International outbreak investigation of Salmonella Heidelberg associated with in-flight catering.

Rapid and wide dispersal of passengers after flights makes investigation of flight-related outbreaks challenging. An outbreak of Salmonella Heidelberg was identified in a group of Irish travellers returning from Tanzania. Additional international cases sharing the same flight were identified. Our aim was to determine the source and potential vehicles of infection. Case-finding utilized information exchange using experts' communication networks and national surveillance systems. Demographic, clinical and food history information was collected. Twenty-five additional cases were identified from Ireland, The Netherlands, Norway, USA and Canada. We conducted a case-control study which indicated a significant association between illness and consumption of milk tart (OR 10.2) and an egg dish (OR 6) served on-board the flight. No food consumed before the flight was associated with illness. Cases from countries other than Ireland provided supplementary information that facilitated the identification of likely vehicles of infection. Timely, committed international collaboration is vital in such investigations.

Let's talk about sex: Mechanisms of neural sexual differentiation in Bilateria.

In multicellular organisms, sexed gonads have evolved that facilitate release of sperm versus eggs, and bilaterian animals purposefully combine their gametes via mating behaviors. Distinct neural circuits have evolved that control these physically different mating events for animals producing eggs from ovaries versus sperm from testis. In this review, we will describe the developmental mechanisms that sexually differentiate neural circuits across three major clades of bilaterian animals-Ecdysozoa, Deuterosomia, and Lophotrochozoa. While many of the mechanisms inducing somatic and neuronal sex differentiation across these diverse organisms are clade-specific rather than evolutionarily conserved, we develop a common framework for considering the developmental logic of these events and the types of neuronal differences that produce sex-differentiated behaviors. This article is categorized under: Congenital Diseases > Stem Cells and Development Neurological Diseases > Stem Cells and Development.

Integrated surveillance and potential sources of Salmonella enteritidis in human cases in Canada from 2003 to 2009.

Salmonella enteritidis has emerged as the most prevalent cause of human salmonellosis in Canada. Recent trends of S. enteritidis subtypes and their potential sources were described by integrating Salmonella data from several Canadian surveillance and monitoring programmes. A threefold increase in S. enteritidis cases from 2003 to 2009 was identified to be primarily associated with phage types 13, 8 and 13a. Other common phage types (4, 1, 6a) showed winter seasonality and were more likely to be associated with cases linked to international travel. Conversely, phage types 13, 8 and 13a had summer seasonal peaks and were associated with cases of domestically acquired infections. During agri-food surveillance, S. enteritidis was detected in various commodities, most frequently in chicken (with PT13, PT8 and PT13a predominating). Antimicrobial resistance was low in human and non-human isolates. Continued integrated surveillance and collaborative prevention and control efforts are required to mitigate future illness.

Factors related to Campylobacter spp. carriage in client-owned dogs visiting veterinary clinics in a region of Ontario, Canada.

From July 2008 until May 2009, 240 client-owned pet dogs from seven veterinary clinics in the Region of Waterloo, Ontario, Canada participated in a study to determine pet-related management factors that may be associated with the presence of Campylobacter spp. in dogs. The prevalence of Campylobacter spp. carriage in our study population of pet dogs was 22%, with 19% of the dogs positive for C. upsaliensis, and 3% positive for C. jejuni. A significant risk factor from multivariable logistic regression models for both Campylobacter spp. and C. upsaliensis carriage was having homemade cooked food as the dog's diet or added to its diet, and a significant sparing factor for both models was treatment with antibiotics in the previous month. Increasing age of the dog decreased the odds of Campylobacter spp. and C. upsaliensis carriage. Based on the high prevalence of Campylobacter, and specifically C. upsaliensis, further research concerning pet dogs as a risk factor for campylobacteriosis in humans is warranted.

Evaluation of Clostridium difficile in dogs and the household environment.

Clostridium difficile may be an emerging community-associated pathogen but little is known about its sources of exposure. This study evaluated C. difficile contamination in households and colonization of pets. C. difficile was isolated from 44/836 (5.3%) sites in 26/84 (31%) households. Ribotype 027 was the most common (25%) environmental strain. C. difficile was isolated from 14/139 (10%) dogs. Living with an immunocompromised individual was associated with C. difficile colonization in dogs. All toxigenic strains identified in pets have been isolated from humans in Ontario. C. difficile was isolated concurrently from dogs and the environment in four households, but in all cases canine and environmental ribotypes were different. C. difficile was relatively common in households, suggesting that exposure to this pathogen may be a regular event. There was no evidence that dogs are a significant source of household C. difficile contamination.

Characterization of antimicrobial resistance, molecular and phage types of Salmonella enterica serovar Typhi isolations.

Isolation rates in Canada of Salmonella enterica serovar Typhi increased from 0.29 to 0.55 isolations/100,000 population during 2000-2006. Although no ciprofloxacin resistance was detected, nalidixic acid resistance increased from 41% to 80%. Multidrug-resistant S. Typhi represented 18% of the strains tested. Pulsed-field gel electrophoresis (PFGE) analysis of 222 isolates resulted in 91 distinct patterns clustering into four major genetic similarity groups. The five most frequently occurring PFGE patterns accounted for 46% of the isolates. Drug-resistant isolates predominantly occurred in one PFGE similarity group. There were 39 phage types identified in 826 isolates analysed with 60% described by five phage types; 134 were untypable. The phage types associated with multidrug resistance were phage types 53, B1, D1, E1, E9, G3 and M1. Improved integration of epidemiological and laboratory case data will facilitate the protection of public health in Canada during an era of increasing travel and globalization.

A change in clinical practice: a partially stapled cervical esophagogastric anastomosis reduces morbidity and improves functional outcome after esophagectomy for cancer.

Cervical esophagogastric anastomoses are commonly used for reconstruction after esophagectomy because of the lower mortality rate associated with an anastomotic leak compared to intrathoracic anastomoses. However, cervical esophagogastric anastomoses have been criticized for their higher leak rates, stricture formation and greater need for later dilatations when compared with intrathoracic anastomoses. Multiple studies have looked at varying techniques to improve the outcome of the cervical esophagogastric anastomosis. This study was performed to determine whether a partially stapled (posterior stapled wall and anterior hand-sewn wall) anastomosis reliably reduced leaks and the need for later dilatation. From January 2001 to March 2006, 168 patients who underwent cervical esophagogastric anastomosis following esophagectomy (transhiatal or three-hole) for cancer were identified. Beginning in September 2003, the partially stapled technique was introduced and used in 79 patients. Clinical outcomes were compared to patients in whom hand-sewn technique was used (n = 89). Outcomes related to anastomotic leak, other hospital complications, length of stay, postoperative dilatations and survival were compared using Student's t-tests and chi-square tests (P < 0.05), as well as multiple regression analyses. An anastomotic leak occurred in 10 (12.7%) patients who received a partially stapled anastomosis. A hand-sewn anastomosis was complicated by an anastomotic leak in 24 patients (27.0%). This difference was statistically significant (P = 0.021). This lowered incidence of leak was associated with an earlier initiation of oral feeds (median 7 vs. 9.5 days, P < 0.001) and a reduction in hospital stay (median 10 vs. 15 days, P < 0.001). Furthermore, dysphagia associated with stricture requiring postoperative dilatations was markedly diminished in the stapled anastomosis [23 (31.3%) vs. 49 (55.1%), P = 0.001]. The partially stapled cervical esophagogastric anastomosis significantly decreased the incidence of postoperative anastomotic leaks and the need for postoperative dilatation to treat strictures compared to the hand-sewn anastomosis.

Targeted localized degradation of Paired protein in Drosophila development.

BACKGROUND: Selective spatial regulation of gene expression lies at the core of pattern formation in the embryo. In the fruit fly Drosophila, localized transcriptional regulation accounts for much of the embryonic pattern. RESULTS: We identified a gene, partner of paired (ppa), whose properties suggest that localized receptors for protein degradation are integrated into regulatory networks of transcription factors to ensure robust spatial regulation of gene expression. We found that the Ppa protein interacts with the Pax transcription factor Paired (Prd) and contains an F-box, a motif found in receptors for ubiquitin-mediated protein degradation. In normal development, Prd functions only in cells in which ppa mRNA expression has been repressed by another segmentation protein, Even-skipped (Eve). When ppa was expressed ectopically in these cells, Prd protein, but not mRNA, levels diminished. When ppa function was removed from cells that express prd mRNA, Prd protein levels increased. CONCLUSIONS: Ppa co-ordinates Prd degradation and is important for expression of Prd to be correctly localized. In the presence of Ppa, Prd protein is targeted for degradation at sites where its mis-expression would disrupt development. In the absence of Ppa, Prd is longer-lived and regulates downstream target genes.

Differential repression of GAL4 and adjacent transcription activators by operators in the yeast GAL upstream activating sequence.

The upstream activating sequence of the adjacent and divergently transcribed GAL1 and GAL10 genes of Saccharomyces cerevisiae (UASG) contains at least three distinct classes of overlapping transcriptional control sites. The transcription activator GAL4 binds to four related sites in UASG and induces expression of GAL1 and GAL10 when galactose is available. We showed that UASG contains two additional positive control sites, designated GAL4/galactose-independent activating elements (GAEs), which reside at positions adjacent to or overlapping the GAL4-binding sites. When separated from neighboring sequences in UASG, the GAEs activate transcription independently of GAL4 with no requirement for galactose. In the intact GAL1-GAL10 divergent promoter region, their activity is ordinarily repressed by multiple negative control elements, the GAL operators. When galactose is available, GAL4 overcomes the activity of the GAL operators, while the putative GAE-binding proteins stay repressed. Combined, these results imply that distinct activators (GAL4 and GAE proteins) bound at adjacent or overlapping sites in UASG are differentially regulated by putative repressor proteins simultaneously bound at adjacent GAL operators. We surmise that GAE1 and GAE2 may have a physiological function other than regulation of galactose catabolism per se and discuss three hypotheses to account for their presence in UASG.

Opposing regulatory functions of positive and negative elements in UASG control transcription of the yeast GAL genes.

The yeast GAL1 and GAL10 genes are transcribed at a remarkably low basal level when galactose is unavailable and are induced by over 4 orders of magnitude when it becomes available. Approximately six negative control elements (designated GAL operators GALO1 to GALO6) are located adjacent to or overlapping four binding sites for the transcription activator GAL4 in the GAL upstream activating sequence UASG. The negative control elements contribute to the broad range of inducibility of GAL1 and GAL10 by inhibiting two GAL4/galactose-independent activating elements (GAE1 and GAE2) in UASG. In turn, multiple GAL4-binding sites in UASG are necessary for GAL4 to overcome repression by the negative control elements under fully inducing conditions. When glucose in addition to galactose is available (repressing conditions), the ability of GAL4 to activate transcription is diminished as a result of its reduced affinity for DNA and the reduced availability of inducer. Under these conditions, the negative control elements inhibit transcriptional activation from the glucose-attenuated GAL4 sites, thus accounting at least in part for glucose repression acting in cis. A normal part of transcriptional regulation of the GAL1 and GAL10 genes, therefore, appears to involve a balance between the opposing functions of positive and negative control elements.

Anterior fundoplication decreases esophageal clearance in patients undergoing Heller myotomy for achalasia.

BACKGROUND: Anterior fundoplication (AF) following laparoscopic Heller myotomy (LHM) for achalasia may prevent esophageal leaks and gastroesophageal reflux but cause dysphagia. Our study attempts to determine the effect of AF on esophageal leaks, nuclear medicine esophageal clearance (EC), symptom frequency (SF), and Van Trappen symptom scores (SS) for dysphagia, regurgitation, and heartburn. METHODS: Between 1995 and 2004, pre- and postoperative (2-12 months) EC, SF, and SS scores were compared in 95 patients undergoing LHM for achalasia with AF (n = 71) and without (n = 24) AF. RESULTS: There were no leaks or deaths. Laparoscopic Heller myotomy decreased the frequency of postoperative dysphagia, regurgitation, and heartburn with AF (96% preoperation versus 6% postoperation, 94% versus 3%, 58% versus 6%) (p = 0.001) and without AF (100% versus 0%, 83% versus 0%, 50% versus 4%) (p = 0.001). Laparoscopic Heller myotomy improved all SS in both groups. There was no difference between postoperative dysphagia (1.38 +/- 0.64 versus 1.17 +/- 38) p = 0.06, regurgitation (1.17 +/- 51 versus 1.04 +/- 0.20) p = 0.08, and heartburn (1.29 +/- 62 versus 1.53 +/- 0.80) p = 0.185 scores between the AF and no-AF group, respectively. There is a trend toward improvement in dysphagia and regurgitation in the no-AF group. Laparoscopic Heller myotomy improved EC in the supine and upright positions in both groups of patients (p = 0.001). There was an improved mean change in EC (10 min upright) in the no-AF group versus the AF group (50.7% +/- 30.8 versus 29.7% +/- 30.2) p = 0.004. CONCLUSIONS: Laparoscopic Heller myotomy improves esophageal transit and the frequency and severity of dysphagia, heartburn, and regurgitation in a safe manner. Patients without AF show a statistically better upright EC with a trend toward improved dysphagia and regurgitation.

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions.

The functions of roughly a third of all proteins in Streptococcus pneumoniae, a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein's function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae. We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae, the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins.

Effect of cancer on the in vivo energy state of rat liver and skeletal muscle.

The effect of increasing tumor burden on host liver and skeletal muscle energy status was studied using P-31 nuclear magnetic resonance spectroscopy (NMR), in rats inoculated with a nonmetastasizing methylcholanthrene-induced sarcoma (TB), and compared to nontumor bearing (NTB) and pair-fed (PF) rats. During the 28-day study, serial measurements of body weight, food intake, and tumor volume were obtained. Using a 0.9-cm double-turn surface coil, weekly NMR measurements were obtained from liver and skeletal muscle. An increasing ratio of [Pi]/[ATP] was used as one measure of intracellular energy depletion. [Pi]/[ATP] in NTB rats remained constant over time at 0.78 +/- 0.10 in liver, and 0.30 +/- 0.10 in skeletal muscle. In TB rats, the [Pi]/[ATP] ratio increased significantly in liver (P = 0.00002) and skeletal muscle (P = 0.04) with increasing tumor burden. In PF rats, no significant change occurred in [Pi]/[ATP] in liver or skeletal muscle, indicating that declining food intake was not responsible for the change in [Pi]/[ATP] seen in TB rats. Surface-coil spectroscopy of liver and skeletal muscle permits serial measurement of visceral energy stores. Increasing tumor burden results in early, ongoing depletion of energy stores as reflected by increasing [Pi]/[ATP] in these organs.

Trimethoprim/sulfamethoxazole versus placebo: a double-blind comparison of infection prophylaxis in patients with small cell carcinoma of the lung.

The suppression of pathogenic aerobes and the preservation of anaerobes provides a degree of infection prevention during granulocytopenia. Trimethoprim/sulfamethoxazole (TMP/SMZ) suppresses Enterobacteriaceae and probably maintains colonization resistance through sparing of anaerobes. TMP/SMZ (320/1600 mg/day) treatment was compared to placebo in a double-blind, randomized trial in patients with newly diagnosed small cell carcinoma of the lung during the initial courses of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. Infections were evaluated as microbiologically documented, with or without bacteremia, and clinically documented and were correlated to granulocytopenia. Of the 61 patients evaluated, 32 were given TMP/SMZ and 29 were given placebo; both groups had similar characteristics with regard to disease extent, performance status, age, sex, chemotherapy, and days of granulocytopenia. Incidence of infection at less than 100 granulocytes/microliters was significantly reduced in the TMP/SMZ group (2 infections/100 days) compared to placebo (11 infections/100 days, p = 0.005). Also reduced were the number of bacteremias and the mean proportion of study time on broad-spectrum antibiotics (p less than 0.01). Compared to placebo, TMP/SMZ provided infection prophylaxis without an increase in marrow suppression among patients with small cell carcinoma of the lung receiving intensive chemotherapy.

Ethiodized oil emulsion 13 in computed tomography of hepatoma.

Six patients with biopsy-proven hepatoma were prospectively evaluated both by conventional computed tomography (CT) and by scans using ethiodized oil emulsion 13 (EOE 13) as a contrast agent. EOE 13 infusion resulted in marked improvement in the demonstration of the neoplasm in all cases and allowed more accurate definition of tumor extent than was possible with standard scanning techniques. In two cases EOE 13 enhancement was essential for complete radiographic depiction of tumor location, size, and extent. EOE 13 also proved to be of considerable value in assessment of therapeutic response in three patients, permitting more objective determination of tumor growth or regression. EOE 13--enhanced CT scanning provides a valuable means of staging patients presenting with hepatoma and is a reliable, accurate means of radiographic follow-up.

Taxol: a history of pharmaceutical development and current pharmaceutical concerns.

Taxol, a unique diterpene anticancer compound derived from the bark of the Taxus brevifolia (Pacific yew) tree, induces cytotoxicity by a novel mechanism of action. An antimicrotubule agent, Taxol promotes the formation and stabilization of the tubulin polymer unlike other anticancer agents that induce microtubule disassembly. Because of its poor aqueous solubility, Taxol is formulated as a solution in 50% Cremophor EL and 50% dehydrated alcohol, USP. The Cremophor EL and dehydrated alcohol vehicle used in the formulation of Taxol creates some interesting challenges for its preparation and administration. The pharmaceutical concerns associated with the preparation and administration of Taxol are discussed.

The redox state and regulation of amino acid metabolism in man.

Traditionally, regulation of amino acid metabolism in both postabsorptive and prolonged-fasted man has been generally regarded as being hormonal in nature. In particular, insulin, and to a lesser extent glucagon, have been nominated for key roles in this process. More recently, however, reconsideration of previous studies involving insulin, glucagon, and protein meals as well as previously unreported studies (cortisol and tri-iodothyronine) from this laboratory, have suggested another means of regulating amino acid metabolism in fasting man. This new hypothesis is centered on the redox state of muscle of fasting man, which is remarkably reduced in both cytosolic and mitochondrial compartments. It was found that insulin, and to a lesser extent glucagon, when infused into fasting subjects (1) rendered muscle significantly more reduced, and (2) resulted in a diminution in urinary nitrogen excretion. In contrast, when either tri-iodothyronine or cortisol were administered to fasting individuals (1) muscle was found to become more oxidized when compared with the control period, and (2) increased urinary nitrogen excretion was observed in both cases. It was noteworthy that the ingestion of a protein meal by a nitrogen-depleted individual was followed by a dramatic change in muscle redox state (the muscle became more reduced), together with marked uptakes of a variety of amino acids. It is therefore proposed that the protein conservation evidenced by fasting man may be dependent on the reduced state of muslce tissue.

Future directions in the treatment of non-small cell lung cancer.

In recent years significant advances have been made in the treatment of metastatic non-small cell lung cancer. These advances have been due to both the discovery of new, more active drugs and an enhanced understanding of the biology of the disease, which has guided treatment decisions. Today, agents such as paclitaxel, docetaxel, vinorelbine, irinotecan, and gemcitabine are used in combinations that have demonstrated higher overall response rates and longer median overall survival durations than the previous generation of regimens based primarily on cisplatin, etoposide, and vinblastine. Of these new agents, paclitaxel has been the most widely studied and has demonstrated considerable activity when administered in a wide range of doses and schedules. Regimens with significant activity include paclitaxel and carboplatin as well as paclitaxel, carboplatin, and gemcitabine. However, because the optimal doses and schedules have not been clearly elucidated, current research efforts continue to focus on variations of these regimens. Just as advances have been made in the treatment of metastatic disease, it also has been clearly demonstrated that preoperative chemotherapy (+/- radiation) dramatically improves the overall survival for patients with stage III disease. The identification of growth factors, growth factor receptors, oncogenes, and tumor suppressor genes, which influence this disease, is providing new targets for future treatment strategies. Likewise, new therapeutic entities such as antiangiogenesis agents and matrix metalloproteinase inhibitors are being evaluated.

Anaerobic myocardial abscess following myocardial infarction.

An anaerobic myocardial abscess due to Bacteroides fragilis developed in a 60-year-old man when he had an acute myocardial infarction while recuperating from surgery for a paracolonic abscess. Anaerobic bacteremia is a common event and may lead to infection in areas of low oxygen tension far removed from the original portal of entry.

Norfloxacin for prevention of bacterial infections in granulocytopenic patients.

The efficacy and safety of norfloxacin were compared with those of placebo, vancomycin-polymyxin, and trimethoprim-sulfamethoxazole (TMP/SMX) for prophylaxis of bacterial infections in granulocytopenic patients. The study results showed that norfloxacin treatment, which was well tolerated and not associated with any serious systemic adverse effects, prevented acquisition of gram-negative bacillary organisms. Fewer norfloxacin-treated patients (38 of 108 patients, or 35 percent) experienced microbiologically documented infections compared with patients receiving placebo (27 of 40 patients, or 68 percent), vancomycin-polymyxin (16 of 30 patients, or 53 percent), or TMP/SMX (14 of 28 patients, or 50 percent). Gram-negative bacteremia developed in five of 108 norfloxacin-treated patients (5 percent), compared with 17 of 40 placebo-treated patients (43 percent), five of 30 treated with vancomycin-polymyxin (17 percent), and one of 28 patients treated with TMP/SMX (4 percent). The incidence of gram-positive bacteremia was similar in all study groups and was not affected by norfloxacin or any other oral prophylactic antibiotics. These results suggest that norfloxacin is both safe and effective for the prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive bacterial infections, however, is needed.