Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Glycogen synthase kinase (GSK3) is a constitutively active serine-threonine kinase associated to neurological and psychiatric disorders. GSK3 inhibition is considered a mediator of the efficacy of the mood-stabiliser lithium. This study aimed at comparing the central nervous system effect of lithium with the selective GSK3 inhibitors AZ1080 and compound A in biochemical, cellular, and behavioural tests. Collapsin response mediator protein 2 is a neuron-specific GSK3 substrate. Lithium, AZ1080, and compound A inhibited its phosphorylation in rat primary neurons with different pIC₅₀. After systemic treatments with lithium or GSK3 inhibitors to assess specific functional responses, phosphorylation was unchanged in adult rat brain, while it was strongly inhibited by GSK3 inhibitors in pups, differently from lithium. Lithium may exert neurotrophic effect by increasing brain-derived neurotrophic factor (BDNF) levels: in the present experimental conditions, lithium exerted opposite effects on plasma BDNF levels compared to GSK3 inhibitors, suggesting this effect might not be necessarily mediated by GSK3 inhibition alone. While plasma thyroid-stimulating hormone and luteinising hormone were not affected by lithium, they were decreased by selective inhibitors. GH and prolactin displayed similar responses towards reduction. Follicle-stimulating hormone levels were not altered by treatments, whereas melatonin was specifically increased by AZ1080. Lithium impaired mouse spontaneous locomotion and decreased amphetamine-induced hyper-locomotion. AZ1080 had no effects on locomotion, while compound A reduced spontaneous locomotor activity without effects on amphetamine-induced hyper-locomotion. The present results indicate that a broad correlation between the effects of lithium and selective GSK3 inhibitors could not be devised, suggesting alternative mechanisms, whereas overlapping results could be obtained in specific assays.     

Risk of Respiratory Cancer around a Sewage Plant in Prato,Italy

In this study, the authors evaluated the risk of respiratory cancer related to environmental pollutants among a population that resided near a sewage plant in Prato, Italy. Subjects included lung cancer deaths (1987-1996) and incident cases of lung and laryngeal cancers (1987-1994) among residents of Prato. The authors used the mortality or incidence rates for the entire population of Prato (by gender and by 5-yr age group) to calculate the expected cases in each census unit. Data were analyzed and adjusted for an index of social deprivation (Stone test). Among males, the excess risk of lung cancer mortality decreased as distance from the plant increased for 2 time periods (1987-1996 [p = .008] and 1990-1996 [p = .030]) and for lung cancer incidence during 1987-1994 (p = .011). Similar results were obtained when sewage plant workers were excluded from the analysis. A similar, but not statistically significant, trend was observed among female incident lung cancer cases, as well as among male incident laryngeal cancer cases. Despite methodological limitations common to geographic studies, the results were consistent with those previously published on mortality excesses for lung cancer among plant workers under study. The role of environmental pollutants as a risk for respiratory cancer must be further clarified with additional epidemiological studies and an environmental monitoring program.     

Development and psychometric testing of a new tool for detecting moral distress: the Moral Distress Thermometer

Aim. To report the development and psychometric testing of the Moral Distress Thermometer. The Moral Distress Thermometer is a new screening tool to measure moral distress in nurses who practise in the hospital setting. Background. Moral distress occurs when one knows the ethically correct thing to do, but is prevented from acting on that perceived obligation. It is a well documented phenomenon with negative consequences that may be experienced by nurses. Creating an instrument to effectively and efficiently measure moral distress in a timely way has been identified as a priority for nursing. Design. This study used a cross‐sectional survey design. Methods. Data collection for this research occurred in 2009. Participants simultaneously completed either the adult or pediatric version of the Moral Distress Scale version 2009 and the Moral Distress Thermometer. A total of 529 participants from various clinical areas completed both tools. Results. Coefficients alpha were adequate for both Adult (0·90) and Pediatric (0·92) Moral Distress Scale 2009 scales. Statistically significant Pearson correlations were found for the Moral Distress Thermometer with Adult Moral Distress Scale 2009 and Pediatric Moral Distress Scale 2009 and higher Moral Distress Thermometer, Adult Moral Distress Scale 2009 and Pediatric Moral Distress Scale 2009 means for participants who had left or who considered leaving a position because of moral distress. Conclusion. These findings provide support for the validity of the Moral Distress Thermometer.     

Validation of the Sexual Inhibition/Sexual Excitation Scales (SIS/SES) in Italy: Assessing Gender and Age Differences of Sexual Functioning

The Sexual Inhibition Scales and Sexual Excitation Scales (Janssen et al., 2002a), based on the dual control model by Bancroft and Janssen (2000), are part of a 45-item self-report questionnaire evaluating individual tendencies to sexual inhibition or excitation according to three factors: two inhibition factors, SIS1, threat of performance failure, and SIS2, threat of performance consequences, and one excitation factor, SES. In this paper, we aimed to validate and explore psychometric properties of the SIS/SES in a sample of 2260 Italian men and women aged 18 to 75 years. Confirmatory factor analyses showed that the three-factor structure proposed in the original version of the scales fit with our sample. Moreover, our data confirmed the results of the original validation sample: Women scored higher on the SIS and lower on the SES than men did, but no significant differences appeared in the factor scores by age group, except for a gender × age interaction, where younger women had higher SIS2 scores. The SIS/SES appeared to be an effective, appropriate cross-cultural measurement of human sexuality in Italian samples, also shedding light on sexual arousal differences in women and men in our country. We also discuss clinical and therapeutic aspects.