The control of mitosis in mammalian tissues

The question of which factors are central in determining whether a cell will undertake a new round of mitosis or will decycle has been examined in the isolated thymic lymphocyte model. Such cell populations possess both in vivo and in vitro a subpopulation of quiescent lymphoblasts which may be induced to reinitiate their mitotic programme. In the intact animal the major determinant of proliferative activity is the plasma ionised calcium concentration. However it has been established in culture that a variety of hormones, ions, cyclic nucleotides, plant lectins and ionophores may like calcium elicit a mitogenic response. These agents do not appear however to initiate DNA synthesis in an identical fashion. Rather there are two distinct intracellular mitogenic axes. The first axis includes a number of adenylate cyclase stimulants, cyclic AMP, phosphodiesterase inhibitors and magnesium ions. It was found that all these mitogens required extracellular magnesium ions to exhibit their stimulatory capacity. This dichotomy in mitogenic activity was further emphasised by the observation that these mitogens are all inhibited by testosterone, whilst the magnesium-independent mitogens were insensitive to this androgen. Indeed this second group of stimulatory factors required the presence of calcium ions in the extracellular milieu for activity, and were, in contrast to the magnesium-dependent mitogens inhibited by the presence of oestradiol in the culture. By examining the interrelationships between these various mitogens and inhibitors it has been possible to propose a mechanism to describe the activation process in the thymocyte. Studies of the metabolism of cyclic nucleotides, membrane potential and transmembrane ion fluxes indicate that there may be a complex relationship between membrane fluidity, ion balance and cyclic nucleotide levels which may individually or in concert promote the initiation of DNA synthesis. A number of possible mechanisms are discussed to account for these observations.

Investigation of the antiproliferative properties of tumour promoting phorbol esters and related compounds

Tumour promoting phorbol esters such as 12-0-tetradecanoylphorbol-13-acetate (TPA) exert a multitude of biological effects on many cellular systems, many of which are believed to be mediated via the activation of the enzyme protein kinase C (PKC). TPA and other biologically active phorbol esters inhibited the proliferation of the A549 human lung carcinoma cell line. However, after 5-6 days culture in the continued presence of the phorbol ester cells began to proliferate at a rate similar to that of untreated cells. Resistance to TPA was lost following subculturing, although subculture in the presence of 10 nM TPA for more than 9 weeks resulted in a more resistant phenotype. The selection of a TPA-resistant subpopulation was not responsible for the observed resistance. The antiproliferative properties of other PKC activators were investigated. Mezerein induced the same antiproliferative effects as TPA but synthetic diacylglycerols (DAGs), the presumed physiological ligands of PKC, exerted only a non-specific cytotoxic influence on growth. Bryostatins 1 and 2 were able to induce transient growth arrest of A549 cells in a manner similar to phorbol esters at nanomolar concentrations, but at higher concentrations blocked both their own antiproliferative action and also that of phorbol esters and mezerein. Fourteen compounds synthesized to mimic features of the phorbol ester pharmacophore and/or DAGs did not mimic the antiproliferative properties of TPA in A549 cells and exerted only a DAG-like non-specific cytotoxicity at high concentrations. The subcellular distribution and activity of PKC was determined following partial purification by non-denaturing polyacrylamide gel electrophoresis. Treatment with TPA, mezerein or bryostatins resulted in a concentration-dependent shift of PKC activity from the cytosol to cellular membranes within 30 min. Significant translocation was not observed on treatment with DAGs. Chronic exposure of cells to TPA caused a time- and concentration dependent down-regulation of functional PKC activity. A complete loss of PKC activity was also observed on treatment with growth-inhibitory concentrations of bryostatins. No PKC activity was detected in cells resistant to the growth-inhibitory influence of TPA. Measurement of intracellular Ca2+ concentrations using A549 cells cultured on Cytodex 1 microcarrier beads revealed that TPA, mezerein and the bryostatins induced a similar rapid rise in intracellular Ca2+ levels.

36 monocyte subpopulations counts and associations with global longitudinal strain in st-elevation myocardial infarction patients with normal ejection fraction

Introduction - Monocytes, with 3 different subsets, are implicated in the initiation and progression of the atherosclerotic plaque contributing to plaque instability and rupture. Mon1 are the “classical” monocytes with inflammatory action, whilst Mon3 are considered reparative with fibroblast deposition ability. The function of the newly described Mon2 subset is yet to be fully described. In PCI era, fewer patients have globally reduced left ventricular ejection fraction post infarction, hence the importance of studying regional wall motion abnormalities and deformation at segmental levels using longitudinal strain. Little is known of the role for the 3 monocyte subpopulations in determining global strain in ST elevation myocardial infarction patients (STEMI). Conclusion In patients with normal or mildly impaired EF post infarction, higher counts of Mon1 and Mon2 are correlated with GLS within 7 days and at 6 months of remodelling post infarction. Adverse clinical outcomes in patients with reduced convalescent GLS were predicted with Mon1 and Mon2 suggestive of an inflammatory role for the newly identified Mon2 subpopulation. These results imply an important role for monocytes in myocardial healing when assessed by subclinical ventricular function indices. Methodology - STEMI patients (n = 101, mean age 64 ± 13 years; 69% male) treated with percutaneous revascularisation were recruited within 24 h post-infarction. Peripheral blood monocyte subpopulations were enumerated and characterised using flow cytometry after staining for CD14, CD16 and CCR2. Phenotypically, monocyte subpopulations are defined as: CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3). Phagocytic activity of monocytes was measured using flow cytometry and Ecoli commercial kit. Transthoracic 2D echocardiography was performed within 7 days and at 6 months post infarct to assess global longitudinal strain (GLS) via speckle tracking. MACE was defined as recurrent acute coronary syndrome and death. Results - STEMI patients with EF ≥50% by Simpson’s biplane (n = 52) had GLS assessed. Using multivariate regression analysis higher counts of Mon1 and Mon 2 and phagocytic activity of Mon2 were significantly associated with GLS (after adjusting for age, time to hospital presentation, and peak troponin levels) (Table 1). At 6 months, the convalescent GLS remained associated with higher counts of Mon1, Mon 2. At one year follow up, using multivariate Cox regression analysis, Mon1 and Mon2 counts were an independent predictor of MACE in patients with a reduced GLS (n = 21)

A Limit Theorem for Multi-Type Subcritical Age-Dependent Branching Processes with two Types of Immigration

Марусия Н. Славчова-Божкова - В настоящата работа се обобщава една гранична теорема за докритичен многомерен разклоняващ се процес, зависещ от възрастта на частиците с два типа имиграция. Целта е да се обобщи аналогичен резултат в едномерния случай като се прилагат “coupling” метода, теория на възстановяването и регенериращи процеси.

BRACHYURY confers cancer stem cell characteristics on colorectal cancer cells

Cancer stem cells (CSCs) are initiating cells in colorectal cancer (CRC). Colorectal tumours undergo epithelial to mesenchymal transition (EMT)-like processes at the invasive front, enabling invasion and metastasis, and recent studies have linked this process to the acquisition of stem cell-like properties. It is of fundamental importance to understand the molecular events leading to the establishment of cancer initiating cells and how these mechanisms relate to cellular transitions during tumourigenesis. We use an in vitro system to recapitulate changes in CRC cells at the invasive front (mesenchymal-like cells) and central mass (epithelial-like cells) of tumours. We show that the mesoderm inducer BRACHYURY is expressed in a subpopulation of CRC cells that resemble invasive front mesenchymal-like cells, where it acts to impose characteristics of CSCs in a fully reversible manner, suggesting reversible formation and modulation of such cells. BRACHYURY, itself regulated by the oncogene β-catenin, influences NANOG and other 'stemness' markers including a panel of markers defining CRC-CSC whose presence has been linked to poor patient prognosis. Similar regulation of NANOG through BRACHYURY was observed in other cells lines, suggesting this might be a pathway common to cancer cells undergoing mesenchymal transition. We suggest that BRACHYURY may regulate NANOG in mesenchymal-like CRC cells to impose a 'plastic-state', allowing competence of cells to respond to signals prompting invasion or metastasis. Copyright © 2011 UICC.

Monocyte subset counts associations with left ventricular systolic function post ST elevation myocardial infarction

Background: Monocytes are implicated in the initiation and progression of theatherosclerotic plaque contributing to plaque instability and rupture. Little is knownof the role played by the 3 phenotypically and functionally different monocytesubpopulations in determining ventricular remodeling following ST elevation my-ocardial infarction (STEMI). Mon1 are "classical" inflammatory monocytes, whilstMon3 are considered reparative with fibroblast deposition ability. The function ofthe newly described Mon2 is yet to be elucidated. Method: STEMI patients (n=196, mean age 62±13 years; 72% male) treatedwith percutaneous revascularization were recruited within the first 24 hours. Pe-ripheral blood monocyte subpopulations were enumerated and characterizedusing flow cytometry after staining for CD14, CD16 and CCR2. Phenotypi-cally, monocyte subpopulations are defined as: CD14+CD16-CCR2+ (Mon1),CD14+CD16+CCR+ (Mon2) and CD14lowCD16+CCR2- (Mon3) cells. Transtho-racic 2D echocardiography was performed within 7 days and 6 months post infarctto assess ventricular volumes, mass, systolic, and diastolic functions. Results: Using linear regression analysis higher counts for Mon1, and lowercounts for Mon2 and Mon3 were significantly associated with the baseline leftventricular ejection fraction (LVEF) within seven days post infarction. At 6 monthspost STEMI lower counts of Mon2 remained positively associated with decreasedLVEF (p value= 0.002).Monocyte subsets correlation with LVEFMonocytes mean florescence Baseline left ventricular Left ventricular ejectionintensity (cells/μl) ejection fraction (%) fraction (%) at 6 months post infarctβ-value P-valueβ-value P-valueTotal Mon0.31 P<0.001 0.360.009Mon 10.019 0.020.070.62Mon 2−0.28 0.001 −0.420.002Mon 3−0.27 0.001 −0.180.21 Conclusion: Peripheral monocytes of all three subsets correlate with LVEF af-ter a myocardial infarction. High counts of the inflammatory Mon1 are associatedwith reduction in the baseline LVEF. Post remodelling, the convalescent EF wasindependently predicted by monocyte subpopulation 2. As lower counts depictednegative ventricular remodeling, this suggests a reparative role for the newly de-scribed Mon2, possibly via myofibroblast deposition and angiogenesis, in contrastto an anticipated inflammatory role.

From foster care to college: Young adults' perceptions of factors that impacted their academic achievement

Despite increased Federal, state, and local efforts in the United States to improve outcomes among young adults who emancipate from foster care, low educational achievement and attainment continue to characterize this vulnerable subpopulation. Approximately 50% of foster children do not obtain a high school diploma or a general equivalency diploma (GED). Only about 20% of former foster children enroll in college, compared to 60% of youth not in foster care. The purpose of this study was to explore, describe and explain the perceptions of college students who had lived in foster care regarding the external and internal influences that impacted their academic achievement and attainment. Interviews with a purposefully selected sample of 24 Florida college students were conducted; transcripts were coded and analyzed thematically. Findings included that participants experienced a particular set of external and internal influences at school, in foster care settings, and in the community. External influences include interactions with (a) multiple non-relative guardians and case workers, (b) relatives, especially siblings, (c) mentors, (d) teachers and school administrators, and (e) school counselors. Internal influences include the barriers of anger and bad behavior and a newly identified set of internal characteristics, called success strengths by the researcher, that promote academic achievement and college attainment. Implications are as follows: (a) Future theory on academic achievement concerning foster youth should reflect the importance of the affective aspect of school interactions. (b) Policy should mandate awareness training for educators, social workers, and other adults who work with former foster youth to increase professionals' awareness of the barriers, supports and success strengths that impact the academic lives of children and youth in foster care. (c) Adult educators and human resource development professionals should develop and implement appropriate new education and training materials and interventions. Future research may include a similar interview with former foster youth who graduated from college and with foster youth who leave school before graduating. Finally, a study with a nationally representative sample of college enrolled former foster children should be conducted to determine the relative importance of the barriers, supports and success strengths identified in this study.

Effect of Hydrologic Restoration on the Habitat of The Cape Sable Seaside Sparrow, Annual Report of 2002-2003

After developing field sampling protocols and making a series of consultations with investigators involved in research in CSSS habitat, we determined that vegetationhydrology interactions within this landscape are best sampled at a combination of scales. At the finer scale, we decided to sample at 100 m intervals along transects that cross the range of habitats present, and at the coarser scale, to conduct an extensive survey of vegetation at sites of known sparrow density dispersed throughout the range of the CSSS. We initiated sampling in the first week of January 2003 and continued it through the last week of May. During this period, we established 6 transects, one in each CSSS subpopulation, completed topographic survey along the Transects A, C, D, and F, and sampled herb and shrub stratum vegetation, soil depth and periphyton along Transects A, and at 179 census points. We also conducted topographic surveys and completed vegetation and soil depth sampling along two of five transects used by ENP researchers for monitoring long-term vegetation change in Taylor Slough. We analyzed the data by summarizing the compositional and structural measures and by using cluster analysis, ordination, weighted averaging regression, and weighted averaging calibration. The mean elevation of transects decreased from north to south, and Transect F had greater variation than other transects. We identified eight vegetation assemblages that can be grouped into two broad categories, ‘wet prairie’ and ‘marsh’. In the 2003 survey, wet prairies were most dominant in the northeastern sub-populations, and had shorter inferred-hydroperiod, higher species richness and shallower soils than marshes, which were common in Subpopulations A, D, and the southernmost regions of Sub-population B. Most of the sites at which birds were observed during 2001 or 2002 had an inferred-hydroperiod of 120-150 days, while no birds were observed at sites with an inferred-hydroperiod less than 120 days or more than 300 days. Management-induced water level changes in Taylor Slought during the 1980’s and 1990’s appeared to elicit parallel changes in vegetation. The results described in detail in the following pages serve as a basis for evaluating and modifying, if necessary, the sampling design and analytical techniques to be used in the next three years of the project.

On the use of transgenic mice and optogenetics to characterize genetically defined subpopulations of neurons

Neuroscientists have a variety of perspectives with which to classify different parts of the brain. With the rise of genetic-based techniques such as optogenetics, it is increasingly important to identify whether a group of cells, defined by morphology, function or anatomical location possesses a distinct pattern of expression of one or more genetic promoters. This would allow for better ways to study of these genetically defined subpopulations of neurons. In this work, I present a theoretical discussion and threeexperimental studies in which this was the main question being addressed. Paper I discusses the issues involved in selecting a promoter to study structures and subpopulations in the Ventral Tegmental Area. Paper II characterizes a subpopulation of cells in the Ventral Tegmental Area that shares the expression of a promoter and is anatomically very restricted, and induces aversion when stimulated. Paper III utilizes a similar strategy to investigate a subpopulation in the subthalamic nucleus that expresses PITX2 and VGLUT2 which, when inactivated, causes hyperlocomotion. Paper IV exploits the fact that a previously identified group of cells in the ventral hippocampus expresses CHRNA2, and indicates that this population may be necessary and sufficient for the establishment of the theta rhythm (2-8 Hz) in the Local Field Potential of anesthetized mice. All of these studies were guided by the same strategy of characterizing and studying the role of a genetically defined subpopulation of cells, and they demonstrate the different ways in which this approach can generate new discoveries.

Receptores de citocinas proinflamatórias na pré-eclâmpsia

Preeclampsia is a disease specific of human pregnancy that affects 3-8% of pregnant women, and it is one of the three leading causes of maternal mortality and morbidity. The disease is characterized by hypertension and proteinuria after the 20th week of gestation. The risk factors for this disease are not completely understood but appear to include dysregulation of the immune response arising from defects in placentation, environmental and genetic factors. This study aimed to determine whether the variation in the amount of proinflammatory cytokine receptors IL-1R2, IL-6R and TNF-αR1 would be involved in preeclampsia. They were recruited women with preeclampsia (n=24) and women who evolved during pregnancy without changes in blood pressure (n=12) were recruited. Clinical and laboratory data were collected. The cytokine receptors (IL-1R2, TNF-αR1 and IL-6R) were assessed in mononuclear cells isolated from peripheral blood using flow cytometry (Control = 8; PE = 24). C-reactive protein (CRP) was determined by CRP ultrasensitive method (Control = 7; PE = 18) was performed using sera pregnant women. Women with preeclampsia had higher weight at the beginning of the pregnancy (p=0.0171) and lower gestational age at delivery (0.0008). Classical monocytes were decreased in preeclampsia but not intermediate or non-classical monocytes. The frequency of IL-1R2 pro inflammatory cytokine receptors is decreased in women with PE only in the subpopulation of non-classical monocytes (p = 0.0011). TNF-αR1 receptor and IL-6R, had a decreased frequency in the three subpopulations of monocyte (classic, intermediate and non-classical) when compared to women with normal pregnancy. An increase in IL-1R2 receptor in TCD4+ lymphocytes, but a decrease in TNF-receptor and IL-6R in women with preeclampsia were found. No differences in the frequency of those receptors in CD3+/CD8+ in preeclampsia. There was no difference in C-reactive protein in preeclampsia. The reduction in the amount of IL-1R2, TNF- αR1 and IL-6R monocytes and lymphocytes can be involved in the regulation of inflammation observed in preeclampsia, contributing to disease.

Concentrations of brominated and chlorinated contaminants in adipose tissue of polar bears (Ursus maritimus) between 1991-2007

Adipose tissue was sampled from the western Hudson Bay (WHB) subpopulation of polar bears at intervals from 1991 to 2007 to examine temporal trends of PCB and OCP levels both on an individual and sum-contaminant basis. We also determined levels and temporal trends of emerging polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), polybrominated biphenyls (PBBs) and other current-use brominated flame retardants. Over the 17-year period, sum DDT (and p,p'-DDE, p,p'-DDD, p,p'-DDT) decreased (-8.4%/year); alpha-hexachlorocyclohexane (alpha-HCH) decreased (-11%/year); beta-HCH increased ( + 8.3%/year); and sum PCB and sum chlordane (CHL), both contaminants at highest concentrations in all years (>1 ppm), showed no distinct trends even when compared to previous data for this subpopulation dating back to 1968. Some of the less persistent PCB congeners decreased significantly (-1.6%/year to -6.3%/year), whereas CB153 levels tended to increase (+ 3.3%/year). Parent CHLs (c-nonachlor, t-nonachlor) declined, whereas non-monotonic trends were detected for metabolites (heptachlor epoxide, oxychlordane). sum chlorobenzene, octachlorostyrene, sum mirex, sum MeSO2-PCB and dieldrin did not significantly change. Increasing sum PBDE levels (+13%/year) matched increases in the four consistently detected congeners, BDE47, BDE99, BDE100 and BDE153. Although no trend was observed, total-(alpha)-HBCD was only detected post-2000. Levels of the highest concentration brominated contaminant, BB153, showed no temporal change. As long-term ecosystem changes affecting contaminant levels may also affect contaminant patterns, we examined the influence of year (i.e., aging or "weathering" of the contaminant pattern), dietary tracers (carbon stable isotope ratios, fatty acid patterns) and biological (age/sex) group on congener/metabolite profiles. Patterns of PCBs, CHLs and PBDEs were correlated with dietary tracers and biological group, but only PCB and CHL patterns were correlated with year. DDT patterns were not associated with any explanatory variables, possibly related to local DDT sources. Contaminant pattern trends may be useful in distinguishing the possible role of ecological/diet changes on contaminant burdens from expected dynamics due to atmospheric sources and weathering.

(Tables S1,2) Stable isotopes in muscle tissue of polar bears (Ursus maritimus) from various regions of the Arctic

The relative contribution of regional contamination versus dietary differences to geographic variation in polar bear (Ursus maritimus) contaminant levels is unknown. Dietary variation between Alaska, Canada, East Greenland, and Svalbard subpopulations was assessed by muscle nitrogen and carbon stable isotope (d15N, d13C) and adipose fatty acid (FA) signatures relative to their main prey (ringed seals). Western and southern Hudson Bay signatures were characterized by depleted d15N and d13C, lower proportions of C20 and C22 monounsaturated FAs and higher proportions of C18 and longer chain polyunsaturated FAs. East Greenland and Svalbard signatures were reversed relative to Hudson Bay. Alaskan and Canadian Arctic signatures were intermediate. Between-subpopulation dietary differences predominated over interannual, seasonal, sex, or age variation. Among various brominated and chlorinated contaminants, diet signatures significantly explained variation in adipose levels of polybrominated diphenyl ether (PBDE) flame retardants (14-15%) and legacy PCBs (18-21%). However, dietary influence was contaminant class-specific, since only low or nonsignificant proportions of variation in organochlorine pesticide (e.g., chlordane) levels were explained by diet. Hudson Bay diet signatures were associated with lower PCB and PBDE levels, whereas East Greenland and Svalbard signatures were associated with higher levels. Understanding diet/food web factors is important to accurately interpret contaminant trends, particularly in a changing Arctic.

Targeting treatment resistant breast cancer stem cells with FKBPL and its peptide derivative, AD-01

FKBPL and its peptide derivative, AD-01, have already demonstrated well-established inhibitory effects on breast cancer growth and CD44 dependent anti-angiogenic activity1, 2, 3. Since breast cancer stem cells (BCSCs) are CD44 positive, we wanted to explore if AD-01 could specifically target BCSCs. FKBPL stable overexpression or AD-01 treatment were highly effective at reducing the BCSC population measured by inhibiting mammosphere forming efficiency (MFE) in cell lines and primary breast cancer samples from both solid breast tumours and pleural effusions. Flow cytometry, to assess the ESA+/CD44+/CD24- subpopulation, validated these results. The ability of AD-01 to inhibit the self-renewal capacity of BCSCs was confirmed across three generations of mammospheres, where mammospheres were completely eradicated by the third generation (p<0.001). Clonogenic assays suggested that AD-01 mediated BCSC differentiation, with a significant decrease in the number of holoclones and an associated increase in meroclones/paraclones. In support of this, the stem cell markers, Nanog and Oct4 were significantly reduced following AD-01 treatment, whilst transfection of FKBPL-targeted siRNAs led to an increase in these markers and in mammosphere forming potential, highlighting the endogenous role of FKBPL in stem cell signalling. The clinical relevance of this was confirmed using a publically available microarray data set (GSE7390), where, high FKBPL and low Nanog expression were independently associated with improved overall survival in breast cancer patients (log rank test p=0.03; hazard ratio=3.01). When AD-01 was combined with other agents, we observed synergistic activity with the Notch inhibitor, DAPT and AD-01 was also able to abrogate a chemo- and radiotherapy induced enrichment in BCSCs. Importantly, using ‘gold standard’ in vivo limiting dilution assays we demonstrated a delay in tumour initiation and reoccurrence in AD-01 treated xenografts. In summary, AD-01 appears to have dual anti-angiogenic and anti-BCSC activity which will be advantageous as this agent enters clinical trial.

The use of motivational interviews by nurses to promote health behaviors in adolescents: A scoping review protocol

Abstract The developmental changes during adolescence may affect subsequent risk for diseases and health-related behaviors. Traditionally, professionals assume that knowledge is sufficient for behavioral changes; however adolescents continue to engage in unhealthy behaviors despite clearly knowing what they should do and how to change. "What is lacking is the motivation to apply that knowledge". Motivational Interview (MI) may be taken as an essential tool in the provision of nursing care to adolescents, being itself a workspace with possible therapeutic effects. Objectives The objective of this scoping is to examine and map the use of MI by nurses in their clinical practice with adolescents to promote health behaviors. The review will focus on knowing what is the current extent of the use of nurse-led MI; which adolescent populations were included; in which contexts nurses use MI; which MI techniques/strategies have been used and what outcomes on health behaviors promotion have been reported. Methodology This scoping review will be informed by JBI methodology. The population of this study is adolescents aged 10 to 19 years participating in nurse-led MI. The concept of MI include MI done by personal or telephone call, with any number of sessions, brief interventions and other motivational interventions grounded but not limited to the principles described by Miller & Rollnick (2008). All geographical and all clinical practice contexts where nurses' undertake MI with adolescents such as hospitals, primary health care, health care centers, community or schools will be contemplated. English, Spanish and Portuguese published studies will be considered for inclusion. Results An initial limited search of MEDLINE and CINAHL was undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the concepts, synonyms (with truncations), MeSH Terms and Cinhal headings of this study. It was identified 5 synonyms for "Adolescents", 7 for "MI" and 2 for "nurse". A first search using the all 14 identified keywords and index terms was made at Medline (Title/Abstract) and brought up 125 articles. Other 16 databases referenced at the protocol will be searched to identify additional studies. Articles identified from the final search will be assessed for relevance to the review, based on information provided in the title and abstract. The full article will be retrieved for all studies that meet the inclusion criteria of the review. It is expected that findings from this Scoping Review provide needed information to nurses related to the use of MI to promote health behaviors in adolescents. Conclusions There is little knowledge of what works for whom (which adolescent subpopulation) under what circumstances (in which setting, for what problem) in relation to nurse-led MI. There is a need for scoping or mapping the nurse-led MI with adolescents to identify evidence gaps and to inform opportunities for future development in nursing practice. Moreover, information regarding implemented and evaluated interventions, techniques used, contexts of application and adolescents groups is dispersed in the literature which impedes the formulation of questions about the outcomes and effectiveness of those interventions. The practical implication of this mapping will be clarifying all these aspects.

The use of motivational interviews by nurses to promote health behaviors in adolescents: a scoping review protocol

Adolescents - defined as young people between 10 and 19 years of age1 - are, in general, a relatively healthy segment of the population.2 However, the developmental changes that take place during adolescence may affect their subsequent risk for diseases and for a variety of health-related behaviors. In fact, early onset of preventable health problems (e.g. obesity, malnutrition, STDs) and the engagement in health risk behaviors (e.g., sedentary life style, excessive alcohol consumption, unprotected sex) during adolescence, are likely to put them at greater risk for physical and mental health problems at a later stage in life. Moreover, health related problems and health risk behaviors may disrupt adolescents' physical and cognitive development and therefore may affect their ability to think and act in relation to decisions about their health in the future.1 In summary, health-related behaviors in adolescence, apart from their influence on the continuum of "health-disease", they also have the potential to influence future behaviors. In fact, several studies have shown that past behaviors are good predictors of future behaviors .3,4 Thus, promoting healthy practices during adolescence and taking measures to better protect young people from health risks are essential for the prevention of health problems in adulthood.5 According to the World Health Organization, the main problems affecting young people include mental health problems (such as behavioral disorders, eating disorders, suicide, anxiety or depression), the use of substances (illegal substances, alcohol and tobacco), interpersonal violence, nutrition (a proper nutrition consists of healthy eating habits and physical exercise), unintentional injuries (which are a leading cause of death and disability among young people, with road traffic injuries accounting for about 700 deaths per day), sexual and reproductive health (for example, risky sexual behaviors, early pregnancy and childbirth) and HIV (resulting from sexual transmission and drug injection).5,6 On the other hand, the number of children and youth with chronic health conditions has increased dramatically in the past four decades7 as larger numbers of chronically ill children survive beyond the age of 10.8 Despite the lack of data on adolescents' health making it difficult to determine the prevalence of chronic illnesses in this age group9, it is known that one in ten adolescents suffers from a chronic condition worldwide.10 In fact, national population based studies from Western countries show that 20-30% of teenagers have a chronic illness, defined as one that lasts longer than six months.8 The most prevalent chronic illness among adolescents is asthma and the one with the highest incidence is diabetes mellitus, particularly type II.9 Traditionally, healthcare professionals have been mainly investing in health education activities, through the transmission of knowledge with a view to creating habits, customs and behaviors, and promoting healthy lifestyles. However, empowering people does not only consist of giving them the right information11 , i.e. good information is not enough to cause people to make changes.12 The motivation or desire to change unhealthy behaviors and habits depends on many factors, namely intrinsic motivation, control over personal decisions, self-confidence and perception of effectiveness, personal ambivalence, and individualized assistance.12 Many professionals assume that supplying knowledge is sufficient for behavioral changes; however, even very good advice often fails to generate behavioral change. After all, people continue to engage in unhealthy behaviors despite clearly knowing what they should do and how to change. "What is lacking is the motivation to apply that knowledge".13, p.1233 In fact, behavioral change is a complex phenomenon with multiple determinants that also includes motivational variables. It is associated with ambivalent processes expressed in the dilemma between keeping the current status and moving on to new ways of acting. For example, telling adolescents that if they keep on engaging in a certain behavior, they are increasing the risk of developing a long-term condition such as cardiovascular disease, stroke or diabetes is rarely enough to trigger the desired behavioral change; people are more likely to change when they believe that the change is really effective and that they are able to implement it.12 Therefore, it is essential to provide specific training for "healthcare professionals to master motivational techniques, avoid confrontation with the users, and facilitate behavioral changes".14 In this context, motivating patients to make behavioral changes is also an important nursing task where change in lifestyle is a major element of patients' treatment and preventive interventions.15 One of the nurse's goals is to help improve a patient's health or help them to manage existing health conditions. Once nurses are in a position where they have to focus on accomplishing tasks and telling patients what needs to be accomplished16, the role of the nurse is expanding even more into the use of motivational strategies.17 MI is bringing nurses back to therapeutic communication and moving them closer to successful health promotion and disease management, by promoting behavior change and empowering their patients. As the nursing profession evolves, MI is seen as a challenge and the basis of nurse's interactions with individuals, families and communities.16, 17 In the same way, MI may be taken as an essential tool in the provision of nursing care to adolescents, being itself a workspace with possible therapeutic effects regarding problems, clarification of doubts, and development of skills.18 In fact, MI may be particularly applicable in work with adolescents because of their specific developmental stage. Adolescents attempt to establish their own autonomy and identity while struggling with social interactions and moral issues, which leads to ambivalence.19 Consistent with the developmental challenges during adolescence, "MI explicitly honors autonomy, people's right and irrevocable ability to decide about their own behavior"20 while allowing the person to explore possibilities for change of risky or maladaptive behaviours.19 MI can be defined as a directive, client-centred counselling style for eliciting behavior change by helping clients to explore and resolve ambivalence. It is most centrally defined not by technique but by its spirit as a facilitative style of interpersonal relationship.21 It is a set of strategies and techniques widely used in clinical practice based on the transtheoretical model of change. The Stages of Change model describes five stages of readiness—precontemplation, contemplation, preparation, action, and maintenance—and provides a framework for understanding behavior change.22 The MI has been widely tested and applied in different areas, such as modification of addictive behaviors, interventions with offenders in the context of justice, eating disorders, promotion of therapeutic adherence among chronic patients, promotion of learning in school settings or intervention with adolescents at risk.18,23 In general, clinical practice has been adopting the perspective of motivation as something relatively immutable, i.e., the adolescent is either motivated for change/treatment and, in these conditions, the professional's role is to help him/her, or the adolescent is not motivated and then change/treatment is not feasible. Alternatively the theoretical model underlying the MI technique postulates that the individual's adherence to change/treatment depends on his/her motivation, which can change throughout the therapeutic intervention. As several studies found positive results for effects of MI24-26 and its use by health professionals is encouraged23,27 nurses may play an important role in patients' process of change. As nurses have a crucial role in clinical contexts, they can facilitate the process of ending risk behaviors and/or adopting positive health behaviors through some motivational techniques, namely with adolescents. A considerable number of systematic reviews about MI already exist pointing to some benefits of its use in the treatment of a broad range of behavioral problems and diseases.13,28,29 Some of the current reviews focus on examining the effectiveness of MI for adolescents with diverse health risks/problems 30-32. However, to date there are no reviews that present and assess the evidence for the use of nurse-led MI in adolescents. Therefore, we have little knowledge of what works for whom (which adolescent subpopulation) under what circumstances (in which setting, for what problem) in relation to motivational interviewing by nurses. There is a clear need for scoping or mapping the use of MI by nurses with adolescents to identify evidence gaps and to inform opportunities for future development in nursing practice. On the other hand, information regarding nurse-led implemented and evaluated interventions, techniques and/or strategies used, contexts of application and adolescents subpopulation groups is dispersed in the literature33-36 which impedes the formulation of precise questions about the effectiveness of those interventions conducted by nurses and therefore the realization of a systematic review. In other words, it is known that different kind of motivational interventions have been implemented in different contexts by nurses, however does not exist a map about all the motivational techniques and/or strategies used. Furthermore the literature does not clarify which is the role of nurses at cross professional motivational intervention implemented programs and finally the outcomes and evaluation of interventions are unclear. Thus, the practical implication of this mapping will be clarifying all these aspects. Without this clarification is not possible to proceed to the realization of a systematic review about the effectiveness of the use of motivational interviews by nurses to promote health behaviors in adolescents, in a particular context and/or health risk behavior; or regarding the effectiveness of certain technique and/or strategy of MI. Consequently, there are important questions about the nature of the evidence in this area that need to be answered before formulating a precise question of effectiveness. This scoping review aims to respond to these questions. An initial search of the JBI Database of Systematic Reviews & Implementation Reports, Cochrane Database of Systematic Reviews, , Database of promoting health effectiveness reviews (DoPHER), The Campbell Library, Medline and CINAHL, has revealed that currently there is no Scoping Review (published or in progress) on the subject. In this context, this scoping review will examine and map the published and unpublished research around the use of MI by nurses implemented and evaluated to promote health behaviors in adolescents; to establish its current extent, range and nature and identify its feasibility, outcomes and gaps in the evidence defining research priorities in this field. This scoping review will be informed by the JBI methodology37 that suggests a five stage methodological framework for conducting scoping reviews which includes: identifying the research question, searching for relevant studies, selecting studies, charting data, collating, summarizing and reporting the results.