A One Health investigation of Salmonella enterica serovar Wangata in north-eastern New South Wales, Australia, 2016-2017.

Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case-control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06-6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58-26.83)), wild frogs (aOR 3.65, 95% CI 1.32-10.07) and wild birds (aOR 6.93, 95% CI 2.29-21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases' residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.

Barriers to accessing care in patients with chronic hepatitis C: the impact of depression.

BACKGROUND: Patients with hepatitis C viral (HCV) may perceive barriers to accessing speciality care for HCV, and these barriers may be related to depressive symptoms. AIM: To evaluate the relationship between barriers to care, demographics, and depressive symptoms. METHODS: A cross-sectional analysis of 126 patients referred for HCV at two speciality HCV clinics. Barriers to care, depressive symptoms and sociodemographics were measured using standardized instruments. A retrospective chart review was conducted to collect clinical outcome data. RESULTS: Depressive symptoms were reported in 26%. Common barriers included lack of personal financial resources; lack of HCV knowledge in the community; lack of professionals competent in HCV care; stigmatization of HCV; and long distances to clinics offering care. After we controlled for sociodemographics, depression accounted for an additional 7-18% of variability in all barriers (all p values <0.01). Lower depression, marital and employment status were associated with subsequent receipt of HCV treatment in 38% (45/120) of patients; perceived barriers were not. CONCLUSIONS: Depression is independently associated with perceived barriers to care. Higher depressive scores, but not perceived barriers, were associated with nontreatment. Healthcare providers who diagnose HCV need to be cognizant of numerous perceived barriers to accessing HCV care, and the impact that depression may have on these perceptions and receipt of treatment.

FIRMA: a method for detection of alternative splicing from exon array data.

MOTIVATION: Analyses of EST data show that alternative splicing is much more widespread than once thought. The advent of exon and tiling microarrays means that researchers now have the capacity to experimentally measure alternative splicing on a genome wide level. New methods are needed to analyze the data from these arrays. RESULTS: We present a method, finding isoforms using robust multichip analysis (FIRMA), for detecting differential alternative splicing in exon array data. FIRMA has been developed for Affymetrix exon arrays, but could in principle be extended to other exon arrays, tiling arrays or splice junction arrays. We have evaluated the method using simulated data, and have also applied it to two datasets: a panel of 11 human tissues and a set of 10 pairs of matched normal and tumor colon tissue. FIRMA is able to detect exons in several genes confirmed by reverse transcriptase PCR. AVAILABILITY: R code implementing our methods is contributed to the package aroma.affymetrix.

A comparison of match-only algorithms for the analysis of Plasmodium falciparum oligonucleotide arrays.

This study is motivated by two data sets which employ a custom Plasmodium falciparum version of the Affymetrix GeneChip, containing only perfect match (PM) oligonucleotides. A PM-only chip cannot be analysed using the standard Affymetrix-supplied software. We compared the performance of three match-only algorithms on these data: the Match Only Integral Distribution (MOID) algorithm, Robust Multichip Analysis (RMA), and the Model Based Expression Index (MBEI). We validated the differential expression of several genes using quantitative reverse transcriptase-PCR. We also performed a comparison using two publicly available 'benchmarking' data sets: the Latin Square spike-in data set generated by Affymetrix, and the Gene Logic dilution series. Since we know what the true fold changes are in these special data sets, they are helpful for assessment of expression algorithms.

Measurement of the flux of ultrahigh energy cosmic rays from monocular observations by the High Resolution Fly's Eye experiment.

We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.

Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia.

Recent studies have shown that the serum transferrin receptor is a sensitive, quantitative measure of tissue iron deficiency. This study was undertaken to determine the serum transferrin receptor's ability to distinguish iron-deficiency anemia from the anemia of chronic inflammation and to identify iron deficiency in patients with liver disease. The mean transferrin receptor level in 17 normal controls was 5.36 +/- 0.82 mg/L compared with 13.91 +/- 4.63 mg/L in 17 patients with iron-deficiency anemia (p less than 0.001). The mean serum receptor level was normal in all 20 patients with acute infection, including five with acute hepatitis, and was also normal in 8 of 10 anemic patients with chronic liver disease. Receptor levels were in the normal range in all but 4 of 41 patients with anemia of chronic disease. We conclude that unlike serum ferritin levels, which are disproportionately elevated in relation to iron stores in patients with inflammation or liver disease, the serum transferrin receptor level is not affected by these disorders and is therefore a reliable laboratory index of iron deficiency anemia.

Sacroiliitis: MR imaging findings.

Magnetic resonance (MR) imaging was performed in seven asymptomatic volunteers and 17 patients with clinical and radiologic evidence of sacroiliitis. MR imaging findings were compared with those at computed tomography (CT) to determine the MR imaging appearance of the sacroiliac joint when normal and in sacroiliitis. The normal articulation was well depicted with MR imaging. Findings of sacroiliitis were identified in 20 sacroiliac joints (12 patients). MR imaging findings characteristic of sacroiliitis included abnormal cartilage signal intensity (95% of joints) and erosions (75% of joints) on T1-weighted images. Areas of increased intensity in the articulation (80% of joints) or in erosions (60% of joints) were seen on T2-weighted images. MR imaging was superior to CT for evaluation of cartilage and detection of erosions. Four sacroiliac joints (20%) and two patients (17%) with MR imaging findings of sacroiliitis were negative at CT. The authors conclude that MR imaging is a valuable method for detecting sacroiliitis, particularly when results of other imaging techniques are inconclusive.

Potentiation of antigen-induced mast cell activation by 1-34 bovine parathyroid hormone.

Peptides such as parathyroid hormone (PTH), somatostatin, and gastrin have been reported to stimulate mast cell mediator release. Preincubation of rat serosal mast cells with synthetic 1-34 bovine parathyroid hormone (1-34bPTH) significantly enhanced antigen-induced 5-hydroxytryptamine (5-HT) release. Enhancement of 5-HT release by 1-34bPTH was dose dependent between 5 and 2000 nM. In the absence of antigen, mean net 5-HT release was less than 1% when naive or passively sensitized mast cells were incubated with 1000 nM 1-34bPTH for time intervals up to 90 min. These findings indicate that 1-34bPTH, at relatively low concentration, potentiates antigen-induced 5-HT release from mast cells.

Methotrexate-associated, early-onset pancytopenia in rheumatoid arthritis.

A patient with rheumatoid arthritis presented with pancytopenia 3 weeks after initiation of low-dose methotrexate administered orally. She had minimal renal insufficiency and hypoalbuminemia prior to initiation of methotrexate therapy, and had received a nonsteroidal anti-inflammatory drug concurrently. Bone marrow recovery occurred within 3 weeks. Patients receiving low-dose methotrexate therapy for rheumatoid arthritis require early monitoring for bone marrow injury, especially those who have risk factors for possible methotrexate toxicity.

Modulation of macrophage superoxide-induced cytochrome c reduction by mast cells.

The effect of mast cells and mast cell granules on macrophage O2- release as determined by cytochrome c reduction was studied. In vitro activation of mast cells before macrophage activation caused a decrease in O2- -mediated cytochrome c reduction. This decrease was proportional to mast cell activation and reached 80% to 100% when mast cell mediator release was 40% to 50%. Incubation of isolated mast cell granules with macrophages before activation also inhibited O2- -mediated cytochrome c reduction in a dose-dependent manner. Mast cell granule-mediated inhibition of cytochrome c reduction was not caused by histamine, serotonin, or any other dialyzable components but was found to be caused by the scavenging of O2- by mast cell granule-bound superoxide dismutase. Macrophage uptake of sulfur 35-labeled mast cell granules, electron microscopic localization of mast cell granules in the macrophage phagosomes, and the abrogation of mast cell granule effect when the cells were preincubated at 0 degree C indicate that the effect was associated with the adherence or phagocytosis (or both) of mast cell granules. These results suggest that mast cell granules interact with macrophages and that granule superoxide dismutase scavenges O2- generated by the phagocytes.

Effect of the mi allele on mast cells, basophils, natural killer cells, and osteoclasts in C57Bl/6J mice.

The osteopetrotic, microphthalmic (mi/mi) mouse lacks functional osteoclasts and has also been reported to be deficient in mast cells and natural-killer (NK) cells. The later deficiencies could be secondary to the osteopetrotic marrow, or a direct result of the mi allele. Therefore, heterozygotes were examined for these cell types, since these mice do not exhibit osteopetrosis. Adult +/mi animals have approximately 50%, and mi/mi animals examined by histologic techniques or tissue histamine levels have 0-10%, of the peritoneal, dermal, and intestinal mast cells compared with that of +/+ animals. Leukocyte histamine, indicative of the number of basophils, demonstrates the same pattern. Histamine content per mast cell in +/+ and +/mi animals is identical. The number of large granular lymphocytes (LGL) in splenic leukocyte preparations from +/mi animals is 50% that of +/+ animals, and these cells are undetectable in preparations from mi/mi mice. NK activity against YAC-1 cells paralleled the number of LGL present. The resorptive response of neonatal calvaria to parathyroid hormone was delayed in the case of cultured +/mi bone compared with that of +/+ bone, but the final rate of calcium release was identical. These data indicate that 1) the presence of one mi allele can affect the development of four distinct cell types, and 2) osteopetrosis alone does not account for the lack of mast cells, basophils, and NK cells in mi/mi mice.

The action of dazopride to enhance gastric emptying and block emesis.

The substituted benzamide derivatives, dazopride and metoclopramide, enhanced field stimulation-induced contractions of guinea-pig stomach strips and gastric emptying in the guinea-pig after peripheral, intracerebroventricular and intrahypothalamic injection. In the isolated vagal nerve preparation from the rabbit, both compounds were shown to be 5-hydroxytryptamine M-receptor antagonists. Dazopride and metoclopramide were equipotent in antagonising cisplatin-induced emesis in the ferret, whereas metoclopramide was approximately 200 times more potent than dazopride in antagonising the emesis caused by the dopamine agonist 2-di-n-propylamino-5,6-dihydroxytetralin in the marmoset. In behavioural tests which indicate dopamine receptor antagonism in the rat, metoclopramide induced catalepsy, antagonised amphetamine-induced stereotypy and the hyperactivity induced by the intrastriatal injection of dopamine, caused body asymmetry on unilateral injection into the striatum and also antagonised apomorphine-induced climbing and circling behaviour in the mouse. In contrast, dazopride had little or no action in these tests and failed to displace [3H]spiperone in radioligand binding assays. The use of dazopride provides evidence to dissociate a dopamine receptor blockade from an ability to facilitate gastric emptying and to antagonise cisplatin-emesis, and indicates that antagonism of 5-hydroxytryptamine M-receptors is the essential basis of action for dazopride and plays an important role in the actions of metoclopramide.

The effect of high ascorbic acid supplementation on body iron stores.

The level of assimilation of dietary iron is believed to have an important influence on iron status. To examine the effect of enhancing the availability of dietary iron on iron balance, 17 adult volunteer subjects were given 2 g of ascorbic acid daily with meals for 16 weeks. Serum ferritin levels before and after the study averaged 46 and 43 micrograms/L, respectively, indicating a negligible effect on iron stores. When vitamin C supplementation was continued for an additional 20 months in five iron-replete and four iron-deficient subjects, serum ferritin determinations again failed to indicate any significant effect of the vitamin C on iron reserves. These findings were not explained by intestinal adaptation to the enhancing effect of the vitamin, because radioisotopic measurements of nonheme iron absorption showed no reduction in the enhancing effect of 1 g of ascorbic acid after four months of megadoses of vitamin C. It is concluded that altering the availability of nonheme dietary iron has little effect on iron status when the diet contains substantial amounts of meat.

The inhibitory effect of bran on iron absorption in man.

The effects of whole wheat bran and its components on the absorption of nonheme dietary iron were measured using a double isotope technique in human volunteers. When 12 g bran was added to a light meal, absorption decreased by 51 to 74%; this inhibitory effect of bran was shown for meals of both high and low iron availability. Inhibition was not explained by monoferric phytate, the major form of iron in bran, because labeled iron from monoferric phytate was absorbed at least as well as the common pool of nonheme dietary iron. Furthermore, removal of phytate from bran by endogenous phytase did not in itself alter the inhibitory effect of the bran on iron absorption. Studies in which dephytinized bran was separated into a soluble, phosphate-rich fraction and an insoluble, high-fiber fraction indicated that the soluble fraction was more inhibitory than the insoluble fraction.

Absorption of monoferric phytate by dogs.

Recent studies have shown that the iron in wheat is predominantly in the form of monoferric phytate (MFP). Unlike phytate complexed with two or more iron atoms, MFP is soluble at pH 7.0 and above and may therefore be a relatively available form of dietary iron. To examine this point, we tested iron absorption in adult dogs using a double radioisotope method and total body counting. When given without food, MFP was about one-half as available as ferrous sulphate at an iron-equivalent dose of 1.5 mg and only about one-seventh as available at a dose of 15 mg iron. When administered with food, MFP underwent complete isotopic exchange with the nonheme pool of dietary iron. When added to meals of either high or low iron availability in amounts that might be used for iron fortification, the absorption was the same for MFP iron as for the major pool of dietary inorganic iron.