The effects of police duty belt and seat design changes on lumbar spine posture, driver contact pressure and discomfort.

Police officers spend large amounts of time performing duties within a police cruiser and report a high prevalence of musculoskeletal problems. This study evaluated the effects of driver seat and duty belt design on posture, pressure and discomfort. Ten male and 10 female university students attended two sessions involving simulated driving in a standard police seat (CV) and an active lumbar support (ALS) seat. Participants wore a full duty belt (FDB) or reduced duty belt (RDB) in each seat. Lumbar postures, driver-seat and driver-duty belt pressures and perceived discomfort were measured. Gender × Seat interactions were found for pelvic (p = 0.0001) and lumbar postures (p = 0.003). Females had more lumbar flexion than males and were more extended in the ALS seat (-9.8 ± 11.3°) than CV seat (-19.8 ± 9.6°). The FDB had greater seat pressure than the RDB (p < 0.0001), which corresponded to increased pelvis discomfort. This study supports the use of an ALS seat and RDB to reduce injury risk associated with prolonged sitting in police officers. PRACTITIONER SUMMARY: Police officers report a high prevalence of musculoskeletal problems to the lower back, associated with prolonged driving and further investigation is needed to reduce injury risk. This simulated driving study investigated seat and duty belt configuration on biomechanical measures and discomfort. Seat design had the greatest impact, regardless of gender and males benefited more from a reduced belt configuration.

A transthalamic pathway crucial for perception.

Perception arises from activity between cortical areas, first primary cortex and then higher order cortices. This communication is served in part by transthalamic (cortico-thalamo-cortical) pathways, which ubiquitously parallel direct corticocortical pathways, but their role in sensory processing has largely remained unexplored. Here, we show that the transthalamic pathway linking somatosensory cortices propagates task-relevant information required for correct sensory decisions. Using optogenetics, we specifically inhibited the pathway at its synapse in higher order somatosensory thalamus of mice performing a texture-based discrimination task. We concurrently monitored the cellular effects of inhibition in primary or secondary cortex using two-photon calcium imaging. Inhibition severely impaired performance despite intact direct corticocortical projections, thus challenging the purely corticocentric map of perception. Interestingly, the inhibition did not reduce overall cell responsiveness to texture stimulation in somatosensory cortex, but rather disrupted the texture selectivity of cells, a discriminability that develops over task learning. This discriminability was more disrupted in the secondary than primary somatosensory cortex, emphasizing the feedforward influence of the transthalamic route. Transthalamic pathways thus appear critical in delivering performance-relevant information to higher order cortex and are critical hierarchical pathways in perceptual decision-making.

Fine-mapping in African-American women confirms the importance of the 10p12 locus to sarcoidosis.

Sarcoidosis is a chronic granulomatous disease with a wide spectrum of symptoms. Genome-wide association studies in European populations have reported significant associations between sarcoidosis and single-nucleotide polymorphisms (SNPs) located in the intergenic region between the C10ORF67 and OTUD1 genes on chromosome 10p12, and the ANXA11 gene (chromosome 10q22). We carried out fine-mapping at 10p12 and 10q22 to assess associations of genetic variants in these regions with sarcoidosis risk in African-American women, based on 486 sarcoidosis cases and 943 age- and geography-matched controls in a nested case-control study within the Black Women's Health Study. There were no significant associations with variants of the ANXA11 gene (P=0.17). Haplotypic analyses of the C10ORF67-OTUD1 intergenic region revealed a strong inverse association of the variants rs1398024 and rs11013452 with sarcoidosis (odds ratio=0.52; P=0.01). Both SNPs are located inside an ∼300 kb low recombination region of chromosome 10p12, suggesting that both SNPs are tagging the same causal variant. Our top SNP (rs11013452) is located inside a smaller linkage disequilibrium block in HapMap YRI, further narrowing the position of the causal SNP to a region of ~8 kb on chromosome 10p12. The present findings confirm the potential importance of the 10p12 locus in the etiology of sarcoidosis.

The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA.

The high-affinity NGF receptor is thought to be a complex of two receptors , gp75 and the tyrosine kinase TrkA, but direct biochemical evidence for such an association had been lacking. In this report, we demonstrate the existence of such a gp75-TrkA complex by a copatching technique. Gp75 on the surface of intact cells is patched with an anti-gp75 antibody and fluorescent secondary antibody, the cells are then fixed to prevent further antibody-induced redistributions, and the distribution of TrkA is probed with and anti-TrkA antibody and fluorescent secondary antibody. We utilize a baculovirus-insect cell expression of wild-type and mutated NGF receptors. TrkA and gp75 copatch in both the absence and presence of NGF. The association is specific, since gp75 does not copatch with other tyrosine kinase receptors, including TrkB, platelet-derived growth factor receptor-beta, and Torso (Tor). To determine which domains of TrkA are required for copatching, we used a series of TrkA-Tor chimeric receptors and show that the extracellular domain of TrkA is sufficient for copatching with gp75. A chimeric receptor with TrkA transmembrane and intracellular domains show partial copatching with gp75. Deletion of the intracellular domain of gp75 decreases but does not eliminate copatching. A point mutation which inactivates the TrkA kinase has no effect on copatching, indicating that this enzymatic activity is not required for association with gp75. Hence, although interactions between the gp75 and TrkA extracellular domains are sufficient for complex formation, interactions involving other receptor domains also play a role.

Sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone: a quantitative trait locus study of common genetic influence.

Previous studies have suggested that common genetic mechanisms influence sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone. We conducted two quantitative trait locus (QTL) studies to identify chromosomal regions that harbor genes that influence locomotor response to ethanol (2 g/kg) and allopregnanolone (17 mg/kg) using F2 crosses between C57BL/6J and DBA/2J mice. Because our previous data from the BXD recombinant inbred strains had indicated that chromosome 2 contained QTL for sensitivity to the locomotor-stimulant effects of both ethanol and allopregnanolone, we also tested reciprocal chromosome 2 congenic strains for sensitivity to the locomotor-stimulant effects of both drugs. The F2 analysis for ethanol sensitivity identified significant QTL on chromosomes 1 and 2 and suggestive QTL on chromosomes 5 and 9. The analysis of the allopregnanolone F2 study identified suggestive QTL on chromosomes 3, 5 and 12. Suggestive evidence for a female-specific QTL on chromosome 2 was also found. The studies of congenic mouse strains indicated that both the congenic strains captured one or more QTL for sensitivity to the locomotor-stimulant effects of both ethanol (2 g/kg) and allopregnanolone (17 mg/kg). When Fisher's method was used to combine the P values for the RI, F2 and congenic studies of the chromosome 2 QTL, cumulative probability scores of 9.6 x 10(-15) for ethanol and 7.7 x 10(-7) for allopregnanolone were obtained. These results confirm the presence of QTL for ethanol and allopregnanolone sensitivity in a common region of chromosome 2 and suggest possible pleiotropic genetic influence on sensitivity to these drugs.

Sensitivity to psychostimulants in mice bred for high and low stimulation to methamphetamine.

Methamphetamine (MA) and cocaine induce behavioral effects primarily through modulation of dopamine neurotransmission. However, the genetic regulation of sensitivity to these two drugs may be similar or disparate. Using selective breeding, lines of mice were produced with extreme sensitivity (high MA activation; HMACT) and insensitivity (low MA activation; LMACT) to the locomotor stimulant effects of acute MA treatment. Studies were performed to determine whether there is pleiotropic genetic influence on sensitivity to the locomotor stimulant effect of MA and to other MA- and cocaine-related behaviors. The HMACT line exhibited more locomotor stimulation in response to several doses of MA and cocaine, compared to the LMACT line. Both lines exhibited locomotor sensitization to 2 mg/kg of MA and 10 mg/kg of cocaine; the magnitude of sensitization was similar in the two lines. However, the lines differed in the magnitude of sensitization to a 1 mg/kg dose of MA, a dose that did not produce a ceiling effect that may confound interpretation of studies using higher doses. The LMACT line consumed more MA and cocaine in a two-bottle choice drinking paradigm; the lines consumed similar amounts of saccharin and quinine, although the HMACT line exhibited slightly elevated preference for a low concentration of saccharin. These results suggest that some genes that influence sensitivity to the acute locomotor stimulant effect of MA have a pleiotropic influence on the magnitude of behavioral sensitization to MA and sensitivity to the stimulant effects of cocaine. Further, extreme sensitivity to MA may protect against MA and cocaine self-administration.

Behavioral sensitization to ethanol is modulated by environmental conditions, but is not associated with cross-sensitization to allopregnanolone or pentobarbital in DBA/2J mice.

RATIONALE: The ability of ethanol to facilitate GABA(A) receptor-mediated transmission may result in GABA(A) receptor alterations during repeated ethanol administration, and lead to dynamic behavioral changes, including sensitization to the locomotor stimulant effect of ethanol. Since alterations in GABA(A) receptors are likely to alter sensitivity to GABAergic drugs such as 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) and pentobarbital, we determined whether enhanced sensitivity to ethanol was associated with enhanced sensitivity (cross-sensitization) to these drugs. Two procedures that produced differences in the magnitude of expression of ethanol-induced locomotor sensitization were used. METHODS: After habituation to testing procedures for 2 days, female DBA/2J mice were injected with ethanol or saline for 12 days. On the following day, locomotion was recorded after a challenge injection of ethanol (2 g/kg), allopregnanolone (10 or 17 mg/kg), or pentobarbital (10 or 20 mg/kg). Due to evidence that exposure to the test chambers influenced sensitization, in some experiments, mice were exposed to the test apparatus on the day prior to challenge. RESULTS: Exposure to the test apparatus prior to drug challenge attenuated the expression of ethanol sensitization, compared with mice without this pre-exposure. Cross-sensitization was not observed to either allopregnanolone or pentobarbital under any condition; however, some groups of repeated ethanol-treated mice displayed tolerance to the initial stimulant effects of allopregnanolone and pentobarbital. CONCLUSIONS: These studies indicate that behavioral sensitization to ethanol is not associated with cross-sensitization to pentobarbital or allopregnanolone, and that the expression of ethanol sensitization is influenced by the relative novelty of the test chamber. In addition, these results do not support a mechanism in which alterations in the neurosteroid or barbiturate modulatory sites of the GABA(A) receptor are responsible for the expression of sensitization to the locomotor stimulant effects of ethanol.

Two omeprazole-based Helicobacter pylori eradication regimens for the treatment of duodenal ulcer disease in general practice.

BACKGROUND: Helicobacter pylori is the main acquired factor in the pathogenesis of duodenal ulcer disease. METHODS: This multicentre study conducted in 32 general practice centres in the UK and Ireland was a double-blind, placebo-controlled, randomized, parallel-group comparison of triple therapy (n = 98: omeprazole 40 mg once daily and amoxycillin 1 g b.d. for 2 weeks, and metronidazole 400 mg t.d.s. for the first week) and dual therapy (n = 85: omeprazole 40 mg once daily and amoxycillin 1 g b.d. for 2 weeks, with placebo during the first week) for the eradication of H. pylori in patients with symptomatic duodenal ulcer disease. Patients who were successfully treated entered a follow-up phase for 12 months to assess symptomatic relapse and use of health-care resources. RESULTS: Eradication of H. pylori based on a second 13C-urea breath test was successful in 95% (95% confidence interval (CI) = 90-100%) of patients receiving omeprazole triple therapy and 53% (95% CI = 41-65%) of those receiving omeprazole dual therapy (P < 0.0001 between groups, all data available analysis). The all-patients-treated analysis gave eradication rates of 80 and 44% for omeprazole triple therapy and omeprazole dual therapy, respectively. Symptomatic relapse occurred in 16% (18/116) of the H. pylori-negative patients who entered the 12-month follow-up period, and there were significant reductions in the number of consultations, investigations and prescriptions relating to upper gastrointestinal symptoms compared with the 12 months prior to the eradication therapies (all P < 0.0001). The two treatment strategies were comparable in terms of the number of adverse events reported. CONCLUSIONS: Omeprazole triple therapy provides a highly effective treatment for the eradication of H. pylori infection in patients in general practice, with an adverse event profile similar to that seen with omeprazole dual therapy. The successful eradication of H. pylori with these omeprazole regimens results in a significant decrease in the use of health-care resources in the 12 months following treatment.

Evaluation of membranes for feeding Culicoides variipennis (Diptera: Ceratopogonidae) with an improved artificial blood-feeding apparatus.

An artificial blood-feeding apparatus for Culicoides variipennis (Coquillett) was improved by developing a simpler design to heat and mix the blood meal and by increasing the surface area for insect feeding. The skin from a 1- to 3-d-old chick and a reinforced silicone membrane were the most satisfactory of nine membranes evaluated for C. variipennis, with 81 and 83% mean blood-feeding rates, respectively. The operational advantages of the reinforced silicone membrane for feeding C. variipennis included its composition of readily available synthetic materials, easy fabrication, faster preparation than the chick skin, and its suitability for repeated use in colony maintenance and virus infection studies.

Sympatry in the Culicoides variipennis complex (Diptera: Ceratopogonidae): a taxonomic reassessment.

We report sympatry among larval populations of the Culicoides variipennis complex in widespread and diverse aquatic habitats throughout the United States. Six sites in California, Nevada, New Mexico, and Texas were co-inhabited by C. v. occidentalis and C. v. sonorensis, whereas 8 sites in Florida, Georgia, Louisiana, Maryland, and Texas were co-occupied by C. v. sonorensis and C. v. variipennis. No intermediate forms were identified either electrophoretically or morphologically in adults reared from field-collected larvae and pupae. The absence of intergrades in zones of sympatry represents sufficient evidence to confirm species status for Culicoides variipennis (Coquillett) and Culicoides occidentalis Wirth & Jones, and to elevate Culicoides sonorensis to species rank (NEW STATUS). Culicoides v. albertensis Wirth & Jones is a synonym of C. sonorensis (NEW SYNONYMY); C. v. australis Wirth & Jones also is confirmed as a synonym of C. sonorensis. We also demonstrated a correlation between population taxonomic status as determined by electrophoresis and adult morphology.

American Society of Clinical Oncology--34th Annual Meeting. Treatments for prostate cancer and new molecular targets. 16-19 May 1998, Los Angeles, California, USA.

The American Society of Clinical Oncology (ASCO) is the world's largest professional society representing physicians and researchers in the field of cancer treatment. Almost 19,000 clinicians, researchers and specialists from academia and industry attended this 34th Annual Meeting. The four-day meeting consisted of lecture sessions, education sessions, "meet the professor" sessions, tumor panel sessions, plenary sessions, oral sessions, scientific and integrated symposia and poster presentations. A wide range of topics of interest to the oncologist were discussed, broadly covering the biology, prevention, diagnosis, staging, management and treatment of cancer, as well as psychosocial and economic implications.

New agents for colon and breast cancer.

The education session, chaired by Dr Yousef Rustum (Roswell Park Cancer Institute, Buffalo, NY, USA), described many of the newer agents being evaluated for the treatment of colorectal cancer, including thymidylate synthase inhibitors, antifolate antimetabolites, dihydrofolate reductase inhibitors, GAR trans-formylase inhibitors, topoisomerase I inhibitors and alkylating agents. The integrated HER-2neu in breast cancer symposium was large and very interesting; it was co-chaired by Dr Nancy Davidson (Johns Hopkins Oncology Center, Baltimore, MD, USA) and Dr Silvana Martino (The Breast Center, Van Nuys, USA). The latest research on HER-2neu was grouped into one session and was followed by a discussion of the abstracts by Dr Edison Liu (National Cancer Institute, Bethesda, MD, USA).

Vaccines in cancer therapy.

This report provides an overview of recent developments in cancer vaccine methodology. The first session was co-chaired by Dr Ronald Mertelsmann and Dr David Scheinberg (Memorial Sloan-Kettering Cancer Center, New York, USA).

Gene therapy and immunotherapy.

The 35th annual meeting of the American Society of Clinical Oncology (ASCO), held at the Georgia World Congress Center, was attended by 20,260 cancer clinicians, academics and research and pharmaceutical industry scientists. The meeting program consisted of a varied series of poster and poster discussion sessions, education sessions, oral abstract presentations, plenary sessions, 'meet the professor' sessions, special lectures and integrated symposia. Some of the main 'hot topics' included gene therapy, immunotherapy, biological therapy (including vaccines and antibodies), prostate cancer, signal transduction inhibitors, anti-angiogenesis agents and several novel therapies and approaches.

Topoisomerase inhibitors and other new agents.

At ASCO there was an oral presentation session on the pharmacology of topoisomerase inhibitors and other new agents. It was co-chaired by Dr. Herbert M. Pinedo (University Hospital, Vrije Universiteit, Amsterdam, The Netherlands) and Dr. Mark J. Ratain (University of Chicago, IL, USA).

Prostate cancer, biological therapy, signal transduction inhibitors and anti-angiogenesis agents.

New systemic approaches to the treatment of prostate cancer, biological therapy (including vaccines and antibodies), signal transduction inhibitors and anti-angiogenesis agents were the focus of these ASCO sessions.

Epidermal growth factor receptor targeting.

Dr. Jose Baselga (Hospital Vall d'Hebron, Barcelona, Spain) chaired and led a discussion of several posters on the marking and detection of the epidermal growth factor receptor (EGFR), and compounds that target this receptor. The posters consisted of biological studies and phase I trials with EGFR tyrosine kinase (TK) inhibitors. The basis of EGFR targeting in cancer therapy depends on the overexpression in malignancy and potential inhibition with antibodies and TK inhibitors. Correlations have been made between receptor function and inhibition of growth.

Pediatric studies and hematological malignancies.

This report contains some of the more interesting studies presented from the many poster sessions at this year's American Society of Clinical Oncology meeting.

New approaches in drug development and novel compounds.

This report focuses on the novel compounds which are in development and clinical trials and also highlights some of the data presented at the poster sessions.