Relations Among Anhedonia, Reinforcement Learning, and Global Functioning in Help-seeking Youth

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αβ = .22, 95% CI = 0.02, 0.48) and social functioning (αβ = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

Research workshop to research work: initial steps in establishing health research systems on Malaita, Solomon Islands

<p>Abstract</p> <p>Introduction</p> <p>Atoifi Adventist Hospital is a 90 bed general hospital in East Kwaio, Malaita, Solomon Islands providing services to the population of subsistence villagers of the region. Health professionals at the hospital and attached College of Nursing have considerable human capacity and willingness to undertake health research. However they are constrained by limited research experience, training opportunities, research systems, physical infrastructure and access to resources. This brief commentary describes an 'Introduction to Health Research' workshop delivered at Atoifi Adventist Hospital in September 2009 and efforts to move from 'research workshop' to 'research work'.</p> <p>The Approach</p> <p>Using a participatory-action research approach underpinned by decolonising methodologies, staff from Atoifi Adventist Hospital and James Cook University (Queensland, Australia) collaboratively designed, implemented and evaluated a health research workshop. Basic health research principles and methods were presented using active learning methodologies. Following the workshop, Atoifi Adventist Hospital and Atoifi College of Nursing staff, other professionals and community members reported an increased awareness and understanding of health research. The formation of a local Research Committee, improved ethics review procedures and the identification of local research mentors followed the week long workshop. The workshop has acted as a catalyst for research activity, increasing structural and human resource capacity for local health professionals and community leaders to engage in research.</p> <p>Discussion and Conclusions</p> <p>Participants from a variety of educational backgrounds participated in, and received benefit from, a responsive, culturally and linguistically accessible health research workshop. Improving health research systems at a remote hospital and aligning these with local and national research agendas is establishing a base to strengthen public health research and practice on Malaita, Solomon Islands.</p

Preeclampsia: a gestational cardiorenal syndrome.

It is generally accepted today that there are two different types of preeclampsia: an early-onset or placental type and a late-onset or maternal type. In the latent phase, the first one presents with a low output/high resistance circulation eventually leading in the late second or early third trimester to an intense and acutely aggravating systemic disorder with an important impact on maternal and neonatal mortality and morbidity; the other type presents initially as a high volume/low resistance circulation, gradually evolving to a state of circulatory decompensation usually in the later stages of pregnancy, with a less severe impact on maternal and neonatal outcome. For both processes, numerous dysfunctions of the heart, kidneys, arteries, veins and interconnecting systems are reported, most of them presenting earlier and more severely in early- than in late-onset preeclampsia; however, some very specific dysfunctions exist for either type. Experimental, clinical and epidemiological observations before, during and after pregnancy are consistent with gestation-induced worsening of subclinical pre-existing chronic cardiovascular dysfunction in early-onset preeclampsia, and thus sharing the pathophysiology of cardiorenal syndrome type II, and with acute volume overload decompensation of the maternal circulation in late-onset preeclampsia, thus sharing the pathophysiology of cardiorenal syndrome type 1. Cardiorenal syndrome type V is consistent with the process of preeclampsia superimposed upon clinical cardiovascular and/or renal disease, alone or as part of a systemic disorder. This review focuses on the specific differences in haemodynamic dysfunctions between the two types of preeclampsia, with special emphasis on the interorgan interactions between heart and kidneys, introducing the theoretical concept that the pathophysiological processes of preeclampsia can be regarded as the gestational manifestations of cardiorenal syndromes

Issues and challenges in international doctoral education

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88184/1/ketefian-issues_challenges_international_doctoral.pd

Public health research outputs from efficacy to dissemination: a bibliometric analysis

<p>Abstract</p> <p>Background</p> <p>More intervention research is needed, particularly 'real world' intervention replication and dissemination studies, to optimize improvements in health. This study assessed the proportion and type of published public health intervention research papers over time in physical activity and falls prevention, both important contributors to preventable morbidity and mortality.</p> <p>Methods</p> <p>A keyword search was conducted, using Medline and PsycINFO to locate publications in 1988-1989, 1998-1999, and 2008-2009 for the two topic areas. In stage 1, a random sample of 1200 publications per time period for both topics were categorized as: non-public health, non-data-based public health, or data-based public health. In stage 2 data-based public health articles were further classified as measurement, descriptive, etiological or intervention research. Finally, intervention papers were categorized as: efficacy, intervention replication or dissemination studies. Inter-rater reliability of paper classification was 88%.</p> <p>Results</p> <p>Descriptive studies were the most common data-based papers across all time periods (1988-89; 1998-1999;2008-2009) for both issues (physical activity: 47%; 54%; 65% and falls 75%; 64%; 63%), increasing significantly over time for physical activity. The proportion of intervention publications did not increase over time for physical activity comprising 23% across all time periods and fluctuated for falls across the time periods (10%; 21%; 17%). The proportion of intervention articles that were replication studies increased over the three time periods for physical activity (0%; 2%; 11%) and for falls (0%; 22%; 35%). Dissemination studies first appeared in the literature in 2008-2009, making up only 3% of physical activity and 7% of falls intervention studies.</p> <p>Conclusions</p> <p>Intervention research studies remain only a modest proportion of all published studies in physical activity and falls prevention; the majority of the intervention studies, are efficacy studies although there is growing evidence of a move towards replication and dissemination studies, which may have greater potential for improving population health.</p

Nurse managers' experience with ethical issues in six government hospitals in Malaysia: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Nurse managers have the burden of experiencing frequent ethical issues related to both their managerial and nursing care duties, according to previous international studies. However, no such study was published in Malaysia. The purpose of this study was to explore nurse managers' experience with ethical issues in six government hospitals in Malaysia including learning about the way they dealt with the issues.</p> <p>Methods</p> <p>A cross-sectional study was conducted in August-September, 2010 involving 417 (69.2%) of total 603 nurse managers in the six Malaysian government hospitals. Data were collected using three-part self-administered questionnaire. Part I was regarding participants' demographics. Part II was about the frequency and areas of management where ethical issues were experienced, and scoring of the importance of 11 pre-identified ethical issues. Part III asked how they dealt with ethical issues in general; ways to deal with the 11 pre-identified ethical issues, and perceived stress level. Data were analyzed using descriptive statistics, cross-tabulations and Pearson's Chi-square.</p> <p>Results</p> <p>A total of 397 (95.2%) participants experienced ethical issues and 47.2% experienced them on weekly to daily basis. Experiencing ethical issues were not associated with areas of practice. Top area of management where ethical issues were encountered was "staff management", but "patient care" related ethical issues were rated as most important. Majority would "discuss with other nurses" in dealing generally with the issues. For pre-identified ethical issues regarding "patient care", "discuss with doctors" was preferred. Only 18.1% referred issues to "ethics committees" and 53.0% to the code of ethics.</p> <p>Conclusions</p> <p>Nurse managers, regardless of their areas of practice, frequently experienced ethical issues. For dealing with these, team-approach needs to be emphasized. Proper understanding of the code of ethics is needed to provide basis for reasoning.</p

Epistasis between COMT and MTHFR in Maternal-Fetal Dyads Increases Risk for Preeclampsia

Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1α, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C→T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor “T” allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of including allelic variation in MTHFR

A Signature of Maternal Anti-Fetal Rejection in Spontaneous Preterm Birth: Chronic Chorioamnionitis, Anti-Human Leukocyte Antigen Antibodies, and C4d

Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth.This cross-sectional study included women with (1) normal pregnancy and term delivery (n = 140) and (2) spontaneous preterm delivery (n = 140). We analyzed maternal and fetal sera for panel-reactive anti-HLA class I and class II antibodies, and determined C4d deposition on umbilical vein endothelium by immunohistochemistry. Maternal anti-HLA class I seropositivity in spontaneous preterm births was higher than in normal term births (48.6% vs. 32.1%, p = 0.005). Chronic chorioamnionitis was associated with a higher maternal anti-HLA class I seropositivity (p<0.01), significant in preterm and term birth. Villitis of unknown etiology was associated with increased maternal and fetal anti-HLA class I and II seropositivity (p<0.05, for each). Fetal anti-HLA seropositivity was closely related to maternal anti-HLA seropositivity in both groups (p<0.01, for each). C4d deposition on umbilical vein endothelium was more frequent in preterm labor than term labor (77.1% vs. 11.4%, p<0.001). Logistic regression analysis revealed that chronic chorioamnionitis (OR = 6.10, 95% CI 1.29–28.83), maternal anti-HLA class I seropositivity (OR = 5.90, 95% CI 1.60–21.83), and C4d deposition on umbilical vein endothelium (OR = 36.19, 95% CI 11.42–114.66) were associated with preterm labor and delivery.A major subset of spontaneous preterm births has a signature of maternal anti-fetal cellular and antibody-mediated rejections with links to fetal graft-versus-host disease and alloimmune reactions