Neurophysiological action of centrally-acting spider toxin polypeptides derived from Hadronyche versuta and Tegenaria agrestis venoms.

Established dogma concerning the action of insecticidal arthropod-derived peptides (e.g., scorpion toxins), was that they acted on the peripheral nervous system and were excluded from the central nervous system (CNS) by barrier systems. Initial evidence for a CNS-directed toxicological effect following parenteral administration was for a novel peptide from the Hobo spider, Tegeneria agrestis. This toxin was inactive on peripheral sensory and motor nerves, but had a potent excitatory effect on the CNS of larval Musca domestica. Recently, a commercialized formulation of GS-omega/kappa-Hxtx-Hv1a (HXTX), derived from the venom of the Australian blue mountain funnel web spider (Hadronyche versuta) was introduced for use in agriculture by Vestaron Corp. Its primary mode of action was found to be central neuroexcitation via positive allosteric modulation of nicotinic acetylcholine receptors (nAchR) of cockroach neurons. In the present study, this peptide showed hyperexcitation followed by a decrease in firing of the Drosophila melanogaster larval CNS that was prevented by co-exposure to 100 nM α-bungarotoxin (α-BGTX), a classical nAchR noncompetitive antagonist. This effect was mirrored in isobologram analysis, which showed clear antagonism between the two toxins when injected into adult houseflies. Interestingly, U1-agatoxin-Ta1b-QA derived from Tegeneria agrestis (VST-7304) had a similar biphasic action, but showed increased nerve discharge when co-exposed with 100 nM α-BGTX, and had additive effects when injected together with α-BGTX in isobologram analyses. Binary mixtures of HXTX or VST-7304 with 30 nM nicotine showed clear evidence of synergized nerve block, which was also observed for mixtures of HXTX and VST-7304. Taken together, these data suggest that HXTX and VST-7304 have somewhat different and complementary modes of action.

Geographic distribution of Ovavesicula popilliae in the United States and sensitivity of visual diagnosis compared with qPCR detection.

The Japanese beetle (Popillia japonica) is one of the most destructive invasive pests in North America, causing significant economic impact to many fruit crops, turfgrass and the nursery industry. A microsporidian pathogen of Japanese beetle, Ovavesicula popilliae, discovered in 1985, proliferates in the Malpighian tubules of larvae and adults, disrupting waste-removal, mineral filtering, and fluid balance in heavily infected individuals. Most infected larvae do not survive from fall to spring, and egg production by infected females is reduced by 50%. Ovavesicula popilliae is promising as a classical biological control agent for Japanese beetle, but outside of surveys completed in Connecticut and Michigan little is known about its geographic distribution in North America. The objective of this research is to obtain a better understanding of the distribution of O. popilliae in North America. Japanese beetles were collected at 59 locations in a total of 19 different states in the USA for pathogen analysis. Overall, the proportion of Japanese beetle adults infected by O. popilliae was much greater in Michigan, Ohio, Tennessee and four states in the northeastern USA compared with sites located west of the Mississippi River (18.6 ± 13.3% and 0.6 ± 1.2%, respectively). Nucleotide sequences of the gene encoding a small subunit of nuclear ribosomal RNA (ssrDNA), obtained from GenBank for O. popilliae was used to develop a highly specific qPCR test for O. popilliae DNA. A subsample of 110 individual Japanese beetles were visually diagnosed first, then analyzed via qPCR. Visual diagnosis and qPCR detection agreed for 80.9% of the beetles tested. The qPCR assay is more sensitive than visual diagnosis (56 visually positive, 73 qPCR positive), is highly specific for O. popilliae, and will be useful for detecting the pathogen in large batches of beetles, or in beetle frass.

Histories of host shifts and cospeciation among free-living parasitoids of Rhagoletis flies.

Host shifts by specialist insects can lead to reproductive isolation between insect populations that use different hosts, promoting diversification. When both a phytophagous insect and its ancestrally associated parasitoid shift to the same novel host plant, they may cospeciate. However, because adult parasitoids are free living, they can also colonize novel host insects and diversify independent of their ancestral host insect. Although shifts of parasitoids to new insect hosts have been documented in ecological time, the long-term importance of such shifts to parasitoid diversity has not been evaluated. We used a genus of flies with a history of speciation via host shifting (Rhagoletis [Diptera: Tephritidae]) and three associated hymenopteran parasitoid genera (Diachasma, Coptera and Utetes) to examine cophylogenetic relationships between parasitoids and their host insects. We inferred phylogenies of Rhagoletis, Diachasma, Coptera and Utetes and used distance-based cophylogenetic methods (ParaFit and PACo) to assess congruence between fly and parasitoid trees. We used an event-based method with a free-living parasitoid cost model to reconstruct cophylogenetic histories of each parasitoid genus and Rhagoletis. We found that the current species diversity and host-parasitoid associations between the Rhagoletis flies and parasitoids are the primary result of ancient cospeciation events. Parasitoid shifts to ancestrally unrelated hosts primarily occur near the branch tips, suggesting that host shifts contribute to recent parasitoid species diversity but that these lineages may not persist over longer time periods. Our analyses also stress the importance of biologically informed cost models when investigating the coevolutionary histories of hosts and free-living parasitoids.

The new consultant survey 2005.

BACKGROUND: Consultants in emergency medicine have to deal with a wide range of problems, many of which they will not have encountered during their training. One way to assess the adequacy of specialist training is to ask recently appointed consultants whether or not they feel adequately prepared for their role. METHODS: A questionnaire was sent out to 60 newly appointed consultants in emergency medicine in January and February 2005 and the results analysed. RESULTS: Many respondents feel that there should be greater emphasis on acquiring clinical skills, partly by greater consultant supervision and partly by providing more experience of anaesthetics and intensive care. New consultants also feel inadequately prepared for their management responsibilities, and this is a source of great stress. CONCLUSIONS: Specialist training in emergency medicine needs to pay more attention to the acquisition of clinical skills and to preparation for management responsibility.

Improving the delivery of analgesia to children in pain.

OBJECTIVES: To improve the time taken for children arriving to the accident and emergency (A&E) department in pain to receive analgesia. Delivery within 30 minutes of triage was taken as an achievable goal. METHODS: 262 children who had received analgesia in the "minor injuries" area of West Middlesex University Hospital A&E department were studied over a four month period. Current practice was indicated over the first two months by retrospectively looking at data from 129 children's A&E cards. A Paediatric Pain Protocol was then introduced and another 133 children's cards studied to see if this had made an improvement. The protocol for those children aged over 4 years differed to that for children aged 4 years and under. RESULTS: For children aged 4 years and over, the introduction of the protocol significantly increased the number that received analgesia within 30 minutes of triage: 55.3% (n=54) post-protocol versus 34.0% (n=33) pre-protocol (p=0.003). However, for children aged 4 years and under there was no change in the proportion that received analgesia within 30 minutes of triage: 56.7% (n=17) postprotocol versus 59.4% (n=19) pre-protocol (p=0.829). CONCLUSIONS: The introduction of a simple Paediatric Pain Protocol has improved the time taken to deliver analgesia to children arriving in this A&E department.

Spontaneous carotid artery dissection presenting as migraine--a diagnosis not to be missed.

Two cases are reported in which the diagnosis of a serious condition was delayed as the symptoms had been attributed to migraine. Spontaneous carotid artery dissection is a serious but treatable cause of headache that may be misdiagnosed as recent onset migraine. The importance of correctly identifying this condition is emphasised.

An audit of litigation costs in four accident and emergency departments.

OBJECTIVE: To carry out an audit of cases of litigation relating to accident and emergency departments to determine the outcome and costs to the hospitals involved. METHODS: The experience of four similar hospitals was examined over a three year period. All cases which required at least an exchange of solicitors' letters were included. RESULTS: In total 32 claims were made, of which 17 were settled by solicitors' letters, six cases proceeded to court and were lost by the hospital involved, and in nine cases an out-of-court settlement was reached. The costs to the hospitals ranged from 180 pounds to 30,000 pounds, with an average cost of 4080 pounds. Over the course of the audit the number of cases of litigation remained constant at three per year, while the number of complaints rose threefold to 150. The majority of successful claims concerned missed fractures. CONCLUSIONS: Litigation is uncommon and litigation costs reasonable. Given the frequency of missed fractures as a reason for a successful claim, early x ray reporting probably reduces the risk of litigation.

'Bats below the bridge': is a potentially treatable neurovascular disorder being underdiagnosed in accident and emergency departments?

Basilar artery thrombosis (BATS) is a progressive disorder which may present with fluctuating neurological signs of varying degrees of severity. Unless the diagnosis is considered, the confused young patient may be thought to be under the influence of drugs or to be psychologically ill, and indeed the Munchausen syndrome may be considered. The more elderly patient may be diagnosed simply as having had a cerebrovascular accident. This paper presents the cases of three patients admitted through the accident and emergency (A&E) department of St Mary's Hospital, London with basilar artery thrombosis during a 6-month period. All these patients demonstrated the classic triad for this syndrome of: (1) long tract neurological signs, (2) impaired conscious level, and (3) complex ocular signs. The concern is that, for patients with more subtle signs, a diagnosis of BATS may not be considered, and a neurological opinion may be thus delayed and no treatment with anticoagulants or thrombolytic agents would be given. Two of the three patients were treated with anticoagulants and improved, while in the third patients anticoagulation was judged inappropriate and the patients died from progression of the disease with respiratory complications.

The sexuality of women in physically abusive marriages: a comparative study.

PIP: This study compared 60 abused women with a demographically matched sample of nonabused women in distressed marriages to examine female sexuality in physically abusive marriages. The total study population consisted of 120 women aged 19-29 years. The sample of abused women was obtained from couples who were enrolled under the Domestic Conflict Containment Program, while the sample of nonabused women was selected from couples who were enrolled in marital group therapy to control for any confounding effects of marital discord and dissatisfaction. With the exception of religion, both groups were equally matched in numbers, but no significant differences were discovered between the two samples on any of the demographic variables. Results of the study showed that physically abused women expressed lower levels of intimacy (p 0.001) and compatibility (p = 0.034) in their marriages than did nonabused women. Lower degrees of sexual assertiveness (p 0.001), sexual arousal (p = 0.026), and a more traditional sex-role ideology (p 0.001) was reported by women in abusive relationships. In addition, abused women reported greater sexual dissatisfaction (p = 0.022), a more negative disposition regarding sex (p = 0.054), and a stronger tendency to avoid sexual activity (p 0.01). Despite these findings, abused women reported a higher frequency of sexual intercourse with their spouses (p 0.001) than women in nonviolent marriages.^ieng

Screening for carbohydrate intolerance in pregnancy: a comparison of two tests and reassessment of a common approach.

The usefulness of glycosylated hemoglobin as a prenatal screening test for carbohydrate intolerance was studied in 806 consecutive subjects by correlating glycosylated hemoglobin to 1-hour post-50 gm Glucola plasma glucose levels, 3-hour oral glucose tolerance tests, and perinatal and maternal outcomes. Sixty-seven subjects whose 1-hour post-50 gm Glucola plasma glucose levels were greater than or equal to 150 mg/100 ml underwent 3-hour oral glucose tolerance tests; 12 were diagnostic of carbohydrate intolerance. Compared to carbohydrate-tolerant control subjects, gravid patients with carbohydrate intolerance were older, more obese, had higher 1-hour post-50 gm Glucola plasma glucose and glycosylated hemoglobin levels, and infants with increased birth weight percentiles, depressed 5-minute Apgar scores, and an increased incidence of shoulder dystocia and perinatal mortality. Three of 10 carbohydrate-intolerant patients who were evaluated post partum were found to have previously undiagnosed diabetes. Division of measurements of 1-hour post-50 gm Glucola plasma glucose and glycosylated hemoglobin into normal, borderline, and suspicious groups demonstrated a reduction in discriminatory capability of glycosylated hemoglobin as compared to the 1-hour post-50 gm Glucola plasma glucose. We conclude that laboratory screening for carbohydrate intolerance should be a standard element of the prenatal evaluation; gravid patients found to have carbohydrate intolerance should be reevaluated post partum to rule out overt diabetes, and the 1-hour post-50 gm Glucola plasma glucose test is the preferred means of routine screening for carbohydrate intolerance in pregnancy.