Mortality In Adolescence Research Articles

MicroRNA-605-3p Inhibited the Growth and Chemoresistance of Osteosarcoma Cells via Negatively Modulating RAF1.

Osteosarcoma (OS) is the leading cancer-associated mortality in childhood and adolescence. Increasing evidence has demonstrated the key function of microRNAs (miRNAs) in OS development and chemoresistance. Among them, miRNA-605-3p acted as an important tumor suppressor and was frequently down-regulated in multiple cancers. However, the function of miR-650-3p in OS has not been reported. The aim of this work is to explore the novel role of miR-605-3p in osteosarcoma and its possible involvement in OS chemotherapy resistance. The expression levels of miR-605-3p in OS tissues and cells were assessed by reverse transcription quantitative PCR (RT-qPCR). The relevance of miR-605-3p with the prognosis of OS patients was determined by the Kaplan-Meier analysis. Additionally, the influence of miR-605-3p on OS cell growth was analyzed using the cell counting kit-8, colony formation assay, and flow cytometry. The mRNA and protein expression of RAF1 were detected by RT-qPCR and western blot. The binding of miR-605-3p with the 3'-UTR of RAF1 was confirmed by dual-luciferase reporter assay. Our results showed that miR-605-3p was markedly decreased in OS tissues and cells. A lower level of miR-605-3p was strongly correlated with lymph node metastasis and poor 5-year overall survival rate of OS patients. In vitro assay found that miR-605-3p suppressed OS cell proliferation and promoted cell apoptosis. Mechanistically, the proto-oncogene RAF1 was seen as a target of miR-605-3p and strongly suppressed by miR-605-3p in OS cells. Restoration of RAF1 markedly eliminated the inhibitory effect of miR-605-3p on OS progression, suggesting RAF1 as a key mediator of miR-605-3p. Consistent with the decreased level of RAF1, miR-605-3p suppressed the activation of both MEK and ERK in OS cells, which are the targets of RAF1. Moreover, lower levels of miR-605-3p were found in chemoresistant OS patients, and downregulated miR-605-3p increased the resistance of OS cells to therapeutic agents. Our data revealed that miR-605-3p serves as a tumor suppressor gene by regulating RAF1 and increasing the chemosensitivity of OS cells, which provided the novel working mechanism of miR-605-3p in OS. Engineering stable nanovesicles that could efficiently deliver miR-605-3p with therapeutic activity into tumors could be a promising therapeutic approach for the treatment of OS.

Cancer mortality in childhood and adolescence: analysis of trends and spatial distribution in the 133 intermediate Brazilian regions grouped by macroregions

RESUMO Objetivo: Avaliar magnitude, tendência e padrões espaciais da mortalidade por câncer na infância e adolescência, entre 1996 e 2017, nas 133 regiões intermediárias brasileiras, utilizando indicadores socioeconômicos e de serviços de saúde. Métodos: É um estudo ecológico que analisa a tendência da mortalidade por câncer na infância e adolescência por meio de séries temporais. Os dados sobre óbitos foram extraídos do Sistema de Informações sobre Mortalidade. Os dados referentes à população foram extraídos dos censos demográficos de 1991, 2000 e 2010 do Instituto Brasileiro de Geografia e Estatística, com interpolação para os anos intercensitários. Foram delineadas séries temporais para a mortalidade por tipo de câncer em cada região intermediária. Tais regiões foram agrupadas por macrorregiões para a apresentação dos resultados. O cálculo e interpretação das tendências de mortalidade utilizaram o procedimento de autorregressão de Prais-Winsten. Resultados: As taxas de mortalidade para todas as neoplasias foram maiores na Região Norte (7,79 óbitos por 100 mil habitantes), enquanto para as leucemias foram maiores na Região Sul (1,61 óbitos por 100 mil habitantes). Em ambas a mortalidade foi maior no sexo masculino e na faixa etária de zero a quatro anos. A tendência mostrou-se decrescente (annual percent change — APC -2,11 [intervalo de confiança — IC95% -3,14; -1,30]) para todas as neoplasias nas regiões brasileiras e estacionária (APC -0.43 [IC95%: -1.61; 2.12]) para as leucemias, no período analisado. Conclusão: A taxa de mortalidade, para todas as neoplasias, apresentou valores mais elevados nas regiões que dispõem de menores números de leito de Unidade de Terapia Intensiva do Sistema Único de Saúde.

MiR-137–LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma

Osteosarcoma (OS) is a rare malignant bone tumor but is one leading cause of cancer mortality in childhood and adolescence. Cancer metastasis accounts for the primary reason for treatment failure in OS patients. The dynamic organization of the cytoskeleton is fundamental for cell motility, migration, and cancer metastasis. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is an oncogene participating in various biological progress central to cancer biogenesis. However, the potential roles of LAPTM4B in OS and the related mechanisms remain unknown. Here, we established the elevated LAPTM4B expression in OS, and it is essential in regulating stress fiber organization through RhoA–LIMK–cofilin signaling pathway. In terms of mechanism, our data revealed that LAPTM4B promotes RhoA protein stability by suppressing the ubiquitin-mediated proteasome degradation pathway. Moreover, our data show that miR-137, rather than gene copy number and methylation status, contributes to the upregulation of LAPTM4B in OS. We report that miR-137 is capable of regulating stress fiber arrangement, OS cell migration, and metastasis via targeting LAPTM4B. Combining results from cells, patients’ tissue samples, the animal model, and cancer databases, this study further suggests that the miR-137–LAPTM4B axis represents a clinically relevant pathway in OS progression and a viable target for novel therapeutics.

Therapeutic Exon Skipping Through a CRISPR-Guided Cytidine Deaminase Rescues Dystrophic Cardiomyopathy in Vivo.

Loss of dystrophin protein causes Duchenne muscular dystrophy (DMD), characterized by progressive degeneration of cardiac and skeletal muscles, and mortality in adolescence or young adulthood. Although cardiac failure has risen as the leading cause of mortality in patients with DMD, effective therapeutic interventions remain underdeveloped, in part, because of the lack of a suitable preclinical model. We analyzed a novel murine model of DMD created by introducing a 4-bp deletion into exon 4, one of the exons encoding the actin-binding domain 1 of dystrophin (referred to as DmdE4* mice). Echocardiography, microcomputed tomography, muscle force measurement, and histological analysis were performed to determine cardiac and skeletal muscle defects in these mice. Using this model, we examined the feasibility of using a cytidine base editor to install exon skipping and rescue dystrophic cardiomyopathy in vivo. AAV9-based CRISPR/Cas9-AID (eTAM) together with AAV9-sgRNA was injected into neonatal DmdE4* mice, which were analyzed 2 or 12 months after treatment to evaluate the extent of exon skipping, dystrophin restoration, and phenotypic improvements of cardiac and skeletal muscles. DmdE4* mice recapitulated many aspects of human DMD, including shortened life span (by ≈50%), progressive cardiomyopathy, kyphosis, profound loss of muscle strength, and myocyte degeneration. A single-dose administration of AAV9-eTAM instituted >50% targeted exon skipping in the Dmd transcripts and restored up to 90% dystrophin in the heart. As a result, early ventricular remodeling was prevented and cardiac and skeletal muscle functions were improved, leading to an increased life span of the DmdE4* mice. Despite gradual decline of AAV vector and base editor expression, dystrophin restoration and pathophysiological rescue of muscular dystrophy were long lasted for at least 1 year. Our study demonstrates the feasibility and efficacy to institute exon skipping through an enhanced TAM (eTAM) for therapeutic application(s).

Connectome Wide Study of Intrinsic Functional Connectivity Associated With Impulsive Choice in Adolescence

Impulsive risk-taking behavior is associated with psychopathology and morbidity and mortality in adolescence. However, individual differences in functional networks that underlie impulsive choice in adolescence remain poorly understood.

Comparison of ECG, laboratory and echocardiographic parameters in patients with acute myocarditis at acute attack and clinical remission

Aim: The pathogenesis of myocarditis, which has high morbidity and mortality in childhood and adolescence, has not been fully elucidated. The pathogenesis of acute myocarditis is a complex process in which multiple agents play a role. We aimed to compare ECG, laboratory and echocardiographic parameters of patients during acute exacerbation of myocarditis and clinical remission. Material and Method: 144 patients (124 males, 20 females) with an acute myocarditis episode were included in the study (28 ± 5). These patients were called for control during the clinical remission period of 3-12 months. The ECG, laboratory and echocardiographic parameters of the patients were compared during acute exacerbation and clinical remission. QT and Tp-e ECG parameters were measured. In addition to routine biochemistry and hemogram parameters, troponin I, uric acid, CRP, sedimentation, TSH and cholesterol levels were measured. Left ventricular ejection fraction was measured as an echocardiographic parameter. Results: When compared with the clinical remission Tp-e interval (p: 0.032), QT-max (p=0.014), QT-min (p=0.001), TSH (p<0.001), Trop (p<0.00), Urea (p=0.028), Alt (p=0.010), Ast (p<0.001), Wbc (p<0.001), Hb (p<0.001), Htc (p<0.001), Rdw (p<0.001), Plt (p<0.001), Mpv (p<0.001), Neu (p=0.003), Lym (p=0.013), Mon (p<0.001), Eo (p=0.003), Pdw (p<0.001), CRP (p=0.001), ESR (p<0.001), and HDL-C (p=0.002) were significantly changed in patients with acute attack myocarditis. Conclusion: ECG parameters, inflammation markers, and HDL cholesterol levels were significantly improved in the clinical remission in addition to the left ventricular ejection fraction during acute exacerbation of the patients. LVEF, ECG parameters, inflammation markers, TSH and HDL cholesterol levels were thought to be important in terms of clinical course and pathogenesis of the disease.

The uroplakin plaque promotes renal structural integrity during congenital and acquired urinary tract obstruction.

Urinary tract obstruction represents a common cause of kidney injury across the human life span, resulting in chronic kidney disease and end-stage renal disease. Yet, the extent of obstructive renal damage can be heterogeneous between individuals, implying the existence of unknown mechanisms that protect against or accelerate kidney injury. In this study, we investigated the role of urothelial remodeling in renal adaptation during congenital and acquired obstruction. In the Megabladder ( Mgb-/-) model of congenital obstruction and unilateral ureteral ligation model of acute obstruction, progressive hydronephrosis is strongly associated with dynamic reorganization of the renal urothelium, which elaborates a continuous uroplakin (Upk) plaque. This led us to postulate that the Upk plaque prevents parenchymal injury during urinary tract obstruction. To test this hypothesis, we interbred Mgb-/- and Upk1b-/- mice, which lack the critical Upk1b subunit for Upk plaque formation. Upk1b-/-; Mgb-/- mice experienced an accelerated onset of bilateral hydronephrosis with severe (>67%) parenchymal loss, leading to renal failure and mortality in adolescence. To investigate the function of the renal Upk plaque during acute obstruction, we destabilized the Upk plaque by Upk1b deletion or genetically depleted Upk+ cells following unilateral ureteral obstruction. Both of these strategies accelerated renal parenchymal loss following ureteral ligation, attesting to a conserved, stabilizing role for Upk plaque deposition in the acutely obstructed kidney. In aggregate, these complementary experiments provide the first evidence that the Upk plaque confers an essential, protective adaptation to preserve renal parenchymal integrity during congenital and acquired urinary tract obstruction.

Mortalidade por suicídio na adolescência: uma revisão

O suicídio entre jovens é um importante agravo que vem aumentando de maneira preocupante, tornando-se um problema de saúde pública mundial. Esta é uma revisão integrativa que tem como objetivo deste conhecer a produção científica acerca do suicídio em adolescentes no período de 1996 a 2013. Os descritores foram suicídio: adolescentes, tentativa de suicídio, suicídio. As bases de dados pesquisadas foram: Lilacs, Bireme, Scielo.e Pubmed. Foram selecionados 55 artigos, dos quais 14 foram excluídos por não atenderem a proposta da pesquisa. Os resultados sugerem associações com transtornos mentais, questões afetivas/emocionais, histórico familiar, problemas socioeconômicos. A maior prevalência de casos ocorre em indivíduos do sexo feminino, na faixa etária entre 15 e 19 anos. Acredita-se que a continuidade das investigações contribuirá para melhor entendimento sobre o tema.

OP-74 - Comparison of Ecg, Laboratory and Echocardiographic Parameters in Patients with Acute Myocarditis at Acute Attack and Clinical Remission

Purpose: The pathogenesis of myocarditis, which has high morbidity and mortality in childhood and adolescence, has not been fully elucidated. Pathogenesis of acute myocarditis is a complex process in which multiple agents play a role. Patients' ECG, laboratory and echocardiographic parameters were compared during myocarditis acute exacerbation and clinical remission. We planned this research to identify the presence of factors that could change the course of the disease in patients' follow-ups.

A new parametric model to assess delay and compression of mortality.

BackgroundA decrease in mortality across all ages causes a shift of the age pattern of mortality, or mortality delay, while differences in the rate of decrease across ages cause a change in the shape of the age-at-death distribution, mortality compression or expansion. Evidence exists for both compression and delay of mortality. Existing parametric models to describe the full age pattern of mortality are not able to capture mortality delay versus mortality compression. More recent models that assess delay versus compression mostly focused on the adult or old ages alone and did not distinguish mortality compression below and above the modal age at death, although they represent different mechanisms.MethodsThis paper presents a new parametric model that describes the full age pattern of mortality and assesses compression – at different stages of life – and delay of mortality: the CoDe model. The model includes 10 parameters, of which five are constant over time. The five time-varying parameters reflect delay of mortality and compression of mortality in infancy, adolescence, young adulthood, late adulthood, and old age. The model describes infant and background mortality by two simple functions, uses a mixed logistic model with different slopes in adult, middle, and old age, and includes the modal age at death as a parameter to account for the delay in mortality.ResultsApplying the CoDe model to age-specific probabilities of death for Japanese, French, American, and Danish men and women between 1950 and 2010 showed a very good fit of the full age pattern of mortality. Delay of mortality explained about two-thirds of the increase in life expectancy at birth, whereas compression of mortality due to mortality declines in young age explained about one-third. No strong compression of mortality in late adulthood age was observed. Mortality compression in old age has had a small negative impact on life expectancy.ConclusionsThe CoDe model proved a valid instrument for describing the full age pattern of mortality and for disentangling the effects of mortality delay and compression – at different stages of life – on the increase in life expectancy.

All-Cause Mortality of Low Birthweight Infants in Infancy, Childhood, and Adolescence: Population Study of England and Wales.

BackgroundLow birthweight (LBW) is associated with increased mortality in infancy, but its association with mortality in later childhood and adolescence is less clear. We investigated the association between birthweight and all-cause mortality and identified major causes of mortality for different birthweight groups.Methods and FindingsWe conducted a population study of all live births occurring in England and Wales between 1 January 1993 and 31 December 2011. Following exclusions, the 12,355,251 live births were classified by birthweight: 500–1,499 g (very LBW [VLBW], n = 139,608), 1,500–2,499 g (LBW, n = 759,283), 2,500–3,499 g (n = 6,511,411), and ≥3,500 g (n = 4,944,949). The association of birthweight group with mortality in infancy (<1 y of age) and childhood/adolescence (1–18 y of age) was quantified, with and without covariates, through hazard ratios using Cox regression. International Classification of Diseases codes identified causes of death. In all, 74,890 (0.61%) individuals died between birth and 18 y of age, with 23% of deaths occurring after infancy. Adjusted hazard ratios for infant deaths were 145 (95% CI 141, 149) and 9.8 (95% CI 9.5, 10.1) for the VLBW and LBW groups, respectively, compared to the ≥3,500 g group. The respective hazard ratios for death occurring at age 1–18 y were 6.6 (95% CI 6.1, 7.1) and 2.9 (95% CI 2.8, 3.1). Male gender, the youngest and oldest maternal age bands, multiple births, and deprivation (Index of Multiple Deprivation score) also contributed to increased deaths in the VLBW and LBW groups in both age ranges. In infancy, perinatal factors, particularly respiratory issues and infections, explained 84% and 31% of deaths in the VLBW and LBW groups, respectively; congenital malformations explained 36% and 23% in the LBW group and ≥2,500 g groups (2,500–3,499 g and ≥3,500 g groups combined), respectively. Central nervous system conditions explained 20% of deaths in childhood/adolescence in the VLBW group, with deaths from neoplasms and external conditions increasingly prevalent in the 1,500–2,499 g and ≥2,500 g birthweight groups. The study would have benefited had we had access to information on gestational age and maternal smoking, but since the former is highly correlated with birthweight and the latter with deprivation, we believe that our findings remain robust despite these shortcomings.ConclusionsLBW is associated with infant and later child and adolescent mortality, with perinatal factors and congenital malformations explaining many of the deaths. By understanding and ameliorating the influences of upstream exposures such as maternal smoking and deprivation, later mortality can be decreased by reducing the delivery of vulnerable infants with LBW.

Validation of Accelerometer Thresholds and Inclinometry for Measurement of Sedentary Behavior in Young Adult University Students.

Sedentary behavior (SB) is a major contributor to obesity and significant morbidity and mortality in adolescence and adulthood, yet measurement of SB is still evolving. The purpose of this study was to assess the degree of construct validity of the inclinometer function and single-axis and vector magnitude accelerometry metrics of the ActiGraph GT3X+ in objectively measuring SB and physical activity in 28 young adult university students who performed nine semi-structured activities, each for five minutes: lying, sitting, reading, seated video gaming, video watching, seated conversation, standing, stationary biking, and treadmill walking. Inclinometry and four output metrics from the ActiGraph were analyzed in comparison to direct observation by a researcher recorded each minute. For overall accuracy in measuring both SB and physical activity, all four accelerometer metrics (94.7-97.8%) outperformed the inclinometer function (70.9%). Vector magnitude accelerometry with a threshold of 150 counts per minute as the cut point for sedentary behavior was superior to other methods. While accelerometry was more accurate overall at detecting the behaviors tested, inclinometry had some advantages over accelerometry methods at detecting walking, biking, and standing. The findings support use of accelerometry as a valid objective measure of body movement, while use of inclinometry as a sole measure is not recommended. Additional research would be beneficial to improve the calibration of the inclinometer and explore ways of combining this with accelerometer data for objectively measuring SB and physical activity.

Neurosurgical conditions and procedures in infancy are associated with mortality and academic performances in adolescence: a nationwide cohort study.

Few human cohort studies on anesthesia-related neurotoxicity and the developing brain have focused on and compared specific surgeries and conditions. These studies cannot disentangle the effects of anesthesia from those of the surgery and underlying conditions. This study aimed at assessing the impact of specific neurosurgical conditions and procedures in infancy on mortality and academic achievements in adolescence. A nationwide unselected register-based follow-up study of the Danish birth cohorts 1986-1990 compared academic performances of all children having undergone neurosurgeries as infants with a randomly selected, age-matched 5% sample of the same cohorts. The two groups were compared regarding mortality prior to June 1st, 2006, average test scores at ninth grade, and finally the proportion of children not attaining test scores. The exposure group comprised 228 and the control group 14 698 individuals. Hydrocephalus (n = 130), craniotomy (n = 43), and myelomeningocele/encephalocele children (n = 55) had a higher mortality (18.5.0%, 18.6%, and 7.3%, respectively) vs controls (1.3%; P < 0.00001, P < 0.00001, and P = 0.0052, respectively). Average test scores were significantly lower than controls in hydrocephalus and craniotomy (P = 0.0043 and P = 0.0077) but not myelomeningocele/encephalocele children (P = 0.2785); the proportion of available test scores were significantly lower in all three groups (40.8%, 60.0%, and 67.3%, respectively) vs 86.8% in controls (P < 0.00001, P = 0.000077, and P = 0.000064). Neurosurgery in infancy was associated with high mortality and significantly impaired academic achievements in adolescence. When studying anesthesia-related neurotoxicity and the developing brain, focus on specific surgeries/conditions is important. Pooling of major/minor conditions and major/minor surgeries should be avoided.

TRENDS OF SUICIDE MORTALITY IN ADOLESCENCE AND ITS RELATIONSHIP WITH ALCOHOL CONSUMPTION IN MURMANSK REGION

The dynamics of suicide mortality in adolescence and its relationship with the level of alcohol consumption in the Murmansk region have been analyzed. The method of autoregression and integrated moving average (ARIMA) was used. The alcohol attributiveness of the male population mortality has been revealed.

Global adolescent health: is there a role for general practice?

Young people are a nation’s greatest asset for growth, prosperity, innovation, and current and future workforce and social support: it makes sense to invest in their health. The 21st century heralds the largest global population of young people ever previously known with a total of 1.8 billion individuals aged 10–24 years, 90% of whom live in low-income countries.1 Young people represent more than one-third of the population in low-income countries, and one-sixth to one-fifth of the population in high-income countries such as the UK. Yet, until recently the health needs of young people have been poorly understood and marginalised. The first WHO/UNFPA/UNICEF report on programming for adolescent health and development was issued less than 20 years ago.1 The need for a global focus on young people’s health is evidenced by a landmark study of 50-year global mortality trends showing that mortality in young people aged 15–24 years is now higher than in children aged 1–4 years, with mortality of young males in this age group, two- to threefold higher than in the first decade of life.2 Furthermore, the major causes of morbidity and mortality in adolescence are largely preventable such as transport injuries, violence, suicide, rising rates of mental health issues, substance abuse, sexually transmitted infections including HIV, and precancerous lesions. Prevention and early intervention have thus dominated the recommended healthcare responses to these health risks. The World Health Organization definition of adolescence refers to young people between the ages of 10 and 19 years. However, in this article we define adolescence to be synonymous with young people, encompassing the ages of 10–24 years, because the biological, psychological, and social role transitions of adolescence affect the health of young people throughout this age range. Many of the risk factors for disease in adulthood begin in adolescence; for …

Prenatal Smoking Exposure and the Risk of Psychiatric Morbidity Into Young Adulthood

Prenatal smoking exposure modulates brain development, which may deviate mental development of the offspring. To study the effects of prenatal smoking exposure on psychiatric morbidity and mortality among Finnish young adults by means of population-based longitudinal register data. Information on maternal smoking as reported by the mothers (0, <10, or >10 cigarettes a day) and other background factors (maternal age and parity and child's sex, gestational age, birth weight, and 5-minute Apgar score) was derived from the Finnish Medical Birth Register. Information on children's psychiatric diagnoses related to outpatient visits (1998-2007), children's inpatient care (1987-2007), and mothers' psychiatric inpatient care (1969-1989) was derived from the Finnish Hospital Discharge Register. Information on deaths and their causes for the children (1987-2007) was received from the Cause-of-Death Register. Population-based study of all singletons born in Finland from 1987 to 1989 with information on prenatal smoking exposure. Patients The source population included all singleton births in Finland from January 1, 1987, through December 31, 1989 (n = 175 869), excluding children with major congenital anomalies (3.1%) and children who died during the first week of life (0.3%). Psychiatric morbidity and mortality. The prevalence of maternal smoking was 15.3%. The risk of psychiatric morbidity was significantly higher in the exposed children than in the unexposed children. Among the offspring of mothers who smoked fewer than 10 cigarettes a day, 21.0% had any psychiatric diagnoses (adjusted odds ratio [OR], 1.53 [95% confidence interval (CI), 1.47-1.60]) compared with 24.7% among those of mothers who smoked more than 10 cigarettes a day (1.85 [1.74-1.96]) and 13.7% in the unexposed children (the reference group). The risk was significantly increased for most of the psychiatric diagnoses. The strongest effects were in psychiatric disorders due to psychoactive substance use and in behavioral and emotional disorders. The risk of mortality was significantly higher in children exposed to more than 10 cigarettes a day (OR, 1.69 [95% CI, 1.31-2.19]) compared with unexposed children. Prenatal smoking exposure is associated with an increased risk of psychiatric morbidity, whereas prenatal exposure to more than 10 cigarettes a day increases the risk of mortality in childhood, adolescence, and young adulthood.

Triadic model of the neurobiology of motivated behavior in adolescence

Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems-based model of adolescent decision-making. We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e. amygdala, nucleus accumbens, and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed. The propensity during adolescence for reward/novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm-avoidant system (amygdala), and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety. A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior.

Adolescent injury risk behavior

Health-risk behaviors that contribute to the leading causes of morbidity and mortality among adolescents and young adults are often established during adolescence and extended into adulthood. Unintentional motor vehicle injury is the leading cause of mortality in childhood and adolescence in developed countries. This review presents some of the risk factors found in research on unintentional injury and death in adolescence, including risk factors for siblings and adolescents with intellectual disability. These findings should be connected with the findings of a recent study that showed that about one third of all unintentional childhood injury deaths in the United States were preventable. For injury prevention to take place and being effective a multidisciplinary approach is needed to identify host, agent and environmental factors using epidemiology research and biomechanics. In the population of adolescents with intellectual disability there has been little research on injury epidemiology or injury prevention and the service provider will need to focus and educate staff on this issue in order to prevent injury that can result in further disability.

Alcohol and road safety behaviour among New Zealand tertiary students

In New Zealand, as in most developed countries, rates of injury mortality and morbidity peak in late adolescence (15-19 years), when they account for around three quarters of fatalities and a third of hospitalisations. Road traffic crashes account for over half of fatal injuries in New Zealand as in most developed countries. Individuals engaged in post-secondary education, i.e., tertiary students, are a large and important subgroup of young people exposed to the risk of road traffic injury. The aims of this study were to estimate the prevalence of unsafe road behaviours and to examine the role of demographic variables, alcohol use, driver licence status, and transport needs. Participants were 1,480 students (899 women) from 12 residential halls in Dunedin, New Zealand. They anonymously completed a questionnaire on alcohol use and road safety at the start of the 2000 academic year. A sub-sample of 967 students completed a follow-up survey six months later. The mean age of the sample was 18.3 years (SD=1.6), and 88% had a driver licence. Male gender and drinking status were independently associated with speeding, drink-driving and drink-riding, but not seatbelt use. Drinking levels showed a strong dose-response relationship with the prevalence of unsafe behaviours with the exception of seatbelt use. In marked contrast to drinking levels, which increased from baseline to follow-up, drink-driving and drink-riding levels decreased, probably reflecting the reduced motor vehicle transport needs of students in residential halls, relative to their out-of-term living environments. In addition to various existing, evidence-based countermeasures, application of interventions for reducing hazardous drinking may be required to help reduce road traffic injury rates in this population.

Long-term follow-up and prognosis of chronic granulomatous disease in Yugoslavia: is there a role for early bone marrow transplantation?

We report the long-term follow-up of 12 pediatric-aged patients with chronic granulomatous disease (CGD). The mean age at the onset of infections was 5 months with a median delay in diagnosis of 2.5 years. Bacille Calmette-Guérin lymphadenitis was the most common presenting infection (6) followed by suppurative lymphadenitis (4), liver abscess (1), or Salmonella sepsis (1). Prophylaxis with cotrimoxazole was recommended to all patients. During the mean follow-up of 10 years (range, 4-23 years) pneumonitis was the most prevalent infection (91%) followed by lymphadenitis (83%), aphtous stomatitis (58%), and liver abscesses (25%). Seven (58%) patients developed chronic lung disease due to grossly delayed diagnosis (3) or poor compliance with antimicrobial prophylaxis (4). Five (41%) patients died during the second decade of life of aspergillosis (3) or chronic lung disease (2). Probability of survival into the third decade of life was estimated to be only 19%. We argue that HLA-identical bone marrow transplantation (BMT), if possible, should be attempted at early age because of significant morbidity and mortality in adolescence. BMT also should be considered in patients who suffer severe infections despite antimicrobial prophylaxis or patients with evidence of chronic lung disease. Possibility of elective BMT from unrelated donors remains to be carefully evaluated.