Insulin augments tumor necrosis factor-alpha stimulated expression of vascular cell adhesion molecule-1 in vascular endothelial cells

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis is an inflammatory disease that is marked by increased presence of Tumor Necrosis Factor-alpha (TNFα), increased expression of Vascular Cell Adhesion Molecule-1 (VCAM-1), increased presence of serum monocytes and activation of the canonical inflammatory molecule, Nuclear Factor Kappa-B (NFκB). Hyperinsulinemia is a hallmark of insulin resistance and may play a key role in this inflammatory process.</p> <p>Methods</p> <p>Using Western blot analysis, immunocytochemistry, flow cytometry and biochemical inhibitors, we measured changes in VCAM-1 protein expression and NFκB translocation in vascular endothelial cells in the presence of TNFα and/or hyperinsulinemia and in the absence or presence of kinase pathway inhibitors.</p> <p>Results</p> <p>We report that hyperinsulinemia augmented TNFα stimulated increases in VCAM-1 protein greater than seen with TNFα alone and decreased the time in which VCAM-1 translocated to the cell surface. We also observed that in the presence of Wortmannin, a biochemical inhibitor of phosphatidylinositol 3-kinase (a hallmark of insulin resistance), VCAM-1 expression was greater in the presence of TNFα plus insulin as compared to that seen with insulin or TNFα alone. Additionally, nuclear import of NFκB occurred sooner in the presence of insulin and TNFα together as compared to each alone, and in the presence of Wortmannin, nuclear import of NFκB was greater than that seen with insulin and TNFα alone.</p> <p>Conclusions</p> <p>hyperinsulinemia and insulin resistance appear to augment the inflammatory effects of TNFα on VCAM-1 expression and NFκB translocation, both of which are markers of inflammation in the vasculature.</p

Understanding Human Scale and the Importance of its Relationship with Enclosure

The main objective of the research is to better understand the concept of human scale and the role that it has to play in the design of our urban environments. The need for a clearer, less ambiguous understanding of human scale is identified as a result of its poor definition and numerous manifestations across a multitude of literature. Human scale is an important part of design that flourished particularly in the middle ages, but has largely been neglected in the industrial and technological ages. Its remergence comes with the return of consideration for the comfort of people. Yet we cannot successfully apply a concept we do not wholly understand. Human scale is therefore redefined as a collective concept that embodies the multitude of existing definitions and treats them as aspects of a larger theory. As a broader but more comprehensive definition it better facilitates the identification and exploration of relationships with what are currently treated as separate urban design objectives, such as enclosure, in an endeavour to better understand the influence of human scale. The design case study proposes a design that tests the relationship between enclosure and human scale. A large site is chosen to display how human scale operates at urban, as well as architectural and detailed levels. Through aspiring to achieve a thorough human scale design, without any exclusive emphasis on enclosure, the process and the outcome still reveal that the theoretical relationship identified in the research (that aspects of human scale foster the formation of enclosure) is unavoidable in design practice. Enclosure simply results as a consequence of thorough human scale design. The research suggests that many urban design objectives may fall under human scale's sphere of influence meaning it is not a singular concept, but an ethic of design that has many desireable consequences. While the idealistic nature of the design may be unrealistic to achieve at present, it highlights the incompatibilities with contemporary approaches and succeeds in generating discussion

Taimi Tonu - Just in Time: an Evaluation of Tonga's Restorative Youth Diversion Scheme

In November of 2006, a number of young people under the age of 18 were involved in rioting that destroyed a large portion of the Kingdom of Tonga's capital city, Nuku'alofa. The Government of Tonga (GoT) responded by implementing a youth diversion scheme (YDS) based on the principles and practices of restorative justice. The intention was that through the YDS, youth could be held accountable for their actions whilst avoiding time consuming and life damaging criminal prosecutions. This thesis evaluated the YDS to determine what its outcomes were and whether the continuation of the scheme would provide the Tongan justice system with an effective tool for addressing youth in conflict with the law. Literature on how the Tongan justice system addressed youth in conflict with the law prior to the YDS, is reviewed and barriers to effectiveness are identified. Literature relating to the design of the YDS, restorative justice and aspects of New Zealand's own youth justice system is also reviewed and used to develop YDS evaluation criteria. Data on the YDS has been collected from records, interviews with those involved and observations of practice. This data is evaluated and the outcomes are assessed for their effectiveness in responding to youth in conflict with the law. The study concludes that the YDS is an effective tool for responding to youth in conflict with the law. It provides an effective alternative to punitive responses to youth offending; it advances compliance with a number of those international human rights provisions relevant to the protection of youth in conflict with the law; it has relieved pressure on a backlogged criminal justice system; and it enabled 34 of 35 youth to be held accountable for their actions without recourse to criminal prosecution. At the same time a number of challenges were identified that could impede its ability to sustain these outcomes. Nevertheless, the YDS achieved considerable success and provides Tonga with a unique tool for effectively responding to youth in conflict with the law

The Influence of Self-efficacy on The Relationship Between Depression and HIV-related Stigma with ART Adherence Among The Youth in Malawi

 Depression and HIV-related stigma, among other factors, have been inversely linked independently with adherence to antiretroviral therapy (ART) among the youth. However, the processes through which the various factors influence this relationship is not fully known. Guided by Social Action Theory, we examined the interactive mechanisms through which depression, HIV-related stigma, and self-efficacy influenced ART adherence and whether or not these relationships are moderated by gender. A total of 450 HIV-positive youth (13–24 years) in Malawi receiving ART participated in this cross-sectional study. Moderated mediation analyses were conducted using Hayes’ PROCESS macro 2.11 in SPSS. ART adherence was measured by pill count. Findings showed that self-efficacy mediated the effects of depression and stigma on ART adherence. The analyses also revealed that gender moderated both the direct and indirect influence of depression and stigma (via self-efficacy) on ART adherence. Furthermore, self-efficacy simultaneously mediated and moderated the relationship between stigma and ART adherence. The interactive mechanisms through which various factors influence ART nonadherence must be considered to design effective interventions. To reduce the impact of depression and stigma on ART adherence, medication self-efficacy should be bolstered while taking gender in consideration. Keywords: Adolescent, Antiretroviral adherence, Malawi, Moderated mediation, Social action theory, Youth Abstrak Pengaruh Efikasi Diri Terhadap Hubungan antara Depresi dan Stigma HIV dengan Kepatuhan Terapi ART pada Remaja di Malawi. Depresi dan stigma HIV, di antara faktor-faktor lain, berhubungan terbalik secara independen dengan kepatuhan terapi antiretroviral (ART) pada remaja. Akan tetapi, dalam prosesnya faktor yang memengaruhi hubungan ini belum sepenuhnya diketahui. Berdasarkan Teori Perilaku Sosial, penelitian ini dilakukan bertujuan untuk mengkaji mekanisme interaktif depresi, stigma HIV, dan efikasi diri yang memengaruhi kepatuhan ART, dan untuk mengetahui apakah hubungan ini dimoderasi oleh gender atau tidak. Sebanyak 450 remaja dengan HIV-positif (13–24 tahun) di Malawi yang menerima ART ikut berpartisipasi dalam penelitian potong lintang ini. Analisis mediasi moderated dilakukan dengan menggunakan Hayes 'PROCESS macro 2.11 pada SPSS. Kepatuhan ART diukur menggunakan jumlah pil. Hasil penelitian menunjukkan bahwa efikasi diri memediasi efek depresi dan stigma pada kepatuhan ART. Hasil analisis juga mengungkapkan bahwa jenis kelamin memoderasi pengaruh langsung dan tidak langsung dari depresi dan stigma (melalui efikasi diri) terhadap kepatuhan ART. Lebih lanjut,efikasi diri secara bersamaan mediasi dan moderasi hubungan antara stigma dan kepatuhan ART. Mekanisme interaktif dengan berbagai faktor yang memengaruhi ketidakpatuhan ART harus dipertimbangkan untuk merancang intervensi yang efektif. Untuk mengurangi dampak depresi dan stigma terhadap kepatuhan ART, efikasi diri pengobatan harus didukung saat mempertimbangkan jenis kelamin. Kata kunci: Kepatuhan antiretroviral, Malawi, Mediasi tingkat menengah, Teori Perilaku Sosial, Remaj

The case for investing in family planning in the Pacific: costs and benefits of reducing unmet need for contraception in Vanuatu and the Solomon Islands

Background: Unmet need for family planning in the Pacific is among the highest in the world. Better understanding of required investments and associated benefits of increased access to family planning in the Pacific may assist prioritisation and funding. Methods: We modelled the costs and associated health, demographic and economic impacts of reducing unmet need for family planning between 2010-2025 in Vanuatu and the Solomon Islands. Baseline data were obtained from census reports, Demographic and Health Surveys, and UN agency reports. Using a demographic modelling program we compared a scenario of no change in unmet need with two distinct scenarios: 1) all family planning needs met by 2020; and, 2) all needs met by 2050. Results: Meeting family planning needs by 2020 would increase prevalence of modern contraception in 2025 from 36.8 to 65.5% in Vanuatu and 28.5 to 37.6% in the Solomon Islands. Between 2010-2025 the average annual number of unintended pregnancies would decline by 68% in Vanuatu and 50% in the Solomon Islands, and high-risk births would fall by more than 20%, averting 2,573 maternal and infant deaths. Total fertility rates would fall from 4.1 to 2.2 in Vanuatu and 3.5 in the Solomon Islands, contributing to slowed population growth and lower dependency ratios. The direct cost of reducing unmet need by 2020 was estimated to be $5.19 million for Vanuatu and$3.36 million for the Solomon Islands between 2010-2025. Preventing unintended pregnancies would save $112 million in health and education expenditure. Conclusions: In small island developing states such as Vanuatu and the Solomon Islands, increasing investment in family planning would contribute to improved maternal and infant outcomes and substantial public sector savings

Licit and illicit substance use among persons who inject drugs and the association with subsequent suicidal attempt

AIM: To estimate associations between recent licit and illicit substance use and subsequent suicide attempt among people who inject drugs (PWID). DESIGN: Secondary analysis of longitudinal data from a prospective cohort study of PWID followed bi-annually between 2004 and 2011. SETTING: Montréal, Canada. PARTICIPANTS: Seven hundred and ninety-seven PWID who reported injection drug use in the previous 6 months, contributing to a total of 4460 study visits. The median number of visits per participant was five (interquartile range: 3-8). MEASUREMENTS: An interviewer-administered questionnaire eliciting information on socio-demographic factors, detailed information on substance use patterns and related behaviours, mental health markers and suicide attempt. The primary exposure variables examined were past-month use of alcohol [heavy (≥ 60 drinks); moderate (one to 59 drinks); none], sedative-hypnotics, cannabis, cocaine, amphetamine and opioids [regular (≥ 4 days); occasional (1-3 days); none]. The outcome was a binary measure of suicide attempt assessed in reference to the previous 6 months. FINDINGS: In multivariate analyses, a positive association was found among licit substances between heavy alcohol consumption [adjusted odds ratio (AOR) = 2.05; 95% confidence interval (CI) = 1.12-3.75], regular use of sedative-hypnotics (AOR = 1.89; 95% CI = 1.21-2.95) and subsequent attempted suicide. Among illicit substances, occasional use of cannabis (AOR = 1.84; 95% CI = 1.09-3.13) had a positive association with subsequent suicide attempt. No statistically significant association was found for the remaining substances. CONCLUSION: Among people who inject drugs, use of alcohol, sedative-hypnotics and cannabis, but not cocaine, amphetamine or opioids, appears to be associated with an increased likelihood of later attempted suicide

Parental Substance Abuse As an Early Traumatic Event. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs Early.

open5noParental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents’ addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18–24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and intervention programs are needed for children of drug-misusing parents, addressing EF and adopting a trauma-focused approach.openParolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, M.; Cristofalo, P.Parolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, M.; Cristofalo, P

Pathways from witnessing community violence to mental health problems among South African adolescents

The intersection of violence exposure and mental health problems is a public health crisis for South African (SA) adolescents. Understanding the impact of community violence on adolescent mental health can inform future interventions. Objectives. To assess pathways between community violence exposure and internalising and externalising problems in SA adolescents receiving mental healthcare, and the roles of parent and peer relationships in these associations. Methods. Participants (N=120 parent-adolescent pairs) were recruited from four mental health clinics in Western Cape Province to participate in a pilot test of a family-based HIV prevention study. Adolescents reported on their exposure to community violence, parental attachment, peer support of risk behaviour, and mental health. Parents reported on adolescents' internalising and externalising mental health problems. Participants received transport money (ZAR30 = USD3) and a shopping voucher or cash (ZAR50 = USD5) for their time. Results. Adolescents were 12 - 18 years old (mean (standard deviation) 14.39 (1.82) years), 53% were male, and 67% and 33% reported black African and mixed-race ethnicity, respectively. Parents were 94% female and reported an average monthly income of ZAR3 973 (USD397)

Physician and Clinical Integration Among Rural Hospitals

The pressures for closer alignment between physicians and hospitals in both rural and urban areas are increasing. This study empirically specifies independent dimensions of physician and clinical integration and compares the extent to which such activities are practiced between rural and urban hospitals and among rural hospitals in different organizational and market contexts. Results suggest that both rural and urban hospitals practice physician integration, although each emphasizes different types of strategies. Second, urban hospitals engage in clinical integration with greater frequency than their rural counterparts. Finally, physician integration approaches in rural hospitals are more common among larger rural hospitals, those proximate to urban facilities, those with system affiliations, and those not under public control.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72074/1/j.1748-0361.1998.tb00637.x.pd