Public health investigation and response to a hepatitis A outbreak from imported scallops consumed raw-Hawaii, 2016.

During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.

Epidemiology and risk factors for hepatitis C virus infection in a high-prevalence population.

To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case-control study among persons who use drugs. During June-October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case-control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1-51.9), IDU alone (aOR 52.7, CI 25.3-109.9), intranasal drug use alone (aOR 2.6, CI 1.8-3.9) and incarceration (aOR 2.7, CI 2.0-3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1-18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.

Ultrabroadband supercontinuum generation in a CMOS-compatible platform.

We demonstrate supercontinuum generation spanning 1.6 octaves in silicon nitride waveguides. Using a 4.3 cm-long waveguide, with an effective nonlinearity of γ=1.2 W(-1) m(-1), we generate a spectrum extending from 665 nm to 2025 nm (at -30 dB) with 160 pJ pulses. Our results offer potential for a robust, integrated, and low-cost supercontinuum source for applications including frequency metrology, optical coherence tomography, confocal microscopy, and optical communications.

Central venous catheter-related bloodstream infections: improving post-insertion catheter care.

Patients with central venous catheters (CVCs) are at increased risk of bloodstream infections and sepsis-related death. CVC-related bloodstream infections (CRBSIs) are costly and account for a significant proportion of hospital-acquired infections. The aim of this audit was to assess current practice and staff knowledge of CVC post-insertion care and therefore identify aspects of CVC care with potential for improvement. We conducted a prospective audit over 28 consecutive days at a university teaching hospital investigating current practice of CVC post-insertion care in wards with high CVC usage. A multiple choice questionnaire on best practice of CVC insertion and care was distributed among clinical staff. Rates of breaches in catheter care and CRBSIs were calculated and statistical significance assumed when P<0.05. Data was recorded from 151 CVCs in 106 patients giving a total of 721 catheter days. In all, 323 breaches in care were identified giving a failure rate of 44.8%, with significant differences between intensive care unit (ICU) and non-ICU wards (P<0.001). Dressings (not intact) and caps and taps (incorrectly placed) were identified as the major lapses in CVC care with 158 and 156 breaches per 1000 catheter days, respectively. During the study period four CRBSIs were identified, producing a CRBSI rate of 5.5 per 1000 catheter days (95% confidence interval: 0.12-10.97). There are several opportunities to improve CVC post-insertion care. Future interventions to improve reliability of care should focus on implementing best practice rather than further education.

The burden of hepatitis C virus infection in Punjab, India: A population-based serosurvey.

INTRODUCTION: Hepatitis C virus (HCV) infection prevalence is believed to be elevated in Punjab, India; however, state-wide prevalence data are not available. An understanding of HCV prevalence, risk factors and genotype distribution can be used to plan control measures in Punjab. METHODS: A cross-sectional, state-wide, population-based serosurvey using a multi-stage stratified cluster sampling design was conducted October 2013 to April 2014. Children aged ≥5 years and adults were eligible to participate. Demographic and risk behavior data were collected, and serologic specimens were obtained and tested for anti-HCV antibody, HCV Ribonucleic acid (RNA) on anti-HCV positive samples, and HCV genotype. Prevalence estimates and adjusted odds ratios for risk factors were calculated from weighted data and stratified by urban/rural residence. RESULTS: 5,543 individuals participated in the study with an overall weighted anti-HCV prevalence of 3.6% (95% Confidence Interval [CI]: 3.0%-4.2%) and chronic infection (HCV Ribonucleic acid test positive) of 2.6% (95% CI: 2.0%-3.1%). Anti-HCV was associated with being male (adjusted odds ratio 1.52; 95% CI: 1.08-2.14), living in a rural area (adjusted odds ratio 2.53; 95% CI: 1.62-3.95) and was most strongly associated with those aged 40-49 (adjusted odds ratio 40-49 vs. 19-29-year-olds 3.41; 95% CI: 1.90-6.11). Anti-HCV prevalence increased with each blood transfusion received (adjusted odds ratio 1.36; 95% CI: 1.10-1.68) and decreased with increasing education, (adjusted odds ratio 0.37 for graduate-level vs. primary school/no education; 95% CI: 0.16-0.82). Genotype 3 (58%) was most common among infected individuals. DISCUSSION: The study findings, including the overall prevalence of chronic HCV infection, associated risk factors and demographic characteristics, and genotype distribution can guide prevention and control efforts, including treatment provision. In addition to high-risk populations, efforts targeting rural areas and adults aged ≥40 would be the most effective for identifying infected individuals.

Comparing the surgical timelines of military and civilians traumatic lower limb amputations.

The care and challenges of injured service have been well documented in the literature from a variety of specialities. The aim of this study was to analyse the surgical timelines of military and civilian traumatic amputees and compare the surgical and resuscitative interventions. A retrospective review of patient notes was undertaken. Military patients were identified from the Joint Theatre Trauma Registry (JTTR) in 2009. Civilian patients were identified using the hospital informatics database. Patient demographics, treatment timelines as well as surgical and critical care interventions were reviewed. In total 71 military patients sustained traumatic amputations within this time period. This represented 11% of the total injury demographic in 2009. Excluding upper limb amputees 46 patients sustained lower extremity amputations. These were investigated further. In total 21 civilian patients were identified in a 7-year period. Analysis revealed there was a statistically significant difference between patient age, ITU length of stay, blood products used and number of surgical procedures between military and civilian traumatic amputees. This study identified that military patients were treated for longer in critical care and required more surgical interventions for their amputations. Despite this, their time to stump closure and length of stay were not statistically different compared to civilian patients. Such observations reflect the importance of an Orthoplastic approach, as well as daily surgical theatre co-ordination and weekly multi-disciplinary meetings in providing optimal care for these complex patients. This study reports the epidemiological observed differences between two lower limb trauma groups.

Resolution of the coenzyme B-12-dependent dehydratases of Klebsiella sp. and Citrobacter freundii.

Diol dehydratase (1,2-propanediol hydro-lyase, EC 4.2.1.28) and glycerol dehydratase (glycerol hydro-lyase, EC 4.2.1.30) are shown to be distinct, separable enzymes that occur individually or together in different strains of Klebsiella sp. Anaerobic growth with propan-1,2-diol induces diol dehydratase alone, whereas glycerol fermentation induces both enzymes in K. pneumoniae ATCC 25955 and in Citrobacter freundii NCIB 3735. The dehydratases can be resolved by polyacrylamide-gel electrophoresis or separated by anion-exchange chromatography alone. Sucrose density gradient centrifugation failed to distinguish the enzymes and indicated a molecular weight of 1.9 . 10(5) for both. The enzymes can be assayed individually, even when present in the same crude extract, using the 67-fold difference in their Km values for coenzyme B-12. For both enzymes inactivation kinetics are observed with glycerol as substrated, and monovalent cations influence both the inactivation rate and catalytic rate of the reaction.

Seasonal Variations in Rubber Biosynthesis, 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase, and Rubber Transferase Activities in Parthenium argentatum in the Chihuahuan Desert.

The rubber content and the activities of enzymes in the polyisoprenoid pathway in Parthenium argentatum (guayule) were examined throughout the growing season in field plots in the Chihuahuan Desert. The rubber content of the plants was low in July and August and slowly increased until October. From October to December there was a rapid increase in rubber formation (per plant) from 589.0 mg to 4438.0 mg. The percentage of rubber in the plants increased from 0.7% (mg/g dry weight) in August and 1.27% in October to 5.5% in December. The rapid increase in rubber formation may result from exposing the plants to low temperatures of 5 to 7[deg]C. The activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) was 21.1 nmol mevalonic acid (MVA) h-1 g-1 fresh weight in the bark of the lower stems in June during seedling growth and decreased to 5.1 nmol MVA h-1g-1 fresh weight in July and 2.9 nmol MVA h-1 g-1 fresh weight in September. From October to December, the activity increased from 5.0 to 29.9 nmol MVA h-1 g-1 fresh weight. The activity of rubber transferase was 65.5 nmol isopentenyl pyrophosphate (IPP) h-1 g-1fresh weight in the bark in September and increased to 357.5 nmol IPP h-1 g-1 fresh weight in December. The rapid increase in the activities of HMGR and rubber transferase coincided with the rapid increase in rubber formation. The activities of MVA kinase and IPP isomerase did not significantly increase in the fall and winter. A tomato HMGR-1 cDNA probe containing a highly conserved C-terminal region of HMGR genes hybridized at low stringency with several bands on blots of HindIII-digested genomic DNA from guayule. In northern blots with the HMGR-1 cDNA probe at low stringency, HMGR mRNA was high in June and November, corresponding to periods of high HMGR activity during seedling growth and rapid increase in rubber formation. The seasonal variations in rubber formation and HMGR mRNA, HMGR activity, and rubber transferase activity may be due to low temperature stimulation in the fall and winter months.

Detection of nitrosyl-iron complexes by proton-electron-double-resonance imaging.

The nitrogen monoxide radical (NO*) forms paramagnetic mono- and dinitrosyl-iron complexes in biologic tissues. To establish a noninvasive technique for in vivo NO* imaging, we evaluated the suitability of these complexes as magnetic resonance (MR) contrast agents, making use of the ability of the unpaired electrons of the complexes to enter into dynamic nuclear polarization with water protons and hence produce enhancement on images generated by the technique of proton-electron-double-resonance imaging (PEDRI). Phantom solutions of synthetic nitrosyl-iron complexes (NICs) altered the signal intensity of PEDRI images. The dinitrosyl-iron complex (DNIC) with serum albumin induced a significantly larger signal alteration than the mononitrosyl-iron complex (MNIC) with dithiocarbamate. Exposure of rat liver to sodium nitroprusside (SNP) by ex vivo and in situ perfusion induced a composite X-band electron spin resonance (ESR) spectrum of the isolated liver characteristic of a MNIC and DNIC. On storage of the tissue, the MNIC signal disappeared and the DNIC signal intensity increased. Correspondingly, in cross-sectional PEDRI images taken at room temperature, the SNP-exposed livers initially exhibited a weak signal that strongly increased with time. In conclusion, NICs can be detected using PEDRI and could be exploited for in vivo NO* imaging.

Validation of the in vivo measurement of adipose tissue by magnetic resonance imaging of lean and obese pigs.

In vivo quantification of adipose tissue with magnetic resonance imaging (MRI) was validated with pigs. Thirteen transaxial MRI sections were collected, at intervals proportional to body length, from each pig, which was then killed, frozen, and sliced at the locations of the MRI sections. Adipose-tissue quantities were determined by dissecting each slice, and lipid contents of the dissected slices and of the tissue segments between slices were measured. Compared with dissection, MRI underestimated abdominal percent adipose tissue and overestimated cervical percent adipose tissue by less than 6%. When all 13 sections were used, MRI closely predicted percent lipid and dissected percent adipose tissue with small residual SDs (RSD = 1.9 and 2.1, respectively), which increased only slightly if two sections (4, upper thorax and 8, upper abdomen) were used (RSD = 2.3 and 2.6, respectively). In conclusion MRI accurately quantifies adipose tissue in vivo, matching values produced by dissection and chemical analysis.

Total and subcutaneous adipose tissue in women: the measurement of distribution and accurate prediction of quantity by using magnetic resonance imaging.

Total and subcutaneous adipose tissue in seven lean and seven obese women were quantified using magnetic resonance imaging (MRI). The distributions of adipose tissues along the body were closely correlated: subcutaneous with total, both within and between lean and obese groups. Lean women had proportionally less adipose tissue in the lower thorax and upper abdomen than did obese women. Reducing the number of MRI scans from 17 to 4 did not increase the residual SD of predicted body adipose tissue (2.9 percent) when body density was used as the reference measure. MRI gave an estimate of total-body adipose tissue significantly closer to the value for fat percent produced when the results from five other techniques (skinfold thickness, underwater weighing, 40K whole-body counting, isotopic water dilution, and tetrapolar bioelectrical impedance) were averaged than when any other technique was used alone. MRI-determined percent body adipose tissue in women is close to, and proportional to, estimates derived by underwater weighing.

Paramagnetic NMR contrast agents. Development and evaluation.

Paramagnetic ions could be theoretically used as NMR contrast agents because of their effect upon T1. However, the toxicity of these ions prevents their application. By the formation of appropriate chemical complexes with these ions, the toxicity of these agents can be substantially reduced while maintaining the paramagnetic effect. Two potential NMR contrast agents, one for oral use and one for intravenous administration, were developed and evaluated both in vitro and in vivo. The effect upon T1 in vitro of these paramagnetic compounds was determined using a JEOL FX-90Q NMR spectrometer. These agents were evaluated in vivo in dogs with a Technicare 0.3 tesla superconducting magnet system and in rabbits with the Aberdeen 0.04 tesla resistive NMR imager. Using calculated T1 NMR images, a nontoxic dose of gadolinium oxalate provided visualization of the gastrointestinal tract. Intravenous administration of chromium EDTA provided enhancement of the kidneys, ureters, and bladder, thereby potentially allowing for the evaluation of renal function with magnetic resonance imaging. Stable paramagnetic complexes can serve as effective, nontoxic, oral and intravenous NMR contrast agents.

Taste of glutamate salts in young and elderly subjects: role of inosine 5'-monophosphate and ions.

Taste sensitivity to five glutamate salts (sodium glutamate, potassium glutamate, ammonium glutamate, calcium diglutamate, and magnesium diglutamate) were determined in sixteen young (mean age 25.58 years) and eighteen elderly (mean age 86.89 years) subjects. The effect of inosine 5'-monophosphate (IMP) and ions on taste perception of glutamate compounds was also investigated. The detection thresholds for glutamate salts were 5.04 times higher in elderly subjects than in young subjects; the recognition thresholds were 3.84 times higher. For young subjects, 0.1 mM IMP lowered detection and recognition thresholds for all 5 salts. A stronger concentration of IMP (1 mM) had this effect in both young and elderly groups. Elderly subjects perceived suprathreshold concentrations as less intense than young subjects. Chloride and acetate salts of sodium, potassium, and calcium reduced the detection and recognition thresholds of L-glutamic acid but had no effect sodium glutamate thresholds.

Changes in NMR relaxation time associated with local inflammatory response.

T1 and T2 relaxation values and water contents of rat and rabbit tissues have been measured during the course of local inflammatory reaction to turpentine. For rabbits, NMR transverse sectional images were also obtained by spin-warp imaging. Elevations in T1 values around the injection site occurred within 24 h. In rats, T1 values of fibrosed muscle at the centre of the reaction continued to rise as a cyst formed, encapsulating the turpentine. T1 values of the surrounding muscle decreased towards normal as the reaction progressed. Good correlation between relaxation rate and water content was observed. In the rabbits. T1 values measured in vitro around the injection site were compared with the values obtained from NMR images of living and dead rabbits, T1 values obtained immediately after death were consistently lower than values of the same tissues before death. Factors affecting a comparison of T1 values obtained by the different methods are discussed.

The application of PEDRI to the study of free radicals in vivo.

Proton-electron double-resonance imaging (PEDRI) has considerable value for study of the distribution and elimination pathways of nitroxide free radicals (NFRs). This has been illustrated by its use in studies of kidney function in the living rat in which the NFR proxyl carboxylic acid (PCA) has been employed as a 'tracer'. The technique, at its present stage of development, can demonstrate location of PCA in enough detail to observe the passage through kidney cortex and medulla differentially, and to see the NFR within the major abdominal blood vessels. These studies are helping towards an understanding of the metabolic fate of PCA, as well as providing information about kidney performance after challenge with a nephrotoxin. In addition, nitric oxide complexes, formed in vivo by providing rats with a nitrite-rich diet, have been observed ex vivo using PEDRI and field-cycled DNP.

Rapid imaging of free radicals in vivo using field cycled PEDRI.

Imaging of free radicals in vivo using an interleaved field-cycled proton-electron double-resonance imaging (FC-PEDRI) pulse sequence has recently been investigated. In this work, in order to reduce the EPR (electron paramagnetic resonance) irradiation power required and the imaging time, a centric reordered snapshot FC-PEDRI pulse sequence has been implemented. This is based on the FLASH pulse sequence with a very short repetition time and the use of centric reordering of the phase-encoding gradient, allowing the most significant free induction decay (FID) signals to be collected before the signal enhancement decays significantly. A new technique of signal phaseshift correction was required to eliminate ghost artefacts caused by the instability of the main magnetic field after field cycling. An FID amplitude correction scheme has also been implemented to reduce edge enhancement artefacts caused by the rapid change of magnetization population before reaching the steady state. Using the rapid pulse sequence, the time required for acquisition of a 64 x 64 pixel FC-PEDRI image was reduced to 6 s per image compared with about 2.5 min with the conventional pulse sequence. The EPR irradiation power applied to the sample was reduced by a factor of approximately 64. Although the resulting images obtained by the rapid pulse sequence have a lower signal to noise than those obtained by a normal interleaved FC-PEDRI pulse sequence, the results show that rapid imaging of free radicals in vivo using snapshot FC-PEDRI is possible.

Design, construction and use of a large-sample field-cycled PEDRI imager.

The design, construction and use of a large-scale field-cycled proton-electron double-resonance imaging (FC-PEDRI) imager is described. The imager is based on a whole-body sized, vertical field, 59 mT permanent magnet. Field cycling is accomplished by the field compensation method, and uses a secondary, resistive magnet with an internal diameter of 52 cm. The magnetic field can be switched from zero to 59 mT or vice versa in 40 ms. It is used with a double-resonance coil assembly (NMR/EPR) comprising a solenoidal NMR transmit/receive coil and a coaxial, external birdcage resonator for EPR irradiation. Experiments to image the distribution of an exogenous nitroxide free radical in anaesthetized rabbits are described.

Nitroxide free radical clearance in the live rat monitored by radio-frequency CW-EPR and PEDRI.

The use of RF (100 to 300 MHz) PEDRI and CW-EPR techniques allows the in vivo study of large animals such as whole rats and rabbits. Recently a PEDRI instrument was modified to also allow CW-EPR spectroscopy with samples of similar size and under the same experimental conditions. In the present study, this CW-EPR and PEDRI apparatus was used to assess the feasibility of the detection of a pyrrolidine nitroxide free radical (2,2,5,5,-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid, PCA) in the abdomen of rats. In particular, we have shown that after the PCA administration (4 mmol kg(-1) b.w.): (i) the PCA EPR linewidth does not show line broadening due to concentration effects; (ii) a similar PCA up-take phase is observed by EPR and PEDRI; and (iii) the PCA half-lives in the whole abdomen of rats measured with the CW-EPR (T1/2=26+/-4 min, mean+/-sd, n=10) and PEDRI (T1/2=29+/-4 min, mean+/-sd, n=4) techniques were not significantly different (p > 0.05). These results show, for the first time, that information about PCA pharmacokinetics obtained by CW-EPR is the same as that from PEDRI under the same experimental conditions.

Pulsed magnetic field exposure during pregnancy and implications for NMR foetal imaging: a study with mice.

Following the recent progress in NMR imaging of the foetus in utero an investigation has been made of the effect of exposure to strong pulsed magnetic fields on the pregnancy of mice and the post natal development of their litters. 23 pregnant mice received exposures ranging from 3.5-12kT/s with pulse periods in the range 0.33-0.56ms at various times during gestation. A similar number of pregnant mice served as controls. No adverse effect was observed on the pregnancy. There was no significant difference between the litter numbers and growth rates of the exposed litters compared with controls. The implications of these results are discussed with regard to the safety of NMR imaging during pregnancy.

Lanthanide-EDTA doped agarose gels for use in NMR imaging phantoms.

Gadolinium-ethylene-diamine-tetraacetic acid (Gd-EDTA) doped agarose gels have been used extensively to produce magnetic resonance imaging test materials. These materials are limited in their use in imagers operating at different frequencies and temperatures. The aim of this paper is to show that the theories used to predict the relaxation times for Gd-EDTA doped gels could be used for other paramagnetic lanthanide-EDTA gels with the aim of producing materials whose relaxation times can be theoretically determined but are less temperature and frequency dependent. In the present work, various lanthanide-EDTA gels were studied regarding their NMR T1 and T2 water proton relaxation time dependencies with temperature and proton Larmor frequency. Gd-EDTA doped agarose gels have a T1 relaxation time dependence with temperature of 7.5 ms/K. However an Er-EDTA doped gel has a temperature dependence of only 3.2 ms/K. Similarly Gd-EDTA doped agarose gels vary by 3.48 ms/MHz over the frequency range 2.5 MHz to 80 MHz compared to Ho-EDTA, which varies 0.359 ms/MHz over the same range. These results show that it is possible to produce lanthanide-EDTA doped agarose gels that have markedly reduced temperature and frequency dependences of their relaxation times, but are still predictable using existing theories. This would allow the direct comparison of the performance of imagers operating at different frequencies and temperatures.