Kainic acid alters the metabolism of Met5-enkephalin and the level of dynorphin A in the rat hippocampus

Male Fischer-344 rats were given a single intrastriatal injection of kainic acid (KA; 1 microgram/rat), which caused recurrent motor seizures lasting 3-6 hr. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A (1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 hr after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 hr ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 hr and had increased markedly by 48 hr following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 hr was followed by a substantial increase by 48 hr. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 hr), mRNAenk was 400% of control, and by 24 hr, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex

Transformation kinetics of alloys under non-isothermal conditions

The overall solid-to-solid phase transformation kinetics under non-isothermal conditions has been modeled by means of a differential equation method. The method requires provisions for expressions of the fraction of the transformed phase in equilibrium condition and the relaxation time for transition as functions of temperature. The thermal history is an input to the model. We have used the method to calculate the time/temperature variation of the volume fraction of the favored phase in the alpha-to-beta transition in a zirconium alloy under heating and cooling, in agreement with experimental results. We also present a formulation that accounts for both additive and non-additive phase transformation processes. Moreover, a method based on the concept of path integral, which considers all the possible paths in thermal histories to reach the final state, is suggested.Comment: 16 pages, 7 figures. To appear in Modelling Simul. Mater. Sci. En

The contribution of inherited genotype to breast cancer

The etiology of breast cancer is complex, and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. These inherited genotypes include those that affect the propensity to be exposed to breast carcinogens, and those associated with breast tumorigenesis directly. In addition, inherited genotypes may influence response to breast cancer chemoprevention and treatment. Studies relating inherited genotypes with breast cancer incidence and mortality should consider a broader spectrum of genes and their potential roles in multistage carcinogenesis than have been typically evaluated to date. Understanding the role of inherited genotype at different stages of carcinogenesis could improve our understanding of cancer biology, may identify specific exposures or events that correlate with carcinogenesis, or target relevant biochemical pathways for the development of preventive or therapeutic interventions

Diarrhoea in the critically ill is common, associated with poor outcome, and rarely due to Clostridium difficile

Diarrhoea is common in Intensive Care Unit (ICU) patients, with a reported prevalence of 15-38%. Many factors may cause diarrhoea, including Clostridium difficile, drugs (e.g. laxatives, antibiotics) and enteral feeds. Diarrhoea impacts on patient dignity, increases nursing workload and healthcare costs, and exacerbates morbidity through dermal injury, impaired enteral uptake and subsequent fluid imbalance. We analysed a cohort of 9331 consecutive patients admitted to a mixed general intensive care unit to establish the prevalence of diarrhoea in intensive care unit patients, and its relationship with infective aetiology and clinical outcomes. We provide evidence that diarrhoea is common (12.9% (1207/9331) prevalence) in critically ill patients, independently associated with increased intensive care unit length of stay (mean (standard error) 14.8 (0.26) vs 3.2 (0.09) days, p < 0.001) and mortality (22.0% (265/1207) vs 8.7% (705/8124), p < 0.001; adjusted hazard ratio 1.99 (95% CI 1.70-2.32), p < 0.001) compared to patients without diarrhoea even after adjusting for potential confounding factors, and infrequently caused by infective aetiology (112/1207 (9.2%)) such as Clostridium difficile (97/1048 (9.3%) tested) or virological causes (9/172 (5.7%) tested). Our findings suggest non-infective causes of diarrhoea in ICU predominate and pathophysiology of diarrhoea in critically ill patients warrants further investigation

Routine Opt-Out HIV Testing Strategies in a Female Jail Setting: A Prospective Controlled Trial

Background: Ten million Americans enter jails annually. The objective was to evaluate new CDC guidelines for routine optout HIV testing and examine the optimal time to implement routine opt-out HIV testing among newly incarcerated jail detainees. Methods: This prospective, controlled trial of routine opt-out HIV testing was conducted among 323 newly incarcerated female inmates in Connecticut’s only women’s jail. 323 sequential entrants to the women’s jail over a five week period in August and September 2007 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 108), early (next day, n = 108), or delayed (7 days, n = 107). The primary outcome was the proportion of women in each group consenting to testing. Results: Routine opt-out HIV testing was significantly highest (73%) among the early testing group compared to 55 % for immediate and 50 % for 7 days post-entry groups. Other factors significantly (p = 0.01) associated with being HIV tested were younger age and low likelihood of early release from jail based on bond value or type of charge for which women were arrested. Conclusions: In this correctional facility, routine opt-out HIV testing in a jail setting was feasible, with highest rates of testing if performed the day after incarceration. Lower testing rates were seen with immediate testing, where there is a high prevalence of inability or unwillingness to test, and with delayed testing, where attrition from jail increases with each passing day

Highway infrastructure and building information modelling in UK

Traditional methods of design are becoming less relevant and prevalent, due to institutionalising of Building Information Modelling (BIM) within statutory regulations and the huge amount of data that BIM presents to practice; especially in 3D models. This can be seen in the A1 Dishforth-to-Barton road infrastructure improvement scheme which comprises the A1 Dishforth-to-Leeming and A1 Leeming-to-Barton schemes. The traditional method of design was central to the A1 Dishforth-to-Leeming scheme and BIM central to the A1 Leeming-to-Barton scheme. So this report presents a comparative study of the traditional and BIM methods in relation to the A1 Dishforth-to-Barton improvement scheme through the perception of key professionals involved in this project. A qualitative research study was conducted through the use of an open-ended questionnaire intended to bridge gaps in perceptions and understanding of both methods. Judgemental sampling technique was used to select experienced respondents who understand and participated in the A1 Dishforth-to-Barton road infrastructure improvement scheme. The study reveals an incontrovertible complementary nature of both methods and that the realisation of the 2016 mandate appears doubtful due to lack of standardization, training and level of awareness. It is highly recommended that a statutory incentivization framework for BIM be conceptualised and considered for implementation to attract and encourage small scale participants. Of high priority is the subsidization of in-house training by local authorities and localized joint ventures by smaller companies for specialist training

Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

<p>Abstract</p> <p>Background</p> <p>The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide), and major depressive disorder (MDD). We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls.</p> <p>Methods</p> <p>Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared.</p> <p>Results</p> <p>The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ²= 4.182, p = 0.041). Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively). Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p < 0.001; β = 0.15, p = 0.026; β = 1.11, p < 0.001). Structural equation modeling (SEM) showed that nongenetic factors, such as age, paternal overprotection, and somatic symptoms, were associated with MDD, whereas depressed suicide were associated with severity of depression, personality traits, age, marital status, and inversely associated with anxiety symptoms. However, depression did not affect suicidal behavior in the community group.</p> <p>Conclusion</p> <p>The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.</p

Genome-wide Linkage Scan to Identify Loci for Age at First Cigarette in Dutch Sibling Pairs

Most smokers begin smoking during adolescence and early age of smoking initiation is related to more frequent current smoking, daily smoking and more dependent smoking (Everret et al., 1999; Lando et al.