Parental violence and adolescent mental health

Being the target of parental violent acts decreases child adjustment and increases the likelihood of mental health problems in childhood and adolescence. Our study analyses how different types of parental violence ranging from verbal threats and swearing to hitting and kicking a child, are associated with child adjustment, indicated by strengths and difficulties scale (SDQ) total problem score, internalizing and externalizing problems as well as prosocial behaviour. We also study whether girls and boys and youths in two Nordic countries respond differently to parental violence. The data consists of a large-scale community sample of 15–16-year old Finnish (n = 5,762) and Danish (n = 3,943) adolescents. The representative data of continental Finland and its Finnish and Swedish speaking ninth graders as well as representative data of Danish ninth grade pupils were collected by the Police College of Finland and in Denmark by the National Institute of Public Health, University of Southern Denmark. The results show a clear dose–response effect between parental violent behaviour and the adolescent’s problems. The more severe forms of parental violence were associated with higher levels of SDQ total difficulties and internalizing and externalizing symptoms. There was also a connection between parental violence and the deterioration of prosocial behaviour. The association was gender and nationality specific. The findings imply a high prevalence of parental violence and adverse mental health among the affected Finnish and Danish adolescents. Though the laws have been set in motion to prevent the use of parental physical violence the challenges remain in several domains of child protection, general health care, prevention and intervention

Efflux transport of nicotine, cotinine and trans-3 '-hydroxycotinine glucuronides by human hepatic transporters

Nicotine is the addiction causing alkaloid in tobacco, and it is used in smoking cessation therapies. Although the metabolic pathways of nicotine are well known and mainly occur in the liver, the transport of nicotine and its metabolites is poorly characterized. The highly hydrophilic nature and urinary excretion of nicotine glucuronide metabolites indicate that hepatic basolateral efflux transporters mediate their excretion. We aimed here to find the transporters responsible for the hepatic excretion of nicotine, cotinine and trans-3 '-hydroxycotinine (OH-cotinine) glucuronides. To this end, we tested their transport by multidrug resistance-associated proteins 1 (MRP1, ABCC1) and MRP3-6 (ABCC3-6), which are located on the basolateral membranes of hepatocytes, as well as MRP2 (ABCC2), breast cancer resistance protein (BCRP, ABCG2) and multidrug resistance protein 1 (MDR1, P-gp, ABCB1) that are expressed in the apical membranes of these cells. ATP-dependent transport of these glucuronides was evaluated in inside-out membrane vesicles expressing the transporter of interest. In addition, potential interactions of both the glucuronides and parent compounds with selected transporters were tested by inhibition assays. Considerable ATP-dependent transport was observed only for OH-cotinine glucuronide by MRP3. The kinetics of this transport activity was characterized, resulting in an estimated K-m value of 895 mu mol/L. No significant transport was found for nicotine or cotinine glucuronides by any of the tested transporters at either 5 or 50 mu mol/L substrate concentration. Furthermore, neither nicotine, cotinine nor OH-cotinine inhibited MRP2-4, BCRP or MDR1. In this study, we directly examined, for the first time, efflux transport of the three hydrophilic nicotine glucuronide metabolites by the major human hepatic efflux transporters. Despite multiple transporters studied here, our results indicate that an unknown transporter may be responsible for the hepatic excretion of nicotine and cotinine glucuronides.Peer reviewe

Transmembrane Domain Single-Nucleotide Polymorphisms Impair Expression and Transport Activity of ABC Transporter ABCG2

To study the function and expression of nine naturally occurring single-nucleotide polymorphisms (G406R, F431L, S441N, P480L, F489L, M515R, L525R, A528T and T542A) that are predicted to reside in the transmembrane regions of the ABC transporter ABCG2. The transport activity of the variants was tested in inside-out membrane vesicles from Sf9 insect and human derived HEK293 cells overexpressing ABCG2. Lucifer Yellow and estrone sulfate were used as probe substrates of activity. The expression levels and cellular localization of the variants was compared to the wild-type ABCG2 by western blotting and immunofluorescence microscopy. All studied variants of ABCG2 displayed markedly decreased transport in both Sf9-ABCG2 and HEK293-ABCG2 vesicles. Impaired transport could be explained for some variants by altered expression levels and cellular localization. Moreover, the destructive effect on transport activity of variants G406R, P480L, M515R and T542A is, to our knowledge, reported for the first time. These results indicate that the transmembrane region of ABCG2 is sensitive to amino acid substitution and that patients harboring these ABCG2 variant forms could suffer from unexpected pharmacokinetic events of ABCG2 substrate drugs or have an increased risk for diseases such as gout where ABCG2 is implicated.Peer reviewe

Transcription factor GATA4 associates with mesenchymal-like gene expression in human hepatoblastoma cells

GATA4, a transcription factor crucial for early liver development, has been implicated in the pathophysiology of hepatoblastoma, an embryonal tumor of childhood. However, the molecular and phenotypic consequences of GATA4 expression in hepatoblastoma are not fully understood. We surveyed GATA4 expression in 24 hepatoblastomas using RNA in situ hybridization and immunohistochemistry. RNA interference was used to inhibit GATA4 in human HUH6 hepatoblastoma cells, and changes in cell migration were measured with wound healing and transwell assays. RNA microarray hybridization was performed on control and GATA4 knockdown HUH6 cells, and differentially expressed genes were validated by quantitative polymerase chain reaction or immunostaining. Plasmid transfection was used to overexpress GATA4 in primary human hepatocytes and ensuring changes in gene expression were measured by quantitative polymerase chain reaction. We found that GATA4 expression was high in most hepatoblastomas but weak or negligible in normal hepatocytes. GATA4 gene silencing impaired HUH6 cell migration. We identified 106 differentially expressed genes (72 downregulated, 34 upregulated) in knockdown versus control HUH6 cells. GATA4 silencing altered the expression of genes associated with cytoskeleton organization, cell-to-cell adhesion, and extracellular matrix dynamics (e.g. ADD3, AHNAK, DOCK8, RHOU, MSF, IGFBP1, COL4A2). These changes in gene expression reflected a more epithelial (less malignant) phenotype. Consistent with this notion, there was reduced F-actin stress fiber formation in knockdown HUH6 cells. Forced expression of GATA4 in primary human hepatocytes triggered opposite changes in the expression of genes identified by GATA4 silencing in HUH6 cells. In conclusion, GATA4 is highly expressed in most hepatoblastomas and correlates with a mesenchymal, migratory phenotype of hepatoblastoma cells

What is a Green Economy? Review of National-Level Green Economy Policies in Cambodia and Lao PDR

A green economy that simultaneously promotes environmental sustainability, social inclusiveness, and economic growth is expected to benefit the heavily resource-dependent least developed countries. Yet, internationally, there is very little empirically based research on how the “green development” agenda translates into natural resource management policies in the least developed countries. This paper examines the implementation of green economy policies at the national level in the energy and forestry sectors in the Lao PDR and Cambodia. Both countries have adopted green growth targets; however, in terms of natural resources management, two contradictory processes have taken place during the past decade. While there have been some initiatives to decentralize natural resource management by enhancing the role of local communities role, such as community-based forest or fishery management, the far greater trend has been the opening up of the economies of the Lao PDR and Cambodia to large-scale investments by multinational enterprises. Large-scale hydropower projects and increasing deforestation pose challenges to more sustainable natural resource management efforts. This article is based on an analysis of the national green economy strategies and expert interviews with the government, academia, private sector and international and national development organizations. Focusing on the energy and forestry sectors, but also analysing the national green economy strategies as a whole, our analysis sheds light on the choices made in the national development versus green economy strategies. While green economy thinking rests on strong state regulation, the policies are often formulated within a complex dynamic of donor and investor interests. The achievement of a green economy depends on the state; thus, it should steer investments to ecologically less harmful industries and ensure social inclusiveness in land-use decisions. Our results show, however, that implementing a green economy is far more complex. Despite the quest for synergies, at the sectoral level there are still many unaddressed trade-offs between, for example, energy sources and forms of land use

What is a Green Economy? Review of National-Level Green Economy Policies in Cambodia and Lao PDR

A green economy that simultaneously promotes environmental sustainability, social inclusiveness, and economic growth is expected to benefit the heavily resource-dependent least developed countries. Yet, internationally, there is very little empirically based research on how the “green development” agenda translates into natural resource management policies in the least developed countries. This paper examines the implementation of green economy policies at the national level in the energy and forestry sectors in the Lao PDR and Cambodia. Both countries have adopted green growth targets; however, in terms of natural resources management, two contradictory processes have taken place during the past decade. While there have been some initiatives to decentralize natural resource management by enhancing the role of local communities role, such as community-based forest or fishery management, the far greater trend has been the opening up of the economies of the Lao PDR and Cambodia to large-scale investments by multinational enterprises. Large-scale hydropower projects and increasing deforestation pose challenges to more sustainable natural resource management efforts. This article is based on an analysis of the national green economy strategies and expert interviews with the government, academia, private sector and international and national development organizations. Focusing on the energy and forestry sectors, but also analysing the national green economy strategies as a whole, our analysis sheds light on the choices made in the national development versus green economy strategies. While green economy thinking rests on strong state regulation, the policies are often formulated within a complex dynamic of donor and investor interests. The achievement of a green economy depends on the state; thus, it should steer investments to ecologically less harmful industries and ensure social inclusiveness in land-use decisions. Our results show, however, that implementing a green economy is far more complex. Despite the quest for synergies, at the sectoral level there are still many unaddressed trade-offs between, for example, energy sources and forms of land use

Analysis of Non-Relapsed and Relapsed Adult Type Granulosa Cell Tumors Suggests Stable Transcriptomes during Tumor Progression

Adult-type granulosa cell tumor (AGCT) is a rare ovarian malignancy characterized by slow growth and hormonal activity. The prognosis of AGCT is generally favorable, but one-third of patients with low-stage disease experience a late relapse, and over half of them die of AGCT. To identify markers that would distinguish patients at risk for relapse, we performed Lexogen QuantSeq 3′ mRNA sequencing on formalin-fixed paraffin-embedded, archival AGCT tissue samples tested positive for the pathognomonic Forkhead Box L2 (FOXL2) mutation. We compared the transcriptomic profiles of 14 non-relapsed archival primary AGCTs (follow-up time 17–26 years after diagnosis) with 13 relapsed primary AGCTs (follow-up time 1.7–18 years) and eight relapsed tumors (follow-up time 2.8–18.9 years). Non-relapsed and relapsed primary AGCTs had similar transcriptomic profiles. In relapsed tumors three genes were differentially expressed: plasmalemma vesicle associated protein (PLVAP) was upregulated (p = 0.01), whereas argininosuccinate synthase 1 (ASS1) (p = 0.01) and perilipin 4 (PLIN4) (p = 0.02) were downregulated. PLVAP upregulation was validated using tissue microarray RNA in situ hybridization. In our patient cohort with extremely long follow-up, we observed similar gene expression patterns in both primary AGCT groups, suggesting that relapse is not driven by transcriptomic changes. These results reinforce earlier findings that molecular markers do not predict AGCT behavior or risk of relapse

Analysis of non-relapsed and relapsed adult type granulosa cell tumors suggests stable transcriptomes during tumor progression

Adult-type granulosa cell tumor (AGCT) is a rare ovarian malignancy characterized by slow growth and hormonal activity. The prognosis of AGCT is generally favorable, but one-third of patients with low-stage disease experience a late relapse, and over half of them die of AGCT. To identify markers that would distinguish patients at risk for relapse, we performed Lexogen QuantSeq 3\u27 mRNA sequencing on formalin-fixed paraffin-embedded, archival AGCT tissue samples tested positive for the pathognomonic Forkhead Box L2