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1.  Proceedings of the 14th annual conference of INEBRIA 
Holloway, Aisha S. | Ferguson, Jennifer | Landale, Sarah | Cariola, Laura | Newbury-Birch, Dorothy | Flynn, Amy | Knight, John R. | Sherritt, Lon | Harris, Sion K. | O’Donnell, Amy J. | Kaner, Eileen | Hanratty, Barbara | Loree, Amy M. | Yonkers, Kimberly A. | Ondersma, Steven J. | Gilstead-Hayden, Kate | Martino, Steve | Adam, Angeline | Schwartz, Robert P. | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | McNeely, Jennifer | Berman, Anne H. | Kolaas, Karoline | Petersén, Elisabeth | Bendtsen, Preben | Hedman, Erik | Linderoth, Catharina | Müssener, Ulrika | Sinadinovic, Kristina | Spak, Fredrik | Gremyr, Ida | Thurang, Anna | Mitchell, Ann M. | Finnell, Deborah | Savage, Christine L. | Mahmoud, Khadejah F. | Riordan, Benjamin C. | Conner, Tamlin S. | Flett, Jayde A. M. | Scarf, Damian | McRee, Bonnie | Vendetti, Janice | Gallucci, Karen Steinberg | Robaina, Kate | Clark, Brendan J. | Jones, Jacqueline | Reed, Kathryne D. | Hodapp, Rachel M. | Douglas, Ivor | Burnham, Ellen L. | Aagaard, Laura | Cook, Paul F. | Harris, Brett R. | Yu, Jiang | Wolff, Margaret | Rogers, Meighan | Barbosa, Carolina | Wedehase, Brendan J. | Dunlap, Laura J. | Mitchell, Shannon G. | Dusek, Kristi A. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla T. | Hosler, Colleen | O’Grady, Kevin E. | Brown, Barry S. | Angus, Colin | Sherborne, Sidney | Gillespie, Duncan | Meier, Petra | Brennan, Alan | de Vargas, Divane | Soares, Janaina | Castelblanco, Donna | Doran, Kelly M. | Wittman, Ian | Shelley, Donna | Rotrosen, John | Gelberg, Lillian | Edelman, E. Jennifer | Maisto, Stephen A. | Hansen, Nathan B. | Cutter, Christopher J. | Deng, Yanhong | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Bedimo, Roger | Gibert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria C. | Simberkoff, Michael S. | Justice, Amy C. | Bryant, Kendall J. | Fiellin, David A. | Giles, Emma L. | Coulton, Simon | Deluca, Paolo | Drummond, Colin | Howel, Denise | McColl, Elaine | McGovern, Ruth | Scott, Stephanie | Stamp, Elaine | Sumnall, Harry | Vale, Luke | Alabani, Viviana | Atkinson, Amanda | Boniface, Sadie | Frankham, Jo | Gilvarry, Eilish | Hendrie, Nadine | Howe, Nicola | McGeechan, Grant J. | Ramsey, Amy | Stanley, Grant | Clephane, Justine | Gardiner, David | Holmes, John | Martin, Neil | Shevills, Colin | Soutar, Melanie | Chi, Felicia W. | Weisner, Constance | Ross, Thekla B. | Mertens, Jennifer | Sterling, Stacy A. | Shorter, Gillian W. | Heather, Nick | Bray, Jeremy | Cohen, Hildie A. | McPherson, Tracy L. | Adam, Cyrille | López-Pelayo, Hugo | Gual, Antoni | Segura-Garcia, Lidia | Colom, Joan | Ornelas, India J. | Doyle, Suzanne | Donovan, Dennis | Duran, Bonnie | Torres, Vanessa | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Paroz, Sophie | Bertholet, Nicolas | Daeppen, Jean-Bernard | Satterfield, Jason M. | Gregorich, Steven | Alvarado, Nicholas J. | Muñoz, Ricardo | Kulieva, Gozel | Vijayaraghavan, Maya | Adam, Angéline | Cunningham, John A. | Díaz, Estela | Palacio-Vieira, Jorge | Godinho, Alexandra | Kushir, Vladyslav | O’Brien, Kimberly H. M. | Aguinaldo, Laika D. | Sellers, Christina M. | Spirito, Anthony | Chang, Grace | Blake-Lamb, Tiffany | LaFave, Lea R. Ayers | Thies, Kathleen M. | Pepin, Amy L. | Sprangers, Kara E. | Bradley, Martha | Jorgensen, Shasta | Catano, Nico A. | Murray, Adelaide R. | Schachter, Deborah | Andersen, Ronald M. | Rey, Guillermina Natera | Vahidi, Mani | Rico, Melvin W. | Baumeister, Sebastian E. | Johansson, Magnus | Sinadinovic, Christina | Hermansson, Ulric | Andreasson, Sven | O’Grady, Megan A. | Kapoor, Sandeep | Akkari, Cherine | Bernal, Camila | Pappacena, Kristen | Morley, Jeanne | Auerbach, Mark | Neighbors, Charles J. | Kwon, Nancy | Conigliaro, Joseph | Morgenstern, Jon | Magill, Molly | Apodaca, Timothy R. | Borsari, Brian | Hoadley, Ariel | Scott Tonigan, J. | Moyers, Theresa | Fitzgerald, Niamh M. | Schölin, Lisa | Barticevic, Nicolas | Zuzulich, Soledad | Poblete, Fernando | Norambuena, Pablo | Sacco, Paul | Ting, Laura | Beaulieu, Michele | Wallace, Paul George | Andrews, Matthew | Daley, Kate | Shenker, Don | Gallagher, Louise | Watson, Rod | Weaver, Tim | Bruguera, Pol | Oliveras, Clara | Gavotti, Carolina | Barrio, Pablo | Braddick, Fleur | Miquel, Laia | Suárez, Montse | Bruguera, Carla | Brown, Richard L. | Capell, Julie Whelan | Paul Moberg, D. | Maslowsky, Julie | Saunders, Laura A. | McCormack, Ryan P. | Scheidell, Joy | Gonzalez, Mirelis | Bauroth, Sabrina | Liu, Weiwei | Lindsay, Dawn L. | Lincoln, Piper | Hagle, Holly | Wallhed Finn, Sara | Hammarberg, Anders | Andréasson, Sven | King, Sarah E. | Vargo, Rachael | Kameg, Brayden N. | Acquavita, Shauna P. | Van Loon, Ruth Anne | Smith, Rachel | Brehm, Bonnie J. | Diers, Tiffiny | Kim, Karissa | Barker, Andrea | Jones, Ashley L. | Skinner, Asheley C. | Hinman, Agatha | Svikis, Dace S. | Thacker, Casey L. | Resnicow, Ken | Beatty, Jessica R. | Janisse, James | Puder, Karoline | Bakshi, Ann-Sofie | Milward, Joanna M. | Kimergard, Andreas | Garnett, Claire V. | Crane, David | Brown, Jamie | West, Robert | Michie, Susan | Rosendahl, Ingvar | Andersson, Claes | Gajecki, Mikael | Blankers, Matthijs | Donoghue, Kim | Lynch, Ellen | Maconochie, Ian | Phillips, Ceri | Pockett, Rhys | Phillips, Tom | Patton, R. | Russell, Ian | Strang, John | Stewart, Maureen T. | Quinn, Amity E. | Brolin, Mary | Evans, Brooke | Horgan, Constance M. | Liu, Junqing | McCree, Fern | Kanovsky, Doug | Oberlander, Tyler | Zhang, Huan | Hamlin, Ben | Saunders, Robert | Barton, Mary B. | Scholle, Sarah H. | Santora, Patricia | Bhatt, Chirag | Ahmed, Kazi | Hodgkin, Dominic | Gao, Wenwu | Merrick, Elizabeth L. | Drebing, Charles E. | Larson, Mary Jo | Sharma, Monica | Petry, Nancy M. | Saitz, Richard | Weisner, Constance M. | Young-Wolff, Kelly C. | Lu, Wendy Y. | Blosnich, John R. | Lehavot, Keren | Glass, Joseph E. | Williams, Emily C. | Bensley, Kara M. | Chan, Gary | Dombrowski, Julie | Fortney, John | Rubinsky, Anna D. | Lapham, Gwen T. | Forray, Ariadna | Olmstead, Todd A. | Gilstad-Hayden, Kathryn | Kershaw, Trace | Dillon, Pamela | Weaver, Michael F. | Grekin, Emily R. | Ellis, Jennifer D. | McGoron, Lucy | McGoron, Lucy
doi:10.1186/s13722-017-0087-8
PMCID: PMC5606215
3.  RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3 
Current Biology  2017;27(5):638-650.
Summary
Cooling and hypothermia are profoundly neuroprotective, mediated, at least in part, by the cold shock protein, RBM3. However, the neuroprotective effector proteins induced by RBM3 and the mechanisms by which mRNAs encoding cold shock proteins escape cooling-induced translational repression are unknown. Here, we show that cooling induces reprogramming of the translatome, including the upregulation of a new cold shock protein, RTN3, a reticulon protein implicated in synapse formation. We report that this has two mechanistic components. Thus, RTN3 both evades cooling-induced translational elongation repression and is also bound by RBM3, which drives the increased expression of RTN3. In mice, knockdown of RTN3 expression eliminated cooling-induced neuroprotection. However, lentivirally mediated RTN3 overexpression prevented synaptic loss and cognitive deficits in a mouse model of neurodegeneration, downstream and independently of RBM3. We conclude that RTN3 expression is a mediator of RBM3-induced neuroprotection, controlled by novel mechanisms of escape from translational inhibition on cooling.
Graphical Abstract
Highlights
•Cooling-induced reprogramming of the translatome increases synthesis of RTN3•The neuroprotective protein RBM3 binds RTN3 mRNA and drives its expression•RTN3 overexpression prevents synaptic loss in mice with prion disease•RTN3 expression is a mediator of RBM3-induced neuroprotection
Therapeutic hypothermia is neuroprotective, and the cold shock protein RMB3 plays a critical role in mediating synaptic repair processes that accompany cooling. Bastide and Peretti et al. show that cooling selectively reprograms the translatome and identify RTN3 as a cold-induced protein that acts downstream of RBM3 in the neuroprotection pathway.
doi:10.1016/j.cub.2017.01.047
PMCID: PMC5344685  PMID: 28238655
cold shock; protein synthesis; mRNA translation; RTN3; neuroprotection; RBM3
4.  Adolescent substance use screening in primary care: validity of computer self-administered vs. clinician-administered screening 
Substance abuse  2015;37(1):197-203.
Background
Computer self-administration may help busy pediatricians’ offices increase adolescent substance use screening rates efficiently and effectively, if proven to yield valid responses. The CRAFFT screening protocol for adolescents has demonstrated validity as an interview, but a computer self-entry approach needs validity testing. The aim of this study was to evaluate the criterion validity and time efficiency of a computerized adolescent substance use screening protocol implemented by self-administration or clinician-administration.
Methods
12- to 17-year-old patients coming for routine care at three primary care clinics completed the computerized screen by both self-administration and clinician-administration during their visit. To account for order effects, we randomly assigned participants to self-administer the screen either before or after seeing their clinician. Both were conducted using a tablet computer and included identical items (any past-12-month use of tobacco, alcohol, drugs; past-3-months frequency of each; and six CRAFFT items). The criterion measure for substance use was the Timeline Follow-Back, and for alcohol/drug use disorder, the Adolescent Diagnostic Interview, both conducted by confidential research assistant-interview after the visit. Tobacco dependence risk was assessed with the self-administered Hooked on Nicotine Checklist (HONC). Analyses accounted for the multi-site cluster sampling design.
Results
Among 136 participants, mean age was 15.0±1.5 yrs, 54% were girls, 53% were Black or Hispanic, and 67% had ≥3 prior visits with their clinician. Twenty-seven percent reported any substance use (including tobacco) in the past 12 months, 7% met criteria for an alcohol or cannabis use disorder, and 4% were HONC-positive. Sensitivity/specificity of the screener were high for detecting past-12-month use or disorder and did not differ between computer and clinician. Mean completion time was 49 seconds (95%CI 44-54) for computer and 74 seconds (95%CI 68-87) for clinician (paired comparison p<0.001).
Conclusions
Substance use screening by computer self-entry is a valid and time-efficient alternative to clinician-administered screening.
doi:10.1080/08897077.2015.1014615
PMCID: PMC4573375  PMID: 25774878
Adolescents; substance use; primary care; screening; validity (epidemiology); computers; alcohol; tobacco; cannabis; drugs
5.  THE KNOWLEDGE GAPS FOR MEDICAL MARIJUANA IN PEDIATRIC CONDITIONS 
doi:10.1097/DBP.0000000000000219
PMCID: PMC4648553  PMID: 26535886
adolescent; cannabis; marijuana abuse; attention deficit disorder with hyperactivity; child development disorders; pervasive
6.  Brief Interventions for Alcohol Use: Where, When, and How? 
Pediatrics  2015;136(4):e1002-e1004.
doi:10.1542/peds.2015-2713
PMCID: PMC4586734  PMID: 26347439
7.  Proceedings of the 13th annual conference of INEBRIA 
Watson, Rod | Morris, James | Isitt, John | Barrio, Pablo | Ortega, Lluisa | Gual, Antoni | Conner, Kenneth | Stecker, Tracy | Maisto, Stephen | Paroz, Sophie | Graap, Caroline | Grazioli, Véronique S | Daeppen, Jean-Bernard | Collins, Susan E | Bertholet, Nicolas | McNeely, Jennifer | Kushnir, Vlad | Cunningham, John A. | Crombie, Iain K | Cunningham, Kathryn B | Irvine, Linda | Williams, Brian | Sniehotta, Falko F | Norrie, John | Melson, Ambrose | Jones, Claire | Briggs, Andrew | Rice, Peter | Achison, Marcus | McKenzie, Andrew | Dimova, Elena | Slane, Peter W | Grazioli, Véronique S. | Collins, Susan E. | Paroz, Sophie | Graap, Caroline | Daeppen, Jean-Bernard | Baggio, Stéphanie | Dupuis, Marc | Studer, Joseph | Gmel, Gerhard | Magill, Molly | Grazioli, Véronique S. | Tait, Robert J. | Teoh, Lucinda | Kelty, Erin | Geelhoed, Elizabeth | Mountain, David | Hulse, Gary K. | Renko, Elina | Mitchell, Shannon G. | Lounsbury, David | Li, Zhi | Schwartz, Robert P. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla | Hosler, Colleen | Dusek, Kristi | Brown, Barry S. | Finnell, Deborah S. | Holloway, Aisha | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | Wallhed Finn, Sara | Andreasson, Sven | Dvorak, Robert D. | Kramer, Matthew P. | Stevenson, Brittany L. | Sargent, Emily M. | Kilwein, Tess M. | Harris, Sion K. | Sherritt, Lon | Copelas, Sarah | Knight, John R. | Mdege, Noreen D | McCambridge, Jim | Bischof, Gallus | Bischof, Anja | Freyer-Adam, Jennis | Rumpf, Hans-Juergen | Fitzgerald, Niamh | Schölin, Lisa | Toner, Paul | Böhnke, Jan R. | Veach, Laura J. | Currin, Olivia | Dongre, Leigh Z. | Miller, Preston R. | White, Elizabeth | Williams, Emily C. | Lapham, Gwen T. | Bobb, Jennifer J. | Rubinsky, Anna D. | Catz, Sheryl L. | Shortreed, Susan | Bensley, Kara M. | Bradley, Katharine A. | Milward, Joanna | Deluca, Paolo | Khadjesari, Zarnie | Watson, Rod | Fincham-Campbell, Stephanie | Drummond, Colin | Angus, Kathryn | Bauld, Linda | Baumann, Sophie | Haberecht, Katja | Schnuerer, Inga | Meyer, Christian | Rumpf, Hans-Jürgen | John, Ulrich | Gaertner, Beate | Barrault-Couchouron, Marion | Béracochéa, Marion | Allafort, Vincent | Barthélémy, Valérie | Bonnefoi, Hervé | Bussières, Emmanuel | Garguil, Véronique | Auriacombe, Marc | Saint-Jacques, Marianne | Dorval, Michel | M’Bailara, Katia | Segura-Garcia, Lidia | Ibañez-Martinez, Nuria | Mendive-Arbeloa, Juan Manuel | Anoro-Perminger, Manel | Diaz-Gallego, Pako | Piñar-Mateos, Mª Angeles | Colom-Farran, Joan | Deligianni, Marianthi | Yersin, Bertrand | Adam, Angeline | Weisner, Constance | Chi, Felicia | Lu, Wendy | Sterling, Stacy | Kraemer, Kevin L. | McGinnis, Kathleen A. | Fiellin, David A. | Skanderson, Melissa | Gordon, Adam J. | Robbins, Jonathan | Zickmund, Susan | Korthuis, P. Todd | Edelman, E. Jennifer | Hansen, Nathan B. | Cutter, Christopher J. | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Maisto, Stephen A. | Bedimo, Roger | Gilbert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria | Simberkoff, Michael | Justice, Amy C. | Bryant, Kendall J. | Berman, Anne H | Shorter, Gillian W | Bray, Jeremy W | Barbosa, Carolina | Johansson, Magnus | Hester, Reid | Campbell, William | Souza Formigoni, Maria Lucia O. | Andrade, André Luzi Monezi | Sartes, Laisa Marcorela Andreoli | Sundström, Christopher | Eék, Niels | Kraepelien, Martin | Kaldo, Viktor | Fahlke, Claudia | Hernandez, Lynn | Becker, Sara J. | Jones, Richard N. | Graves, Hannah R. | Spirito, Anthony | Diestelkamp, Silke | Wartberg, Lutz | Arnaud, Nicolas | Thomasius, Rainer | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Malan, Zelra | Mash, Bob | Everett-Murphy, Katherine | Grazioli, Véronique S. | Studer, Joseph | Mohler-Kuo, M. | Bertholet, Nicolas | Gmel, Gerhard | Doi, Lawrence | Cheyne, Helen | Jepson, Ruth | Luna, Vanesa | Echeverria, Leticia | Morales, Silvia | Barroso, Teresa | Abreu, Ângela | Aguiar, Cosma | Stewart, Duncan | Abreu, Angela | Brites, Riany M. | Jomar, Rafael | Marinho, Gerson | Parreira, Pedro | Seale, J. Paul | Johnson, J. Aaron | Henry, Dena | Chalmers, Sharon | Payne, Freida | Tuck, Linda | Morris, Akula | Gonçalves, Cátia | Besser, Bettina | Casajuana, Cristina | López-Pelayo, Hugo | Balcells, María Mercedes | Teixidó, Lídia | Miquel, Laia | Colom, Joan | Hepner, Kimberly A. | Hoggatt, Katherine. J. | Bogart, Andy | Paddock, Susan. M. | Hardoon, Sarah L | Petersen, Irene | Hamilton, Fiona L | Nazareth, Irwin | White, Ian R. | Marston, Louise | Wallace, Paul | Godfrey, Christine | Murray, Elizabeth | Sovinová, Hana | Csémy, Ladislav
doi:10.1186/s13722-016-0062-9
PMCID: PMC5032602  PMID: 27654147
8.  Medical Marijuana: Review of the Science and Implications for Developmental Behavioral Pediatric Practice 
Marijuana policy is rapidly evolving in the United States and elsewhere, with cannabis sales fully legalized and regulated in some jurisdictions and use of the drug for medicinal purposes permitted in many others. Amidst this political change, patients and families are increasingly asking whether cannabis and its derivatives may have therapeutic utility for a number of conditions, including developmental and behavioral disorders in children and adolescents. This review examines the epidemiology of cannabis use among children and adolescents, including those with developmental and behavioral diagnoses. It then outlines the increasingly well-recognized neurocognitive changes shown to occur in adolescents who use cannabis regularly, highlighting the unique susceptibility of the developing adolescent brain and describing the role of the endocannabinoid system in normal neurodevelopment. The review then discusses some of the proposed uses of cannabis in developmental and behavioral conditions, including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Throughout, the review outlines gaps in current knowledge and highlights directions for future research, especially in light of a dearth of studies specifically examining neurocognitive and psychiatric outcomes among children and adolescents with developmental and behavioral concerns exposed to cannabis.
doi:10.1097/DBP.0000000000000129
PMCID: PMC4318349  PMID: 25650954
adolescent; cannabis; marijuana abuse; attention deficit disorder with hyperactivity; child development disorders; pervasive
9.  Alcohol Use and Religiousness/Spirituality Among Adolescents 
Southern medical journal  2007;100(4):349-355.
Background
Previous studies indicate that religiousness is associated with lower levels of substance use among adolescents, but less is known about the relationship between spirituality and substance use. The objective of this study was to determine the association between adolescents’ use of alcohol and specific aspects of religiousness and spirituality.
Methods
Twelve- to 18-year-old patients coming for routine medical care at three primary care sites completed a modified Brief Multidimensional Measure of Religiousness/Spirituality; the Spiritual Connectedness Scale; and a past-90-days alcohol use Timeline Followback calendar. We used multiple logistic regression analysis to assess the association between each religiousness/spirituality measure and odds of any past-90-days alcohol use, controlling for age, gender, race/ethnicity, and clinic site. Timeline Followback data were dichotomized to indicate any past-90-days alcohol use and religiousness/spirituality scale scores were z-transformed for analysis.
Results
Participants (n = 305) were 67% female, 74% Hispanic or black, and 45% from two-parent families. Mean ± SD age was 16.0 ± 1.8 years. Approximately 1/3 (34%) reported past-90-day alcohol use. After controlling for demographics and clinic site, Religiousness/Spirituality scales that were not significantly associated with alcohol use included: Commitment (OR = 0.81, 95% CI 0.36, 1.79), Organizational Religiousness (OR = 0.83, 95% CI 0.64, 1.07), Private Religious Practices (OR = 0.94, 95% CI 0.80, 1.10), and Religious and Spiritual Coping – Negative (OR = 1.07, 95% CI 0.91, 1.23). All of these are measures of religiousness, except for Religious and Spiritual Coping – Negative. Scales that were significantly and negatively associated with alcohol use included: Forgiveness (OR = 0.55, 95% CI 0.42–0.73), Religious and Spiritual Coping –Positive (OR = 0.67, 95% CI 0.51–0.84), Daily Spiritual Experiences (OR = 0.67, 95% CI 0.54–0.84), and Belief (OR = 0.76, 95% CI 0.68–0.83), which are all measures of spirituality. In a multivariable model that included all significant measures, however, only Forgiveness remained as a significant negative correlate of alcohol use (OR = 0.56, 95% CI 0.41, 0.74).
Conclusions
Forgiveness is associated with a lowered risk of drinking during adolescence.
doi:10.1097/SMJ.0b013e3180316a32
PMCID: PMC4143181  PMID: 17458392
spirituality; religion; substance-related disorders; alcoholism; adolescence
10.  Putting the Screen in Screening 
Alcohol is strongly linked to the leading causes of adolescent and adult mortality and health problems, making medical settings such as primary care and emergency departments important venues for addressing alcohol use. Extensive research evidence supports the effectiveness of alcohol screening and brief interventions (SBIs) in medical settings, but this valuable strategy remains underused, with medical staff citing lack of time and training as major implementation barriers. Technology-based tools may offer a way to improve efficiency and quality of SBI delivery in such settings. This review describes the latest research examining the feasibility and efficacy of computer- or other technology-based alcohol SBI tools in medical settings, as they relate to the following three patient populations: adults (18 years or older); pregnant women; and adolescents (17 years or younger). The small but growing evidence base generally shows strong feasibility and acceptability of technology-based SBI in medical settings. However, evidence for effectiveness in changing alcohol use is limited in this young field.
PMCID: PMC4432859
Alcohol use, abuse, and dependence; screening and brief intervention; medical setting; primary care; emergency room; adult; adolescent; pregnant women; technology; computer-based screening and brief intervention; literature review
11.  Do Risky Friends Change the Efficacy of a Primary Care Brief Intervention for Adolescent Alcohol Use? 
Purpose
To determine if peer risk (having friends who drink or approve of drinking) modifies the effects of a computer-facilitated Screening and provider Brief Advice (cSBA) intervention on adolescent alcohol use.
Methods
We assessed intervention effect using logistic regression modeling with generalized estimating equations on a sample of 2092 adolescents. Effect modification by peer risk was analyzed separately for alcohol initiation (drinking at follow-up in baseline non-drinkers) and cessation (no drinking at follow-up in baseline drinkers) by testing an interaction term (treatment condition by peer risk). Interpretation of the interaction effect was further clarified by subsequent stratification by peer risk.
Results
The intervention effect on alcohol cessation was significantly greater among those with peer risk (aRRR: Risk 1.44, 1.18–1.76 vs. No Risk 0.98, 0.41–2.36) at 3 months follow-up. There was no such finding for alcohol initiation.
Conclusions
Alcohol screening and brief provider counseling may differentially benefit adolescent drinkers with drinking friends.
doi:10.1016/j.jadohealth.2013.09.012
PMCID: PMC3965615  PMID: 24216313
adolescent; alcohol use; prevention; peer risk
12.  Active regulator of SIRT1 is required for ribosome biogenesis and function 
Nucleic Acids Research  2013;41(7):4185-4197.
Active regulator of SIRT1 (AROS) binds and upregulates SIRT1, an NAD+-dependent deacetylase. In addition, AROS binds RPS19, a structural ribosomal protein, which also functions in ribosome biogenesis and is implicated in multiple disease states. The significance of AROS in relation to ribosome biogenesis and function is unknown. Using human cells, we now show that AROS localizes to (i) the nucleolus and (ii) cytoplasmic ribosomes. Co-localization with nucleolar proteins was verified by confocal immunofluorescence of endogenous protein and confirmed by AROS depletion using RNAi. AROS association with cytoplasmic ribosomes was analysed by sucrose density fractionation and immunoprecipitation, revealing that AROS selectively associates with 40S ribosomal subunits and also with polysomes. RNAi-mediated depletion of AROS leads to deficient ribosome biogenesis with aberrant precursor ribosomal RNA processing, reduced 40S subunit ribosomal RNA and 40S ribosomal proteins (including RPS19). Together, this results in a reduction in 40S subunits and translating polysomes, correlating with reduced overall cellular protein synthesis. Interestingly, knockdown of AROS also results in a functionally significant increase in eIF2α phosphorylation. Overall, our results identify AROS as a factor with a role in both ribosome biogenesis and ribosomal function.
doi:10.1093/nar/gkt129
PMCID: PMC3627601  PMID: 23462953
14.  Primary Care Follow-up Plans for Adolescents With Substance Use Problems 
Pediatrics  2009;124(1):144-150.
OBJECTIVE
Primary care visits provide an opportunity to screen adolescents for substance use and offer early intervention. Little is known, however, about what follow-up plans primary care providers (PCPs) make for adolescent patients who screen positive. The objective of this study was to determine follow-up recommendations by PCPs and assess the relationship between their diagnostic impressions of substance use severity and plans for intervention.
METHODS
Data were collected through a prospective observational study conducted at 7 primary care practices in New England. Patients aged 12 to 18 years completed an interview, which included sociodemographic characteristics and the CRAFFT substance abuse screen. PCPs received screen results, noted their diagnostic impression of participants’ substance use severity, and recorded follow-up plans. Follow-up plans other than “periodic screening” alone were defined as “active intervention.” We examined the relationship of provider impressions with follow-up recommendations by using the χ2 test.
RESULTS
For the entire sample of 2034 adolescents, PCPs recommended no plan for 369 patients, periodic screening for 1557 patients, a return visit for 98 patients, and referral to counseling for 44 patients. PCPs’ diagnostic impressions identified 97 (4.8%) patients with problem use and 19 (0.01%) patients with abuse or dependence. Recommendations for active intervention were more likely with patients’ higher severity of use. However, 1 in 5 patients thought to have problem use did not receive a recommendation for an active intervention. Parent notification was planned for only 13 patients.
CONCLUSIONS
When concerned about substance use, PCPs recommend to patients a return visit to their office more than twice as often as referral to counseling, and they seldom plan to inform parents of adolescents’ substance use. PCPs need greater opportunities for training in the delivery of medical office–based therapeutic interventions and in strategies for managing adolescent substance use in the outpatient setting.
doi:10.1542/peds.2008-2979
PMCID: PMC4103426  PMID: 19564294
adolescence; substance abuse; treatment recommendations
15.  Active regulator of SIRT1 is required for cancer cell survival but not for SIRT1 activity 
Open Biology  2013;3(11):130130.
The NAD+-dependent deacetylase SIRT1 is involved in diverse cellular processes, and has also been linked with multiple disease states. Among these, SIRT1 expression negatively correlates with cancer survival in both laboratory and clinical studies. Active regulator of SIRT1 (AROS) was the first reported post-transcriptional regulator of SIRT1 activity, enhancing SIRT1-mediated deacetylation and downregulation of the SIRT1 target p53. However, little is known regarding the role of AROS in regulation of SIRT1 during disease. Here, we report the cellular and molecular effects of RNAi-mediated AROS suppression, comparing this with the role of SIRT1 in a panel of human cell lines of both cancerous and non-cancerous origins. Unexpectedly, AROS is found to vary in its modulation of p53 acetylation according to cell context. AROS suppresses p53 acetylation only following the application of cell damaging stress, whereas SIRT1 suppresses p53 under all conditions analysed. This supplements the original characterization of AROS but indicates that SIRT1 activity can persist following suppression of AROS. We also demonstrate that knockdown of AROS induces apoptosis in three cancer cell lines, independent of p53 activation. Importantly, AROS is not required for the viability of three non-cancer cell lines indicating a putative role for AROS in specifically promoting cancer cell survival.
doi:10.1098/rsob.130130
PMCID: PMC3843821  PMID: 24258275
active regulator of SIRT1; regulation of SIRT1; p53 acetylation
16.  Computer-Facilitated Substance Use Screening and Brief Advice for Teens in Primary Care: An International Trial 
Pediatrics  2012;129(6):1072-1082.
OBJECTIVE:
Primary care providers need effective strategies for substance use screening and brief counseling of adolescents. We examined the effects of a new computer-facilitated screening and provider brief advice (cSBA) system.
METHODS:
We used a quasi-experimental, asynchronous study design in which each site served as its own control. From 2005 to 2008, 12- to 18-year-olds arriving for routine care at 9 medical offices in New England (n = 2096, 58% females) and 10 in Prague, Czech Republic (n = 589, 47% females) were recruited. Patients completed measurements only during the initial treatment-as-usual study phase. We then conducted 1-hour provider training, and initiated the cSBA phase. Before seeing the provider, all cSBA participants completed a computerized screen, and then viewed screening results, scientific information, and true-life stories illustrating substance use harms. Providers received screening results and “talking points” designed to prompt 2 to 3 minutes of brief advice. We examined alcohol and cannabis use, initiation, and cessation rates over the past 90 days at 3-month follow-up, and over the past 12 months at 12-month follow-up.
RESULTS:
Compared with treatment as usual, cSBA patients reported less alcohol use at follow-up in New England (3-month rates 15.5% vs 22.9%, adjusted relative risk ratio [aRRR] = 0.54, 95% confidence interval 0.38–0.77; 12-month rates 29.3% vs 37.5%, aRRR = 0.73, 0.57–0.92), and less cannabis use in Prague (3-month rates 5.5% vs 9.8%, aRRR = 0.37, 0.17–0.77; 12-month rates 17.0% vs 28.7%, aRRR = 0.47, 0.32–0.71).
CONCLUSIONS:
Computer-facilitated screening and provider brief advice appears promising for reducing substance use among adolescent primary care patients.
doi:10.1542/peds.2011-1624
PMCID: PMC3362902  PMID: 22566420
adolescents; substance use; primary care; screening; brief intervention; computer-assisted; alcohol; cannabis
18.  A Deacetylase-Deficient SIRT1 Variant Opposes Full-Length SIRT1 in Regulating Tumor Suppressor p53 and Governs Expression of Cancer-Related Genes 
Molecular and Cellular Biology  2012;32(3):704-716.
SIRT1 is an NAD-dependent deacetylase and epigenetic regulator essential for normal mammalian development and homeostasis. Here we describe a human SIRT1 splice variant, designated SIRT1-Δ2/9, in which the deacetylase coding sequence is lost due to splicing between exons 2 and 9. This work aimed to determine if SIRT1-Δ2/9 is a novel functional product of the SIRT1 gene. Endogenous SIRT1-Δ2/9 protein was identified in human cell lysate by immunoblotting and splice variant-specific RNA interference (RNAi). SIRT1-Δ2/9 mRNA is bound by CUGBP2, which downregulates its translation. Using pulldown assays, we demonstrate that SIRT1-Δ2/9 binds p53 protein. SIRT1-Δ2/9 maintains basal p53 protein levels and supports p53 function in response to DNA damage, as evidenced by RNAi-mediated depletion of SIRT1-Δ2/9 prior to damage. In turn, basal p53 downregulates SIRT1-Δ2/9 RNA levels, while stress-activated p53 eliminates SIRT1-Δ2/9. Loss of wild-type (wt) p53 has been correlated with overexpression of SIRT1-Δ2/9 in a range of human cancers. Exogenous SIRT1-Δ2/9 protein associates with specific promoters in chromatin and can regulate cancer-related gene expression, as evidenced by chromatin immunoprecipitation analysis and RNAi/genomic array data. SIRT1 is of major therapeutic importance, and potential therapeutic drugs are screened against SIRT1 deacetylase activity. Our discovery of SIRT1-Δ2/9 identifies a new, deacetylase-independent therapeutic target for SIRT1-related diseases, including cancer.
doi:10.1128/MCB.06448-11
PMCID: PMC3266595  PMID: 22124156
20.  Cyclin E is recruited to the nuclear matrix during differentiation, but is not recruited in cancer cells 
Nucleic Acids Research  2010;39(7):2671-2677.
Cyclin E supports pre-replication complex (pre-RC) assembly, while cyclin A-associated kinase activates DNA synthesis. We show that cyclin E, but not A, is mounted upon the nuclear matrix in sub-nuclear foci in differentiated vertebrate cells, but not in undifferentiated cells or cancer cells. In murine embryonic stem cells, Xenopus embryos and human urothelial cells, cyclin E is recruited to the nuclear matrix as cells differentiate and this can be manipulated in vitro. This suggests that pre-RC assembly becomes spatially restricted as template usage is defined. Furthermore, failure to become restricted may contribute to the plasticity of cancer cells.
doi:10.1093/nar/gkq1190
PMCID: PMC3074132  PMID: 21109536
21.  Screening adolescents for substance use-related high-risk sexual behaviors 
Background:
This analysis was undertaken to determine whether adolescents who screened positive for high-risk substance use with the CRAFFT questions were also more likely to engage in risky sexual behaviors than their peers, and to determine the test-retest reliability of a substance use related sexual risk behaviors inventory.
Methods:
12- to 18-year-old clinic patients completed a multi-part questionnaire that included 8 demographic items, the CRAFFT substance use screen, and a 14-item scale assessing sexual behaviors associated with substance use. Participants were invited to return one week later to complete an identical assessment battery.
Results:
Of the 305 study participants, 49 (16.1%) had a positive CRAFFT screen (score of 2 or greater, indicating high risk for substance abuse/dependence) and 101 (33.9%) reported sexual contact during the past 90 days. After controlling for gender, age, race, and number of parents in household, adolescents with a positive CRAFFT screen had significantly greater odds of having sexual contact after using alcohol or other drugs, of having a sexual partner who used alcohol or other drugs, of having sex without a condom, and of having multiple sexual partners within the past year, compared to their CRAFFT negative peers. The substance use related sexual risk behaviors inventory has acceptable test-retest reliability and the 10 frequency questions have scale-like properties with acceptable internal consistency (standardized Cronbach's Alpha = .79).
Conclusion:
Clinicians should pay special attention to counseling CRAFFT-positive adolescents regarding use of condoms, and the risks associated with sexual activity with multiple partners, while intoxicated, or with an intoxicated partner.
doi:10.1016/j.jadohealth.2009.03.028
PMCID: PMC2813707  PMID: 19837353
22.  Alcohol policy enforcement and changes in student drinking rates in a statewide public college system: a follow-up study 
Background
Heavy alcohol use among U.S. college students is a major contributor to young adult morbidity and mortality. The aim of this study was to examine whether college alcohol policy enforcement levels predict changes in student drinking and related behaviors in a state system of public colleges and universities, following a system-wide change to a stricter policy.
Methods
Students and administrators at 11 Massachusetts public colleges/universities completed surveys in 1999 (N of students = 1252), one year after the policy change, and again in 2001 (N = 1074). We calculated policy enforcement scores for each school based on the reports of deans of students, campus security chiefs, and students, and examined the correlations between perceived enforcement levels and the change in student drinking rates over the subsequent two year period, after weighting the 2001 data to adjust for demographic changes in the student body.
Results
Overall rates of any past-30-days drinking, heavy episodic drinking, and usual heavy drinking among past-30-days drinkers were all lower in 2001 compared to 1999. School-level analyses (N = 11) found deans' baseline reports of stricter enforcement were strongly correlated with subsequent declines in heavy episodic drinking (Pearson's r = -0.73, p = 0.011). Moreover, consistently high enforcement levels across time, as reported by deans, were associated with greater declines in heavy episodic drinking. Such relationships were not found for students' and security chiefs' reports of enforcement. Marijuana use did not rise during this period of decline in heavy drinking.
Conclusions
Study findings suggest that stronger enforcement of a stricter alcohol policy may be associated with reductions in student heavy drinking rates over time. An aggressive enforcement stance by deans may be an important element of an effective college alcohol policy.
doi:10.1186/1747-597X-5-18
PMCID: PMC2924849  PMID: 20684777

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