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Aberrant gene expression patterns in acute myeloid leukemia (AML) with balanced chromosomal translocations are often associated with dysregulation of epigenetic modifiers. The AML1/ETO (RUNX1/MTG8) fusion protein, caused by the translocation (8;21)(q22;q22), leads to the epigenetic repression of its target genes. We aimed in this work to identify critical epigenetic modifiers, on which AML1/ETO-positive AML cells depend on for proliferation and survival using shRNA library screens and global transcriptomics approaches. Using shRNA library screens, we identified 41 commonly depleted genes in two AML1/ETO-positive cell lines Kasumi-1 and SKNO-1. We validated, genetically and pharmacologically, DNMT1 and ATR using several AML1/ETO-positive and negative cell lines. We also demonstrated in vivo differentiation of myeloblasts after treatment with the DNMT1 inhibitor decitabine in a patient with an AML1/ETO-positive AML. Bioinformatic analysis of global transcriptomics after AML1/ETO induction in 9/14/18-U937 cells identified 973 differentially expressed genes (DEGs). Three genes (PARP2, PRKCD, and SMARCA4) were both downregulated after AML1/ETO induction, and identified in shRNA screens. In conclusion, using unbiased shRNA library screens and global transcriptomics, we have identified several driver epigenetic regulators for proliferation in AML1/ETO-positive AML. DNMT1 and ATR were validated and are susceptible to pharmacological inhibition by small molecules showing promising preclinical and clinical efficacy.
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There is growing evidence suggesting an increased perception of control is associated with reduced psychological distress among survivors of sexual trauma. The current study advances the extant literature by investigating the association between depressive symptoms, sexual trauma, and an external locus of control or the perception life events are outside one's own control. To do so, we analyze data from the New Family Structures Study, a nationally representative survey of U.S. adults ages 18-39. Results from ordinary least square regression analyses suggest sexual trauma and an external locus of control are associated with significantly greater depressive symptoms and that external control exacerbates the association between sexual trauma and depression. Such findings suggest future research should investigate environmental control for sexual trauma survivors in areas such as prenatal care and the justice system.
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Depresión , Control Interno-Externo , Trauma Sexual , Humanos , Femenino , Adulto , Masculino , Adulto Joven , Adolescente , Estados Unidos , Sobrevivientes/psicología , Encuestas y CuestionariosRESUMEN
PURPOSE: Since Hawaii has the highest rate of per capita of persons experiencing homelessness (PEH) in the United States, the purpose of this qualitative evaluation study was to evaluate the experiences of both the providers and clients of a Street Medicine (SM) program serving one side of the island of O'ahu. METHOD: This evaluation used Story Inquiry to qualitatively assess one SM program serving one side of the island of O'ahu in Hawa'i. Since the culture in Hawaii is largely based upon stories, a qualitative approach was taken to better understand the lived experiences of PEH who utilized the SM services, as well as provider perspectives. RESULTS: The findings of this evaluation include strengths of increased primary care engagement and improved quality of life for PEH; barriers to success included transportation scarcity and limitations of services available. CONCLUSIONS: The findings lend implications for new SM programs, including gathering community support, having culturally aware outreach and that mobility and flexibility can overcome health-care barriers for PEH.
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Personas con Mala Vivienda , Calidad de Vida , Humanos , Estados Unidos , Hawaii , Investigación Cualitativa , Problemas SocialesRESUMEN
Elderly patients with AML ineligible for induction have a dismal prognosis; hence disease stabilization is a primary treatment goal. This case of a 75-year-old patient with secondary AML receiving the combination of decitabine and ATRA (within the DECIDER trial, NCT00867672) demonstrates an above-average survival. The therapy administered over 52 cycles led to complete molecular and hematological remission and resulted in 5.3 years overall survival. Clonal evolution of the leukemic clone could be demonstrated using DNA sequencing methods. According to the literature, this case constitutes the longest continued HMA exposure in an elderly AML patient ineligible for standard chemotherapy.
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Leucemia Mieloide Aguda , Tretinoina , Humanos , Anciano , Decitabina/farmacología , Decitabina/uso terapéutico , Tretinoina/farmacología , Tretinoina/uso terapéutico , Metilación de ADN , Pronóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: American Indian/Alaskan Native (AI/AN) women disproportionally experience postpartum depression in the United States as compared to the rest of the population. Despite being disproportionately represented, the current body of knowledge lacks research on depression in this particular population. Specifically, the current literature lacks research pertaining to the experiences of postpartum AI/AN women, their culture, birthing and mothering expectations, and trauma. This qualitative study used the theories of becoming a mother, historical-trauma framework, and reproductive justice as they relate to Indigenous women's personal and historical trauma to assess their lived experiences of becoming a mother. METHODS: Keetoowah mothers (N = 8) were interviewed by using a story inquiry method to understand the perinatal experiences of members of one Indigenous tribe in the US. FINDINGS: The story inquiry coding resulted in two main themes, namely maternal mental health challenges and inadequacies of perinatal care. CONCLUSION: The subthemes illuminate the intersection of historical trauma and the perinatal experience, continued colonization of mothering, and the resilience of tribal culture during the postpartum period. Implications include advocacy for increasing culturally derived perinatal interventions, increased healthcare coverage of culturally appropriate birthing practices, and future research evaluating the correlation between historical trauma and maternal mental health challenges.
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Depresión Posparto , Trauma Histórico , Femenino , Humanos , Madres/psicología , Periodo Posparto/psicología , Embarazo , Investigación Cualitativa , Estados Unidos , Indio Americano o Nativo de AlaskaRESUMEN
OBJECTIVES: ⢠To describe a novel method of split-skin graft (SSG) fixation for neo-glans formation after distal penectomy for penile cancer and glans resurfacing for carcinoma in situ or lichen sclerosus (LS); the TODGA technique. ⢠Rather than 'quilting' the graft onto the neo-glans, which requires up to 5 days bed rest, the tie-over method fixes the graft adequately enough to allow immediate patient mobilization. PATIENTS AND METHODS: ⢠In all, 41 consecutive operations, with a follow-up of ≥ 12 months, were performed on 40 patients (mean age 62 years, range 32-83) from December 2000 to October 2008, where a SSG was applied to the raw glans or penile stump. ⢠The protocol varied for the first 12 operations on 11 patients. The tie-over dressing was left in place for 6 (one patient) or 7 days (11) and various materials were used; paraffin gauze (one), expanded foam (five) and proflavine-soaked gauze (six). The first two patients had their dressing removed under general anaesthetic but all subsequent patients had their dressing removed on the ward. ⢠The subsequent 29 operations used the same protocol where a proflavine-soaked gauze dressing was left undisturbed for 10 days. RESULTS: ⢠In the original 11 patients, two required re-grafting. After this initial development period, we amended the technique to use stronger sutures and left the dressing undisturbed for 10 days. ⢠In addition, we standardized the use of proflavin-soaked gauze, as we found it easy to apply and remove. Since we adopted this protocol, we have performed 29 operations over a 3-year period. ⢠The cosmetic results were excellent with only one patient requiring re-grafting. The mean and median postoperative length of stay was 2 days. ⢠One patient with a urethral squamous cell carcinoma associated with urethral and glans LS required a urethral dilatation to allow a check cystoscopy, and a further asymptomatic patient had a meatal dilatation in the clinic but meatal stenosis was otherwise not seen, with no patients requiring regular meatal dilatation. CONCLUSION: ⢠The TODGA technique of SSG application and fixation allows immediate mobilization and reduces hospital stay whilst providing excellent cosmetic results with a high percentage of graft uptake.
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Enfermedades del Pene/cirugía , Pene/cirugía , Procedimientos de Cirugía Plástica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Vendajes , Ambulación Precoz , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Piel , Técnicas de Sutura , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos Masculinos/métodosRESUMEN
OBJECTIVE: To investigate the perceived risks and benefits that elite athletes associate with illicit drugs and their beliefs concerning the effects of recreational drug use on athletic performance. DESIGN: Self-administered survey. PARTICIPANTS: Nine hundred seventy-four elite athletes (mean age, 23 years; range, 18-30 years) were recruited from 8 national sporting organizations in Australia and the Australian Institute of Sport. INTERVENTIONS: Participants completed a self-administered survey that included questions exploring participants' perceptions regarding the effects of illicit drug use on physical performance. SETTING: National sporting organization meetings or competitions. MAIN OUTCOME MEASURES: The main outcome measure was risk perception on athletic performance associated with illicit drug use. RESULTS: The majority of athletes believed that illicit drug use would impact negatively on athletic performance. The main perceived effects of illicit drugs on athletic performance were physical and mental functioning. A minority of athletes indicated that drug use would not impact on physical performance when taken during the off-season or in moderation. CONCLUSIONS: The main risks perceived in association with illicit drug use were short-term consequences, such as physical and mental functioning, rather than long-term health consequences. The current findings may contribute to the development of harm reduction strategies that communicate drug-related consequences to elite athletes in an appropriate and effective manner.
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Atletas/psicología , Rendimiento Atlético/fisiología , Drogas Ilícitas , Medición de Riesgo , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Actitud , Australia , Recolección de Datos , Humanos , Adulto JovenRESUMEN
This study evaluates microdochectomy as a means for diagnosis and treatment of patients with pathological nipple discharge (PND) but with benign or normal imaging and cytology. From 1999 until 2006, in St. Mary's Hospital, 76 patients with the aforementioned condition underwent microdochectomy because of the presence of epithelial cells on nipple smear or for symptomatic relief. Most of the patients had intraductal papillomas (48.7%), duct ectasia (15.8%) or a combination of the two (13.2%). Other benign causes occurred in 11.8% of the patients. Eight patients, including one who was operated for symptomatic relief, had cancer. Of those patients with benign condition, 98% had symptomatic relief while PND recurred twice in one patient. Pre-operative workup and imaging may not be suspicious in patients with single-duct PND and underlying malignancy, therefore, microdochectomy should be considered in such cases.
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Enfermedades de la Mama/cirugía , Neoplasias de la Mama/cirugía , Exudados y Transudados , Glándulas Mamarias Humanas/cirugía , Pezones/metabolismo , Pezones/cirugía , Adulto , Anciano , Enfermedades de la Mama/diagnóstico , Neoplasias de la Mama/diagnóstico , Dilatación Patológica , Femenino , Humanos , Persona de Mediana Edad , Pezones/patologíaRESUMEN
We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging.
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Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Cálculos Renales/tratamiento farmacológico , Adulto , Infecciones por Escherichia coli/diagnóstico por imagen , Humanos , Cálculos Renales/diagnóstico por imagen , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Much of the literature investigating the relationship between sports participation and substance use has focused upon student populations, with little focus being given to athletes who participate at elite levels. Identifying why some athletes may be at a greater risk for substance use can help in the design and implementation of prevention initiatives. Data for the current study was from 1684 self-complete surveys with elite Australian athletes. Eight percent (n=134) of the sample reported the use of at least one of the six illicit drugs under investigation (ecstasy, cannabis, cocaine, meth/amphetamine, ketamine and GHB) in the past year. Having been offered or having had the opportunity to use illicit drugs in the past year, knowing other athletes who use drugs and identifying as a 'full-time athlete' were significant predictors of past-year illicit drug use, while having completed secondary education or a post-school qualification was associated with a lower likelihood of past-year illicit drug use. Athletes are part of a sportsnet that includes family, coaches, support staff and other athletes, and these relationships may encourage the use, supply and demand for drugs. The current findings suggest that relationships with some of those in the sportsnet may play an important role when understanding illicit drug use among elite athletes. As education appears to be associated with a lower likelihood of illicit drug use among this group, initiatives should encourage athletes to engage in off-field pursuits which may also help prepare them for life after sport.
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Atletas/psicología , Drogas Ilícitas , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Atletas/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Riesgo , Autoinforme , Distribución por Sexo , Factores Sexuales , Factores Socioeconómicos , Deportes , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION AND AIMS: The false consensus effect (FCE) is the tendency for people to assume that others share their attitudes and behaviours to a greater extent than they actually do. The FCE has been demonstrated for a range of health behaviours, including substance use. The study aimed to explore the relationship between elite athlete's engagement in recreational drug use and their consensus estimates (the FCE) and to determine whether those who engage in the behaviour overestimate the use of others around them. DESIGN AND METHOD: The FCE was investigated among 974 elite Australian athletes who were classified according to their drug use history. RESULTS: Participants tended to report that there was a higher prevalence of drug use among athletes in general compared with athletes in their sport, and these estimates appeared to be influenced by participants' drug use history. While overestimation of drug use by participants was not common, this overestimation also appeared to be influenced by athletes' drug use history. DISCUSSION AND CONCLUSIONS: The results suggest that athletes who have a history of illicit drug use overestimate the prevalence of drug use among athletes. These findings may be helpful in the formulation of normative education initiatives.
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Atletas/psicología , Percepción Social , Deportes/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Atletas/estadística & datos numéricos , Australia/epidemiología , Recolección de Datos , Femenino , Humanos , Masculino , Grupo Paritario , Prevalencia , Trastornos Relacionados con Sustancias/psicología , Adulto JovenRESUMEN
OBJECTIVE: Many sporting organisations in Australia conduct drug information seminars for their athletes; however, it is uncertain whether these programs provide athletes with pertinent drug information in formats that are conducive to information retention. The aims of the current study were to investigate self-reported confidence in knowledge of illicit drugs and information seeking behaviours among elite athletes. METHODS: Data were collected from two sources: (1) quantitative surveys with elite Australian athletes; and (2) qualitative interviews with key experts who come into contact with elite athletes. RESULTS: Athletes were confident in their knowledge of the effects of illicit drugs such as cannabis and meth/amphetamine, but less confident in their knowledge of the effects of illicit drugs such as GHB and ketamine. A substantial proportion felt that athletes in their sport would benefit from more information concerning illicit drugs. CONCLUSIONS: Both athletes and key expert believed that information on illicit drugs should be delivered to athletes in a specific and relevant manner. There may be stigma attached to information seeking within a sports club or organisation. Accordingly, improving the accessibility to creditable information via the Internet may prove to be an effective means by which to educate athletes on the effects of illicit drugs.
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Atletas/psicología , Conocimientos, Actitudes y Práctica en Salud , Drogas Ilícitas , Atletas/estadística & datos numéricos , Educación en Salud , Encuestas Epidemiológicas , Humanos , Deportes , Trastornos Relacionados con Sustancias/prevención & control , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
INTRODUCTION AND AIMS: The study aimed to investigate the prevalence of illicit drug use among elite Australian athletes with a focus upon cannabis, ecstasy, meth/amphetamine, cocaine, GHB and ketamine; explore perceptions concerning the extent of drug use among this group; ascertain opinions regarding specific drugs of concern; and investigate predictors of recent drug use. DESIGN AND METHODS: Data were taken from surveys with 974 elite athletes. RESULTS: One-third of the sample had been offered or had the opportunity to use illicit drugs in the past year; despite this, the self-reported prevalence of all six drugs under investigation was lower than that reported by the general population. Sixteen per cent of athletes believed that there was a drug of concern in their sport, with ecstasy, cocaine and alcohol being nominated. Knowing other athletes who use illicit drugs, being offered or having the opportunity to use drugs and identifying as a 'full-time athlete' were significant predictors of recent drug use. DISCUSSION AND CONCLUSIONS: The present study found that one-third of the athlete sample had been offered or had the opportunity to use illicit drugs in the past year; despite this, there was low self-reported drug use. Despite media discussion regarding alcohol use in sport, alcohol was nominated as a drug of concern only by a small proportion of athletes, and further research investigating this issue may be warranted.
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Atletas , Actitud Frente a la Salud , Drogas Ilícitas , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Recolección de Datos , Femenino , Humanos , Masculino , Modelos Estadísticos , Deportes , Adulto JovenRESUMEN
BACKGROUND: We systematically reviewed availability and quality of data on the prevalence of use and dependence on meth/amphetamine, cannabis, cocaine and opioids. METHODS: Multiple search strategies: (a) peer-reviewed literature searches (1990-2008) using methods recommended by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group; (b) systematic searches of online databases; (c) Internet searches to find other published evidence of drug use; (d) repeated consultation and feedback from experts around the globe; (e) a viral email sent to lists of researchers in the illicit drug and HIV fields. Data were extracted and graded according to predefined variables reflecting quality of data source. RESULTS: Qualitative evidence of illicit drug use and dependence was found for most countries, which hold over 98% of the world's population aged 15-64 years. Countries where use was identified but prevalence estimates had not been made (evidence of drug supply, trafficking, reports of use, treatment data) were mainly from Asia, Africa, the Middle East, and Oceania. Estimates of the prevalence of use were located in 77 countries for meth/amphetamine, 95 for cannabis, 86 for cocaine and 89 for opioids. Dependence prevalence estimates existed in very few countries; 9 meth/amphetamine dependence estimates, 7 cannabis dependence estimates, 5 cocaine dependence estimates, and 25 opioid dependence estimates were located. CONCLUSIONS: Data on the extent of meth/amphetamine, cannabis, cocaine and opioid use and dependence must be improved in quality and coverage. Dependence estimates are lacking even in high income countries that have required resources. Responses to illicit drug dependence require better estimates of its scale.
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Minería de Datos , Drogas Ilícitas , Proyectos de Investigación/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: This study aimed to investigate, among a sample of elite Australian athletes, the extent to which this group supports drug testing as a deterrent to drug use. METHOD: Data was collected from a convenience sample of (n=974) elite Australian athletes who self-completed a questionnaire, and semi-structured telephone surveys with key experts. RESULTS: The athletes surveyed endorsed testing for banned substances as an effective way of deterring drug use; believed that the current punishments for being caught using a banned substance was of the appropriate severity; and indicated that there should be separate policies regarding illicit drug (ID) and performance-enhancing drug (PED) use. CONCLUSION: A large proportion of elite athletes in Australia endorse drug testing as an effective means of deterring drug use. They perceive a difference between being detected using a PED and an ID and believe that penalties should reflect this difference. Future research may wish to investigate attitudes towards newer methods employed to detection drug use.