RESUMO
BACKGROUND: Hackathons are organized to bring together both experienced and novice individuals from a variety of backgrounds to brainstorm creative solutions to complex issues. Hackathons may last from a few hours to a few days and may provide rewards for winning entries. PURPOSE: In this article, we describe an experience with a scientific hackathon at an international nursing research congress in Calgary, Canada. We discuss the purpose, process, benefits, and challenges of this hackathon. APPROACH: For this article, we have used a descriptive approach. OUTCOMES: The scientific hackathon experience united international nursing scholars into a community with a common focus enabling the continuation of mutual, future endeavors. CONCLUSION: Hackathons are a means of connecting novices and experts from different backgrounds to develop technology-based solutions for health care issues. The ideas generated at hackathons may be further developed to bring the project to fruition to positively impact health care.
Assuntos
Pesquisa em Enfermagem , Canadá , Atenção à Saúde , Humanos , Pesquisa em Educação em EnfermagemRESUMO
While the reduction in the overall U.S. smoking prevalence has been declared one of the top 10 public health achievements of the past century, the growing disparity in smoking between American Indians and the general population is one of the biggest challenges of the 21st century. Minnesota in particular has very high smoking rates among American Indians (59%). Tribal Nations in Minnesota share a past of attempted cultural genocide and a present of restoring the strength of their cultural teachings, including the prominence of traditional tobacco as a sacred "first medicine." The Tribal Tobacco Education and Policy initiative works to address this complex and challenging context. This article describes results of a participatory evaluation from 2010 to 2013 in four Minnesota Tribal Nations-three Ojibwe and one Dakota. Tribal Tobacco Education and Policy coordinators used their cultural knowledge to develop community-level strategies, identifying appropriate strategies from best practices on tobacco advocacy, while drawing on the strengths of their own sovereignty and sacred tobacco traditions. Tribal coordinators generated support for policy change by conducting culturally relevant education, engaging tribal members, and nurturing relationships. This approach resulted in norm changes, practices toward restoring traditional tobacco, informal policies, and tribal resolutions to advance smoke-free policies.
Assuntos
Educação em Saúde/organização & administração , Indígenas Norte-Americanos , Política Antifumo/legislação & jurisprudência , Fumar/etnologia , Comportamento Cooperativo , Competência Cultural , Humanos , Minnesota/epidemiologia , Prevenção do Hábito de Fumar/organização & administração , Produtos do Tabaco/legislação & jurisprudênciaRESUMO
AIM: This study's aim was to determine the prevalence of health literacy education in nursing programs. Health literacy content and teaching strategies were also explored. BACKGROUND: Over 75 million Americans have low health literacy, a problem that can cause negative health outcomes. Knowledge about health literacy is important for nurses; yet, the extent to which the topic is included within nursing curricula is unknown. METHOD: An online survey was distributed to 150 nursing programs to obtain information about health literacy education in the curricula. RESULTS: Fifty-seven programs responded, with the majority reporting that health literacy is taught in their curricula. The impact of low health literacy and the importance of plain language were noted as common topics. CONCLUSION: The majority of participants reported inclusion of health literacy in their curricula using various teaching strategies. However, a low response rate prevents generalized conclusions.
Assuntos
Comunicação , Currículo , Bacharelado em Enfermagem/organização & administração , Letramento em Saúde , Relações Enfermeiro-Paciente , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários , Estados Unidos , Adulto JovemRESUMO
As successes mount in reducing commercial tobacco use, an alarming disparity has taken shape in Minnesota. Recent studies revealed that overall smoking rates have dropped to 14%, whereas American Indians' rates remain higher than 50%. With support from ClearWay Minnesota, the organization created from the state's tobacco settlement, advocates working within sovereign tribal governments to create smoke-free policies came together to discuss effective strategies within tribal Nations. We discussed the history behind mainstream tobacco control's failure to resonate with Native audiences and the need to reframe the movement to a goal of restoring traditional tobacco practices. We share our insights on this critical area for achieving health equity and provide recommendations for tribes, non-Indian advocates, and funders, with a plea for tribal inclusion in commercial tobacco "end-game" strategies.
Assuntos
Características Culturais , Indígenas Norte-Americanos/etnologia , Fumar/etnologia , Competência Cultural , Política de Saúde , Humanos , Liderança , Minnesota , Política Antifumo , Fumar/efeitos adversos , Fumar/mortalidade , Normas Sociais/etnologiaRESUMO
BACKGROUND: Colorectal cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer-related death in Wisconsin. Incidence and mortality rates for colorectal cancer vary by age, race/ethnicity, geography, and socioeconomic status. From 2010 through 2012, the Wisconsin Comprehensive Cancer Control Program awarded grants to 5 regional health systems for the purpose of planning and implementing events to increase colorectal cancer screening rates in underserved communities. COMMUNITY CONTEXT: Grantees were chosen for their ability to engage community partners in reaching underserved groups including African American, Hispanic/Latino, Hmong, rural, and uninsured populations in their service areas. METHODS: Grantees identified target populations for proposed screening events, designated institutional planning teams, engaged appropriate local partner organizations, and created plans for follow-up. All grantees implemented 1 or more colorectal cancer screening events within 6 months of receiving their awards. Events were conducted in 2 phases. OUTCOMES: Participating health systems organized 36 screening events and distributed 633 individual test kits; 506 kits were returned, of which 57 (9%) tested positive for colorectal abnormalities. Of attendees who received screening, 63% were uninsured or underinsured, 55% had no previous screening, 46% were of a racial/ethnic minority group, 22% had a family history of cancer, and 13% were rural residents. This project strengthened partnerships between health systems and local organizations. INTERPRETATION: An effective strategy for improving colorectal cancer screening rates, particularly among underserved populations, is to award health systems grants for implementing community-based screening events in conjunction with community partners.
Assuntos
Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Promoção da Saúde , Neoplasias Colorretais/epidemiologia , Serviços de Saúde Comunitária , Relações Comunidade-Instituição , Acessibilidade aos Serviços de Saúde , Humanos , Wisconsin/epidemiologiaRESUMO
Policy advocacy is increasingly recognized as a crucial component of the training provided to health educators but relatively few universities offer advocacy training as part of their professional preparation programs for health educators. Historically Black colleges and universities (HBCUs) represent a natural setting for creating strong Black leaders in tobacco policy advocacy. This case study focuses on experiential education at an HBCU to develop advocacy skills around tobacco issues among Black college students. The authors describe the structure and content of two tobacco policy courses, their efforts to evaluate these courses, and the lessons they learned planning and conducting them. They believe their experience can prove useful to others developing curricula for teaching policy advocacy skills to health education students.
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Negro ou Afro-Americano/educação , Educadores em Saúde/educação , Política de Saúde , Prevenção do Hábito de Fumar , Universidades/organização & administração , Humanos , Liderança , Estudos de Casos Organizacionais , Avaliação de Programas e Projetos de Saúde , Mudança SocialRESUMO
Health promotion professionals are increasingly encouraged to implement evidence-based programs in health departments, communities, and schools. Yet translating evidence-based research into practice is challenging, especially for complex initiatives that emphasize environmental strategies to create community change. The purpose of this article is to provide health promotion practitioners with a method to evaluate the community change process and document successful applications of environmental strategies. The community change chronicle method uses a five-step process: first, develop a logic model; second, select outcomes of interest; third, review programmatic data for these outcomes; fourth, collect and analyze relevant materials; and, fifth, disseminate stories. From 2001 to 2003, the authors validated the use of a youth empowerment model and developed eight community change chronicles that documented the creation of tobacco-free schools policies (n = 2), voluntary policies to reduce secondhand smoke in youth hangouts (n = 3), and policy and program changes in diverse communities (n = 3).
Assuntos
Serviços de Saúde da Criança/organização & administração , Serviços de Saúde Comunitária/organização & administração , Documentação , Promoção da Saúde , Avaliação de Programas e Projetos de Saúde/métodos , Poluição por Fumaça de Tabaco/prevenção & controle , Tabagismo/prevenção & controle , Adolescente , Criança , Medicina Baseada em Evidências , Feminino , Humanos , Modelos Logísticos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Poder PsicológicoRESUMO
Prenatal and childhood environmental exposures are an underrecognized primary cause of intellectual and other developmental disabilities. In addition, individuals with established disabilities are vulnerable to further harm from subsequent environmental exposures. In individuals with communicative impairment or limited ability to independently escape from hazards, these subsequent exposures, too, may occur undetected or untreated. This article introduces the subject of environmental health and developmental disabilities throughout the life span. In particular, we focus on ways that families, communities, and health professionals can prevent both primary and secondary disabilities through better awareness of common environmental health issues.
Assuntos
Deficiências do Desenvolvimento/induzido quimicamente , Exposição Ambiental/efeitos adversos , Consumo de Bebidas Alcoólicas/efeitos adversos , Aleitamento Materno/efeitos adversos , Pré-Escolar , Dieta , Feminino , Humanos , Chumbo/toxicidade , Exposição Materna/efeitos adversos , Mercúrio/toxicidade , Gravidez , Características de Residência , Instituições Acadêmicas , Fumar/efeitos adversos , Estados UnidosRESUMO
During embryonic development in chick, axons pause in a plexus region for approximately 1 day prior to invading the limb. We have previously shown that this "waiting period" is governed by maturational changes in the limb. Here we provide a detailed description of the spatiotemporal pattern of Raldh2 expression in lumbosacral motoneurons and in the limb, and show that retinoid signaling in the limb contributes significantly to terminating the waiting period. Raldh2, indicative of retinoid signaling, first appears in hindlimb mesenchyme near the end of the waiting period. Transcripts are more abundant in connective tissue associated with predominantly fast muscles than predominantly slow muscles, but are not expressed in muscle cells themselves. The tips of ingrowing axons are always found in association with domains of Raldh2, but development of Raldh2 expression is not regulated by the axons. Instead, retinoid signaling appears to regulate axon entry into the limb. Supplying exogenous retinoic acid to proximal limb during the waiting period caused both motor and sensory axons to invade the limb prematurely and altered the normal stereotyped pattern of axon ingrowth without obvious effects on limb morphogenesis or motoneuron specification. Conversely, locally decreasing retinoid synthesis reduced axon growth into the limb. Retinoic acid significantly enhanced motor axon growth in vitro, suggesting that retinoic acid may directly promote axon growth into the limb in vivo. In addition, retinoid signaling may indirectly affect the waiting period by regulating the maturation of other gate keeping or guidance molecules in the limb. Together these findings reveal a novel function of retinoid signaling in governing the timing and patterning of axon growth into the limb.
Assuntos
Axônios/metabolismo , Membro Posterior/inervação , Transdução de Sinais , Tretinoína/metabolismo , Aldeído Oxirredutases/metabolismo , Animais , Embrião de Galinha , Membro Posterior/embriologiaRESUMO
The molecular mechanisms responsible for specifying the dorsal-ventral pattern of neuronal identities in dorsal root ganglia (DRG) are unclear. Here we demonstrate that Sonic hedgehog (Shh) contributes to patterning early DRG cells. In vitro, Shh increases both proliferation and programmed cell death (PCD). Increasing Shh in vivo enhances PCD in dorsal DRG, while inducing greater proliferation ventrally. In such animals, markers characteristic of ventral sensory neurons are expanded to more dorsal positions. Conversely, reducing Shh function results in decreased proliferation of progenitors in the ventral region and decreased expression of the ventral marker trkC. Later arising trkA(+) afferents make significant pathfinding errors in animals with reduced Shh function, suggesting that accurate navigation of later arising growth cones requires either Shh itself or early arising, Shh-dependent afferents. These results indicate that Shh can regulate both cell number and the distribution of cell types in DRG, thereby playing an important role in the specification, patterning and pathfinding of sensory neurons.
Assuntos
Embrião de Galinha/citologia , Embrião de Galinha/fisiologia , Gânglios Espinais/embriologia , Proteínas Hedgehog/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Animais , Bromodesoxiuridina , Técnicas de Cultura de Células , Divisão Celular , Gânglios Espinais/citologia , Proteínas Hedgehog/genética , Imuno-Histoquímica , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Neurônios Aferentes/fisiologiaRESUMO
A central question in neural development is how the broad diversity of neurons is generated in the vertebrate CNS. We have investigated the function of Hoxc10 and Hoxd10 in mouse lumbar motoneuron development. We show that Hoxc10 and Hoxd10 are initially expressed in most newly generated lumbar motoneurons, but subsequently become restricted to the lateral division of the lateral motor column (lLMC). Disruption of Hoxc10 and Hoxd10 caused severe hindlimb locomotor defects. Motoneurons in rostral lumbar segments were found to adopt the phenotype of thoracic motoneurons. More caudally the lLMC and dorsal-projecting axons were missing, yet most hindlimb muscles were innervated. The loss of the lLMC was not due to decreased production of motoneuron precursors or increased apoptosis. Instead, presumptive lLMC neurons failed to migrate to their normal position, and did not differentiate into other motoneurons or interneurons. Together, these results show that Hoxc10 and Hoxd10 play key roles in establishing lumbar motoneuron columnar, divisional and motor pool identity.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Neurônios Motores/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Animais , Membro Posterior/embriologia , Membro Posterior/metabolismo , Proteínas de Homeodomínio/genética , Vértebras Lombares/embriologia , Vértebras Lombares/metabolismo , Camundongos , Camundongos Knockout , Músculos/embriologia , Músculos/metabolismo , Mutação/genética , Medula Espinal/embriologia , Medula Espinal/metabolismo , Fatores de Transcrição/deficiência , Fatores de Transcrição/genéticaRESUMO
The ETS transcription factors ER81 and PEA3 are expressed in discrete populations of sensory and motor neurons and regulate late events in neuronal development and limb innervation. Although initiation of ETS expression requires limb-derived signals, we show here that precocious axon growth into transplanted older donor limbs, which prematurely exposes neurons to limb-derived signals, does not accelerate the onset of expression of Er81 or Pea3. Similarly, neither MN-cadherin, which is reportedly regulated by ER81, nor T-cadherin is expressed precociously in neurons innervating older donor limbs. Thus, neurons must attain a particular level of differentiation to respond to inducing signals from limb. We also show that signals emanating from limb mesenchyme are sufficient to initiate Er81 and Pea3 expression in sensory and motor neurons in the absence of myogenic cells in Sp(d) mutant mice and that induction of ETS expression is unlikely to directly involve retinoid signaling from limb mesenchyme.
Assuntos
Extremidades/embriologia , Extremidades/inervação , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma/fisiologia , Proteínas Proto-Oncogênicas c-ets/genética , Transdução de Sinais , Animais , Proteínas de Ligação a DNA/genética , Extremidades/transplante , Camundongos , Neurônios Motores/química , Neurônios Aferentes/química , Fatores de Transcrição/genéticaRESUMO
EphA-ephrin signaling has recently been implicated in the establishment of motor innervation patterns, in particular in determining whether motor axons project into dorsal versus ventral nerve trunks in the limb. We investigated whether sensory axons, which grow out together with and can be guided by motor axons, are also influenced by Eph-ephrin signaling. We show that multiple EphA receptors are expressed in DRGs when limb innervation is being established, and EphA receptors are present on growth cones of both NGF-dependent (predominantly cutaneous) and NT3-dependent (predominantly proprioceptive) afferents. Both soluble and membrane-attached ephrin-A5 inhibited growth of approximately half of each population of sensory axons in vitro. On average, growth cones that collapsed in response to soluble ephrin-A5 extended more slowly than those that did not, and ephrin-A5 significantly slowed the extension of NGF-dependent growth cones that did not collapse. Finally, we show that ectopic expression of ephrin-A5 in ovo reduced arborization of cutaneous axons in skin on the limb. Together these results suggest that sensory neurons respond directly to A-class ephrins in the limb. Thus, ephrins appear to pattern sensory axon growth in two ways-both directly, and indirectly via their inhibitory effects on neighboring motor axons.
Assuntos
Efrina-A5/fisiologia , Neurônios Aferentes/fisiologia , Animais , Axônios/fisiologia , Crescimento Celular , Membrana Celular/metabolismo , Células Cultivadas , Embrião de Galinha , Efrina-A5/biossíntese , Extremidades/embriologia , Extremidades/inervação , Gânglios Espinais/citologia , Gânglios Espinais/embriologia , Cones de Crescimento/fisiologia , Neurônios Aferentes/metabolismo , Fosforilação , Receptores da Família Eph/biossíntese , Pele/embriologia , Pele/inervaçãoRESUMO
Maternal smoking is associated with a number of adverse effects including neonatal mortality, preterm delivery, low birth weight, decreased lung growth and function, and increased incidence of lower respiratory infections. This study looked at smoking trends among American Indian and white women in Minnesota who gave birth between 1999 and 2003. The authors used data from birth certificates issued by the state to determine the rate of smoking among both groups of women. They broke down the data further to look at and compare smoking rates of American Indian and white women based on where they gave birth (greater Minnesota or the Twin Cities metro area), when they began receiving prenatal care, their level of education, their age, the number of children they already had, and the weight of their baby. They found that 39% of American Indian women in Minnesota who gave birth during that period reported smoking, compared with 11% of white women. In addition, their findings showed that cigarette use among American Indian women in Minnesota who gave birth in 2003, was 36.5%--double the national rate of 18.3% forAmerican Indian women.
Assuntos
Indígenas Norte-Americanos/estatística & dados numéricos , Gravidez/estatística & dados numéricos , Fumar/epidemiologia , Adolescente , Adulto , Declaração de Nascimento , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Recém-Nascido , Minnesota , Fatores de RiscoRESUMO
The ETS transcription factor ER81 is expressed in sensory neurons and motoneurons that innervate the adductor and femorotibialis muscles in chick hindlimb and is essential for the development of monosynaptic connections between these two populations of neurons. Neurons need a signal(s) from limb bud mesoderm to initiate ER81 expression. It is not known whether the mature expression pattern arises because adductor and femorotibialis motoneurons are uniquely competent to respond to peripheral signals and express ER81, or whether all motoneurons are competent to express ER81, but normally only adductor and femorotibialis motoneurons are exposed to the requisite activating signal. To investigate these possibilities, we examined ER81 expression in motoneurons that encountered limb tissue surgically mismatched with their target identity at stages after motor pool identities are established. We found that ER81 expression was not invariably linked to motor pool identity or target innervation and was more malleable in later-born femorotibialis motoneurons than in earlier-born adductor motoneurons. We also found that ER81 expression is regulated differently in sensory neurons and motoneurons. Most striking was the observation that motoneurons caudal to the normal adductor and femorotibialis pools could express ER81 when exposed to the appropriate peripheral signals, although this competence did not extend through the entire lumbosacral (LS) region. Thus, it appears that a prepattern of competence to express ER81 is established in early LS motoneurons, most likely in concert with their target identity, and that the expression domains of motoneurons are subsequently refined by peripheral signals at later stages.
Assuntos
Proteínas de Ligação a DNA/biossíntese , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Neurônios Motores/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Fatores de Transcrição/biossíntese , Animais , Embrião de Galinha , Desenvolvimento Embrionário/fisiologia , Membro Posterior/embriologia , Membro Posterior/inervação , Neurônios Aferentes/metabolismo , Transdução de Sinais/fisiologia , Medula Espinal/citologia , Medula Espinal/embriologiaRESUMO
During development, motor and sensory axons grow to peripheral targets with remarkable precision. Whereas much has been learned about the development of motoneuron connectivity, less is known about the regulation of cutaneous innervation. In adults, dorsal root ganglia (DRG) innervate characteristic skin regions, termed dermatomes, and their axons project somatotopically in the dorsal horn. Here, we have investigated whether cutaneous neurons are selectively matched with specific skin regions, and whether peripheral target skin influences the central connections of cutaneous neurons. To address these questions, we shifted limb buds rostrally in chick embryos prior to axon outgrowth, causing DRGs to innervate novel skin regions, and mapped the resulting dermatomes and central projections. Following limb shifts, cutaneous innervation arose from more rostral and from fewer DRGs than normal, but the overall dermatome pattern was preserved. Thus, DRGs parcel out innervation of skin in a consistent manner, with no indication of matching between skin and DRGs. Similarly, cutaneous nerves established a "normal" somatotopic map in the dorsal horn, but in more rostral segments than usual. Thus, the peripheral target skin may influence the pattern of CNS projections, but does not direct cutaneous axons to specific populations of neurons in the dorsal horn.
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Gânglios Espinais/embriologia , Pele/inervação , Vias Aferentes/embriologia , Animais , Embrião de Galinha , Extremidades/embriologiaRESUMO
The present study uses the embryonic chick to examine in vivo the mechanisms and regulation of Schwann cell programmed cell death (PCD) in spinal and cranial peripheral nerves. Schwann cells are highly dependent on the presence of axons for survival because the in ovo administration of NMDA, which excitotoxically eliminates motoneurons and their axons by necrosis, results in a significant increase in apoptotic Schwann cell death. Additionally, pharmacological and surgical manipulation of axon numbers also affects the relative amounts of Schwann cell PCD. Schwann cells undergoing both normal and induced PCD display an apoptotic-like cell death, using a caspase-dependent pathway. Furthermore, axon elimination results in upregulation of the p75 and platelet-derived growth factor receptors in mature Schwann cells within the degenerating ventral root. During early development, Schwann cells are also dependent on axon-derived mitogens; the loss of axons results in a decrease in Schwann cell proliferation. Axon removal during late embryonic stages, however, elicits an increase in proliferation, as is expected from these more differentiated Schwann cells. In rodents, Schwann cell survival is regulated by glial growth factor (GGF), a member of the neuregulin family of growth factors. GGF administration to chick embryos selectively rescued Schwann cells during both normal PCD and after the loss of axons, whereas other trophic factors tested had no effect on Schwann cell survival. In conclusion, avian Schwann cells exhibit many similarities to mammalian Schwann cells in terms of their dependence on axon-derived signals during early and later stages of development.
Assuntos
Apoptose/fisiologia , Axônios/fisiologia , Neuregulina-1/metabolismo , Células de Schwann/citologia , Animais , Axônios/ultraestrutura , Inibidores de Caspase , Divisão Celular/fisiologia , Embrião de Galinha , Inibidores de Cisteína Proteinase/farmacologia , N-Metilaspartato/farmacologia , Neurregulinas/metabolismo , Nervo Oculomotor/citologia , Nervo Oculomotor/efeitos dos fármacos , Nervo Oculomotor/embriologia , Nervos Periféricos/citologia , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/embriologia , Receptor de Fator de Crescimento Neural/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/ultraestrutura , Transdução de Sinais , Raízes Nervosas Espinhais/citologia , Raízes Nervosas Espinhais/efeitos dos fármacos , Raízes Nervosas Espinhais/embriologia , Regulação para Cima/fisiologiaRESUMO
The efficacy and safety of topiramate in patients with intractable mixed seizures, mental retardation (MR), and developmental disabilities (DD) were investigated. Twenty patients (eight females and 12 males) aged 21-57 years old with intractable epilepsy with mixed seizures, MR [profound (five), severe (three), moderate (two), mild (eight) and borderline (two)], and DD were treated with adjunctive topiramate 25 mg per day for 1 week followed by titration to clinical response (range 50-350 mg per day). Other antiepileptic drugs (AEDs) were decreased simultaneously. Topiramate therapy was discontinued in four patients for adverse events consisting of disorientation, unsteadiness, and pneumonia (one patient); anaphylactic shock from a tuna fish allergy (one); patient choice (one); and loss to follow-up (one). Seizures improved by gt-or-equal, slanted 50% in 11 of 16 patients (69%). Two patients (13%) were seizure free, including one patient who prior to topiramate therapy was seizure free but experiencing an intolerable adverse effect during therapy with another AED. Seizure duration and/or severity decreased in seven patients (44%). An increase in alertness was observed in 11 patients (59%). Topiramate was associated with improvement in seizure severity and alertness in this series and may be useful as adjunctive therapy in patients with mixed seizures, MR, and DD.