Diffusion and implementation of a tobacco prevention program: A replication study

Tobacco use is a major health hazard, and the onset of tobacco use occurs almost entirely in the teenage years. For this reason, schools are an ideal site for tobacco prevention programs. Although studies have shown that effective school-based tobacco prevention programs exist, all too frequently these programs are not used. In order for effective programs to achieve their potential impact, strategies for speeding the diffusion of these programs to school districts and seeing that, once adopted, programs are implemented as they are intended, must be developed and tested.^ This study (SC2) set out to replicate the findings of an earlier quasi-experimental study (The Smart Choices Diffusion Study, or SC1) in which strategies based on diffusion theory and social learning theory were found to be effective in encouraging adoption and implementation of an effective tobacco prevention program in schools. To increase awareness and encourage adoption, intervention strategies in both studies utilized opinion leaders, messages highlighting positive aspects of the program, and modeling of benefits and effective use through videotape and newsletters. To encourage accurate implementation of the curriculum, teacher training for the two studies utilized videotaped modeling and practice of activities by teachers. SC2 subjects were 38 school districts that make up one of Texas' 20 education service regions. These districts had served as the comparison group in SC1, and findings for the SC1 comparison and intervention groups were utilized as historic controls.^ SC2 achieved a 76.3% adoption rate and found that an average of 84% of the curriculum was taught with an 82% fidelity to methods utilized by the curriculum. These rates and rates for implementation of dissemination strategies were equal to or greater than corresponding rates for SC1. The proportion of teachers implementing the curriculum in SC2 was found to be equal to SC1's video-trained districts but lower than the SC1 workshop-trained group.^ SC2's findings corroborate and support the findings from the earlier study, and increase our confidence in its findings. Taken together, the findings from SC2 and SC1 point to the effectiveness of their theory-based intervention strategies in encouraging adoption and accurate implementation of the tobacco prevention curriculum. ^

Role of MicroRNA Modulation in the Interferon-α/Ribavirin Suppression of HIV-1 In Vivo.

BACKGROUND Interferon-α (IFN-α) treatment suppresses HIV-1 viremia and reduces the size of the HIV-1 latent reservoir. Therefore, investigation of the molecular and immunologic effects of IFN-α may provide insights that contribute to the development of novel prophylactic, therapeutic and curative strategies for HIV-1 infection. In this study, we hypothesized that microRNAs (miRNAs) contribute to the IFN-α-mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN-α treatment on global miRNA expression profile, HIV-1 viremia, and potential regulatory networks between miRNAs and cell-intrinsic anti-HIV-1 host factors in vivo. METHODS Global miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated interferon-α/ribavirin therapy (IFN-α/RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors. RESULTS miR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo. CONCLUSIONS The specific reduction of miR-422a is associated with exogenous IFN-α treatment, and likely contributes to the IFN-α suppression of HIV-1 through the enhancement of anti-HIV-1 restriction factor expression and regulation of genes involved in programmed cell death. Moreover, our regulatory network analysis presents additional candidate miRNAs that may be targeted to enhance anti-HIV-1 restriction factor expression in vivo.

Effect of Combined Systemic and Local Morpholino Treatment on the Spinal Muscular Atrophy Δ7 Mouse Model Phenotype

BACKGROUND: Spinal muscular atrophy (SMA) is a fatal motor neuron disease of childhood that is caused by mutations in the SMN1 gene. Currently, no effective treatment is available. One possible therapeutic approach is the use of antisense oligos (ASOs) to redirect the splicing of the paralogous gene SMN2, thus increasing functional SMN protein production. Various ASOs with different chemical properties are suitable for these applications, including a morpholino oligomer (MO) variant with a particularly excellent safety and efficacy profile. OBJECTIVE: We investigated a 25-nt MO sequence targeting the negative intronic splicing silencer (ISS-N1) 10 to 34 region. METHODS: We administered a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) in the SMAΔ7 mouse model and evaluated the effect and neuropathologic phenotype. We tested different concentrations (from 2 to 24 nM) and delivery protocols (intracerebroventricular injection, systemic injection, or both). We evaluated the treatment efficacy regarding SMN levels, survival, neuromuscular phenotype, and neuropathologic features. RESULTS: We found that a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) exhibited superior efficacy in transgenic SMAΔ7 mice compared with previously described sequences. In our experiments, the combination of local and systemic administration of MO (bare or conjugated to octaguanidine) was the most effective approach for increasing full-length SMN expression, leading to robust improvement in neuropathologic features and survival. Moreover, we found that several small nuclear RNAs were deregulated in SMA mice and that their levels were restored by MO treatment. CONCLUSION: These results indicate that MO-mediated SMA therapy is efficacious and can result in phenotypic rescue, providing important insights for further development of ASO-based therapeutic strategies in SMA patients.

“Se querem que façamos algo pela floresta tem que nos pagar”: As lógicas da participação dos camponeses nos Comités de Gestão dos Recursos Naturais nos distritos de Palma e Mocimboa da Praia em 2009: Relatório do trabalho de campo em Namiune, Nkonga e 5º Congresso, Maputo, Dezembro de 2010

Our study considers the natural resources of the Miombo forests in Cabo Delgado from a broad ecosystems perspective. Thus, our view goes beyond the disciplinary approaches of forestry, agronomy, biology or zoology, and also of the social sciences, namely anthropology, history, sociology, political science or economics. The present study aims to establish a dialogue and create synergies between Miti Ltd. – the logging company and owner of the forest concessions – as well as government and state structures at the various levels and the communities – through the Committees on Natural Resources – in order to promote the sustainable use of resources and ecosystems. The research methodology we used can broadly be described as moderated transdisciplinary interaction for action-research based on the approach known as Learning for Sustainability (LforS, http://www.cde.unibe.ch/Pages/Project/2/14/Learning-for-Sustainability-Extension-Approach.aspx). The research methods used include: LforS seminars; field work; forests observations focusing, among others, on ecosystems, trees, wildlife, and burned areas; visits to farms; and interviews. We conducted both collective interviews and individual interviews, including with key informants. The main results indicate that members of the Committee on Natural Resources have a dual attitude: their statements defend the paradigm of sustainable use of natural resources as well as their own immediate monetary gain. They are willing to apply the values, concepts and theories of sustainable development that underpin the establishment of Committees on Natural Resources if they are paid for their work or if they can derive direct benefits from it, i.e. if they can earn a salary or allowance. If this does not happen, however, they are willing to allow actors to engage in illegal hunting or logging activities. This dual attitude also exists in relation to forestry operators. If the concession workers pay the committee members in cash or provide goods, they can run their business even if they violate the law. Natural forest regeneration in Nkonga and Namiune already shows the impact of such use. Although there are many saplings that could basically ensure continuous regeneration under sustainable management, repeated burning is damaging the young trees, deforming them and killing a great number of them. Campaigns against uncontrolled fires are ineffective because the administrative and political authorities have a dual attitude as well and are also part of the group that uses resources to their own profit and benefit. There are institutional structures within the administration, populations, and communities to perform regulating functions, create and implement rules, punish offenders, and oversee resource use. However, they feel that since they are not paid for performing these functions, they do not have to do so. This attitude shows a lack of awareness, but also indicates a situation where everyone seeks to derive maximum benefits from existing resource use patterns. Anything goes.

Resistant hypertension: what the cardiologist needs to know.

Treatment-resistant hypertension (TRH) affects between 3 and 30% of hypertensive patients, and its presence is associated with increased cardiovascular morbidity and mortality. Until recently, the interest on these patients has been limited, because providing care for them is difficult and often frustrating. However, the arrival of new treatment options [i.e. catheter-based renal denervation (RDN) and baroreceptor stimulation] has revitalized the interest in this topic. The very promising results of the initial uncontrolled studies on the blood pressure (BP)-lowering effect of RDN in TRH seemed to suggest that this intervention might represent an easy solution for a complex problem. However, subsequently, data from controlled studies have tempered the enthusiasm of the medical community (and the industry). Conversely, these new studies emphasized some seminal aspects on this topic: (i) the key role of 24 h ambulatory BP and arterial stiffness measurement to identify 'true' resistant patients; (ii) the high prevalence of secondary hypertension among this population; and (iii) the difficulty to identify those patients who may profit from device-based interventions. Accordingly, for those patients with documented TRH, the guidelines suggest to refer them to a hypertension specialist/centre in order to perform adequate work-up and treatment strategies. The aim of this review is to provide guidance for the cardiologist on how to identify patients with TRH and elucidate the prevailing underlying pathophysiological mechanism(s), to define a strategy for the identification of patients with TRH who may benefit from device-based interventions and discuss results and limitations of these interventions, and finally to briefly summarize the different drug-based treatment strategies.

Analysis of left ventricular function of the mouse heart during experimentally induced hyperthyroidism and recovery

Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormones to alter myocardial contractility and cardiovascular hemodynamics, leading to cardiovascular impairment. In contrast, recent studies highlight also the potential beneficial effects of thyroid hormone administration for clinical or preclinical treatment of different diseases such as atherosclerosis, obesity and diabetes or as a new therapeutic approach in demyelinating disorders. In these contexts and in the view of developing thyroid hormone-based therapeutic strategies, it is, however, important to analyze undesirable secondary effects on the heart. Animal models of experimentally induced hyperthyroidism therefore represent important tools for investigating and monitoring changes of cardiac function. In our present study we use high-field cardiac MRI to monitor and follow-up longitudinally the effects of prolonged thyroid hormone (triiodothyronine) administration focusing on murine left ventricular function. Using a 9.4 T small horizontal bore animal scanner, cinematographic MRI was used to analyze changes in ejection fraction, wall thickening, systolic index and fractional shortening. Cardiac MRI investigations were performed after sustained cycles of triiodothyronine administration and treatment arrest in adolescent (8 week old) and adult (24 week old) female C57Bl/6 N mice. Triiodothyronine supplementation of 3 weeks led to an impairment of cardiac performance with a decline in ejection fraction, wall thickening, systolic index and fractional shortening in both age groups but with a higher extent in the group of adolescent mice. However, after a hormonal treatment cessation of 3 weeks, only young mice are able to partly restore cardiac performance in contrast to adult mice lacking this recovery potential and therefore indicating a presence of chronically developed heart pathology.

Supporting Whole-Class Collaborative Inquiry in a Secondary Mathematics Classroom

Recent mathematics education reform efforts call for the instantiation of mathematics classroom environments where students have opportunities to reason and construct their understandings as part of a community of learners. Despite some successes, traditional models of instruction still dominate the educational landscape. This limited success can be attributed, in part, to an underdeveloped understanding of the roles teachers must enact to successfully organize and participate in collaborative classroom practices. Towards this end, an in-depth longitudinal case study of a collaborative high school mathematics classroom was undertaken guided by the following two questions: What roles do these collaborative practices require of teacher and students? How does the community’s capacity to engage in collaborative practices develop over time? The analyses produced two conceptual models: one of the teacher’s role, along with specific instructional strategies the teacher used to organize a collaborative learning environment, and the second of the process by which the class’s capacity to participate in collaborative inquiry practices developed over time.

A Qualitative Study of the Assistive Technology Decision-Making Process in Four Pennsylvania School Districts

The purpose of this study was to gain an understanding of the Assistive Technology decision making process at four regional school districts in Pennsylvania. A qualitative case study research method involving the triangulation of data sources was implemented to collect and analyze data. Through an analysis of the data, three major topics emerged that will be addressed in the body of this paper: (a) the procedure for determining assistive technology needs and the dynamics of the decision-making process, b) the cohesiveness of Special Education and General Education programs, and c) major concerns that impact the delivery of assistive technology services.

Targeting AKT/mTOR Signaling Pathways During Murine Skin Tumor Promotion and the Impact of Dietary Energy Balance Manipulation

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.

Development and Characterization of an in vitro Four-species Anaerobic Dental Biofilm Model

Dental caries is the most common chronic disease worldwide. It is characterized by the demineralization of tooth enamel caused by acid produced by cariogenic dental bacteria growing on tooth surfaces, termed bacterial biofilms. Cariogenesis is a complex biological process that is influence by multiple factors and is not attributed to a sole causative agent. Instead, caries is associated with multispecies microbial biofilm communities composed of some bacterial species that directly influence the development of a caries lesion and other species that are seemingly benign but must contribute to the community in an uncharacterized way. Clinical analysis of dental caries and its microbial populations is challenging due to many factors including low sensitivity of clinical measurement tools, variability in saliva chemistry, and variation in the microbiota. Our laboratory has developed an in vitro anaerobic biofilm model for dental carries to facilitate both clinical and basic research-based analyses of the multispecies dynamics and individual factors that contribute to cariogenicity. The rational for development of this system was to improve upon the current models that lack key elements. This model places an emphasis on physiological relevance and ease of maintenance and reproducibility. The uniqueness of the model is based on integrating four critical elements: 1) a biofilm community composed of four distinct and representative species typically associated with dental caries, 2) a semi-defined synthetic growth medium designed to mimic saliva, 3) physiologically relevant biofilm growth substrates, and 4) a novel biofilm reactor device designed to facilitate the maintenance and analysis. Specifically, human tooth sections or hydroxyapatite discs embedded into poly(methyl methacrylate) (PMMA) discs are incubated for an initial 24 hr in a static inverted removable substrate (SIRS) biofilm reactor at 37°C under anaerobic conditions in artificial saliva (CAMM) without sucrose in the presence of 1 X 106 cells/ml of each Actinomyces odontolyticus, Fusobacterium nucleatum, Streptococcus mutans, and Veillonella dispar. During days 2 and 3 the samples are maintained continually in CAMM with various exposures to 0.2% sucrose; all of the discs are transferred into fresh medium every 24 hr. To validate that this model is an appropriate in vitro representation of a caries-associated multispecies biofilm, research aims were designed to test the following overarching hypothesis: an in vitro anaerobic biofilm composed of four species (S. mutans, V. dispar, A. odontolyticus, and F. nucleatum) will form a stable biofilm with a community profile that changes in response to environmental conditions and exhibits a cariogenic potential. For these experiments the biofilms as described above were exposed on days 2 and 3 to either CAMM lacking sucrose (no sucrose), CAMM with 0.2% sucrose (constant sucrose), or were transferred twice a day for 1 hr each time into 0.2% sucrose (intermittent sucrose). Four types of analysis were performed: 1) fluorescence microscopy of biofilms stained with Syto 9 and hexidium idodine to determine the biofilm architecture, 2) quantitative PCR (qPCR) to determine the cell number of each species per cm2, 3) vertical scanning interferometry (VSI) to determine the cariogenic potential of the biofilms, and 4) tomographic pH imaging using radiometric fluorescence microscopy after exposure to pH sensitive nanoparticles to measure the micro-environmental pH. The qualitative and quantitative results reveal the expected dynamics of the community profile when exposed to different sucrose conditions and the cariogenic potential of this in vitro four-species anaerobic biofilm model, thus confirming its usefulness for future analysis of primary and secondary dental caries.

Images and animation of a complex microboring (Pyrodendrina cupra n. igen. and isp.) from the early Paleozoic of Anticosti Island, Canada

Three complementary imaging techniques were used to describe a complex rosette-shaped microboring that penetrates the shells of brachiopods from the Ordovician–Silurian shallow marine limestones of Anticosti Island, Canada. Pyrodendrina cupra n. igen. and isp. is among the oldest dendrinid microborings and consists of shallow and deep penetrating canals that radiate from a central polygonal chamber. The affinity of the tracemaker is unknown, but a foraminiferal origin, as proposed for some dendrinid borings, is rejected. Combining microCT with traditional stereomicroscopy and SEM helped distinguish and quantify fine morphological features while maintaining contextual information of the microboring within the shell substrate. Different imaging techniques inherently bias the description of microborings. These biases must be accounted for as new methods in ichnotaxonomy are integrated with past research based on different methods.

Currículo y construcción de un habitus investigativo cualitativo entre sociólogos/as en formación

Este artículo analiza el diseño curricular de un Seminario de Investigación Socioeducativa para estudiantes de Sociología de la Universidad de Buenos Aires, y reflexiona acerca de su contribución a forjar un "habitus investigativo cualitativo" entre estudiantes que asumen el rol de investigadores. El trabajo recupera diferentes abordajes acerca de la relación investigación-docencia en otras latitudes, para luego examinar los supuestos, objetivos y modalidades de trabajo del seminario y la utilización de trabajos prácticos secuenciales que vertebran la cursada. Se argumenta que esta experiencia de "enseñanza basada en investigación" contribuiría a inculcar una concepción dialógica, reflexiva y situada de la investigación social

Jóvenes y sujetos de la historia

Este artículo discute las concepciones de jóvenes brasileños, argentinos y uruguayos sobre los sujetos en la historia, en función de su aprendizaje histórico escolar y extra-escolar. Los datos fueron obtenidos a partir de la encuesta internacional " Jóvenes frente a la historia " . Los cuestionarios estuvieron dirigidos a estudiantes de 15 años y sus profesores, y se utilizó mayormente la escala Likert. Teóricamente, la investigación se sustenta en los conceptos de conciencia histórica y cultura histórica, formulados por la Didáctica de la historia alemana, pero también en el concepto de cultura política. Los resultados apuntan que, dentro del universo estudiado, las llamadas " personalidades importantes " típicas de la enseñanza escolar de la historia son reconocidas en lo que se refiere a los "padres fundadores" de las naciones, pero no en cuanto sujetos que hicieron la historia nacional. De la misma manera ocurre en el caso de los personajes femeninos. Ciencia, tecnología e invenciones son vistos como un factor de cambio más importante que las "personas importantes" y estos, a su vez, han sido superados por la importancia reconocida a los movimientos colectivos

Usos sociales del filme. Notas teórico-metodológicas y reseña de una práctica de investigación

El artículo presenta algunas de las principales coordenadas teórico-metodológicas de una investigación doctoral que, sustentada en el enfoque cualitativo ligado al uso de expresiones artístico-culturales, propone al filme como fuente primaria de análisis. Describe, además, las distintas etapas del 'trabajo de campo' sintetizando los recorridos, tareas y actividades realizadas para la conformación del corpus y la delimitación de su modo de abordaje. La puesta en común de estas notas teórico-metodológicas y de la reseña de la práctica investigativa pretende contribuir a la reflexión en torno a la importancia y pertinencia de la incorporación de corpus alternativos y múltiples en la generación de conocimiento científico en el campo de las Ciencias Sociales

Agroindustria láctea, regulación estatal y cooperativismo, 1930-1955

En este artículo presentamos los resultados de la investigación en curso sobre las estrategias institucionales desplegadas por el sector lácteo cooperativo y su injerencia en el diseño de las políticas sectoriales. Consideramos una variado repertorio de fuentes: legislación, diagnósticos, informes éditos e inéditos producidos por el Estado y por diversos actores del cooperativismo lácteo. En el tratamiento de esta temática problematizamos la cuestión de la lógica corporativa entre actores estatales y cooperativos. Consideramos además, los proceso de agregación de intereses en el espacio público que se dieron a partir de los debates y las experiencias de acción, organización y alianzas entre las entidades cooperativas lácteas