and weighing 250–300 gm, were used in the present study. The rats were kept in separate cages, with natural 13- hour light and 11-hour dark periods in a contamination-free environment with a controlled temperature (28.0 ± 1.0°C). In addition, rats were maintained on a standard diet and tap water ad libitum. The rats were randomly allocated to two experimental groups and a control group. The first experimental group (MTX group) included 24 rats injected intraperitoneally with different MTX dilutions with distilled water [12]. It was sub-divided into three sub-groups (eight rats per sub-group) according to MTX concentration as follows: X1 (0.05 mg/kg MTX), X2 (0.125mg/kg MTX) and X3 (0.25 mg/kg MTX). All rats were given a single dose of the specified MTX concentration weekly for eight weeks. The second experimental group (MTX and omega-3 group) included 24 rats allocated to three sub-groups (Y1, Y2 and Y3), which were injected intraperitoneally with 0.05, 0.125 and 0.25 mg/kg MTX, respectively, weekly for eight weeks accompanied by the oral administration of 300 mg/kg omega-3. The control group included eight rats that were intraperitoneally injected with distilled water and given a single dose of distilled water orally weekly for eight weeks. 2.2. Blood collection and processing After the end of the dosing period, 5 ml of blood were withdrawn from the heart (by cardiac puncture) using a 5 cc disposable syringe. The collected blood was immediately poured into a clean sterile screw-capped tube (plain tube) and left for coagulation in a water bath at 37°C for 15 minutes. After coagulation of blood, the plain tube was centrifuged for 5 minutes at 1500 rpm. Then the samples were stored at -20°C for subsequent analysis. 2.3. Measurement of the activity of antioxidant enzymes The antioxidant activities of CAT, SOD and GR were measured using enzyme-linked immunosorbent assay kits purchased from Kamiya Biomedical Company (Seattle, WA, US), according to the manufacturer's instructions. 2.4. Cytogenetic study of bone marrow Rats were killed by cervical dislocation, and their hip bones were cleaned from surrounding muscles and then dissected by cutting both ends of the bone. Five milliliters of physiological buffered saline were injected inside the bone to withdraw bone marrow into a test tube. Tubes were centrifuged at 2000 rpm/10 minutes. The supernatant was then removed, and 10 ml of KCL solution (0.075 M) were added to the sediment. The mixture was then incubated at 37 °C in a water bath for 30 minutes, with shaking from time to time. The tubes were then centrifuged at 2000rpm/10 minutes to remove the supernatant. However, 5 ml of a freshly prepared fixative solution (methanol: glacial acetic acid 1:3) were added gradually in the form of droplets into the inner wall of the tube with constant mixing. After that, the tubes were placed at 4 °C for half an hour to fix the cells. This process was repeated for three times, and the cells were then suspended in 2 ml of the fixative solution. The tubes were centrifuged at 2000 rpm for 5 minutes, and the supernatant was then removed while the cells were re-suspended in 1-2 ml of cold fixative solution. After shaking the tubes, 4–5 drops were then taken from each tube onto a clean slide from a height of about three feet to provide an opportunity for the cells and nuclei to spread well. The slides were stained with acridine orange solution (0.01%) for 4–5 minutes, incubated in Sorensen’s buffer (0.06M, pH 6.5) for a minute. and then examined using a fluorescence microscope Olympus BX 51 America at a wavelength of 450–500 nm [13, 14]. A total of 1000 cells were examined, and both dividing and non-dividing cells were calculated [13]. Mitotic index (MI) was calculated according to the following formula [13]: MI= No. of dividing cells / 1000 × 100 2.5. Analysis of chromosomal aberrations of bone marrow cells A total of 1000 dividing cells were examined on the stained slides under a fluorescence microscope at a wavelength of 45–500 nm. The examined cells were at the first metaphase of the mitotic division, where chromosomal aberrations are clear and can be easily seen [13]. 2.6. Statistical analysis Data were analyzed using the Statistical Analysis System (SAS®) software, version 9.1 (Cary, NC, USA) [15]. Effects were expressed as mean ± standard error (SE) and statistically compared using a completely randomized design analysis of variance and least significant differences. Differences at P values <5 were considered statistically significant. 3. Results 3.1. Effects of MTX and MTX-omega-3 combination on antioxidant enzymatic activities Table (1) shows significantly lower SOD activities among rats treated with MTX or MTX-omega-3 compared to controls. Moreover, sera of rats receiving relatively high doses of MTX (sub-groups X2 and X3) showed the lowest enzymatic activities of 4.29 ± 0.01 IU and 3.93 ± 0.11 IU, respectively. On the other hand, CAT activity differed significantly between treated and control rats as well as among treated rats themselves, In this respect, the controls showed the highest activity of 39.38 ±0.02 IU, while those receiving the highest MTX concentration, either alone or in combination with omega-3 (sub-groups X3 and Y3), showed the lowest activities of 30.97 ± 0.03 IU and 32.12± 0.06 IU, respectively. Regarding GR activity, control rats showed a higher activity of 53.09± 0.05 IU compared to treated ones; however, the differences in GR activities in rats given low doses of MTX, either alone or in combination with omega-3 (sub-groups X1 and Y1), were not statistically significant. On the other hand, rats in sub-groups X3 and Y3 showed the lowest GR activities of 34.59 ± 0.63 IU and 37.15 ±0.01, respectively, with statistically significant differences from other sub-groups. 3.2. Effects of MTX and MTX-omega-3 combination on mitotic index of bone marrow cells Figure (1) shows a significant decrease in the MI in all treated groups compared to control. In addition, there was a reverse association between MTX concentration and MI, where rats treated with the highest dose of MTX (sub-group X3) showed a significant decrease in MI compared to all other treated rat sub-groups. In addition, rats in sub-groups treated with MTX and omega-3 (sub-groups Y1, Y2 and Y3) showed a significant increase in MI compared to their counterpart rats receiving MTX only. Table 1. Activity of antioxidant enzymes in rats treated with MTX and MTX-omega-3 Group Enzymatic activity (mean± SE) SOD (IU) CAT (IU) GR (µmol) Control 6.41±0.02 a 39.38±0.02 a 53.09±0.05 a X1 (0.05 mg MTX/ kg) 5.33±0.01 b 37.81±0.01 c 51.12±0.06 a Y1 (0.05 mg MTX + 300 mg omega-3/ kg) 6.08±0.04 a 38.40±0.02 b 51.97±0.03 a X2 (0.125 mg MTX/ kg) 4.29±0.01 cd 33.13±0.01 e 42.34±0.03 b Y2 (0.125 mg MTX + 300 mg omega-3/ kg) 4.99±0.40 b 36.68±0.02 d 43.02±3.04 b X3 (0.25 mg MTX/ kg) 3.93±0.11 d 30.97±0.03 g 34.59±0.63 c Y3 (0.25 mg MTX + 300 mg omega-3/ kg) 4.47±0.02 c 32.12±0.06 f 37.15±0.01 c SE, Standard error; IU, international unit; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; *statistically significant at P < 0.05; **statistically significant at P < 0.01. Means with different letters within the same column showed a statistically significant difference. 3.3. Effects of MTX and MTX-omega-3 combination on chromosomal aberrations of bone marrow cells Rats receiving higher concentrations of MTX (sub-group X3) showed a significant increase in all types of chromosomal aberrations, i.e., chromatid gaps, chromosome gaps, chromatid breaks, chromosome breaks, deletions and simple fragments (Figure 2 and Table 2) than those of the control group or other treated sub-groups. All rats treated with MTX-omega-3 combination showed a significant decrease in almost all types of chromosomal aberrations compared to their counterpart rats receiving MTX alone (Table 2). Figure 1. Effect of MTX and MTX-omega-3 on the MI of bone marrow cells of treated rats compared to the controls. The groups X1 (0.05 MTX), X2 (0.125 MTX) and X3 (0.250 MTX) were compared to the control group, while the groups Y1 (0.05 MTX+ omega-3), Y2 (0.125 MTX+ omega-3) and Y3 (0.25 MTX+ omega-3) were compared to X1, X2 and X3, respectively. Figure 2. Effect of MTX and MTX-omega-3 on chromosomal aberration as seen under fluorescence microscope after staining with acridine orange: (1) a simple fragment; (2) a chromatid gap; (3) a chromosomal gap (A) and a chromosomal break (B). 4. Discussion The present experiment reveals that the addition of omega-3 to MTX alleviates its effects on the activities of the antioxidant enzymes CAT, SOD and GR, and decreases the MI as well as all types of chromosomal aberrations in the bone marrow cells. Daham et al. [16] showed that the decline in antioxidants associated with chemotherapy is attributed to the increase in lipid peroxidation caused by these kinds of drugs, which increase the level of free radicals. In addition, Weijl et al. [17] showed that some chemotherapeutic drugs have a negative effect on the antioxidant levels such as GR, whose activity decreases as a result of its involvement in many cellular processes such as cell defenses against the toxicity of some compounds. Al-Dalawy et al. [18] found that the decrease in the level of SOD is an evidence of its increased activity due to the increased release of free radicals. MTX causes an increase in the release of free radicals, including the OH radical that causes direct damage to DNA [16]. Al-Helaly [19] showed that the amount of food taken has an effect on antioxidants, where nutritional deficiency decreases the antioxidant levels, thus increasing free radicals that cause damage to DNA. Table 2. Chromosomal aberrations of bone marrow cells in rats treated with MTX and MTX-omega-3 Group Type of chromosomal aberration(mean ± SE) Chromatid gap Chromosome Gap Chromatid breaks Chromosome breaks Deletion Simple Fragments Chromosomal aberration (%) Control 1.33±0.33 e 0.00±0.00 e 1.67±0.33 c 0.33±0.15 c 0.00±0.00 0.67±0.33 cd 0.04±0.005 f X1 2.75±0.47 cd 1.50±0.28 cd 2.50±0.64 bc 1.00±0.41 bc 0.50±0.28 bc 0.75±0.25 bcd 0.09±0.02 de Y1 1.75±0.47 de 0.75±0.25 de 1.50±0.28 c 1.00±0.00 bc 0.75±0.25 abc 0.75±0.25 abc 0.065±0.005 ef X2 4.67±0.33 b 2.67±0.33 ab 2.67±0.33 bc 1.67±0.33 ab 0.67±0.33 abc 1.67±0.33 ab 0.14±0.006 bc Y2 3.00±0.00 c 2.00±0.00 bc 3.00±0.057 bc 1.33±0.33 b 0.67±0.33 abc 0.33±0.15 d 0.106±0.003 cd X3 6.80±0.37 a 3.00±0.31 a 4.60±0.74 a 2.40±0.24 a 1.40±0.24 a 1.80±0.37 a 0.20±0.017 a Y3 5.60±0.40 ab 2.40±0.24 ab 3.60±0.24 ab 1.80±0.20 ab 1.20±0.20 ab 1.40±0.24 abc 0.16±0.003 b LSD 1.231** 0.814** 0.602** 0.841** 0.774* 0.941** 3.499* SE, Standard error; * statistically significant at P < 0.05; ** statistically significant at P < 0.01. Means with different letters within the same column showed a statistically significant difference. X1 (0.05 mg MTX/ kg); X2 (0.125 mg MTX/ kg); X3 (0.25 mg MTX/ kg); Y1 (0.05 mg MTX + 300 mg omega-3/ kg); Y2 (0.125 mg MTX + 300 mg omega-3/ kg); Y3 (0.25 mg MTX + 300 mg omega-3/ kg). In the present study, the intraperitoneal administration of MTX to rats also caused a decrease in the MI of bone marrow and a significant increase in the rate of abnormal chromosomal aberration compared to the control rats. This finding is consistent with those reported previously [20], [21]. The effect of MTX can be attributed to its ability to interfere with the genetic material, leading to the appearance of toxic and mutagenic consequences. Rushworth et al. [22] reported that MTX leads to a lack of dihydrofolate reductase, which is the key to the growth and cell division processes. This, in turn, leads to a reduction of the nucleotides involved in the building of DNA and, therefore, to a stop or obstruction of the repair mechanisms of the damaged DNA. In addition, Wong and Choi [23] concluded that MTX inhibits the action of enzymes controlling the purine metabolism, which leads to the accumulation of adenosine in addition to the damage of the molecule itself and to the occurrence of chromosomal aberrations. Jafer et al. [24] reported the ability of MTX to induce chromosomal aberration in humans or animals by preventing the repair of DNA and affecting the proteins found in chromosomes. These findings were also confirmed by Hussain et al. [25], who found that MTX causes an increase in chromosomal aberrations. In the present study, the MI showed a significant increase in rat sub-groups treated with MTX-omega-3 combination, but there was a decrease in the rate of chromosomal aberration, which confirms the role of omega-3 unsaturated fatty acids in protecting the cell from the impact of free radicals [26], [27]. Attia and Nasr [28] reported the antioxidant effect of omega-3, which was attributed to the reduction in lipid peroxidation and the increase in SOD and CAT or the stimulation of GR. It is noteworthy that GR leads to the synthesis of reduced glutathione, which is important in the defense of the cell against toxic substances and the prevention of the occurrence of mutations [29]. 5. Conclusions MTX significantly decreases the activity of enzymatic antioxidants, reduce the MI and increase the chromosomal aberrations of all types in bone marrow. This gives further evidence on the genotoxic effects of MTX on the bone marrow. 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This study investigates the anti-inflammatory effect of the honeysuckle flower in combination with Oroxylum indicum in search of a new kind of anti-inflammatory therapy drugs with stronger anti-inflammatory effects and without unwanted adverse reactions. The study results show that a honeysuckle flower dose of 0.72 g/kg/day, Oroxylum indicum dose of 1.2 g/kg/day together with honeysuckle flower combined with Oroxylum indicum with 1:1 ratio had an acute anti-inflammatory effect on the white rat on a mouse Leg Edema Model with carrageenin and the model causing mouse peritonitis. The results also show that a honeysuckle flower dose of 1.44 g/kg/day, Oroxylum indicum the dose of 2.4 g/kg/day together with honeysuckle flower combined with Oroxylum indicum with 1:1 ratio had a chronic anti-inflammation effect on the white mouse on the model causing chronic inflammation of the granuloma. These results open up a subsequent research direction on the possibility of combining various anti-inflammatory medicinal herbs to obtain better anti-inflammatory efficacy and contribute to the promoting of the effect of the available domestic medicinal resources. Keywords Honeysuckle flowers, Oroxylum indicum, anti-inflammatory effect References [1] Vu Trieu An, Immunology, Hanoi Medical Publishing House, 2001, pp. 250 - 252.[2] Nguyen Ngoc Lanh, Pathophysiology, Medical Publishing House, 2012, pp. 209 - 229.[3] Le Dinh Roanh, Nguyen Dinh Mao, Inflammatory and infectious pathology, Medical Publishing House,1997, pp. 1 - 132.[4] Vo Van Chi, Dictionary of Vietnamese medicinal plants, Medicine Publishing House,1997, pp. 633-634.[5] Paulina Melega, Lonicera japonica Flower, Veterinarian Reviewed on June 20 (2012).[6] Jin Tae, Seung-Woo Han, et al., Anti-inflammatory effect of Lonicera japonica in proteinase-activated receptor 2-mediated paw edema, Clinica Chimica Acta, Apr; 330(1-2) (2003) 165 - 171.[7] Wie Jong Kwar, Chang Kyun Han, et al., Loniceroside C, an Anti-inflammatory Saponin from Lonicera japonica, Chem. Pharm. Bull (Tokyo) Mar; 51(3) (2003) 333-335.[8] JH. Lee, WS. Ko, YH. Kim, et al., Anti-inflammatory effect of the aqueous extract from Lonicera japonica flower is related to inhibition of NF-KappaB activation through reducing I-kappaBalpha degradation in rat liver, Int J Mol Med, Jan; 7(1) (2001) 79 - 83.[9] Min Ho Han, Won Sup Lee, Arulkumar Nagappan, et al., Flavonoid Isolated from Flowers of Lonicera japonica Thunb. Inhibit Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF-α and IL-β Through PI3K/Akt/NF-Kb Signaling Pathways, Phytotherapy Research, 30(11) (2016) 1824 - 1832. [10] Seung-Hwan Kwon, Shi-Xun Ma, Sa-lk Hong, et al., Lonicera japonica Thunb. Extract Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses by Suppressing NF-κB Signaling in BV-2 Microglial Cells, J Med Food, Jul 1. 18(7) (2015) 762-775.[11] Do Tat Loi, Vietnamese medicinal plants and herbs, Thoi Dai Publishing House, (2011), 75 - 77, 726 - 728.[12] Mamatha Karnati, Rodda H Chandra, Ciddi Veeresham, et al., Anti-arthritic activity of root bark of Oroxylum indicum (L.) vent against adjuvant-induced arthritis, Pharmacognosy Research, Apr-Jun 5(2) (2013) 121-128.[13] Vietnam Pharmacopoeia Council, Vietnam Pharmacopoeia IV, Medical Publishing House, 2009, pp. 806- 856.[14] C.A. Winter, E.A Risley and G.W Nuss, Carrageenin induced edema in hind paw of the rat as an assay for anti-inflammatory drugs, Proc. Soe. Exp. Bio. Med, No 111 (1962) 544 - 547.[15] Julon, J.C.Guyonnet, et al., Etude des propriétés pharmacologiques d’un nowel anti-inflammatoire, J.Pharmacol (Paris), 3(2) (1971) 259 - 286.

This research used descriptive approach to illustrate the Linguistic Landscape of the city of Manila as a center of commerce andmulticulturalism. The goal of the study is to identify or describe the languages that are seen or that exist in public spaces of the city, identify the vitality of languages and assess the implications of the language landscape of Manila in the Filipino language situation at present. The researchers took pictures of signs in four selected areas in Manila. It was then categorized based on the taxonomy of Spolsky and Cooper which include: 1.) road signs; 2.) advertising signs; 3.) warning; 4.) names of buildings; 5.) informational signs; 6.) plaque plots; 7.) things; and 8.) graffiti. Photographs also categorized whether it is monolingual, bilingual or multilingual and if it is “top-down” or “bottom-up”. The measure of the vitality of languages spreading across the city was based on the Ethnolinguistic Vitality (EV) theory used in the studies of Giles, Bourhis and Taylor to determine which language is the most dominant or widely used in the linguistic landscape. This research only covers the description of the linguistic landscape of Manila by determining the languages existing in the city and their vitality as evident in the road signs, advertising signs, warning, name of buildings, informational signs, things and graffiti. . It also examined the implications of the linguistic landscape of Manila to the current situation or state of the Filipino language and the challenges it faces in its development. It was discovered that there are six languages spreading and existing in the city such as: English, Filipino, Chinese, Korean, Japanese and Spanish. Among these languages, English is the most dominantly used. This study shows that English language is given more importance than Filipino, which is the country’s national language. English language is being used in meaningful activities such as providing information, advertising signs, and building names. The researcher proposes further studies of language learning in other major cities in the Philippines to determine the extent of the spread of Filipino language and dialects thereby maintaining, strengthening and improving the country’s national language more than the value exhibited with the use of the English language. References Akindele, D. O. (2011). Linguistic Landscapes as Public Communication: A Study of Public Signage in Gaborone Botswana. International Journal of Linguistics. Retrievedfrom http://www.macrothink.org/journal/index.php/ijl/article/view/1157/pdf Almario, V. S. (2003). Nasyonalisasyon ng Filipino. Wikang Filipino sa Loob atLabas ng Akademya’t Bansa: Unang Soucebook ng SANGFIL 1994 – 2001. 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Mobility and Language in Place:A Linguistic Landscape of LanguageCommodification. Cultural Heritage in European Societies and Spaces. Retrieved fromh t t p : / / s c h o l a r w o r k s . u m a s s . e d u / c g i / v i e w c o n t e n t .cgi?article=1006&context=chess_student_research David, R. S. (2003). Politika ng Wika, Wika ng Politika. Wikang Filipino sa Loobat Labas ng Akademya’t Bansa: Unang Soucebook ng SANGFIL 1994 – 2001. Manila:Pambansang Komisyon para sa Kultura at mga Sining, 15 – 22. De Quiros, C. (2003). Ang Kapangyarihanng Wika, Ang Wika ng Kapangyarihan.Wikang Filipino sa Loob at Labas ng Akademya’t Bansa: Unang Soucebook ngSANGFIL 1994 – 2001. Manila: Pambansang Komisyon para sa Kultura at mga Sining, 28 – 33. Desiderio, L. (2012). NSO: Number of foreign citizens residing in Phl now over177,000. The Philippine Star. Retrieved from http://www.philstar.com:8080/headlines/2012/11/26/873745/nso-number-foreign-citizens-residing-phlnow-over-177000 Espiritu, C. (2015) Language Policies in the Philippines. National Commision forCulture and the Arts. Retrieved from http://www.ncca.gov.ph/about-culture-and-arts/articles-on-c-n a/article.php?igm=3&i=217 Giles, H., Bourhis, R. Y. & Taylor, D. M. (1977). Towards a theory of language inethnic group relations. In H. Giles (Ed.). Language, Ethnicity and Intergroup Relations.London, UK: Academic Press. Retrieved from https://www.researchgate.net/publication/265966525_Giles_H_Bourhis_RY_Taylor_DM_1977_Towards_a_theory_of_language_in_ethnic_group_relations_In_H_Giles_Ed_Language_Ethnicity_and_Intergroup_Relations_pp_307-348_London_UK_Academic_Press Gorter, D. (2013). Linguistic Landscapes in a Multilingual World. Annual Reviewof Applied Linguistic. Cambridge University Press. 33, 190-212. Harwood, J., Giles, H., & Bourhis, R. Y. (1994). The genesis of vitality theory: Historicalpatterns and discoursal dimensions. International Journal of the Sociologyof Language. 108, 167-206. 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Introdução: As lesões cervicais não cariosas (LCNC) apresentam-se como uma perda irreversível dentária na região cervical sem o envolvimento bacteriano e possui etiologia multifatorial. Devido o estresse, a perda de tecido dental tem sido associada ao fator oclusal, comprovando a associação da lesão ao bruxismo, apertamento e contato prematuro. Objetivo: Avaliar o nível de estresse em pacientes LCNC atendidos na Clínica Escola de Odontologia da Universidade Federal de Campina Grande (UFCG). Metodologia: O estudo foi do tipo transversal, observacional, com abordagem indutiva e procedimento comparativo, descritivo, estratégia de coleta de dados através das fichas clínicas, exame clínico e um questionário Inventário de Sintomas de Estresse de Lipp (ISSL). Os dados foram registrados no banco de dados do programa de informática SPSS para Windows 7, versão 13.0 no período de Fevereiro a Setembro de 2018. A fase I corresponde à experiência de estresse nas ultimas 24 horas, a fase II na última semana e a fase III no último mês. A amostra foi por conveniência composta por 150 participantes. Resultados: 86 (57,4%) eram do gênero feminino e 64 (42,6%) do gênero masculino. Do gênero masculino, o maior número de participantes (33) apresentavam-se em fase de exaustão (Fase III), e de 86 pacientes do gênero feminino, o maior número (50) também se apresentavam em nível de exaustão. Quando questionados sobre o sistema estomatognático, a tensão muscular foi a mais relatada com 42,6% (75 assertivas). Conclusão: Portanto, pacientes com LCNC apresentaram-se estressados e sujeitos a alterações bucais e sistêmicas.Descritores: Análise do estresse dentário. Dentística Operatória; Odontologia.ReferênciasBartlett DW, Shah PA. Critical review of non-carious cervical (wear) lesions and the role of abfraction, erosion, and abrasion. J Dent Res. 2006;85(4):306-12.Bonfim RA, Crozato E, Mazzilli LEN, Frias AC. Prevalence and risk factors of non-carious cervical lesions related to occupational exporuse to acid mists. Braz oral res. 2015;29(1):1-8.Molena CCL, Rapoport A, Rezende CP, Queiroz CM, Denardin OVP. Relação entre lesões cervicais não cariosas e hábitos. Rev bras cir Cabeça Pescoço. 2008;37(4):206-111.Ribeiro RP, Martins JT, Marziale MHP, Robazzi MLCC. O adoecer pelo trabalho na enfermagem: uma revisão integrativa. Rev esc enferm USP. 2012;46(2):495-504.Sardá JRJJ, Legal EJ, Jablonski Jr S.J. Estresse: conceitos, métodos, medidas e possibilidades de intervenção. São Paulo: Casa do Psicólogo; 2004.Lipp MEN. Mecanismos neuropsicológicos do stress: teoria e aplicações clínicas. São Paulo: Casa do Psicólogo; 2003.Rees JS, Jagger DC. Abfraction lesions: myth or reality? J Esthet Restor Dent. 2003;15(5):263-71.Xhonga FA. Bruxism and its effect on the teeth. J Oral Rehabil. 1977;4(1):65-76.Pedro A, Ribeiro J, Soler G, Bugdan A. Qualidade de vida em mulheres com incontinência urinaria. SMAD. 2011;7(2):63-70.Rigoni ACC, Silva LF, Silva TP, Fernandes BP, Silva CL. Relações entre a educação física escolar, as práticas corporais e a qualidade de vida. Revista CPAQV. 2017;9(1).Amaral SM, Abad EC, Maia KD, Weyne S, Oliveira MPRPB, Tunãs ITC. Lesões não cariosas: o desafio do diagnóstico multidisciplinar. Arq Int Otorrinolaringol. 2012;16(1):96-102.Petti S. Lifestyle risk factors for oral cancer. Oral Oncol. 2009;45(4-5):340-50.Souza MSVB. Revisitando o significado do estresse no contexto das organizações: uma breve revisão teórico-conceitual [monografia]. Brasília: Centro Universitário de Brasília; 2014.Kliemann C. Lesões cervicais não cariosas por abrasão (escovação traumática). J Bras Clin Odontol Integr. 2002;6(33):204-9.Pegoraro LF, Scolaro JM, Conti PC, Telles D, Pegoraro TA. Noncarious cervical lesions in adults. Prevalence and occlusal aspects. J Am Dent Assoc. 2005;136(12):1694-700.Kliemann C. Avaliação da etiologia e prevalência de lesões cervicais não cariosas com o uso de microscopia clínica e questionários em superfícies vestibulares de pré-molares [tese]. São Paulo: Universidade Estadual Paulista; 2001.Silva FML. Lesões cervicais não cariosas: Prevalência, severidade e correlação com fatores etiológicos [dissertação]. Uberlandia: Faculdade de Odontologia de Uberlândia – UFU; 2006.Lee WC, Eakle WS. Possible role of tensile stress in the etiology of cervical erosive lesions of teeth. J Prosthet Dent. 1984;52(3):374-80.Martins RF, Garcia AR, Garbin CAS, Sundefeld MLMM. Associação entre classe econômica e estresse na ocorrência da disfunção temporomandibular. Rev bras epidemiol. 2007;10(2):215-22.Kelsall A, Decalmer S, McGuinness K, Woodcock A, Smith JA. Sex differences and predictors of objective cough frequency in chronic cough. Thorax. 2009;64(5):393-98.Calais SL, Andrade LMBD, Lipp MEN. Diferenças de sexo e escolaridade na manifestação de stress em adultos jovens. 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Mobile In many countries, more people have mobile phones than they do fixed-line phones. Mobile phones are one of the fastest growing technologies ever, outstripping even the internet in many respects. With the advent and widespread deployment of digital systems, mobile phones were used by an estimated 1, 158, 254, 300 people worldwide in 2002 (up from approximately 91 million in 1995), 51. 4% of total telephone subscribers (ITU). One of the reasons for this is mobility itself: the ability for people to talk on the phone wherever they are. The communicative possibilities opened up by mobile phones have produced new uses and new discourses (see Katz and Aakhus; Brown, Green, and Harper; and Plant). Contemporary soundscapes now feature not only voice calls in previously quiet public spaces such as buses or restaurants but also the aural irruptions of customised polyphonic ringtones identifying whose phone is ringing by the tune downloaded. The mobile phone plays an important role in contemporary visual and material culture as fashion item and status symbol. Most tragically one might point to the tableau of people in the twin towers of the World Trade Centre, or aboard a plane about to crash, calling their loved ones to say good-bye (Galvin). By contrast, one can look on at the bathos of Australian cricketer Shane Warne’s predilection for pressing his mobile phone into service to arrange wanted and unwanted assignations while on tour. In this article, I wish to consider another important and so far also under-theorised aspect of mobile phones: text. Of contemporary textual and semiotic systems, mobile text is only a recent addition. Yet it is already produces millions of inscriptions each day, and promises to be of far-reaching significance. Txt Txt msg ws an acidnt. no 1 expcted it. Whn the 1st txt msg ws sent, in 1993 by Nokia eng stdnt Riku Pihkonen, the telcom cpnies thought it ws nt important. SMS – Short Message Service – ws nt considrd a majr pt of GSM. Like mny teks, the *pwr* of txt — indeed, the *pwr* of the fon — wz discvrd by users. In the case of txt mssng, the usrs were the yng or poor in the W and E. (Agar 105) As Jon Agar suggests in Constant Touch, textual communication through mobile phone was an after-thought. Mobile phones use radio waves, operating on a cellular system. The first such mobile service went live in Chicago in December 1978, in Sweden in 1981, in January 1985 in the United Kingdom (Agar), and in the mid-1980s in Australia. Mobile cellular systems allowed efficient sharing of scarce spectrum, improvements in handsets and quality, drawing on advances in science and engineering. In the first instance, technology designers, manufacturers, and mobile phone companies had been preoccupied with transferring telephone capabilities and culture to the mobile phone platform. With the growth in data communications from the 1960s onwards, consideration had been given to data capabilities of mobile phone. One difficulty, however, had been the poor quality and slow transfer rates of data communications over mobile networks, especially with first-generation analogue and early second-generation digital mobile phones. As the internet was widely and wildly adopted in the early to mid-1990s, mobile phone proponents looked at mimicking internet and online data services possibilities on their hand-held devices. What could work on a computer screen, it was thought, could be reinvented in miniature for the mobile phone — and hence much money was invested into the wireless access protocol (or WAP), which spectacularly flopped. The future of mobiles as a material support for text culture was not to lie, at first at least, in aping the world-wide web for the phone. It came from an unexpected direction: cheap, simple letters, spelling out short messages with strange new ellipses. SMS was built into the European Global System for Mobile (GSM) standard as an insignificant, additional capability. A number of telecommunications manufacturers thought so little of the SMS as not to not design or even offer the equipment needed (the servers, for instance) for the distribution of the messages. The character sets were limited, the keyboards small, the typeface displays rudimentary, and there was no acknowledgement that messages were actually received by the recipient. Yet SMS was cheap, and it offered one-to-one, or one-to-many, text communications that could be read at leisure, or more often, immediately. SMS was avidly taken up by young people, forming a new culture of media use. Sending a text message offered a relatively cheap and affordable alternative to the still expensive timed calls of voice mobile. In its early beginnings, mobile text can be seen as a subcultural activity. The text culture featured compressed, cryptic messages, with users devising their own abbreviations and grammar. One of the reasons young people took to texting was a tactic of consolidating and shaping their own shared culture, in distinction from the general culture dominated by their parents and other adults. Mobile texting become involved in a wider reworking of youth culture, involving other new media forms and technologies, and cultural developments (Butcher and Thomas). Another subculture that also was in the vanguard of SMS was the Deaf ‘community’. Though the Alexander Graham Bell, celebrated as the inventor of the telephone, very much had his hearing-impaired wife in mind in devising a new form of communication, Deaf people have been systematically left off the telecommunications network since this time. Deaf people pioneered an earlier form of text communications based on the Baudot standard, used for telex communications. Known as teletypewriter (TTY), or telecommunications device for the Deaf (TDD) in the US, this technology allowed Deaf people to communicate with each other by connecting such devices to the phone network. The addition of a relay service (established in Australia in the mid-1990s after much government resistance) allows Deaf people to communicate with hearing people without TTYs (Goggin & Newell). Connecting TTYs to mobile phones have been a vexed issue, however, because the digital phone network in Australia does not allow compatibility. For this reason, and because of other features, Deaf people have become avid users of SMS (Harper). An especially favoured device in Europe has been the Nokia Communicator, with its hinged keyboard. The move from a ‘restricted’, ‘subcultural’ economy to a ‘general’ economy sees mobile texting become incorporated in the semiotic texture and prosaic practices of everyday life. Many users were already familiar with the new conventions already developed around electronic mail, with shorter, crisper messages sent and received — more conversation-like than other correspondence. Unlike phone calls, email is asynchronous. The sender can respond immediately, and the reply will be received with seconds. However, they can also choose to reply at their leisure. Similarly, for the adept user, SMS offers considerable advantages over voice communications, because it makes textual production mobile. Writing and reading can take place wherever a mobile phone can be turned on: in the street, on the train, in the club, in the lecture theatre, in bed. The body writes differently too. Writing with a pen takes a finger and thumb. Typing on a keyboard requires between two and ten fingers. The mobile phone uses the ‘fifth finger’ — the thumb. Always too early, and too late, to speculate on contemporary culture (Morris), it is worth analyzing the textuality of mobile text. Theorists of media, especially television, have insisted on understanding the specific textual modes of different cultural forms. We are familiar with this imperative, and other methods of making visible and decentring structures of text, and the institutions which animate and frame them (whether author or producer; reader or audience; the cultural expectations encoded in genre; the inscriptions in technology). In formal terms, mobile text can be described as involving elision, great compression, and open-endedness. Its channels of communication physically constrain the composition of a very long single text message. Imagine sending James Joyce’s Finnegan’s Wake in one text message. How long would it take to key in this exemplar of the disintegration of the cultural form of the novel? How long would it take to read? How would one navigate the text? Imagine sending the Courier-Mail or Financial Review newspaper over a series of text messages? The concept of the ‘news’, with all its cultural baggage, is being reconfigured by mobile text — more along the lines of the older technology of the telegraph, perhaps: a few words suffices to signify what is important. Mobile textuality, then, involves a radical fragmentation and unpredictable seriality of text lexia (Barthes). Sometimes a mobile text looks singular: saying ‘yes’ or ‘no’, or sending your name and ID number to obtain your high school or university results. Yet, like a telephone conversation, or any text perhaps, its structure is always predicated upon, and haunted by, the other. Its imagined reader always has a mobile phone too, little time, no fixed address (except that hailed by the network’s radio transmitter), and a finger poised to respond. Mobile text has structure and channels. Yet, like all text, our reading and writing of it reworks those fixities and makes destabilizes our ‘clear’ communication. After all, mobile textuality has a set of new pre-conditions and fragilities. It introduces new sorts of ‘noise’ to signal problems to annoy those theorists cleaving to the Shannon and Weaver linear model of communication; signals often drop out; there is a network confirmation (and message displayed) that text messages have been sent, but no system guarantee that they have been received. Our friend or service provider might text us back, but how do we know that they got our text message? Commodity We are familiar now with the pleasures of mobile text, the smile of alerting a friend to our arrival, celebrating good news, jilting a lover, making a threat, firing a worker, flirting and picking-up. Text culture has a new vector of mobility, invented by its users, but now coveted and commodified by businesses who did not see it coming in the first place. Nimble in its keystrokes, rich in expressivity and cultural invention, but relatively rudimentary in its technical characteristics, mobile text culture has finally registered in the boardrooms of communications companies. Not only is SMS the preferred medium of mobile phone users to keep in touch with each other, SMS has insinuated itself into previously separate communication industries arenas. In 2002-2003 SMS became firmly established in television broadcasting. Finally, interactive television had arrived after many years of prototyping and being heralded. The keenly awaited back-channel for television arrives courtesy not of cable or satellite television, nor an extra fixed-phone line. It’s the mobile phone, stupid! Big Brother was not only a watershed in reality television, but also in convergent media. Less obvious perhaps than supplementary viewing, or biographies, or chat on Big Brother websites around the world was the use of SMS for voting. SMS is now routinely used by mainstream television channels for viewer feedback, contest entry, and program information. As well as its widespread deployment in broadcasting, mobile text culture has been the language of prosaic, everyday transactions. Slipping into a café at Bronte Beach in Sydney, why not pay your parking meter via SMS? You’ll even receive a warning when your time is up. The mobile is becoming the ‘electronic purse’, with SMS providing its syntax and sentences. The belated ingenuity of those fascinated by the economics of mobile text has also coincided with a technological reworking of its possibilities, with new implications for its semiotic possibilities. Multimedia messaging (MMS) has now been deployed, on capable digital phones (an instance of what has been called 2.5 generation [G] digital phones) and third-generation networks. MMS allows images, video, and audio to be communicated. At one level, this sort of capability can be user-generated, as in the popularity of mobiles that take pictures and send these to other users. Television broadcasters are also interested in the capability to send video clips of favourite programs to viewers. Not content with the revenues raised from millions of standard-priced SMS, and now MMS transactions, commercial participants along the value chain are keenly awaiting the deployment of what is called ‘premium rate’ SMS and MMS services. These services will involve the delivery of desirable content via SMS and MMS, and be priced at a premium. Products and services are likely to include: one-to-one textchat; subscription services (content delivered on handset); multi-party text chat (such as chat rooms); adult entertainment services; multi-part messages (such as text communications plus downloads); download of video or ringtones. In August 2003, one text-chat service charged $4.40 for a pair of SMS. Pwr At the end of 2003, we have scarcely registered the textual practices and systems in mobile text, a culture that sprang up in the interstices of telecommunications. It may be urgent that we do think about the stakes here, as SMS is being extended and commodified. There are obvious and serious policy issues in premium rate SMS and MMS services, and questions concerning the political economy in which these are embedded. Yet there are cultural questions too, with intricate ramifications. How do we understand the effects of mobile textuality, rewriting the telephone book for this new cultural form (Ronell). What are the new genres emerging? And what are the implications for cultural practice and policy? Does it matter, for instance, that new MMS and 3rd generation mobile platforms are not being designed or offered with any-to-any capabilities in mind: allowing any user to upload and send multimedia communications to other any. True, as the example of SMS shows, the inventiveness of users is difficult to foresee and predict, and so new forms of mobile text may have all sorts of relationships with content and communication. However, there are worrying signs of these developing mobile circuits being programmed for narrow channels of retail purchase of cultural products rather than open-source, open-architecture, publicly usable nodes of connection. Works Cited Agar, Jon. Constant Touch: A Global History of the Mobile Phone. Cambridge: Icon, 2003. Barthes, Roland. S/Z. Trans. Richard Miller. New York: Hill & Wang, 1974. Brown, Barry, Green, Nicola, and Harper, Richard, eds. Wireless World: Social, Cultural, and Interactional Aspects of the Mobile Age. London: Springer Verlag, 2001. Butcher, Melissa, and Thomas, Mandy, eds. Ingenious: Emerging youth cultures in urban Australia. Melbourne: Pluto, 2003. Galvin, Michael. ‘September 11 and the Logistics of Communication.’ Continuum: Journal of Media and Cultural Studies 17.3 (2003): 303-13. Goggin, Gerard, and Newell, Christopher. Digital Disability: The Social Construction of Digital in New Media. Lanham, MA: Rowman & Littlefield, 2003. Harper, Phil. ‘Networking the Deaf Nation.’ Australian Journal of Communication 30. 3 (2003), in press. International Telecommunications Union (ITU). ‘Mobile Cellular, subscribers per 100 people.’ World Telecommunication Indicators <http://www.itu.int/ITU-D/ict/statistics/> accessed 13 October 2003. Katz, James E., and Aakhus, Mark, eds. Perpetual Contact: Mobile Communication, Private Talk, Public Performance. Cambridge: Cambridge U P, 2002. Morris, Meaghan. Too Soon, Too Late: History in Popular Culture. Bloomington and Indianapolis: U of Indiana P, 1998. Plant, Sadie. On the Mobile: The Effects of Mobile Telephones on Social and Individual Life. < http://www.motorola.com/mot/documents/0,1028,296,00.pdf> accessed 5 October 2003. Ronell, Avital. The Telephone Book: Technology—schizophrenia—electric speech. Lincoln: U of Nebraska P, 1989. Citation reference for this article MLA Style Goggin, Gerard. "‘mobile text’" M/C: A Journal of Media and Culture <http://www.media-culture.org.au/0401/03-goggin.php>. APA Style Goggin, G. (2004, Jan 12). ‘mobile text’. M/C: A Journal of Media and Culture, 7, <http://www.media-culture.org.au/0401/03-goggin.php>

Introduction "Barbie has a great day every day, but Ken only has a great day if Barbie looks at him", states the narrator in Barbie (2023). Directed by Greta Gerwig, the film not only claimed the title of the highest-grossing film of the year but also prompted its audience to reconsider a character they had previously mostly overlooked; another one of Barbie’s many accessories: Ken. Ken's identity as Barbie's companion is fundamentally dependent upon the presence and recognition of his more prominent female counterpart. This highlights Ken's secondary role, where he serves as a supporting figure to Barbie's idealised existence. Akin to a Manic Pixie Dream Boy (MPDB) overshadowed by Barbie, we realise Ken’s lack of identity. Throughout the film, Ken, initially depicted as identity-less, embarks on a journey of self-discovery, challenging the confines imposed by white patriarchy, although it doesn’t seem that way at first. This article will first establish Ken's MPDB status, highlighting traits such as (a) seeking to elevate and challenge the main character’s beliefs, (b) harbouring both gentleness and deviousness, while also engaging in playful yet mildly destructive mischief, (c) acting as a catalyst for change, (d) exhibiting a desire to escape, disappear, or transform, leaving valuable lessons behind, and (e) existing solely within the perception of or for the benefit of the main character. Subsequently, it will follow his journey, ultimately examining how a humanoid doll undergoes healing particularly concerning gender issues. Through the deconstruction of his narrative, this article aims to uncover the underlying power dynamics at play and to explore how Ken's transformation contributes to broader conversations surrounding gender fluidity and representation. By doing so, the article will provide an understanding of Ken's role and contribution to the feminist cause, while also offering insights into the broader cultural significance of the film. Manic Pixie Dream Girl In contemporary discourse, the term MPDGirl has gained recognition following its coinage by Nathan Rabin: “that bubbly, shallow, cinematic creature that exists solely in the fevered imaginations of sensitive writer-directors to teach broodingly soulful young men to embrace life and its infinite mysteries and adventures” (Rabin, "The Bataan"). It rapidly gained eminence within popular culture, precipitating a widespread societal fixation on the quest for mining more MPDGs, up to the point where Rabin himself voiced his regret about coining the term ("I’m Sorry"). However, the MPDG was already a presence among us. As Laurie Penny states in the article "I Was a Manic Pixie Dream Girl", “Like scabies and syphilis, Manic Pixie Dream Girls were with us long before they were accurately named”. Additionally, Gouck contends that “the Pixie is a descendant of the Classical Muse and also has roots in the Pygmalion myth” (527). Thus, tracing from these foundational mythical and ancient iterations to contemporary relatives such as the Earnest Elfin Dream Gay (EEDG) and the “Magical Negro”, popularised by Spike Lee, reveals a diverse family tree. Although various writers for online platforms have declared the demise of the MPDG (Eby; Harris; Stoeffel), the trope constantly found ways to revive itself. Harris, in her 2012 article "Is the Manic Pixie Dream Girl Dead?", claimed that the trope has been turned on its head with later iterations like Ruby Sparks, “depicting a writer (Paul Dano) whose idealistic, winsome female character comes to life and challenges patriarchal notions of what women actually want”. Tannenbaum, on the other hand, suggested that the MPDG isn’t dead but just evolved through a loophole: the tragic backstory. This article contends that as long as a concept remains in circulation, it cannot die. Thus, even this article itself contributes to the preservation of the phenomenon in question. Manic Pixie Dream Boy In 2012, Molly Lambert introduced a notable extension of the MPDG archetype: the MPDB. Lambert described the MPDB as a character who uplifts the heroine's self-confidence through comfort, inspiration, and nurturing support, without expecting anything in return. He … tamps down her … temper while appreciating her quirks … . He’s a nerd, but not an angry … one. He’s handsome, but he has no idea … . His … hobbies might be immature … but it doesn’t extend to his emotions … . He’s a selfless, responsible Peter Pan. (Lambert) The likening of the MPDB to a selfless and responsible Peter Pan is flawed. One of the main reasons that make Peter Pan Peter Pan is that he doesn’t want to become an adult and be burdened with responsibilities. Additionally, the notion of the MPDB wanting nothing in return is flawed, as the MPDB's actions are usually driven by a fixation obsession rather than genuine altruism. Consequently, rather than epitomising selflessness, the MPDB defined by Lambert aligns more closely with an idealised EveryWoman’sDreamBoy archetype. In 2015, Anna Breslaw introduced another definition, labelling the MPDB as a “self-mythologizing ‘free-spirited’ dude”; however, it still remains unclear and unsatisfactory. Since its inception, there has been a fundamental misunderstanding of the concept of the MPDB. Originally rooted in a female-centric trope, it requires careful interpretation. When the definitions of the MPDB are applied as previously stated, it effectively transforms into an archetype that conventionally represents many women's ideal. However, unlike the MPDG, who is characterised by her eccentricity, the previous definitions of the MPDB reject this norm. Drawing inspiration from figures such as Peter Pan, Puck, King Kong, the Amphibian Man, the Beast, and Edward Scissorhands, the MPDB embodies a blend of comfort and chaos. This dichotomy is exemplified in Ken, who fulfills the role of comfort and chaos for Barbie, yet finds himself unwanted and unneeded. The real MPDB is defined by five core features that distinguish it from the misinterpreted notion often associated with the trope. a) The MPDB seeks to elevate and challenge the main character’s beliefs: Ken consistently tries to alter Barbie’s perceptions, as evidenced by his persistent attempts to reshape her opinion of him beyond superficial interests. This is exemplified by his pursuits beyond conventional activities, such as his daring act of running into the plastic waves, a seemingly unprecedented action that surprises, shocks, or scares those around him. b) The MPDB harbours both gentleness and deviousness, while engaging in playful yet mildly destructive mischief: Ken exhibits a dual nature, demonstrating kindness and charm towards Barbie while simultaneously harbouring ulterior motives, including a deep-seated desire to become Barbie's romantic partner. This complexity in character can be likened to the “nice guy syndrome”, where benevolent actions may mask underlying intentions. Furthermore, upon his return to build patriarchy, this desire is accentuated, showcasing his multilayered personality. c) The MPDB acts as a catalyst for change: Ken serves as an important force in instigating transformation, as demonstrated by the significant shifts that occur in both Barbieland and Barbie's life due to Ken's presence. His actions challenge Barbie's beliefs, whether intentionally or inadvertently, leading her to perceive new perspectives and undergo personal growth. d) The MPDB exhibits a desire to escape, disappear, or transform, leaving valuable lessons behind: Throughout Ken's MPDB journey, his inclination towards escapism, disappearance, or transformation becomes evident. While his initial desire to accompany Barbie may stem from romantic aspirations, it is also fuelled by the rivalry among the Kens. Once Ken realises there is more than Barbieland and he can want different things, he expresses his desire for change. As Ken evolves and heals, he undergoes a transformation, ultimately becoming a changed entity, yet leaving behind significant lessons that pave the way for the transformation of Barbieland and Barbie. e) The MPDB exists solely within the perception of or for the benefit of the main character: Ken’s presence is exclusively crafted within the perspective of, or to serve the needs of, the main character. According to a 2017 GQ article, Michael Shore, the head of Mattel's global consumer insights at the time, states that, “Ken was really viewed as more of an accessory in Barbie’s world, to support the narrative of whatever was happening with the girls” (qtd. in Weaver). This perspective reinforces Ken's role as arm candy within Barbie's world, serving as a complement to her endeavors at a ratio of about 1:7 (Weaver). This aspect highlights the trope's function as a narrative construct intended to support and shape the protagonist's storyline and growth. The MPDB Ken Ken (Ryan Gosling) makes his debut appearance in the Barbie movie at the eight-minute mark. While the narrative primarily revolves around Barbie, Ken's introduction is a subtle but significant moment. As Barbieland unfolds before us, Ken's delayed entrance, as another inhabitant of Barbieland, draws attention. Barbie is everywhere, but where is Ken? Amidst the cheerful exchanges of “Hi Barbie, Hi Ken”, Ken's behavior stands out—he doesn't reciprocate the greeting with other Kens, he only greets Barbie. Ken's omission from acknowledging his fellow Kens seems like a deliberate choice—a denial of their existence, perhaps suggesting that he perceives himself as the sole Ken of significance in Barbieland. His exclusive greeting to Barbie highlights this notion; in his world, Barbie is paramount, and other Kens are unimportant in comparison. We understand that there is a rivalry going on between the Kens; there is no Kenship, mainly between Ken (Gosling) and Ken (Simu Liu). The same evening at the party, while all the Barbies wear complementary yet distinct clothes, the Kens are dressed uniformly in identical outfits. This lack of individuality strips them of identity, claims Roche, “it is a training, an element in the education of controlled individual power ... designed to shape the physique … of [an] individual” (228-9). Uniforms shape individuality into collectivity and thus cause a lack of identity. The white and gold motifs on Kens’ jumpsuits may symbolise collectivity. They are a team; they are minds that have never been shaped before, they are accessories. The 'K' emblem on their jackets further emphasises their lack of identity. Costume designer Jacqueline Durran “imagined Gosling’s character as ‘almost like an accessory’ where his main function is to just be there and match her look. The Kens could all be dressed the same because there wasn’t meant to be anything distinct about them” (Zemler, "Dressing Barbie"). This point is even more highlighted in a scene where Barbie and Ken are in the car going to the real world, where Ken has another jumpsuit that is covered with the letter “B”. In the absence of the other Kens he is even more of an accessory, and even wearing something with his initials is denied, he is Barbie’s property. Contact with Patriarchy Barbie and Ken enter the real world, and interestingly, while throughout the travel sequence, Barbie is in front of Ken, leading Ken, in the shot where they enter the real world, Ken is in front of Barbie. Ken, for the first time alone, somehow ends up at Century City: “it is the antithesis of Barbieland”, says Greenwood, “there is an homage to the male construction industry and the male gaze” (Zemler, "On Location"). Men who are passing him say “excuse me, sir, thanks man, what’s up bud”. This new world that he encounters in Century City is giving him an identity. For the first time, he is something more than an unwanted MPDB. He is sir, he is man, he is bud. Since the Kens exist as a second-class species whose sole purpose is to cheer the Barbies on, he cannot comprehend his actual yearning, he thinks common decency (someone saying excuse me) is what patriarchy is. A fish out of water, the manic pixie Ken creates a pastiche of everything he encounters to assume this new identity: male presidents, mini-fridges, golf, a fur coat, and even horses. His first interaction with horses is through two police officers riding horses. Believing that horses are an important part of patriarchy, Ken wearing a cowboy outfit too, internalises the bond between horse and man. Pickel-Chavelier, in a study about horse stories, states that “the horse has been a fundamental element in the evolution of Western civilization” (120). Robinson argues that historically “the human-horse relationship was male-dominated, reflecting the horses’ role as a work tool and the traditional placing of power and power sources under the control of men” (44). Thus, the rider has been considered to have “increased power and an increased sense of power” while evoking “a sense of inferiority and envy” in pedestrians (Robinson 43). Studying the human-horse relationship through the American mounted police, Lawrence claimed that the mounted police have close relationships with their horses. Robinson states that “the officers spend much time with their animals each day and develop a sense of trust” (43). Ken's admiration of horses likely symbolises his evolving understanding of masculinity and power dynamics within patriarchy. Being introduced to horses as symbols of authority and control, he understands them as companions embodying strength, loyalty, and trust. This explains how he understands masculinity as a realm where power is defined by mutual respect and partnership, rather than dominance, which is also probably the reason why he loses interest in patriarchy when he realises it’s not about horses. Nicholas, in their article "Ken’s Rights?", claims that “radicalization … is often motivated by feelings among … men of being left behind by a feminist world or system that doesn’t value them. This then leads them to long for an imagined natural order of patriarchy where women are back in their place and men regain their entitlements”. Ken’s frustration leads him to introduce patriarchy to his fellow Kens, envisioning a transformation of Barbieland into a new Century City. This shift reflects Ken’s Manic Pixie healing journey: rather than being solely an MPDB, Ken slowly constructs an identity under patriarchy for himself. Drawing from Connell's perspective on hegemonic masculinity, which posits that masculinity is always constructed in response to subordinated masculinities, we see how Ken's desire for change extends to altering the very fabric of Barbieland, from its constitution to its name, renaming it Kendom. This name change holds significance, echoing the concept of “Inceldom” within the larger misogynist ecosystem of the Manosphere, where men perceive themselves as deprived of love and intimacy due to feminist ideals. In addition to incels, the ‘Manosphere’ is comprised of Men’s Right Activists, Men Going Their Own Way (MGTOW), AND Pick-Up Artists (PUAs). Each of these groups subscribe to the same underlying philosophy, referred to as the ‘red pill’… When an individual has ‘taken the red pill’, they have enlightened themselves to a reality in which women wield feminism as a weapon against men, depriving them of sex and love. (Gothard et al. 1) Ken’s new outfit is another important change. As patriarchy leaks into Barbieland, Ken's outfit begins to reflect iconic images of masculinity, such as Sylvester Stallone in a mink coat. Previously, Ken's clothing complemented Barbie's, but now, his fanny pack displays his full name instead of just the letter K, positioned over his non-existent genitalia. This deliberate placement implies a newfound connection between his new identity and his imagined sex. When discontent Barbies strategise to disrupt the new order, they manipulate Kens' fragile egos, inciting conflict just before the crucial constitution vote. The fighting sequence starts with Ryan Gosling’s "I'm just Ken" song and imagery reminiscent of Rodin's iconic statue “The Thinker”. The Rodin Museum describes the figure as “a being with a tortured body, almost a damned soul, and a free-thinking man, determined to transcend his suffering through poetry”, mirroring Ken's current state of turmoil. In Rodin’s lifetime, there were “many marble and bronze editions in several sizes” that have been executed (Zelazko). Similarly, there are countless iterations of Ken, undermining his belief in his uniqueness. The general anticipation of the statue being impressive but then feeling let down when seeing its real size serves as a poignant metaphor for Ken's inflated self-importance, contrasted with his inherent fragility and insignificance. As the chorus “I’m just Ken” starts, Ken (Gosling) rides into the battle “on paddle boats reminiscent of cannon-loaded ships, while [Ken (Liu)]’s crew carries him over their shoulders, spinning umbrellas like wheels and holding stick horses as if they were human chariots” (Lee), having frisbees, tennis rackets, and other sports equipment in their hands. This imagery not only captivates the audience but also serves as a reflection of the sports and war imagery in media representations of men. The notion of hegemonic masculinity is intricately woven into such depictions. Jansen and Sabo point out “that the sport/war metaphor is embedded within a “deep structure” of patriarchal values, beliefs, and power relations that, in turn, reflect and advance the agendas of hegemonic masculinity” (2). This metaphor not only reflects but also advances the agendas of hegemonic masculinity. By glorifying competition and valorising traits associated with aggression and dominance, media representations perpetuate narrow and rigid norms of masculinity, reinforcing the hierarchical gender dynamics prevalent in society. However, through playful exploration of these notions, Barbie introduces a significant step in the healing journey of MPDBs, all while cleverly critiquing the inherent associations society makes between masculinity, competitive sports, and even aspects of warfare. Kenough As Ken continues his performance, seamlessly transitioning from a part-power ballad, part-battle sequence into a dream ballet, the narrative takes a profound turn. Connell's concept of “gender order”, referring to “a historically constructed pattern of power relations between men and women and definitions of femininity and masculinity” that emerge and are transformed within varying institutional contexts (98-99), becomes particularly relevant when applied to dancing, seen as an institutional context. Silvester, discussing how gender dynamics within dancing evolved, notes that in the 60s, with the twist and later with disco dancing, dancers did not have to have partners any more, which made the “presumptions about the effeminacy of professional male dancers” widespread (qtd. in Owen 18). Because in performance culture female dancers were the objects of desire for usually male spectators, dancing found itself a place inside the borders of femininity, “and homophobic prejudices against male dancers grew” (Owen 18). Initially, at the party, dancing symbolises their confinement to their identities as Barbie’s accessory, and later it serves as a catalyst for shedding the performative shackles of masculinity and patriarchy. Through dance, MPDB Ken embraces authenticity, breaking down the barriers of the embarrassment of showing admiration to his fellow Kens and fostering genuine connection and affection. The Kens help each other up, they giggle, and they kiss each other on the cheek; they are no longer threatened by each other or by showing affection. As the battle sequence comes to an end, one Ken acknowledges that they were only fighting because they didn’t know who they were. What initially began as a melodramatic expression of the insecurities of an incel, angry at his object of affection, transforms into a collective affirmation of self-worth, fostering unity and acceptance among the Kens. Lee aptly describes this transformation as an elevation from internal conflict to self-affirming validation, marking a pivotal shift away from self-destructive behaviours towards mutual respect and understanding. Ken finally has an identity that is not defined through Barbie’s gaze or patriarchal vision of masculinity. He is not an MPDB that only exists for the protagonist anymore. He finds an identity; however, one he does not know how to express. Connell and Messerschmidt state that “men can adopt hegemonic masculinity when it is desirable; but the same men can distance themselves strategically from hegemonic masculinity at other moments. Consequently, ‘masculinity’ represents not a certain type of man but, rather, a way that men position themselves through discursive practices” (841). Ken still does not abandon what he has found in the real world. Knowing he has been defeated he tries to “strategically” reposition himself. Like a toddler having a temper tantrum, he runs to his mojo dojo casa house, throws himself on his bed, and starts crying, while Barbie tries to comfort him. Myisha et al. suggest that Barbie, as a woman, again is cast in the role of nurturer and comforter, and thus the movie finds itself repeating gender stereotypes. However, missing the point that Ken is crying in this scene, these criticisms are themselves reinforcing gender stereotypes by mistaking common decency for an intrinsic association with women. Ken later denounces patriarchy and learns from Barbie not to define himself by his possessions, his relationship, or his job. Embracing his individuality, he declares, “I'm Ken, and I'm Kenough”, going down the slide, symbolizing a rebirth. In his final shot, Ken is seen with a sweatshirt proclaiming “I’m Kenough”. In embracing his past identities through the bandana and the color pink, he constructs a new identity, one that welcomes all colors. bell hooks defines feminism as “the struggle to end sexist oppression” for all women without “[privileging] women over men” (26). Greta Gerwig, in an interview with Time, acknowledges the struggles faced by both men and women throughout history, highlighting the universal pressure to meet unrealistic standards (Carlin). This suggests that while women face specific forms of oppression, men too are ensnared by other rigid societal norms, if not the same. By recognising these challenges, feminism advocates for the involvement of men in the movement. Whether it is standing in solidarity with women or confronting their own biases, men play a pivotal role in advancing gender equality. For feminism to thrive, it necessitates men's active participation, urging them to support women's rights and challenge patriarchal structures while remaining open to introspection and growth. Feminism has consistently aimed to dismantle the rigid gender binaries epitomised by the Barbie/Ken dichotomy, advocating for the separation of attributes from their gendered associations. From Barbie, we can glean the lesson that hierarchical and inflexible gender norms benefit no one and that power and social roles should not be determined by one's biological sex. Nicholas, in their article "Ken’s Rights?", claims that online antifeminist discourses reveal parallels between Ken's journey in the movie and themes found in Men’s Rights Activist spaces. Ken's transition from aggrievement to a more enlightened perspective on masculinity mirrors the narratives prevalent in such spaces. This underscores the importance of understanding and addressing men within the context of feminism, as their experiences are intertwined with broader societal structures and expectations. True progress cannot be achieved if we continue to view those who perpetuate patriarchy or toxic masculinity as “others”. We should see them as humanoid Ken dolls, and in doing so help them to help us trigger answers and solutions. Understanding and addressing these issues is crucial for healing and reducing harm inflicted by patriarchal norms. While Barbie may have its flaws, focussing solely on its shortcomings detracts from the opportunity to address deeper issues regarding society. MPDB Ken's portrayal as a subservient accessory to Barbie raises important questions about gender dynamics and the impact of societal expectations on individuals. Rather than vilifying Ken because he brought patriarchy to Barbieland, and reducing him only to a man, I advocate for understanding his journey and recognising him also as a brainwashed character, alongside the brainwashed Barbies, who needed the help of his friends to heal. By acknowledging and addressing the influence of patriarchal norms on all individuals, including men like Ken, we can work towards healing and progress for all. References Barbie. Dir. G. Gerwig. Warner Bros. Pictures, 2023. Breslaw, Anna. “Beware the Manic Pixie Dream Boyfriend.” The Cut, 13 Sep. 2015. <https://www.thecut.com/2015/09/beware-the-manic-pixie-dream-boyfriend.html>. Carlin, Shannon. “The History Behind Barbie’s Ken.” Time, 20 Jul. 2023. <https://time.com/6296386/barbie-ken-history/>. Connell, Raewyn. "The Social Organization of Masculinity." Feminist Theory Reader. Routledge, 2020. 192-200. ———. Gender and Power Cambridge. Polity, 1987. Connell, Raewyn, and James W. Messerschmidt. 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