Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice

Patients with severe mental illness have increased mortality, often linked to cardio-metabolic disease. Non-alcoholic fatty liver disease (NAFLD) incidence is higher in patients with schizophrenia and is exacerbated with antipsychotic treatment. NAFLD is associated with obesity and insulin resistance, both of which are induced by several antipsychotic medications. NAFLD is considered an independent risk factor for cardiovascular disease, the leading cause of death for patients with severe mental illness. Although the clinical literature clearly defines increased risk of NAFLD with antipsychotic therapy, the underlying mechanisms are not understood. Given the complexity of the disorder as well as the complex pharmacology associated with atypical antipsychotic (AA) medications, we chose to use a proteomic approach in healthy mice treated with a low dose of risperidone (RIS) or olanzapine (OLAN) for 28 days to determine effects on development of NAFLD and to identify pathways impacted by AA medications, while removing confounding intrinsic effects of mental illness. Both AA drugs caused development of steatosis in comparison with vehicle controls (p < 0.01) and affected multiple pathways relating to energy metabolism, NAFLD, and immune function. AA-associated alteration in autonomic function appears to be a unifying theme in the regulation of hepatic pathology.     

Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum

Microphthalmia, anophthalmia, and coloboma (MAC) are a group of congenital eye anomalies that can affect one or both eyes. Patients can present one or a combination of these ocular abnormalities in the so called “MAC spectrum”. The KIF17 gene encodes the kinesin-like protein Kif17, a microtubule-based, ATP-dependent, motor protein that is pivotal for outer segment development and disc morphogenesis in different animal models, including mice and zebrafish. In this report, we describe a Sicilian family with two siblings affected with congenital coloboma, microphthalmia, and a mild delay of motor developmental milestones. Genomic DNA from the siblings and their unaffected parents was sequenced with a clinical exome that revealed compound heterozygous variants in the KIF17 gene ({"type":"entrez-nucleotide","attrs":{"text":"NM_020816.4","term_id":"1677537661","term_text":"NM_020816.4"}}NM_020816.4: c.1255C > T (p.Arg419Trp); c.2554C > T (p.Arg852Cys)) segregating with the MAC spectrum phenotype of the two affected siblings. Variants were inherited from the healthy mother and father, are present at a very low-frequency in genomic population databases, and are predicted to be deleterious in silico. Our report indicates the potential co-segregation of these biallelic KIF17 variants with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development across different species.     

Antimicrobial applications of electroactive PVK-SWNT nanocomposites

The antibacterial properties of a nanocomposite containing an electroactive polymer, polyvinyl-N-carbazole (PVK) (97 wt %), and single-walled carbon nanotubes (SWNT) (3 wt %) was investigated as suspensions in water and as thin film coatings. The toxic effects of four different PVK-SWNT (97:3 wt %) nanocomposite concentrations (1, 0.5, 0.05, and 0.01 mg/mL) containing 0.03, 0.015, 0.0015, and 0.0003 mg/mL of SWNT, respectively, were determined for planktonic cells and biofilms of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis). The results showed that the nanocomposite PVK-SWNT had antibacterial activity on planktonic cells and biofilms at all concentration levels. Higher bacterial inactivation (94% for E. coli and 90% for B. subtilis) were achieved in planktonic cells at a PVK-SWNT concentration of 1 mg/mL. Atomic force microscopy (AFM) imaging showed significant reduction of biofilm growth on PVK-SWNT coated surfaces. This study established for the first time that the improved dispersion of SWNTs in aqueous solutions in the presence of PVK enhances the antimicrobial effects of SWNTs at very low concentrations. Furthermore, PVK-SWNT can be used as an effective thin film coating material to resist biofilm formation.     

Assessment of Stochastic Operation Optimization for Reservoirs of Contrasting Scales

Deriving optimal release policies for dams and corresponding reservoirs is crucial for the sustainable water resources management of a region as they directly control the distribution of water to several users. Mathematical optimization algorithms can help in finding efficient reservoir operating strategies taking into account complex system constraints and hydrologic uncertainty. The robustness of operation optimization models may be influenced by physical reservoir characteristics such as size and scale and the effectiveness of a model for a particular case study does not always guarantee the same level of success for another application. This research focused on assessing the applicability of an implicit stochastic optimization (ISO) procedure to derive rule curves for two different dams of contrasting reservoir scales in terms of physical and operational characteristics. The results demonstrated the feasibility of the proposed technique for both small- and large-scale systems in view of the lower vulnerability provided by the ISO-derived policies in contrast to operations carried out by the standard reservoir operating policy as well as the proximity of the ISO operations with those by perfect-forecast deterministic optimization. The ISO procedure also provided operating rules similar to, and even less vulnerable than, those derived by stochastic dynamic programming.     

Trust management for multimedia P2P applications in autonomic networking

In the last years, trust management has become a fundamental basis for facilitating the cooperation between different users in peer-to-peer (P2P) multimedia applications within autonomic networks. In these networks and applications, trust management should fulfill certain requirements (i.e. decentralisation, dynamism, simplicity, interoperability, etc.) for being functional. In this paper, we propose an evolutionary model of trust management that captures dynamic entities’ behaviour over time. Likewise, we explain protection mechanisms against several attacks, which are based on the cooperative behaviour of the entities, trust relationship properties, and trust rules. Finally, we successfully validate our model from several scenarios and compare it with other proposals in this field.     

The Role of Fairness in Mediating the Effects of Voice and Justification on Stress and Other Outcomes in a Climate of Organizational Change.

Organizational change can become a source of resistance and stress if it is implemented without attention to the needs of organizational members. The participants in the present study (604 government employees) work in a climate of ongoing change and, thus, are at particular risk for experiencing high levels of stress and other deleterious consequences. This study examines and finds support for the central role played by procedural and distributive fairness in mediating the effects of change justification and voice on the extent to which employees experience stress, which, in turn, predicts their levels of work effort, intention to leave, and a host of physiological and affective symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High-performance liquid chromatographic determination of the magnetic resonance imaging contrast agent gadobenate ion in plasma, urine, faeces, bile and tissues

The gadobenate ion is an intravascular paramagnetic contrast agent for magnetic resonance imaging. An HPLC method for assaying gadobenate ion in plasma, urine, faeces, bile and tissue samples is described. The analysis is based on the reversed-phase chromatographic separation of gadobenate ion from the endogenous components of biological matrices and detection by UV absorption at 210 nm. The selectivity of the method was satisfactory. The mean absolute recovery was greater than 95%. The precision and accuracy of the analytical methods were in the range 0.1-6.5% and -12 to +9.3%, respectively. The detection limits in plasma (0.1 ml), urine (0.05 ml), dried faeces (200 mg suspended in 4 ml water), bile (0.5 ml), and dried liver tissue (100 mg suspended in 1 ml water) were, respectively, 0.24, 0.47, 2.6, 0.63 and 2.8 nmol ml(-1) (corresponding to 0.16, 0.31, 1.7, 0.42 and 1.9 microg ml(-1)).     

Deriving Lay Models of Uncertainty About Genes' Role in Illness Causation to Guide Communication About Human Genetics

Advances in clinical genetics and biotechnology increase the ability to identify individual genetic makeup through genetic services and testing. As a result, genes have become the focus of an increasing number of health messages associated with medical interaction and public communication. This research explored public perceptions ( N = 858) of the role of genes in health using problematic integration (PI) theory as a framework. A Genetic Relativism Instrument (GRI) associated with macroframeworks about illness causation was developed and used to cluster individuals into 4 groups associated with communicating about genes and health. Uncertainty about the role of personal behaviors, social environments, and religious faith on genes' impact for human health varied significantly among the four groups. In this age of increased use of genetic technologies, communication regarding human genetics in counseling and health promotion may contribute to better informed decision making if tailored to these varied belief systems.     

Ann Elizabeth Kelley (1954-2007).

Ann Elizabeth Kelley was truly a Renaissance woman. Internationally recognized as a conceptual leader in the psychology of brain and behavior, she also excelled as an educator, mentor, athlete, humanist, philanthropist, activist, colleague, friend, and mother. The impact of her contributions to psychology has been particularly significant to our understanding of the neuroanatomical and neurochemical substrates that underlie reward and motivation. Her discoveries shaped current views on numerous pathologies of the human brain including obesity, drug addiction, and affective disorders. On August 5, 2007, at the height of her rich professional and personal life, Ann succumbed to a 16-month battle with metastatic colon cancer in her home in Madison, Wisconsin. (PsycINFO Database Record (c) 2010 APA, all rights reserved)