Usefulness of a new DUV-LED device for the control of infection by Escherichia coli, Staphylococcus aureus, mycobacteria and spore-forming bacteria.

Reliable disinfection and sterilization technologies are needed to deal with the various infectious diseases spreading around the world. Furthermore, bacteria that are difficult to eliminate by ordinary disinfection are also a problem in the medical environment. We examined the germicidal effect of a newly developed deep-ultraviolet light-emitting diode (DUV-LED) prototype device (wavelength of 280 ± 5 nm; power of 0.9 to 1.4 mW/cm2) for floor sterilization against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Mycobacterium gordonae (M. gordonae), and Bacillus subtilis (B. subtilis). This prototype device is equipped with highly practical DUV-LEDs with a high output efficiency and a long life, and was designed with consideration of the irradiation distance and the angle of the DUV-LEDs to provide a uniform irradiation rate. We found a statistically significant reduction of ≥90% in the infectious titers of both E. coli and S. aureus after irradiation for 2 s. Although acid-fast bacilli and spore-type bacilli are generally thought to be resistant to UV light irradiation compared to general bacteria, the acid-fast bacillus M. gordonae was inactivated after irradiation for 10 s, and spore-type cells of the bacillus B. subtilis were inactivated by ≥90% after irradiation for 30 s. We also found that the effects were cumulative when irradiation was performed at intervals. In the future, the usefulness of this device as an infection control measure will be evaluated in daily medical practice.

Association of intrauterine presence of Lactobacillus spp. with inflammation and pathogenic bacteria in the uterus in postpartum dairy cows.

The aim of this study was to clarify the influence of Lactobacillus spp. on the degree of endometrial inflammation in the postpartum period and the relationship between Lactobacillus spp. and pathogenic bacteria in the endometrium of postpartum dairy cows. Endometrial samples were collected from 41 Holstein-Friesian cows at 4 and 8 weeks postpartum using cytobrushes for polymorphonuclear neutrophil (PMN) count and bacterial culture to isolate Lactobacillus spp., Escherichia coli, and Trueperella pyogenes. The 4-week samples were divided into four groups (E+L+), (E+L-), (E-L+), (E-L-) according to whether endometritis was diagnosed (E+) and Lactobacillus spp. was isolated (L+). The diagnostic criterion for cytological endometritis was > 18% PMN. The average PMN% in the E+L+ group was lower than that in the E+L-group (P < 0.05) at 8 weeks postpartum. There were no significant correlations between the number of colonies of Lactobacillus spp. and E. coli or between that of Lactobacillus spp. and T. pyogenes. Lactobacillus spp. could reduce PMN% in dairy cows with endometritis during the puerperal period. In conclusion, the intrauterine presence of Lactobacillus spp. may have a positive effect on uterine involution in postpartum dairy cows.

Evaluation of a booster tuberculosis vaccine containing mycobacterial DNA-binding protein 1 and CpG oligodeoxynucleotide G9.1 using a Guinea pig model that elicits immunity to Bacillus Calmette-Guérin.

Tuberculosis is a major threat to global health and its increased incidence in adolescents as well as onset in the elderly presents a serious problem. One strategy to control tuberculosis involves taking advantage of Bacillus Calmette-Guérin's (BCG) superior effects on childhood tuberculosis. Accordingly, here we aimed to develop a booster vaccine for adults who received the BCG vaccine during early childhood. Therefore, we first devised a system to assess the efficacy of a candidate booster vaccine. Specifically, variant strain BCG-II, a minor component of BCG-Tokyo strain, which elicits weak immunity, was administered to guinea pigs. Vaccine-induced immunity and protection against Mycobacterium tuberculosis (Mtb) infection were evaluated using skin delayed-type hypersensitivity (DTH) and Mtb colony forming unit counts in organs, respectively. Candidate booster vaccine containing the mycobacterial DNA-binding protein 1 (MDP1) as antigen and CpG oligodeoxynucleotide G9.1 as adjuvant increased T-bet expression and IFN-γ production in human peripheral blood mononuclear cells. Intradermal administration of MDP1 or MDP1 and G9.1 to unimmunized guinea pigs produced DTH on MDP1-inoculated skin. Boosting BCG-II-primed guinea pigs with this protocol effectively enhanced DTH against MDP1 and protection against Mtb infection, particularly when combined with G9.1. The candidate vaccine may contribute to efforts to prevent tuberculosis.

Suppurative necrotizing bronchopneumonia caused by Nocardia cyriacigeorgica infection in a stranded striped dolphin (Stenella coeruleoalba) in Japan.

On a coastline in Miyazaki Prefecture, Japan, a wild subadult female striped dolphin was found dead. Necropsy revealed poor nutritional status and bilateral pneumonia, which was histologically diagnosed as severe suppurative necrotizing bronchopneumonia. Special staining detected numerous intralesional filamentous, branching bacteria, which was identified as Nocardia cyriacigeorgica by sequencing of 16S ribosomal RNA and gyrB genes. Other main histological findings included lymphoid depletion in the spleen and superficial cervical and pulmonary lymph nodes. Suppurative nocardiosis without a granulomatous reaction is uncommon, and it is assumed its pathogenesis was related to the host's immune status. This paper discusses the variable inflammatory response to nocardiosis and describes the first case of N. cyriacigeorgica infection in a wild striped dolphin in Japan.

Quantification of extracellular volume fraction by cardiac computed tomography for noninvasive assessment of myocardial fibrosis in hemodialysis patients.

Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index (r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.

Cardiovascular magnetic resonance feature tracking for characterization of patients with heart failure with preserved ejection fraction: correlation of global longitudinal strain with invasive diastolic functional indices.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is the main cause of heart failure with preserved ejection fraction (HFpEF), and is characterized by LV stiffness and relaxation. Abnormal LV global longitudinal strain (GLS) is frequently observed l in HFpEF, and was shown to be useful in identifying HFpEF patients at high risk for a cardiovascular event. Cardiovascular magnetic resonance (CMR) feature tracking (CMR-FT) enables the reproducible and non-invasive assessment of global strain from cine CMR images. However, the association between GLS and invasively measured parameters of diastolic function has not been investigated. We sought to determine the prevalence and severity of GLS impairment in patients with HFpEF by using CMR-FT, and to evaluate the correlation between GLS measured by CMR-FT and that measured by invasive diastolic functional indices. METHODS: Eighteen patients with HFpEF and 18 age- and sex-matched healthy control subjects were studied. All subjects underwent cine, pre- and post-contrast T1 mapping and late gadolinium-enhancement CMR. In the HFpEF patients, invasive pressure-volume loops were obtained to evaluate LV diastolic properties. GLS was quantified from cine CMR, and extracellular volume fraction (ECV) was quantified from pre- and post-contrast T1 mapping as a known imaging biomarker for predicting LV stiffness. RESULTS: GLS was significantly impaired in patients with HFpEF (- 14.8 ± 3.3 vs.-19.5 ± 2.8%, p < 0.001). Thirty nine percent (7/18) of HFpEF patients showed impaired GLS with a cut-off of - 13.9%. Statistically significant difference was found in ECV between HFpEF patients and controls (32.2 ± 3.8% vs. 29.9 ± 2.6%, p = 0.044). In HFpEF patients, the time constant of active LV relaxation (Tau) was strongly correlated with GLS (r = 0.817, p < 0.001), global circumferential strain (GCS) (r = 0.539, p = 0.021) and global radial strain (GRS) (r = - 0.552, p = 0.017). Multiple linear regression analysis revealed GLS as the only independent predictor of altered Tau (beta = 0.817, p < 0.001) among age, LV end-diastolic volume index, LV end-systolic volume index, LV mass index, GCS, GRS and GLS. CONCLUSIONS: CMR-FT is a noninvasive approach that enables identification of the subgroup of HFpEF patients with impaired GLS. CMR LV GLS independently predicts abnormal invasive LV relaxation index Tau measurements in HFpEF patients. These findings suggest that feature-tracking CMR analysis in conjunction with ECV, may enable evaluation of diastolic dysfunction in patients with HFpEF.

Feasibility of extracellular volume fraction calculation using myocardial CT delayed enhancement with low contrast media administration.

BACKGROUND: Myocardial extracellular volume fraction (ECV) derived from CT delayed enhancement (CTDE) may allow assessment of diffuse myocardial fibrosis. However, the amount of contrast medium required for ECV estimation has not been established. Since ECV estimation by CT is typically performed in combination with coronary CT angiography (CCTA) in clinical settings, we aimed to investigate whether reliable ECV estimation is possible using the contrast dose optimized for CCTA without additional contrast administration. METHODS: Twenty patients with known or suspected coronary artery disease who underwent CTDE with a dual-source scanner using two protocols (Protocols A and B) within 2 years were retrospectively enrolled. In Protocol A, CTDE was obtained with 0.84 ml/kg of iopamidol (370 mgI/ml) injected for CCTA. In Protocol B, stress CT perfusion imaging, which requires 40 ml of contrast medium, was added to Protocol A. ECV values calculated from the two protocols were compared. RESULTS: Despite the different contrast doses, no significant difference in mean myocardial ECV was seen between Protocols A and B at the patient level (28.7 ± 4.3% vs. 28.7 ± 4.4%, respectively, P = 0.868). Excellent correlations in ECV were seen between the two protocols (r = 0.942, P < 0.001). Bland-Altman analysis showed slight bias (+0.06%), within a 95% limit of agreement of -2.9% and 3.0%. The coefficient of variation was 5.2%. CONCLUSION: Reliable ECV estimation can be achieved with the contrast doses optimized for CCTA. Despite the differing contrast administration schemes and doses, ECV values calculated from the two protocols showed excellent agreement, indicating the robustness of ECV estimation by CT.

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement.

OBJECTIVES: This study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis. BACKGROUND: The prognostic value of stress dynamic CTP with CTDE is unknown. METHODS: Participants were 540 patients with suspected or known CAD. Major adverse cardiac event(s) (MACE) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score ≥4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE. RESULTS: During a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD (≥50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p = 0.028) and from 0.61 to 0.73 in patients with known CAD (p = 0.004). IPD and scar score of ≥4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p = 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p = 0.001] and 3.2 [p = 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or ≥70% stenosis (12.4% vs. 3.6%; p < 0.001). CONCLUSIONS: Stress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification.

Myocardial Coverage and Radiation Dose in Dynamic Myocardial Perfusion Imaging Using Third-Generation Dual-Source CT.

OBJECTIVE: Third-generation dual-source computed tomography (3rd-DSCT) allows dynamic myocardial CT perfusion imaging (dynamic CTP) with a 10.5-cm z-axis coverage. Although the increased radiation exposure associated with the 50% wider scan range compared to second-generation DSCT (2nd-DSCT) may be suppressed by using a tube voltage of 70 kV, it remains unclear whether image quality and the ability to quantify myocardial blood flow (MBF) can be maintained under these conditions. This study aimed to compare the image quality, estimated MBF, and radiation dose of dynamic CTP between 2nd-DSCT and 3rd-DSCT and to evaluate whether a 10.5-cm coverage is suitable for dynamic CTP. MATERIALS AND METHODS: We retrospectively analyzed 107 patients who underwent dynamic CTP using 2nd-DSCT at 80 kV (n = 54) or 3rd-DSCT at 70 kV (n = 53). Image quality, estimated MBF, radiation dose, and coverage of left ventricular (LV) myocardium were compared. RESULTS: No significant differences were observed between 3rd-DSCT and 2nd-DSCT in contrast-to-noise ratio (37.4 ± 11.4 vs. 35.5 ± 11.2, p = 0.396). Effective radiation dose was lower with 3rd-DSCT (3.97 ± 0.92 mSv with a conversion factor of 0.017 mSv/mGy·cm) compared to 2nd-DSCT (5.49 ± 1.36 mSv, p < 0.001). Incomplete coverage was more frequent with 2nd-DSCT than with 3rd-DSCT (1.9% [1/53] vs. 56% [30/54], p < 0.001). In propensity score-matched cohorts, MBF was comparable between 3rd-DSCT and 2nd-DSCT in non-ischemic (146.2 ± 26.5 vs. 157.5 ± 34.9 mL/min/100 g, p = 0.137) as well as ischemic myocardium (92.7 ± 21.1 vs. 90.9 ± 29.7 mL/min/100 g, p = 0.876). CONCLUSION: The radiation increase inherent to the widened z-axis coverage in 3rd-DSCT can be balanced by using a tube voltage of 70 kV without compromising image quality or MBF quantification. In dynamic CTP, a z-axis coverage of 10.5 cm is sufficient to achieve complete coverage of the LV myocardium in most patients.

Extended-spectrum ß-lactamase-producing Escherichia coli isolated from healthy Thoroughbred racehorses in Japan.

Extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) have become a major health concern in both human and veterinary medicine. These bacteria could become a critical problem in equine medicine due to the limited number of antimicrobial drugs available. However, there are no previous reports of ESBLEC isolated from horses in Japan. The objectives of this study were to investigate the occurrence of ESBLEC isolated from feces in healthy Thoroughbred racehorses in Japan. Feces samples were collected from 147 healthy Thoroughbred racehorses by equine veterinarians at the Japan Racing Association (103 from Miho Training Center and 44 from Ritto Training Center) between March 2017 and April 2018. Samples were screened for ESBLECs using MacConkey agar supplemented with 1 µg/ml cefotaxime. Detection of ESBL genes was performed by PCR and confirmed by DNA sequencing. Horizontal transmission was demonstrated by conjugation assay. In this study, 24 ESBLECs were isolated from twelve horse feces samples (8.2%). All ESBLECs harbored blaCTX-M-2, and both blaTEM-1 and blaCTX-M-2 were detected in nine isolates (37.5%). ESBLECs showed resistance to all ß-lactam antibiotics (100%) tested, followed by trimethoprim (66.7%), streptomycin (62.5%), tetracycline (25.0%), and oxytetracycline (25.0%). Horizontal transmission was successfully demonstrated by conjugation assay in eight of 13 isolates, and blaCTX-M-2 was detected by PCR in all transconjugants. This study showed that racehorses in Japan are potential reservoirs of ESBLECs.

Co-infection of epithelial cells established from the upper and lower bovine respiratory tract with bovine respiratory syncytial virus and bacteria.

Bovine respiratory disease complex is a major disease affecting the global cattle industry. Multiple infections by viruses and bacteria increase disease severity. Previously, we reported that bovine respiratory syncytial virus (BRSV) infection increases adherence of Pasteurella multocida to human respiratory and bovine kidney epithelial cells. To examine the interaction between the virus and bacteria in bovine respiratory cells, we generated respiratory epithelial cell lines from bovine trachea (bTEC), bronchus (bBEC), and lung (bLEC). Although all established cell lines were infected by BRSV and P. multocida susceptibility differed according to site of origin. The cells derived from the lower respiratory tract (bBEC and bLEC) were significantly more susceptible to BRSV than those derived from the upper respiratory tract (bTEC). Pre-infection of bBEC and bLEC with BRSV increased adherence of P. multocida; this was not the case for bTEC. These results indicate that BRSV may reproduce better in the lower respiratory tract and encourage adherence of bacteria. Thus, we identify one possible mechanism underlying severe pneumonia.

Genotyping of swine Mycobacterium avium subsp. hominissuis isolates from Kyushu, Japan.

The incidence of diseases caused by nontuberculous mycobacteria (NTM) is increasing annually worldwide, including Japan. Mycobacterium avium subsp. hoiminissuis (MAH) is one of the most common NTM species responsible for chronic lung diseases in animals and humans. In the current study, mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing was employed to characterize the genetic diversity of swine MAH isolates from Kyushu, Japan. In total, 309 isolates were obtained from the lymph nodes of 107 pigs not displaying any clinical signs of disease, of which 307 were identified as MAH, comprising 173 strains. Based on eight established MIRU-VNTR loci, the MAH strains represented 50 genotypes constituting three lineages, and 29 had not been described in the Mac French National Institute for Agricultural Research Nouzilly MIRU-VNTR (Mac-INMV) database. MAH was the dominant M. avium complex (MAC) in pigs from Kyushu, and there was high genetic diversity among genotype profiles of MAH from Kyushu. We identified three predominant genotype profiles in the tested area sharing high relatedness with genotype profiles of strains isolated in European countries. MAH was the most common NTM in pigs from Kyushu and exhibited high diversity, with new strain-derived genotypes.

Incremental Prognostic Value of Myocardial Blood Flow Quantified With Stress Dynamic Computed Tomography Perfusion Imaging.

OBJECTIVES: This study aimed to evaluate whether myocardial blood flow (MBF) quantified with dynamic computed tomography perfusion imaging (CTP) has an incremental prognostic value over coronary CT angiography (CTA) for major adverse cardiac events (MACEs) in patients with suspected coronary artery disease (CAD). BACKGROUND: The incremental prognostic value of CTP over CTA is unclear. The quantification of MBF with dynamic CTP may potentially enhance risk stratification. METHODS: A total of 332 patients (67% men; age: 67 ± 10 years) with suspected CAD who underwent CTA and dynamic CTP was analyzed. A MACE was defined as cardiac death, nonfatal myocardial infarction (MI), unstable angina, or hospitalization for congestive heart failure. A summed stress score (SSS) was calculated by adding scores of all myocardial segments according to normalized MBF values. Abnormal perfusion was defined as SSS ≥4. Obstructive CAD was defined as ≥50% stenosis in ≥1 vessel on CTA. RESULTS: During a median follow-up of 2.5 years, 19 patients had a MACE. Multivariate analysis showed that, when adjusted for obstructive CAD on CTA, abnormal perfusion was significantly associated with hazards for MACEs (hazard ratio [HR]: 5.7; 95% confidence interval [CI]: 1.9 to 16.9; p = 0.002), with a significant improvement in the prognostic value. Abnormal perfusion was an independent predictor even when adjusted for ≥70% stenosis in ≥1 vessel (HR: 5.4; 95% CI: 1.7 to 16.7; p = 0.003) or adjusted for ≥50% stenosis in ≥2 vessels (HR: 6.5; 95% CI: 2.2 to 18.9; p = 0.001). In the setting of obstructive CAD, annualized event rates showed a significant difference between the patients with and without abnormal perfusion for all events (12.2% vs. 1.5%; p = 0.002) and for cardiac death and nonfatal MI (4.2% vs. 0%; p = 0.015). CONCLUSIONS: MBF quantified with dynamic CTP has an incremental prognostic value over CTA. The addition of dynamic CTP to CTA allows improved risk stratification of patients with CTA-detected stenosis.

Comparison of the different imaging time points in delayed phase cardiac CT for myocardial scar assessment and extracellular volume fraction estimation in patients with old myocardial infarction.

Delayed enhancement cardiac CT is a potential tool for myocardial viability assessment and is essential for extracellular volume fraction (ECV) estimation with CT. The objective of this study is to determine the optimal delay time for acquisition of delayed CT scans. Thirty-five patients with enhancement pattern typical of previous myocardial infarction on delayed CT and 17 control subjects comprised the study population. Delayed scans were acquired at 3, 5 and 7 min after contrast material injection. Image quality and estimated ECV were compared among the three time points. Delayed CT at 5 min showed the highest signal-to-noise ratio of 15.2 ± 1.0 [p < 0.0001; vs. 3 min (13.6 ± 1.0), p = 0.0015; vs. 7 min (14.9 ± 1.0)]. Contrast-to-noise ratio of infarcted and remote myocardium was highest at 7 min (6.4 ± 2.5), but was not significantly different from 5 min (6.1 ± 2.2, p = 0.08). The ECV values were constant over the three time points, although, in segments containing infarcted myocardium, trend of lower values was noted at 3 min compared to 5 and 7 min. ECV values at 5 min was 27.1% ± 2.1% in control subjects, 27.2% ± 3.0% in remote segments of patients with infarction, and 39.6% ± 5.3% in segments containing infarcted myocardium. Myocardial scars are equally best visualized with delay time of 5 and 7 min post contrast administration. No significant difference was observed in ECV of healthy myocardium or focal scars among delay time of 3, 5, and 7 min. Delay time of 5 min after contrast injection may be recommended for CT delayed enhancement imaging.

Full genome analysis of bovine papillomavirus type 1 derived from a calf with severe cutaneous multiple papillomatosis.

Severe papillomatosis occasionally causes astasia leading to euthanizing cattle. There are currently a limited number of reports on virologic approach in severe bovine papillomatosis. Here we report a full genome characterization of bovine papillomavirus type 1 (BPV-1) from the case of severe papillomatosis. A calf developed numerous papillomas on the skin and some nodules in the upper gastrointestinal tract at seven months old. The skin lesion was diagnosed as the epithelial papilloma with BPV antigen expression, while the gastrointestinal lesions were diagnosed as the fibropapilloma without BPV antigen. Full genome analysis revealed that BPV-1s detected in all the lesions were exactly the same. Compared with the reference BPV-1 sequence, there was a single nucleotide insertion in the upstream regulatory region.

Real-time decision-making during emergency disease outbreaks.

In the event of a new infectious disease outbreak, mathematical and simulation models are commonly used to inform policy by evaluating which control strategies will minimize the impact of the epidemic. In the early stages of such outbreaks, substantial parameter uncertainty may limit the ability of models to provide accurate predictions, and policymakers do not have the luxury of waiting for data to alleviate this state of uncertainty. For policymakers, however, it is the selection of the optimal control intervention in the face of uncertainty, rather than accuracy of model predictions, that is the measure of success that counts. We simulate the process of real-time decision-making by fitting an epidemic model to observed, spatially-explicit, infection data at weekly intervals throughout two historical outbreaks of foot-and-mouth disease, UK in 2001 and Miyazaki, Japan in 2010, and compare forward simulations of the impact of switching to an alternative control intervention at the time point in question. These are compared to policy recommendations generated in hindsight using data from the entire outbreak, thereby comparing the best we could have done at the time with the best we could have done in retrospect. Our results show that the control policy that would have been chosen using all the data is also identified from an early stage in an outbreak using only the available data, despite high variability in projections of epidemic size. Critically, we find that it is an improved understanding of the locations of infected farms, rather than improved estimates of transmission parameters, that drives improved prediction of the relative performance of control interventions. However, the ability to estimate undetected infectious premises is a function of uncertainty in the transmission parameters. Here, we demonstrate the need for both real-time model fitting and generating projections to evaluate alternative control interventions throughout an outbreak. Our results highlight the use of using models at outbreak onset to inform policy and the importance of state-dependent interventions that adapt in response to additional information throughout an outbreak.

Bovine respiratory syncytial virus infection enhances Pasteurella multocida adherence on respiratory epithelial cells.

Primary infection with bovine respiratory syncytial virus (BRSV) predisposes cattle to secondary infection with bacteria that cause bovine respiratory disease complex (BRDC). However, the interaction between BRSV and bacteria is unclear. This in vitro study examined the adherence of Pasteurella multocida (PM) to BRSV-infected cells was assessed in colony forming unit assays, by flow cytometry analysis, and by indirect immunofluorescence analysis (IFA) of epithelial cells (A549, HEp-2, and MDBK). An in vitro model based on infection of BRSV-infected epithelial cells revealed that PM adherence to BRSV-infected cells was 2- to 8-fold higher than uninfected cells. This was confirmed by flow cytometry analysis and IFA. Epithelial cell expression of mRNA encoding cytokines and chemokines increased after exposure to PM, but increased further after co-infection with BRSV and PM. BRSV-mediated adherence of PM to epithelial cells may underlie the serious symptoms of BRDC.

Native T1 Mapping and Extracellular Volume Mapping for the Assessment of Diffuse Myocardial Fibrosis in Dilated Cardiomyopathy.

OBJECTIVES: The purpose of this study was to examine the histological correlation of native myocardial T1 and extracellular volume fraction (ECV) measurement at 3-T for the assessment of diffuse pathological changes in the myocardial tissue, including myocardial fibrosis and extracellular space in dilated cardiomyopathy (DCM). BACKGROUND: Cardiac magnetic resonance T1 techniques allow the quantification of diffuse myocardial fibrosis. However, there are no definitive head-to-head studies of native T1 versus ECV for the detection, quantification, and characterization of pathological changes in the myocardial tissue in DCM by using histological samples for confirmation. METHODS: A total of 36 subjects with DCM (31 men, mean age 56 ± 16 years) underwent pre- and post-contrast T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 3-T. Biopsy samples were used for the quantification of collagen volume fraction using picrosirius red staining and an extracellular space component from hematoxylin and eosin-stained myocardium. RESULTS: Nonischemic LGE was observed in 14 of 36 patients. Although patients with LGE had significantly greater biopsy-proven collagen volume fraction than those without LGE (21 ± 12% vs. 11 ± 8%; p < 0.01), there was substantial overlap of collagen volume fraction values between patients with and without LGE. Both native T1 value and ECV were similarly and significantly associated with biopsy-proven collagen volume fraction (r = 0.77 and r = 0.66, respectively; p < 0.05). Furthermore, ECV had a strong correlation with the biopsy-proven extracellular space component (r = 0.86), whereas native T1 had only a moderate correlation (r = 0.55). Interobserver and intraobserver reproducibility for native T1 and ECV were 0.89, 0.95, 0.96, and 0.98, respectively. CONCLUSIONS: Native T1 exhibited comparable ability as ECV measurement in the detection and quantification of histological collagen volume fraction, with high reproducibility, and therefore diffuse myocardial fibrosis in DCM may be reliably assessed by native T1 mapping without the administration of gadolinium contrast agent. In addition, cardiac magnetic resonance-derived ECV showed excellent agreement with histological extracellular space.

Diagnostic Accuracy of Endocardial-to-Epicardial Myocardial Blood Flow Ratio for the Detection of Significant Coronary Artery Disease With Dynamic Myocardial Perfusion Dual-Source Computed Tomography.

BACKGROUND: Previous dynamic stress computed tomography perfusion (CTP) studies used absolute myocardial blood flow (MBF in mL/100 g/min) as a threshold to discriminate flow-limiting coronary artery disease (CAD), but absolute MBF can be vary because of multiple factors. The aim of this study was to compare the diagnostic performance of absolute MBF and the transmural perfusion ratio (TPR) for the detection of flow-limiting CAD, and to clarify the influence of CT delayed enhancement (CTDE) on the diagnostic performance of CTP.Methods and Results:We retrospectively enrolled 51 patients who underwent dual-source CTP and invasive coronary angiography (ICA). TPR was defined as the endocardial MBF of a specific segment divided by the mean of the epicardial MBF of all segments. Flow-limiting CAD was defined as luminal diameter stenosis >90% on ICA or a lesion with fractional flow reserve ≤0.8. Segmental presence and absence of myocardial scar was determined by CTDE. The area under the receiver-operating characteristics curve (AUC) of TPR was significantly greater than that of MBF for the detection of flow-limiting CAD (0.833 vs. 0.711, P=0.0273). Myocardial DE was present in 27 of the 51 patients and in 34 of 143 territories. When only territories containing DE were considered, the AUC of TPR decreased to 0.733. CONCLUSIONS: TPR calculated from absolute MBF demonstrated higher diagnostic performance for the discrimination of flow-limiting CAD when compared with absolute MBF itself.