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Despite much progress, few genetic findings for schizophrenia have been assessed by functional validation experiments at the molecular level. We previously reported evidence for genetic linkage of broadly defined schizophrenia to chromosome 17q25 in a sample of 24 multiplex families. 2,002 SNPs under this linkage peak were analyzed for evidence of linkage disequilibrium using the posterior probability of linkage (PPL) framework. SNP rs1060120 produced the strongest evidence for association, with a PPLD|L score of 0.21. This SNP is located within the 3'UTR of the histone gene H3F3B and colocalizes with potential gene target miR-616. A custom miRNA target prediction program predicted that the binding of miR-616 to H3F3B transcripts would be altered by the allelic variants of rs1060120. We used dual luciferase assays to experimentally validate this interaction. The rs1060120 A allele significantly reduced luciferase expression, indicating a stronger interaction with miR-616 than the G allele (p = 0.000412). These results provide functional validation that this SNP could alter schizophrenia epigenetic mechanisms thereby contributing to schizophrenia-related disease risk.

Organic farming, a low intensity system, may offer benefits for a range of taxa, but what affects the extent of those benefits is imperfectly understood. We explored the effects of organic farming and landscape on the activity density and species density of spiders and carabid beetles, using a large sample of paired organic and conventional farms in the UK. Spider activity density and species density were influenced by both farming system and surrounding landscape. Hunting spiders, which tend to have lower dispersal capabilities, had higher activity density, and more species were captured, on organic compared to conventional farms. There was also evidence for an interaction, as the farming system effect was particularly marked in the cropped area before harvest and was more pronounced in complex landscapes (those with little arable land). There was no evidence for any effect of farming system or landscape on web-building spiders (which include the linyphiids, many of which have high dispersal capabilities). For carabid beetles, the farming system effects were inconsistent. Before harvest, higher activity densities were observed in the crops on organic farms compared with conventional farms. After harvest, no difference was detected in the cropped area, but more carabids were captured on conventional compared to organic boundaries. Carabids were more species-dense in complex landscapes, and farming system did not affect this. There was little evidence that non-cropped habitat differences explained the farming system effects for either spiders or carabid beetles. For spiders, the farming system effects in the cropped area were probably largely attributable to differences in crop management; reduced inputs of pesticides (herbicides and insecticides) and fertilisers are possible influences, and there was some evidence for an effect of non-crop plant species richness on hunting spider activity density. The benefits of organic farming may be greatest for taxa with lower dispersal abilities generally. The evidence for interactions among landscape and farming system in their effects on spiders highlights the importance of developing strategies for managing farmland at the landscape-scale for most effective conservation of biodiversity.

Background: Colic could be accompanied by changes in the morphology and physiology of organs and tissues, such as the intestine. This process might be, at least in part, due to the accumulation of oxidative damage induced by reactive oxygen (ROS) and reactive nitrogen species (RNS), secondary to intestinal ischemia. Glutathione (GSH), being the major intracellular thiol, provides protection against oxidative injury. The aim of this study was to investigate whether ischemia-induced intestinal injury could be related with alterations in GSH metabolism., Results: Ischemia induced a significant increase in lipid hydroperoxides, nitric oxide and carbon monoxide, and a reduction in reduced glutathione, and adenosine triphosphate (ATP) content, as well as in methionine-adenosyl-transferase and methyl-transferase activities., Conclusion: Our results suggest that ischemia induces harmful effects on equine small intestine, probably due to an increase in oxidative damage and proinflammatory molecules. This effect could be mediated, at least in part, by impairment in glutathione metabolism.

Background: Exercise induces changes in several organs and tissues, and this process might be due to oxidative damage caused by free radicals and inflammatory mediators. Methyl Sulphonyl Methane, better known as MSM, is a naturally occurring sulphur compound with well-known antioxidant properties. On the other hand, Vitamin C is important in limiting free radical damage in the aqueous phase of the cell, and cellular vitamin C status may be linked to the mechanisms involved in quenching cellular reactive oxygen species. The aim of this study was to determine if supplementation with MSM and vitamin C could alleviate exercise-induced oxidative stress in horses undergoing jumping competition., Methods: Twenty four jumping horses involved in competition were used. Horses were given the following three treatment diets: control (without supplementation), MSM 8 mg/kg, and combined supplements (MSM 8 mg/kg + Vit-C 5 mg/kg). EDTA blood samples were collected before exercise, upon arrived to the schooling area (control), and each week after last show. Nitric oxide, carbon monoxide, lipid hydroperoxides and the antioxidant enzymes, glutathione peroxidase, glutathione transferase and glutathione reductase, plasma levels were determined., Results: Competition induced a significant increase in lipid peroxidation, nitric oxide and carbon monoxide. By contrary, reduced glutathione as well as antioxidant enzyme activities, were decreased. MSM administration significantly ameliorated all these exercise-related changes, and this effect was potentiated by Vit C reaching values in some of the parameters similar to those found before competition., Conclusion: These results suggest that jumping exercise could induce harmful effects on horses, probably due to an increase in oxidative damage and proinflammatory molecules. In addition, we have demonstrated that MSM could exert some protective effect on oxidative and inflammatory exercise-induced injury.

Habitat and biodiversity differences between matched pairs of organic and non-organic farms containing cereal crops in lowland England were assessed by a large-scale study of plants, invertebrates, birds and bats. Habitat extent, composition and management on organic farms was likely to favour higher levels of biodiversity and indeed organic farms tended to support higher numbers of species and overall abundance across most taxa. However, the magnitude of the response varied; plants showed larger and more consistent responses than other taxa. Variation in response across taxa may be partly a consequence of the small size and isolated context of many organic farms. Extension of organic farming could contribute to the restoration of biodiversity in agricultural landscapes.

The objective of this communication is to introduce a conceptual framework for a study that applies a rigorous systems approach to rural disaster preparedness and planning. System Dynamics is a well-established computer-based simulation modeling methodology for analyzing complex social systems that are difficult to change and predict. This approach has been applied for decades to a wide variety of issues of healthcare and other types of service capacity and delivery, and more recently, to some issues of disaster planning and mitigation. The study will use the System Dynamics approach to create computer simulation models as "what-if" tools for disaster preparedness planners. We have recently applied the approach to the issue of hospital surge capacity, and have reached some preliminary conclusions--for example, on the question of where in the hospital to place supplementary nursing staff during a severe infectious disease outbreak--some of which we had not expected. Other hospital disaster preparedness issues well suited to System Dynamics analysis include sustaining employee competence and reducing turnover, coordination of medical care and public health resources, and hospital coordination with the wider community to address mass casualties. The approach may also be applied to preparedness issues for agencies other than hospitals, and could help to improve the interactions among all agencies represented in a community's local emergency planning committee. The simulation models will support an evidence-based approach to rural disaster planning, helping to tie empirical data to decision-making. Disaster planners will be able to simulate a wide variety of scenarios, learn responses to each and develop principles or best practices that apply to a broad spectrum of disaster scenarios. These skills and insights would improve public health practice and be of particular use in the promotion of injury and disease prevention programs and practices.

Study Objective: We performed an assessment of hospital preparedness for weapons of mass destruction (WMD) incidents in Federal Emergency Management Agency (FEMA) Region III., Methods: Interviews of hospital personnel were completed in 30 hospitals. Data collected included level of preparedness, mass decontamination capabilities, training of hospital staff, and facility security capabilities., Results: No respondents believed their sites were fully prepared to handle a biologic incident, 73% (22/30) believed they were not prepared to manage a chemical weapons incident, and 73% believed they were unprepared to handle a nuclear event. If a WMD incident were to occur, 73% of respondents stated a single-room decontamination process would be set up. Four (13%) hospitals (all rural) reported no decontamination plans. WMD preparedness had been incorporated into hospital disaster plans by 27% (8/30) of facilities. Eighty-seven percent (26/30) believed their emergency department could manage 10 to 50 casualties at once. Only 1 facility had stockpiled any medications for WMD treatment. All facilities had established networks of communication. No hospital had preprepared media statements specific to WMD. Nearly one fourth (7/30) stated that their hospital staff had some training in WMD event management. All reported need for WMD-specific training but identified obstacles to achieving this. Seventy-seven percent (23/30) of hospitals had a facility security plan in place, and half were able to perform a hospital-wide lock down. Ninety-six percent (29/30) reported no awareness regarding the threat of a secondary device., Conclusion: Hospitals in this sample do not appear to be prepared to handle WMD events, especially in areas such as mass decontamination, mass medical response, awareness among health care professionals, health communications, and facility security. Further research is warranted, including a detailed assessment of WMD preparedness using a statistically valid sample representative of hospital emergency personnel at the national level.

Objectives: To better understand conjoint smoking and drinking among young adult emergency department (ED) patients, the purposes of this investigation were: 1) to assess the prevalence of conjoint use; 2) to determine the factors associated with conjoint alcohol use and smoking; and 3) to address the implications for future ED-based investigation of dual-substance intervention., Methods: Data for this investigation were obtained from a battery of questionnaires administered to the routine-care patients during an alcohol screening in the ED, which was part of a larger alcohol intervention study., Results: Study findings revealed that a majority of patients with self-reported alcohol-related problems were smokers. In fact, drinkers who smoked were likely to be pack-a-day smokers. Among the study sample, being female, having low education levels (e.g., high school education or less), having some emotional problems, and currently using marijuana were risk factors for conjoint smoking and drinking., Conclusions: Conjoint users were identifiable through brief screening. Given the prevalence of conjoint smoking and alcohol use among the ED sample and a specific set of risk factors, tailored intervention for alcohol and nicotine dependence may be an important and opportunistic clinical ED service.

Ligand interactions with porcine atrial muscarinic receptor solubilized in a mixed-detergent system (0.4% w/v digitonin and 0.08% w/v cholate) are described. The solubilized receptor interacts with ligands in a stereospecific manner, showing about the same affinity for local anesthetics and antagonists as was found for the membrane-bound protein [Schimerlik, M. I., & Searles, R. P. (1980) Biochemistry 19, 3407-3413]. Agonists appear to interact with a single class of noninteracting sites that correspond to the low-affinity agonist sites in the membrane-bound preparation. Kinetic studies of L-[3H]quinuclidinyl benzilate binding to the receptor indicated a two-step mechanism. The first step, in rapid preequilibrium (K = 5.7 x 10(-9) M), was followed by a slow conformational change (k1 = 4 x 10(-3) s-1; k-1 = 1.7 x 10(-4) s-1) in the receptor-ligand complex. The overall dissociation constant calculated from the association kinetics (2.3 x 10(-10) M) agreed well with the thermodynamic value for Kov (2.5 x 10(-10) M); however, direct determination of K-1 gave a value about 4-fold lower (4.0 x 10(-5) s-1) than predicted. Possible reasons for this discrepancy are discussed.