Bisdemethoxycurcumin Induces Cell Apoptosis and Inhibits Human Brain Glioblastoma GBM 8401/Luc2 Cell Xenograft Tumor in Subcutaneous Nude Mice In Vivo.

Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/luc2 cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/luc2 cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/luc2 cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/luc2 cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/luc2 cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/luc2 cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.

Promoting healthy lifestyles in Brazil: design and method of "VAMOS Program" in public health system / Promoção de estilos de vida saudáveis no Brasil: design e método do "Programa VAMOS" no sistema público de saúde

The "Programa Vida Ativa Melhorando a Saúde ­ VAMOS" (Active Life Improving Health) is a community intervention with a behavioral approach. It uses educational strategies to assist health professionals in support the population about the importance of adherence and maintenance of healthy lifestyles. This descriptive study shows the design and method of the VAMOS Program version 2.0. The intervention is for adults and older adults' users of Brazilian public health and aims to motivate them to adopt an active and healthy lifestyle regarding physical activity and eating. The program follows an intervention design that considers the dimensions of the RE-AIM framework. The VAMOS Program version 2.0 has the potential to be offered as a health promotion tool in the Brazilian public health system by using available resources and accessible and healthy behavioral strategies

O "Programa Vida Ativa Melhorando a Saúde ­ VAMOS" é uma intervenção comunitária com abordagem comportamental. Utiliza estratégias educativas para auxiliar os profissionais de saúde a orientar a população sobre a importância da adesão e manutenção de estilos de vida saudáveis. Este estudo descritivo apresenta o design e método do Programa VAMOS, versão 2.0. A intervenção é voltada para adultos e idosos usuários da saúde pública brasileira e visa motivá-los a adotarem um estilo de vida ativo e saudável no que diz respeito à atividade física e à alimentação. O programa segue um design de intervenção que considera as dimensões da ferramenta RE-AIM. O Programa VAMOS, versão 2.0, tem potencial para ser oferecido como ferramenta de promoção da saúde no sistema público de saúde brasileiro por meio da utilização de recursos disponíveis e acessíveis e estratégias comportamentais saudáveis

Development of a Testing Funnel for Identification of Small-Molecule Modulators Targeting Secretin Receptors.

The secretin receptor (SCTR), a prototypical class B G protein-coupled receptor (GPCR), exerts its effects mainly by activating Gαs proteins upon binding of its endogenous peptide ligand secretin. SCTRs can be found in a variety of tissues and organs across species, including the pancreas, stomach, liver, heart, lung, colon, kidney, and brain. Beyond that, modulation of SCTR-mediated signaling has therapeutic potential for the treatment of multiple diseases, such as heart failure, obesity, and diabetes. However, no ligands other than secretin and its peptide analogs have been described to regulate SCTRs, probably due to inherent challenges in family B GPCR drug discovery. Here we report creation of a testing funnel that allowed targeted detection of SCTR small-molecule activators. Pursuing the strategy to identify positive allosteric modulators (PAMs), we established a unique primary screening assay employing a mixture of three orthosteric stimulators that was compared in a screening campaign testing 12,000 small-molecule compounds. Beyond that, we developed a comprehensive set of secondary assays, such as a radiolabel-free target engagement assay and a NanoBiT (NanoLuc Binary Technology)-based approach to detect ß-arrestin-2 recruitment, all feasible in a high-throughput environment as well as capable of profiling ligands and hits regarding their effect on binding and receptor function. This combination of methods enabled the discovery of five promising scaffolds, four of which have been validated and further characterized with respect to their allosteric activities. We propose that our results may serve as starting points for developing the first in vivo active small molecules targeting SCTRs.

Changes in body weight and health behaviors of overweight children during the COVID-19 pandemic / Mudanças na massa corporal e em comportamentos de saúde de crianças com excesso de peso durante a pandemia da COVID-19

The aim of this study was to describe the perception of parents of overweight children about the effects of the period of social distancing due to COVID-19 on body weight (BW ), level of physical activity (PA), time spent in sedentary behavior (SB) and their children's eating habits and sleep. Parents of 47 overweight children (11.1 ± 1.33 years) were interviewed by telephone. Questions about the perception regarding BW and the four behaviors related to the health of their children during the period of social distancing were asked. The increase in BW was perceived by 61.7% of children and for almost all of them (93.6%) reductions in PA levels were reported, with 72.4% reducing participation in vigorous PA. An increase in time using smartphones, tablets, and microcomputers was observed in 65.9% of children. Favorable changes were noted in relation to quality (34.1%) and daily sleep time (51.1%). Favorable changes in the consumption of fruits (36.2%) and soft drinks (21.2%) and unfavorable changes in the consumption of vegetables (19.1%) and sweets and snacks (26.2%) were also reported. Four and a half months after the start of the social distancing measures due to the COVID-19 pandemic, overweight children increased the BW and changed the levels of PA and SB in an unfavorable way according to their parents. On the other hand, they started sleeping more and with higher quality and consuming more fruits and less soft drinks

O objetivo deste estudo foi descrever a percepção de pais de crianças com excesso de peso sobre os efeitos do período de distanciamento social devido à COVID-19 na massa corporal (MC) no nível de atividade física (AF), no tempo em comportamento sedentário (CS) e nos hábitos alimentares e de sono de seus filhos/as. Pais de 47 crianças (11,1 ± 1,33 anos) com excesso de peso foram entrevistados por ligação telefônica. Questões sobre a percepção em relação à MC e aos quatro comportamentos relacionados à saúde de seus filhos/as durante o período de distanciamento social foram realizadas. O aumento de MC foi percebido para 61,7% das crianças e para quase todas elas (93,6%) reduções nos níveis de AF foram relatadas, tendo 72,4% reduzido a participação em AF vigorosas. Aumento no tempo utilizando smartphone, tablet e microcomputador foram percebidos em 65,9% das crianças. Modificações favoráveis foram percebidas em relação à qualidade (34,1%) e ao tempo diário (51,1%) de sono. Modificações favoráveis relativas ao consumo de frutas (36,2%) e de refrigerantes (21,2%) e desfavoráveis para o consumo de verduras e legumes (19,1%) e de doces e salgadinhos (26,2%) também foram relatadas. Após quatro meses e meio do início das medidas de distanciamento social devido à pandemia da COVID-19, de acordo com a percepção de seus pais, crianças com excesso de peso aumentaram a MC e modificaram de forma desfavorável os níveis de AF e CS. Por outro lado, passaram a dormir mais e com maior qualidade e a consumir mais frutas e menos refrigerantes

Bio-behavioural research in a rare disease population: a doctoral student's experience.

BACKGROUND: Novice researchers who aspire to contribute to the body of knowledge concerning rare diseases face unique challenges in developing and conducting studies. These include unknown effect sizes in previous research, limitations in recruitment and enrolment, and managing data from a multi-site sample. AIM: To describe the challenges in researching rare diseases and possible solutions using a doctoral student exemplar from a cross-sectional correlational study of fatigue. DISCUSSION: The authors discuss the lessons learned from the study, including the challenges in recruitment, communication, collecting biological data and managing data in general. They posit possible solutions, including improving multi-site coordination, feasible methods for exploring sleep and stress, and measures to prevent equipment and data loss. CONCLUSION: Rare populations, such as young survivors of childhood brain tumours, deserve a voice in building the body of knowledge needed for more precise, personalised healthcare. It is possible with foresight for the novice researcher to make such a contribution. IMPLICATIONS FOR PRACTICE: Improved knowledge and assessment of symptoms during childhood will improve the detection of health risk factors and enable earlier intervention.

Perfil de personalidad en pacientes con trasplante renal: el modelo alternativo de los cinco factores / Personality profile of kidney transplant patients: the alternative five factor model

Resumen Introducción: la investigación sobre rasgos de personalidad en pacientes con trasplante renal es limitada. El objetivo de este estudio fue describir el perfil de personalidad de pacientes con trasplante renal, utilizando el modelo alternativo de cinco factores (AFFM), y compararlo con población estándar española. Material y métodos: la personalidad fue evaluada mediante el Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Una muestra de 207 pacientes con trasplante renal se emparejó por edad y género con 207controles de la población estándar. El análisis de regresión logística permitió estudiar la aportación de cada dimensión del ZKPQ al perfil distintivo de los pacientes trasplantados. Resultados: aparecieron diferencias significativas en las dimensiones de Neuroticismo-Ansiedad (p=.001), Agresión-Hostilidad (p=.009) y Actividad (p=.001), con puntuaciones bajas en pacientes trasplantados en comparación con la población estándar. La sociabilidad (p=.024) fue significativamente mayor en pacientes trasplantados. En el análisis de regresión, las bajas puntuaciones en Neuroticismo-Ansiedad (p=.005) y Actividad (p=.001) fueron predictores significativos para caracterizar los rasgos de personalidad de pacientes trasplantados. Conclusiones: desde el AFFM, los pacientes con trasplante renal muestran un perfil diferente de personalidad comparado con la población estándar, con bajas puntuaciones en las dimensiones de Neuroticismo-Ansiedad y Actividad.

Abstract Background: There is limited research on personality traits that characterized kidney transplant patients. The aim of this study was to describe personality profile of kidney transplant patients using the Alternative Five Factor Model (AFFM), and compared it with the Spanish standard population. Method: Personality was assessed using the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). A sample of 207 kidney transplant patients was matched by age and gender with 207 standard range controls. A logistic regression analyses was utilized to study the contribution of each ZKPQ dimension to describe the distinctive transplant patient's profile. Results: Significant differences were showed in Neuroticism-Anxiety (p=.001), Aggression-Hostility (p=.009), and Activity (p=.001) dimensions, with lower scores on transplant patients compared with standard population. But Sociability (p=.024) was significantly higher on kidney transplant patients. In logistic regression analysis low scores on Neuroticism-Anxiety (p=.005) and Activity (p=.001) were the significant predictors to characterize personality traits of kidney transplant patients. Conclusions: Kidney transplant patients had a differential profile under the AFFM compared to standard range sample, with lower scores on Neuroticism-Anxiety and Activity dimensions.

Interventions to increase uptake of cervical screening in sub-Saharan Africa: a scoping review using the integrated behavioral model.

BACKGROUND: Sub-Saharan Africa (SSA) experiences disproportionate burden of cervical cancer incidence and mortality due in part to low uptake of cervical screening, a strategy for prevention and down-staging of cervical cancer. This scoping review identifies studies of interventions to increase uptake of cervical screening among women in the region and uses the Integrated Behavioral Model (IBM) to describe how interventions might work. METHODS: A systematic search of literature was conducted in PubMed, Web of Science, Embase, and CINAHL databases through May 2019. Screening and data charting were performed by two independent reviewers. Intervention studies measuring changes to uptake in screening among women in SSA were included, with no restriction to intervention type, study setting or date, or participant characteristics. Intervention type and implementation strategies were described using behavioral constructs from the IBM. RESULTS: Of the 3704 citations the search produced, 19 studies were selected for inclusion. Most studies were published between 2014 and 2019 (78.9%) and were set in Nigeria (47.4%) and South Africa (26.3%). Studies most often assessed screening with Pap smears (31.6%) and measured uptake as ever screened (42.1%) or screened during the study period (36.8%). Education-based interventions were most common (57.9%) and the IBM construct of knowledge/skills to perform screening was targeted most frequently (68.4%). Willingness to screen was high, before and after intervention. Screening coverage ranged from 1.7 to 99.2% post-intervention, with six studies (31.6%) reporting a significant improvement in screening that achieved ≥60% coverage. CONCLUSIONS: Educational interventions were largely ineffective, except those that utilized peer or community health educators and mHealth implementation strategies. Two economic incentivization interventions were moderately effective, by acting on participants' instrumental attitudes, but resulted in screening coverage less than 20%. Innovative service delivery, including community-based self-sampling, acted on environmental constraints, striving to make services more available, accessible, and appropriate to women, and were the most effective. This review demonstrates that intent to perform screening may not be the major determinant of screening behavior, suggesting other theoretical frameworks may be needed to more fully understand uptake of cervical screening in sub-Saharan Africa, particularly for health systems change interventions.

The PRECEDE-PROCEED model as a tool in Public Health screening: a systematic review.

OBJETCTIVE: The aim of this systematic review was to summarize the scientific literature concerning the use of the Precede-Proceed model (PPM) applied to educational programs and health screenings contextsV. STUDY DESIGN: Systematic review. METHODS: The search process was based on a selection of publications listed in Medline and Scopus. The keywords used were "Precede-Proceed" AND ("screening" OR "educational programs"). Studies included in the systematic review were subdivided into those applying the model in a screening context, and those applying it within educational programs. RESULTS: Twenty-seven studies were retrieved, mostly performed in the USA and, generally, the promoting center was the University. In the context of cancer screening, the PPM model was most of all applied to Mammography Screening (5 of 13 studies in cancer screening), and Cervical Cancer Screening (5 of 13). Another three studies within the cancer field investigated Menopause-Inducing Cancer Treatments, Oral cancer prevention, and cancer screening in general. In the remaining studies, the model was applied in various screening areas, particularly chronic and degenerative diseases. There were many different study designs, most of which cross-sectional (8), though several RTCs (8) and focus groups (5) were also found. For the cross-sectional studies the methodological quality varied between 3/10 and 9/10, whilst for the RCTs it ranged from 2/5 to 3/5. CONCLUSIONS: The PPM provides an excellent framework for health intervention programs especially in screening contexts, and could improve the understanding of the relationship between variables such as knowledge and screening. Given the complexity of a behavioral change process, certain important predisposing factors could be measured in future studies, and during health intervention planning.

Novel insights into astrocyte-mediated signaling of proliferation, invasion and tumor immune microenvironment in glioblastoma.

Glioblastoma (GBM) continues to be the most aggressive cancer of the brain. The dismal prognosis is largely attributed to the microenvironment surrounding tumor cells. Astrocytes, the main component of the GBM microenvironment, play several fundamental physiological roles in the central nervous system. During the development of GBM, tumor-associated astrocytes (TAAs) directly contact GBM cells, which activate astrocytes to form reactive astrocytes, facilitating tumor progression, proliferation and migration through multiple well-understood signaling pathways. Notably, TAAs also influence GBM cell behaviors via suppressing immune responses and enhancing the chemoradiotherapy resistance of tumor cells. These new activities are closely linked with the treatment and prognosis of GBM. In this review, we discuss recent advances regarding new functions of reactive astrocytes, including TAA-cancer cell interactions, mechanisms involved in immunosuppressive regulation, and chemoradiotherapy resistance. It is expected that these updated experimental or clinical studies of TAAs may provide a promising approach for GBM treatment in the near future.

A re-evaluation of silk measurement by the cecropia caterpillar (Hyalophora cecropia) during cocoon construction reveals use of a silk odometer that is temporally regulated.

The late 5th instar caterpillar of the cecropia silk moth (Hyalophora cecropia) spins a silken cocoon with a distinct, multilayered architecture. The cocoon construction program, first described by the seminal work of Van der Kloot and Williams, consists of a highly ordered sequence of events. We perform behavioral experiments to re-evaluate the original cecropia work, which hypothesized that the length of silk that passes through the spinneret controls the orderly execution of each of the discrete events of cocoon spinning. We confirm and extend by three-dimensional scanning and quantitative measurements of silk weights that if cocoon construction is interrupted, upon re-spinning, the caterpillar continues the cocoon program from where it left off. We also confirm and extend by quantitative measurements of silk weights that cecropia caterpillars will not bypass any of the sections of the cocoon during the construction process, even if presented with a pre-spun section of a cocoon spun by another caterpillar. Blocking silk output inhibits caterpillars from performing normal spinning behaviors used for cocoon construction. Surprisingly, unblocking silk output 24-hr later did not restart the cocoon construction program, suggesting the involvement of a temporally-defined interval timer. We confirm with surgical reductions of the silk glands that it is the length of silk itself that matters, rather than the total amount of silk extracted by individuals. We used scanning electron microscopy to directly show that either mono- or dual-filament silk (i.e., equal silk lengths but which vary in their total amount of silk extracted) can be used to construct equivalent cocoons of normal size and that contain the relevant layers. We propose that our findings, taken together with the results of prior studies, strongly support the hypothesis that the caterpillar uses a silk "odometer" to measure the length of silk extracted during cocoon construction but does so in a temporally regulated manner. We further postulate that our examination of the anatomy of the silk spinning apparatus and ablating spinneret sensory output provides evidence that silk length measurement occurs upstream of output from the spinneret.

Multi-domain cognitive assessment of male mice shows space radiation is not harmful to high-level cognition and actually improves pattern separation.

Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56Fe and 28Si. Earth-based preclinical studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as 56Fe and 28Si irradiation led to faster context discrimination in a non-touchscreen task and 56Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.

Geospatial mapping and resource utilization tool in support of a national smoke-free public housing rule.

OBJECTIVE: To advance public health support for the U.S. Department of Housing and Urban Development's smoke-free rule, the Centers for Disease Control and Prevention collaborated with the Georgia Institute of Technology to develop a geospatial mapping tool. The objective was to create a tool state and local public health agencies could use to tailor smoke-free educational materials and cessation interventions for specific public housing development resident populations. RESULTS: The resulting "Extinguish Tool" includes an interactive map of U.S. public housing developments (PHDs) and healthcare facilities that provides detailed information on individual PHDs, their proximity to existing healthcare facilities, and the demographic characteristics of residents. The tool also estimates the number of PHD residents who smoke cigarettes and calculates crude estimates of the potential economic benefits of providing cessation interventions to these residents. The geospatial mapping tool project serves as an example of a collaborative and innovative public health approach to protecting the health and well-being of the nation's two million public housing residents, including 760,000 children, from the harms of tobacco smoking and secondhand smoke exposure in the places where they live, play, and gather.

Identification of inflammatory markers suitable for non-invasive, repeated measurement studies in biobehavioral research: A feasibility study.

INTRODUCTION: Studying the role of the immune system in the interaction between mental and physical health is challenging. To study individuals with an intensive, longitudinal study design that requires repetitive sampling in their daily life, non-invasive sampling techniques are a necessity. Urine can be collected in a non-invasive way, but this may be demanding for participants and little is known about fluctuation of inflammatory markers in urine over time. The aim of this study was to investigate the feasibility of non-invasive sampling, and to explore intra-individual differences in inflammatory markers in urine. MATERIALS & METHODS: Ten healthy individuals collected 24-hour urine for 63 consecutive days. In a pilot analysis, 39 inflammatory markers were examined for detectability in urine, stability over time and under storage conditions, and daily fluctuations. Multiplex analyses were used to quantify levels of eight selected markers: C-reactive protein (CRP), Fractalkine, Interleukin-1 receptor-antagonist (IL-1RA), interferon-α (IFNα), interferon-γ (IFNγ), Interferon gamma-induced protein 10 (IP10), Macrophage inflammatory protein-1ß (MIP-1ß), and Vascular Endothelial Growth Factor (VEGF). Cross-correlations were calculated between the overnight and 24-hour samples were calculated, to examine whether 24-hour urine could be replaced by the overnight portion for better feasibility. We examined intra- and interindividual differences in the levels of inflammatory markers in urine and the fluctuations thereof. RESULTS: This study showed that levels of selected inflammatory markers can be detected in urine. Cross-correlation analyses showed that correlations between levels of inflammatory markers in the night portion and the 24-hour urine sample varied widely between individuals. In addition, analyses of time series revealed striking inter- and intra-individual variation in levels of inflammatory markers and their fluctuations. CONCLUSION: We show that the assessment of urinary inflammatory markers is feasible in an intensive day-to-day study in healthy individuals. However, 24-hour urine cannot be replaced by an overnight portion to alleviate the protocol burden. Levels of inflammatory markers show substantial variation between and within persons.

Tumour growth activation by the central nervous system-An integrative theory of cancer.

The currently recognized mechanisms of the biology of cancer are not yet enough to explain the high incidence of the disease in industrialized countries. Survival and proliferation of cancer cells demand a well-orchestrated combination of functional capabilities, or hallmarks, which requires complex signalling networks that often exceed the tumour boundaries. Based on latest research on environmental health and aiming to provide cancer with a coherent set of organizing principles, we propose an integrative model of carcinogenesis founded on tumour growth activation by the central nervous system as an adaptive, allostatic response to both environmental and emotional challenges. In this way, chronicity of physical as well as psychological stressors may be directly involved in cancer genesis and progression, after an early inflammatory stage. The model also contemplates accidental activation of the tumour growth programme following direct DNA damage, but as a rare event that does not account for most cancers in humans. Bodily and cellular mechanisms designed to facilitate tumorigenesis may include exacerbation of the sympathetic activity, overexpression of membrane ion channels, promotion of selected mutations and methylations, degradation of the mitochondria and reprogramming of adult stem cells.

Single-cell kinetics of siRNA-mediated mRNA degradation.

RNA interference (RNAi) enables the therapeutic use of small interfering RNAs (siRNAs) to silence disease-related genes. The efficiency of silencing is commonly assessed by measuring expression levels of the target protein at a given time point post-transfection. Here, we determine the siRNA-induced fold change in mRNA degradation kinetics from single-cell fluorescence time-courses obtained using live-cell imaging on single-cell arrays (LISCA). After simultaneous transfection of mRNAs encoding eGFP (target) and CayRFP (reference), the eGFP expression is silenced by siRNA. The single-cell time-courses are fitted using a mathematical model of gene expression. Analysis yields best estimates of related kinetic rate constants, including mRNA degradation constants. We determine the siRNA-induced changes in kinetic rates and their correlations between target and reference protein expression. Assessment of mRNA degradation constants using single-cell time-lapse imaging is fast (<30 h) and returns an accurate, time-independent measure of siRNA-induced silencing, thus allowing the exact evaluation of siRNA therapeutics.

Histological Method to Study the Effect of Shear Stress on Cell Proliferation and Tissue Morphology in a Bioreactor.

Background: Tissue engineering represents a promising approach for the production of bone substitutes. The use of perfusion bioreactors for the culture of bone-forming cells on a three-dimensional porous scaffold resolves mass transport limitations and provides mechanical stimuli. Despite the recent and important development of bioreactors for tissue engineering, the underlying mechanisms leading to the production of bone substitutes remain poorly understood. Methods: In order to study cell proliferation in a perfusion bioreactor, we propose a simplified experimental set-up using an impermeable scaffold model made of 2 mm diameter glass beads on which mechanosensitive cells, NIH-3T3 fibroblasts are cultured for up to 3 weeks under 10 mL/min culture medium flow. A methodology combining histological procedure, image analysis and analytical calculations allows the description and quantification of cell proliferation and tissue production in relation to the mean wall shear stress within the bioreactor. Results: Results show a massive expansion of the cell phase after 3 weeks in bioreactor compared to static control. A scenario of cell proliferation within the three-dimensional bioreactor porosity over the 3 weeks of culture is proposed pointing out the essential role of the contact points between adjacent beads. Calculations indicate that the mean wall shear stress experienced by the cells changes with culture time, from about 50 mPa at the beginning of the experiment to about 100 mPa after 3 weeks. Conclusion: We anticipate that our results will help the development and calibration of predictive models, which rely on estimates and morphological description of cell proliferation under shear stress.

Change Theory Contributes to Choosing Wisely for Immune Thrombocytopenia.

OBJECTIVES: Despite 2011 guidelines in which it is suggested that treatment of acute immune thrombocytopenia purpura (aITP) is not needed for patients without significant bleeding, only 14% of children treated for aITP have bleeding symptoms. Our aim was to decrease the percentage of children with first-episode aITP who were unnecessarily treated by 50% within 12 months of guideline implementation. METHODS: An intervention was designed by using the precaution-adoption-process model. A standard-of-practice meeting was organized and focused on clinician readiness for change. After education on current evidence and common cognitive errors, consensus clinical guidelines were created. After implementation, an article in a statewide professional newsletter was published to educate community providers. Unnecessary treatment (UT) was defined as treatment of any patient who only had bruising and/or self-resolving nose bleeds. Statistical process control charts were used to track progress, midline shifts were determined by Nelson's rules, and hospital costs were derived from administrative billing data. RESULTS: One hundred children with aITP were seen from January 2013 to September 2018. UT decreased from 70% to a sustained rate of <30% (P = .008), including a mean of 7% over the past 12 months. The admission rate decreased from 100% to 52% (P = .013), and the total percentage of patients treated decreased from 100% to 48% (P = .016), with both numbers continuing to decline. No adverse bleeding events occurred. An estimated 12 admissions, 4 readmissions, and 5 adverse events were avoided annually. CONCLUSIONS: We demonstrated successful improvement in UT of aITP through an educational intervention informed by the precaution-adoption-process model change theory.

Development of a suicide index model in general adolescents using the South Korea 2012-2016 national representative survey data.

Suicide is a leading cause of death among adolescents and a major public health concern. Here we developed a risk stratification model for adolescent suicide attempts using sociodemographic characteristics, risk behaviours and psychological variables. Participants were 247,222 subjects in the Korea Youth Risk Behavior Web-based Survey (KYRBS). We developed a suicide index based on the suicide risk estimated in the generalized linear model and proposed the risk stratification model using the R language to measure the probability of suicide attempt among adolescents. Among the study population, the annual rate of suicide attempt was approximately 4%. The model provided good prediction for suicide attempt (AUC = 0.85). The important univariate risk factors for the outcome were dimensional measures of age, sex, breakfast consumption, experience of violence, sleep duration, perceived stress, feeling of sadness, current cigarette smoking, current alcohol drinking, perceived general health, perceived academic record, household economic status and living with biological or adoptive parents. Our suicide index model allowed the identification of adolescents who are at a high risk for suicide. This tool may promote the prevention of adolescent suicide and can be particularly useful in everyday settings where it is difficult to contact mental health professionals immediately.

Modelling continuous abstinence rates over time from clinical trials of pharmacological interventions for smoking cessation.

BACKGROUND AND AIM: It is useful, for theoretical and practical reasons, to be able to specify functions for continuous abstinence over time in smoking cessation attempts. This study aimed to find the best-fitting models of mean proportion abstinent with different smoking cessation pharmacotherapies up to 52 weeks from the quit date. METHODS: We searched the Cochrane Database of Systematic Reviews to identify randomized controlled trials (RCTs) of pharmacological treatments to aid smoking cessation. For comparability, we selected trials that provided 12 weeks of treatment. Continuous abstinence rates for each treatment at each follow-up point in trials were extracted along with methodological details of the trial. Data points for each pharmacotherapy at each follow-up point were aggregated where the total across contributing studies included at least 1000 participants per data point. Continuous abstinence curves were modelled using a range of different functions from the quit date to 52-week follow-up. Models were compared for fit using R2 and Bayesian information criterion (BIC). RESULTS: Studies meeting our selection criteria covered three pharmacotherapies [varenicline, nicotine replacement therapy (NRT) and bupropion] and placebo. Power functions provided the best fit (R2  > 0.99, BIC < 17.0) to continuous abstinence curves from the target quit date in all cases except for varenicline, where a logarithmic function described the curve best (R2  = 0.99, BIC = 21.2). At 52 weeks, abstinence rates were 22.5% (23.0% modelled) for varenicline, 16.7% (16.0% modelled) for bupropion, 13.0% (12.4% modelled) for NRT and 8.3% (8.9% modelled) for placebo. For varenicline, bupropion, NRT and placebo, respectively, 55.9, 65.0, 62.3 and 56.5% of participants who were abstinent at the end of treatment were still abstinent at 52 weeks. CONCLUSIONS: Mean continuous abstinence rates up to 52 weeks from initiation of smoking cessation attempts in clinical trials can be modelled using simple power functions for placebo, nicotine replacement therapy and bupropion and a logarithmic function for varenicline. This allows accurate prediction of abstinence rates from any time point to any other time point up to 52 weeks.

Processes of Change for Colonoscopy: Limited Support for Use Among Navigated Latinos.

This study assessed the role of the processes of change (POC), a construct of the transtheoretical model, in colorectal cancer (CRC) screening among Latinos. Latinos participate in CRC screening less often and are diagnosed with CRC at a later stage than whites. POC items were administered to 344 English- and Spanish-speaking Latinos at average risk for CRC who had not had a colonoscopy in the past 5 years and received a colonoscopy referral. POC were measured at three timepoints: following informed consent (T1) at time of referral, 2 weeks prior to scheduled colonoscopy (T2), and 1 month after scheduled colonoscopy (T3). Participants received patient navigation as part of a randomized controlled trial to promote screening colonoscopy. POC scores were examined for changes during the course of the intervention, and logistic regression models assessed the relationship between POC scores and CRC screening adherence. Total POC scores decreased between T1 and T2 (p = 0.03) but were unchanged between T1 and T3. CRC screening adherence was not significantly associated with POC scores or change in POC scores over time. The POC instrument was not found useful for predicting colonoscopy adherence among Latinos in conjunction with patient navigation. Total POC scores did not increase during a patient navigation intervention despite high colonoscopy completion rates.