Assessment of control measures against livestock-associated methicillin-resistant Staphylococcus aureus in a farrow-to-finish pig herd using infectious disease modelling.

Pigs are considered to be the main reservoir for livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), which is a zoonotic opportunistic pathogen. As LA-MRSA is an occupational hazard, there is an incentive to control its spread in pig herds. Currently, knowledge about effective control measures which do not require culling the whole herd are limited, and the control strategies against LA-MRSA vary between countries. This study uses a stochastic compartment model to simulate possible control measures for LA-MRSA in a farrow-to-finish pig herd. The aims of the study were to (1) extend a previously published disease spread model with additional management and control measures; (2) use the extended model to study the effect of the individual LA-MRSA control measures on the within-herd LA-MRSA prevalence; (3) evaluate the effect of control measures when they are implemented in combinations. From the individual control measures tested in the study, thorough cleaning was found to be most effective in reducing the LA-MRSA prevalence in the herd. When the different control measures were combined, cleaning together with disease surveillance had the largest impact on reducing the LA-MRSA and a higher chance of causing disease elimination. The results of the study showed that achieving disease elimination once LA-MRSA had been introduced in the herd was challenging but was more likely when control measures were introduced early during the outbreak. This emphasises the importance of early detection of the pathogen and subsequent rapid implementation of LA-MRSA control measures.

Modelling environmentally mediated spread of livestock-associated methicillin-resistant Staphylococcus aureus in a pig herd.

Infectious disease models are a useful tool to support within-herd disease control strategies. This study presents a stochastic compartment model with environmentally mediated transmission to represent the spread of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in a farrow-to-finish pig herd. The aims of the study were to (1) construct a model of the spread of LA-MRSA that included spread of LA-MRSA through the environment; (2) parameterise the model to fit previously published observational data in order to obtain realistic LA-MRSA transmission rates; (3) and to investigate how changes in the mixing of animals in the farrowing and finishing units may affect the prevalence of LA-MRSA in a herd. The results showed that indirect transmission allowed LA-MRSA to persist in the herd without the assumption of persistently shedding individuals. Reducing the mixing of pigs upon entry to the finishing unit was also shown to lower the LA-MRSA prevalence in the unit if the initial LA-MRSA level in the unit was low, but at high prevalence, no effect of mixing was identified. In the farrowing unit, changing the proportion of piglets that were cross-fostered did not affect the within-herd LA-MRSA prevalence. The study demonstrates that there are several important knowledge gaps regarding the shedding and transmission of LA-MRSA in different animal age groups and further experimental studies are needed. This work also provides a new, robust and flexible model framework for the investigation of control and mitigation strategies for LA-MRSA and other infections in a pig herd.

The Schizophrenia Suicide Risk Scale (SSRS): development and initial validation.

BACKGROUND: Estimations about the lifetime risk of suicide in schizophrenia vary between 4 and 10%. At present, there does not exist a suicide risk scale developed particularly for schizophrenic patients. The aims of the present study were to: (1) develop a clinically useful semi-structured scale for the estimation of short-term suicide risk among schizophrenic patients, and (2) to carry out an initial validation of the scale. METHODS: A 25-item Schizophrenia Suicide Risk Scale (SSRS) was constructed on the base of the literature. The SSRS scores of 69 living schizophrenic patients (LS group) were compared with the scores of 69 schizophrenic suicides (SS group) whose data had been collected previously from The Finnish nationwide and representative psychological autopsy study. Internal consistency of the SSRS was evaluated with Cronbach alpha. The most important SSRS items predicting suicide were identified with a logistic regression analysis. Sensitivity, specificity, positive predictive value, and negative predictive value of the SSRS in predicting suicide with various cut-off scores were calculated. RESULTS: In the final logistic regression model, the following SSRS items significantly predicted suicide: suicide plans communicated to someone during the past 3 months; one or more previous suicide attempts; loss of professional skills demanding job; depression observed during an interview; and suicide plans communicated during an interview. With high cut-off scores the specificity of the SSRS became satisfactory, but the sensitivity dropped below 32%. Internal consistency of the anamnestic history of the SSRS was low, which suggests that anamnestic risk factors for suicide in schizophrenia are multifactorial. Internal consistency of the interview-based items was high, and present state risk factors seemed to consist of two separate factors, depression-anxiety and irritability. CONCLUSIONS: The SSRS may be clinically useful in identifying schizophrenic patients with a particularly high risk for suicide. However, the SSRS seems not to be a practical screening instrument for suicide risk in schizophrenia, and it is probably impossible to construct a suicide risk scale with both high sensitivity and high specificity in this disorder.

Depression Scale (DEPS) in schizophrenia.

OBJECTIVE: To explore the applicability of the Depression Scale (DEPS), a screening instrument for detecting depression in primary health care, in schizophrenia. METHOD: The DEPS was compared with the Calgary Depression Scale (CDS) among 63 patients with schizophrenia. RESULTS: Using the CDS as a gold standard, the positive and negative predictive values of the DEPS for the diagnosis of depression were 41% and 97%, respectively. The correlation between the total CDS scores and the total DEPS scores was 0.73. CONCLUSION: The DEPS appears to be useful for screening depression among schizophrenic patients, but the positive diagnosis must be confirmed with a clinical interview.

Brominated flame retardants induce intragenic recombination in mammalian cells.

In the present study we have examined the effects of brominated flame retardants (BFR) and several other environmental contaminants in two in vitro assays for intragenic recombination at an endogenous locus in mammalian cells. A total ten compounds were investigated, i. e., two technical PCB mixtures (Aroclor 1221 and Aroclor 1254), DDT, PCP, tetrabromobisphenol A (TBBPA), 4,4'-bischlorophenyl sulfone (BCPS), hexabromocyclododecane (HBCD) and the three different polybrominated diphenylethers (PBDEs): 2-bromodiphenylether (MBDE), 3,4-dibromodiphenylether (DBDE) and 2,4,2', 4'-tetrabromodiphenylether (TBDE). In the SPD8 assay system statistically significant increases in recombination frequency were observed with Aroclor 1221, BCPS, DBDE, DDT, HBCD, MBDE and TBDE. In the Sp5 assay system, only DBDE, HBCD and MBDE caused statistically significant increases in recombination frequency. In conclusion, our findings indicate that the modern additives to plastic, i.e., HBCD and PBDEs, as well as the plastic monomer BCPS may have the same effect to human health as DDT and PCBs, in terms of inducing genetic recombination, which is known to provoke a number of diseases, including cancer.

Use of the World Wide Web by family practitioners.

We introduced the World Wide Web to family practitioners through seminars conducted at 13 family practice clinics in northern Minnesota. The seminars included the history and applications of the Web. We also conducted searches on the Web with the family practitioners and graded the searches for physician usefulness. The physicians then evaluated the technology through a subjective survey. Thirty-three searches were attempted with 55% resulting in useful information. The average grade increased 22% over the study period, while the search time decreased 7% to an average of 8.5 minutes per search. The majority of family practitioners surveyed (65%) said they would use the Web in their practice, primarily for patient education, CME, and information retrieval. The major disadvantage they cited was the length of time to retrieve information. Our goal was to introduce the professional community to an available technology that may enhance the quality of medical practice and to determine the technology's present and future applications. These preliminary results indicate that health care professionals recognize the practical usefulness of the Web.

Phenotypic characterization of second generation offspring of alcohol-sensitive ANT and alcohol-insensitive AT rat lines.

The alcohol-sensitive ANT and the alcohol-insensitive AT rat lines developed by selective breeding for differential sensitivity to motor impairment on the tilting plane by a moderate ethanol dose (2 g/kg, IP), were cross-bred to produce second generation (F2) offspring to study phenotypic correlations between various behavioral and biochemical properties and the degree of initial alcohol sensitivity in the tilting plane test. The F2 population (n = 75) was subjected to alcohol sensitivity tests using a tilting plane test and a sleep time test, and to the elevated plus-maze test of sober activity and anxiety. Finally, the animals were sacrificed and the concentrations of dopamine and its acidic metabolites were analyzed in their striatal tissues. Serum corticosterone was determined to obtain information about the stress responses of the animals after the tilting plane test. The behaviors studied had no significant correlations with each other, suggesting that the various genetic and environmental factors affecting these behavioral phenotypes are different for each behavior. The biochemical measures yielded some correlations with the tilting plane test results that were contrary to the differences between the parent rat lines (dopaminergic indices) or that were confounded by the correlations with the body weight of the animals (corticosterone). Body-weight independent correlational tendency between the alcohol-induced impairment in motor performance and serum corticosterone concentration, however, fitted the differences between the parent lines, suggesting that stress mechanisms cannot be fully excluded as factors contributing to the differential alcohol sensitivity between the ANT and AT rat lines.

Characterization of binding sites and effects of calcitonin gene-related peptide (CGRP) and CGRP 8-37 on regional blood flow in rabbit salivary glands.

Calcitonin gene-related peptide (CGRP) is a neuropeptide present in nerve fibres of salivary glands in several species, including man. One of the major targets of these nerve fibres are blood vessels of the glands. The presence and distribution of specific binding sites for CGRP in the rabbit major salivary glands was here investigated autoradiographically. In order to determine the physiological role of CGRP, regional blood flow was measured after intravenous (i.v.) or intra-arterial (i.a.) administration of CGRP or the antagonist CGRP 8-37, using a microsphere technique. Specific binding sites for CGRP were found in the parotid, submandibular and sublingual glands, distributed mainly in the muscular and endothelial layers of the blood vessel walls. CGRP injected i.a. (10 pmol/kg) caused a significant increase in regional blood flow in all major salivary glands. However, i.v. infusion of CGRP (120 pmol/kg) decreased regional blood flow in the parotid and sublingual glands, due to a general decrease in peripheral resistance and redistribution of peripheral blood flow. CGRP 8-37 given i.a. together with CGRP significantly inhibited the blood-flow increase by CGRP alone. It is concluded that most of the CGRP receptors in the rabbit salivary glands are localized in vascular elements. The physiological data show that CGRP acts as a vasodilator in the major salivary glands of the rabbit in vivo, and that the effect of CGRP is inhibited by the CGRP antagonist CGRP 8-37.

Binding of serotonergic ligands to brain membranes of alcohol-preferring AA and alcohol-avoiding ANA rats.

The alcohol-preferring AA rats have higher concentration of 5-hydroxytryptamine (5-HT) in the brain than the alcohol-avoiding ANA rats. In the present study, the 5-HT1, 5-HT2, and 5-HT3 receptors were studied with [3H]5-HT, [3H]ketanserin, and [3H]LY278584, respectively, in membrane homogenates from different brain regions of both rat lines using in vitro binding assays. No differences in the 5-HT1 and 5-HT2 receptor binding in the brainstem, hippocampus, frontal cortex, and hypothalamus or in the 5-HT3 receptor binding in the nucleus accumbens, amygdala, hippocampus, and frontal cortex were observed between the ethanol-naive animals of the rat lines. In rats given the opportunity to voluntarily consume alcohol, there was a tendency to increase 5-HT1 binding in the ANA rats, which tendency was, however, also found in their ethanol-naive controls subjected to the same handling and behavioral tests as the ethanol-experienced animals. The results do not, however, indicate that any genetic modifications of the 5-HT receptor-binding sites have occurred in the process of the selective breeding of AA and ANA rats for alcohol preference and avoidance, respectively.

Need for and influence of feedback from the Finnish birth register to data providers.

Data for the Finnish medical birth register (established 1987) are collected by local hospital personnel as a part of their routine work. The purpose of this study was to study the need of personnel for feedback and the impact of feedback on later data quality. Furthermore, we studied whether such feedback tends to modify extreme cesarean section rates. Data on attitudes towards the birth register and on the need for feedback of data providers were collected through interviews and observations. In March 1988, an information package describing births, birth procedures and infant outcomes in each hospital compared with other hospitals was sent to a random stratified sample of 26 hospitals out of a total of 53. Opinions of the package were obtained by questionnaire from 104 physicians and nurses (82% response rate). Most hospital personnel, especially physicians, had negative attitudes towards the birth register. Comparison of the hospitals which had received feedback with other hospitals in terms of quality of data furnished in 1987 and 1988 suggested that feedback may improve the technical quality of data. There was no evidence, however, that feedback caused hospitals to change their practices in regard to cesarean sections.

Cerebellar GABAA receptors in two rat lines selected for high and low sensitivity to moderate alcohol doses: pharmacological and genetic studies.

Alcohol-sensitive (ANT) rat line produced by selective outbreeding for high acute sensitivity to the motor-impairing effects of ethanol, displays unusual cerebellar GABAA receptor pharmacology. The ANT rats have enhanced benzodiazepine agonist affinity at their binding sites for an imidazobenzodiazepine, [3H]Ro 15-4513, normally not affected by agonists at all, and reduced GABAA agonist, [3H]muscimol, binding, when compared to the alcohol-insensitive (AT) rat line. In the present study, the benzodiazepine receptor difference was localized to the cerebellar granule cell layer. This receptor difference was not found in ex vivo binding studies after lorazepam administration, although brain lorazepam concentrations in both rat lines similarly exceeded 1 microM. An indication for differential binding in vivo between the lines was, however, observed, as pretreatment with lorazepam accentuated the relative accumulation of radioactivity only in the cerebellum of the AT rat line after an intravenous injection of a trace amount of [3H]Ro 15-4513, thus revealing benzodiazepine insensitivity for a portion of the cerebellar [3H]Ro 15-4513 binding in the AT but not in the ANT rats. In the second generation of AT/ANT cross-breeding, there was no clear association of alcohol sensitivity and cerebellar receptor binding. There was, however, a significant positive correlation between the [3H]muscimol binding and the diazepam-insensitive [3H]Ro 15-4513 binding in the cerebellum. In conclusion, the receptor defect in the cerebellar granular cell layer of the alcohol-sensitive ANT rats was also detectable in vivo, but it may not explain the enhanced alcohol sensitivity of these rats.

Hormone responses to sedative drugs and cold exposure in two rat lines with high and low alcohol sensitivity.

Two rat lines bred for differences in motor impairment in the tilting plane test after a moderate dose of ethanol were compared for peripheral hormone responses. The alcohol-sensitive ANT rats had significantly lower plasma corticosterone concentrations than the alcohol-insensitive AT rats 30 min after an IP saline injection. Ethanol (2 g/kg, IP) and lorazepam (3 mg/kg, IP) injections increased the corticosterone concentration in ANT rats. Sodium barbital (160 mg/kg, IP) did not produce any increase in these rats; instead, it prevented any increase caused by a tilting plane test procedure 10 min before decapitation. Three trials on the tilting plane significantly elevated the corticosterone concentration in saline-treated ANT rats, but produced no additional increase in drug-treated ANT rats. In AT rats, drug injections caused no significant corticosterone increase but the tilting plane test procedure after barbital (lorazepam) treatment(s) elevated the corticosterone concentration. Cold exposure (+4 degrees C for 30 min) of the drug-naive animals elevated their concentrations of serum and adrenal corticosterone, thyrotropin, and growth hormone, but not of prolactin and luteinizing hormone. The increase in serum corticosterone was greater in AT than ANT rats, whereas the increase in serum thyrotropin was slightly greater in ANT rats. No differences between the rat lines were found in the growth hormone, prolactin, and luteinizing hormone levels. The results confirm and extend our earlier findings of the inability of ANT rats to produce additional stress responses to behavioral challenges when being intoxicated by sedative drugs, which may at least partly account for their increased sensitivity to sedative drugs.

Diminished stress responses in the alcohol-sensitive ANT rat line.

During behavioral tests of alcohol sensitivity, rapid alcohol-opposing reactions may constitute an important mechanism in reducing the acute performance-impairing actions of alcohol. The alcohol-sensitive ANT (alcohol nontolerant) rats achieve lower plasma corticosterone concentrations after a tilting plane test of alcohol sensitivity (2 g ethanol/kg, IP) than the alcohol-insensitive AT (alcohol tolerant) rats, suggesting a dampening of activated stress mechanisms in the ANT rats. We have extended the comparison of these rat lines by examining central and peripheral stress responses to an acute 10-min swimming stress without ethanol administration. After the stress, plasma and adrenal corticosterone concentrations, adrenal dopamine concentrations, binding of [3H]Ro 5-4864 to adrenal membranes, and hypothalamic norepinephrine turnover were lower in the ANT than AT rats. Habituation to daily handling did not affect the stress effects or the differences between the rat lines. These results suggest that the alcohol-sensitive ANT rats have a diminished reaction to general stress, even in the absence of ethanol. This may impair their capacity to overcome the sedative and motor-impairing effects of moderate ethanol doses.

Lack of effects of handling habituation and swimming stress on ethanol-induced motor impairment and GABAA receptor function.

The effects of handling habituation and swimming stress on ethanol-induced motor impairment and the GABAA receptor function were studied in adult male Wistar rats. Daily handling for 3 to 5 weeks had no significant effect on ethanol-induced motor impairment in the tilting plane test or on the activity of the rats in the elevated plus-maze test of anxiety. Plasma corticosterone concentrations were greatly elevated by the tilting plane test procedure, irrespective of handling habituation. Acute, 10-min swimming stress at +25 degrees C produced an elevated plasma corticosterone concentration comparable to that produced by the tilting plane test, again irrespective of handling habituation. In cerebrocortical homogenates, short-term swimming stress had no statistically significant effect on the muscimol stimulation of the GABAA receptor-mediated 36Cl- flux in handled and non-handled animals. Thus, handling habituation and stress had only minor effects on the activity of the central GABAergic systems in acute tests at behavioural and biochemical levels.

Behavior of alcohol-preferring AA and alcohol-avoiding ANA rat lines in tests of anxiety and aggression.

The present study examined whether behavior in the tests of aggression and anxiety differs between rat lines developed by selective outbreeding for differences in their voluntary alcohol consumption. The animals had either never had alcohol or had been given 10% alcohol solution as their only fluid for seven days followed by a choice between 10% alcohol and water for 30-37 days. The plus-maze test provided no clear evidence for differences in anxiety between the alcohol-preferring AA and alcohol-avoiding ANA rats. In the resident-intruder paradigm of aggressive behavior the AA rats showed more offensive and defensive behaviors than the ANA rats. The opportunity to consume alcohol influenced these behaviors, but did not produce differential responses in the AA and ANA rats.

Plus-maze behavior and susceptibility to 3-mercaptopropionate-induced seizures in rat lines selected for high and low alcohol sensitivity.

Selective outbreeding for high and low acute alcohol sensitivity has produced two rat lines (alcohol-sensitive ANT and alcohol-insensitive AT lines) that also differ in their sensitivity to GABAergic drugs, benzodiazepines and barbiturates. These rats were now compared in two behavioral tests believed to involve central GABAergic mechanisms, in elevated plus-maze test and in 3-mercaptopropionate-induced seizure test. The AT animals spent more time in the open arms of the plus-maze than the ANT rats, suggesting that the AT's behave less anxiously. The ANT's were more susceptible to seizures induced by 3-mercaptopropionate (50 mg/kg, IP) than the AT's, suggesting the ANT's having greater sensitivity to a decrease in brain GABA concentration. At the time of the first seizure signs, there was a tendency, though a nonsignificant one, to greater decreases in brain GABA in the ANT's than AT's. These results suggest that there are differences in GABA-related behaviors between ethanol-naive rats of the lines produced by selective outbreeding for differences in alcohol sensitivity. In theory, these behavioral line differences might physiologically counteract alcohol effects in the ANT's and enhance them in the AT's. In elevated plus-maze test, however, an acute dose of ethanol (1 g/kg, IP) significantly changed the behavior of the ANT animals, but only up to level of the AT rats. The apparent sensitivity to ethanol may thus be dependent on the naive behavior of the alcohol-insensitive AT and alcohol-sensitive ANT rats.

Mechanisms of alcohol intoxication in a rodent model: blunted alcohol-opposing reaction in "alcohol-sensitive" rats.

In this paper we describe new data and review some studies on the mechanisms of alcohol-induced motor impairment in rats. Habituation to handling did not affect the naive behavioural differences between the alcohol sensitive and alcohol insensitive rat lines. Nor was there any effect on the differential sensitivities of the lines to the motor impairing and hypnotic effects of alcohol. Peripheral mechanisms may be involved in the differential behaviours of these lines, as the plasma corticosterone response was much weaker in the alcohol sensitive animals, suggesting a limited capacity to react to stress and alcohol. A similar blunted response to acute ethanol exposure was found in the uptake of the benzodiazepine antagonist [3H]Ro 15-1788 in vivo by the cerebellum of alcohol sensitive rats. The finding that these rat lines do not have any general differences in their brain inhibitory GABAergic receptors was extended to the spinal cord inhibitory glycinergic receptors, which showed only a modest line difference in their dissociation constant. The apparent localisation of the two main receptor differences (high-affinity [3H]muscimol binding and diazepam sensitivity of [3H]Ro 15-4513 binding) to the cerebellar granule layer suggests a genetic modification in the granule cells of alcohol-sensitive rats. In conclusion, our studies on acute intoxication by moderate alcohol doses show that several central nervous and peripheral factors may be involved in this behaviour. As many of these factors mitigate the effects of alcohol, alcohol antagonistic treatments should be aimed at activating and supporting multiple adaptive phenomena.