Cryopreservation of mammalian cells using protic ionic liquid solutions.

Cryopreservation has facilitated considerable advances in both medical technology and scientific research. However, further developments have been limited by the relatively low number of effective cryoprotective agents. Even after fifty years of research, most protocols rely on the same two toxic agents, i.e. dimethylsulfoxide or glycerol. Ionic liquids are a class of promising solvents which are known glass formers and may offer a less-toxic alternative. The research presented here investigates ten protic ionic liquids as potential cryoprotective agents. The liquids are screened for key properties including cellular toxicity, permeability and thermal behaviour. The most promising, ethylammonium acetate, was then tested as a cryoprotective agent on a model cell line and was found to be as effective as the common cryoprotectant, dimethylsulfoxide. This work reports the first use of a protic ionic liquid as an effective cryoprotective agent for a mammalian cell line. This will inform the development of a suite of potential new ionic liquid-based cryoprotectants that could potentially allow the cryopreservation of new cell types.

The need for novel cryoprotectants and cryopreservation protocols: Insights into the importance of biophysical investigation and cell permeability.

BACKGROUND: Cryopreservation is a key method of preservation of biological material for both medical treatments and conservation of endangered species. In order to avoid cellular damage, cryopreservation relies on the addition of a suitable cryoprotective agent (CPA). However, the toxicity of CPAs is a serious concern and often requires rapid removal on thawing which is time consuming and expensive. SCOPE OF REVIEW: The principles of Cryopreservation are reviewed and recent advances in cryopreservation methods and new CPAs are described. The importance of understanding key biophysical properties to assess the cryoprotective potential of new non-toxic compounds is discussed. MAJOR CONCLUSIONS: Knowing the biophysical properties of a particular cell type is crucial for developing new cryopreservation protocols. Similarly, understanding how potential CPAs interact with cells is key for optimising protocols. For example, cells with a large osmotically inactive volume may require slower addition of CPAs. Similarly, a cell with low permeability may require a longer incubation time with the CPA to allow adequate penetration. Measuring these properties allows efficient optimisation of cryopreservation protocols. GENERAL SIGNIFICANCE: Understanding the interplay between cells and biophysical properties is important not just for developing new, and better optimised, cryopreservation protocols, but also for broader research into topics such as dehydration and desiccation tolerance, chilling and heat stress, as well as membrane structure and function.

Interactions of cryoprotective agents with phospholipid membranes - A Langmuir monolayer study.

The influence of four common cryoprotectants (dimethyl sulfoxide, glycerol, ethylene glycol and dimethylformamide) on monolayers of four common phospholipids (DPPC, DOPC, POPC and POPE) have been studied using Langmuir isotherms and monolayer insertion experiments. The cryoprotectant concentrations were chosen to be directly relevant to cryoprotection. We show that DMSO causes an expansion of the DPPC area per lipid (in contrast to previous work at higher concentrations). However, it caused compression for POPC, and had little effect for POPE or DOPC. As most previous studies have involved only DPPC, this highlights the importance of studying different lipid types as these may have a significant effect on the interactions. We show that both ethylene glycol and glycerol cause a small expansion of the monolayer at fixed pressure, implying that they insert into the headgroup regions, regardless of lipid species, and consistent with their ability to penetrate membranes. By contrast, dimethylformamide causes monolayer compression for all lipid species, implying it dehydrates the lipid head groups. Membrane insertion experiments at physiological values of lateral pressure highlight that DPPC is the most difficult lipid to penetrate, implying that the penetrating action of cryoprotectants may only occur for unsaturated phospholipids. Thus, extrapolations of results based solely on the DPPC need to be made with care.

Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve.

Importance: At present, the choice of noninvasive testing for a diagnosis of significant coronary artery disease (CAD) is ambiguous, but nuclear myocardial perfusion imaging with single-photon emission tomography (SPECT) or positron emission tomography (PET) and coronary computed tomography angiography (CCTA) is predominantly used for this purpose. However, to date, prospective head-to-head studies are lacking regarding the diagnostic accuracy of these imaging modalities. Furthermore, the combination of anatomical and functional assessments configuring a hybrid approach may yield improved accuracy. Objectives: To establish the diagnostic accuracy of CCTA, SPECT, and PET and explore the incremental value of hybrid imaging compared with fractional flow reserve. Design, Setting, and Participants: A prospective clinical study involving 208 patients with suspected CAD who underwent CCTA, technetium 99m/tetrofosmin-labeled SPECT, and [15O]H2O PET with examination of all coronary arteries by fractional flow reserve was performed from January 23, 2012, to October 25, 2014. Scans were interpreted by core laboratories on an intention-to-diagnose basis. Hybrid images were generated in case of abnormal noninvasive anatomical or functional test results. Main Outcomes and Measures: Hemodynamically significant stenosis in at least 1 coronary artery as indicated by a fractional flow reserve of 0.80 or less and relative diagnostic accuracy of SPECT, PET, and CCTA in detecting hemodynamically significant CAD. Results: Of the 208 patients in the study (76 women and 132 men; mean [SD] age, 58 [9] years), 92 (44.2%) had significant CAD (fractional flow reserve ≤0.80). Sensitivity was 90% (95% CI, 82%-95%) for CCTA, 57% (95% CI, 46%-67%) for SPECT, and 87% (95% CI, 78%-93%) for PET, whereas specificity was 60% (95% CI, 51%-69%) for CCTA, 94% (95% CI, 88%-98%) for SPECT, and 84% (95% CI, 75%-89%) for PET. Single-photon emission tomography was found to be noninferior to PET in terms of specificity (P < .001) but not in terms of sensitivity (P > .99) using the predefined absolute margin of 10%. Diagnostic accuracy was highest for PET (85%; 95% CI, 80%-90%) compared with that of CCTA (74%; 95% CI, 67%-79%; P = .003) and SPECT (77%; 95% CI, 71%-83%; P = .02). Diagnostic accuracy was not enhanced by either hybrid SPECT and CCTA (76%; 95% CI, 70%-82%; P = .75) or by PET and CCTA (84%; 95% CI, 79%-89%; P = .82), but resulted in an increase in specificity (P = .004) at the cost of a decrease in sensitivity (P = .001). Conclusions and Relevance: This controlled clinical head-to-head comparative study revealed PET to exhibit the highest accuracy for diagnosis of myocardial ischemia. Furthermore, a combined anatomical and functional assessment does not add incremental diagnostic value but guides clinical decision-making in an unsalutary fashion.

Efficacy of triphala extract and chlorhexidine mouth rinse against plaque accumulation and gingival inflammation among female undergraduates: A randomized controlled trial.

AIM: To know the efficacy of Triphala extract and Chlorhexidine mouth rinse against plaque and gingival inflammation. MATERIALS AND METHODS: A double blinded parallel arm randomised control trial was done among 60 participants aged 18-24 years. Participants were randomly allotted to three groups with 20 participants in each group of 0.6% triphala, 0.12% chlorhexidine and control group. Study was done in 2 phases of 21 days duration. During the experimental period, participants rinsed with the allocated mouth rinse 10ml twice daily for 30 seconds without any supervision. The plaque and gingival status were assessed using Silness and Loe and Loe and Silness at baseline and end of the phase. STATISTICAL ANALYSIS USED: The results were analysed using ANOVA(Analysis of Variance), Wilcoxon sign rank test and post hoc test with significant level at P value < 0.05. RESULTS: Triphala and Chlorhexidine showed significant reduction in plaque and gingival scores as compared to Control group (P < 0.001). No significant difference was found between the plaque and gingival scores obtained with triphala extract and chlorhexidine mouth rinse. CONCLUSION: Triphala extract mouth rinse was effective in reducing plaque accumulation and gingival inflammation with reported no side effects.

Findings on Thoracic Computed Tomography Scans and Respiratory Outcomes in Persons with and without Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.

BACKGROUND: Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals. However, clinical relevance of CT abnormalities is uncertain in the general population. METHODS: We evaluated data from 1361 participants aged ≥40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans. CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B). Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up. RESULTS: About 11% of life-time never-smokers demonstrated emphysema on CT scans. Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively. Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score≥10(OR,2.17; 95%CI,1.42-3.30) and risk of ≥2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0). CONCLUSIONS: Burden of thoracic CT abnormalities is high among Canadians ≥40 years of age, including never-smokers and smokers with normal lung function. Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function.

Effectiveness of Peer Group and Conventional Method (Dentist) of Oral Health Education Programme Among 12-15 year Old School Children - A Randomized Controlled Trial.

INTRODUCTION: Oral Health Education (OHE) in schools is routinely delivered by the dentist. Another approach which can be cost-effective, easily accessible and equally effective is the trained group of peer students. AIM: The objective of the present study was to assess and compare the effectiveness of peer-led and conventional method (dentist-led), OHE on oral health status, oral health knowledge, attitude and practices among 12-15 year old government school children in Bengaluru South Zone-I at baseline, 3 months and 6 months. MATERIALS AND METHODS: The study population comprised of 450 subjects, 150 each in peer, dentist and control group. At baseline, a pre-tested 14 item questionnaire was used to assess the existing oral health knowledge, attitude and oral hygiene practices of the subjects. Clinical examination included recording of plaque index and gingival index, by a pre-calibrated examiner. OHE was provided by the peer group and dentist (using power-point presentation, chalk and talk presentation, using charts, posters, booklets and tooth brushing demonstration models). Data was analyzed using Kruskal Wallis and Chi-square test. RESULTS: Both the peer-led and dentist-led OHE intervention were effective in improving oral health knowledge, attitude, oral hygiene practices and oral health status at three and six months when compared to control group. The adolescents in the peer-led group, however, exhibited statistically better oral health behavior than their counterparts in the dentist-led group and control group. CONCLUSION: The two educator-led strategies (peer group and dentist) had a modest effect on the outcome variables included in the study, the results provide some evidence to show that the peer-led strategy may provide a feasible and almost equally effective alternative to the traditional dentist led strategy of oral health education.

Comparison of Rates of Coronary Angiography and Combined Testing Procedures in Patients Seen in the Emergency Room With Chest Pain (But No Objective Acute Coronary Syndrome Findings) Having Coronary Computed Tomography Versus Exercise Stress Testing.

Coronary computed tomography angiography (CCTA) appears comparable to standard care, including exercise stress testing (EST), in diagnosing acute coronary syndrome in emergency department (ED) patients with chest pain but may increase downstream testing. The objective of this study was to investigate rates of post-CCTA versus post-EST testing for (1) invasive angiography and (2) all combined cardiac testing. This was a retrospective cohort study performed at 2 urban Canadian EDs involving patients aged up to 65 years with chest pain but no objective ACS findings that were evaluated with CCTA or EST at the physician's discretion. The primary outcome was the proportion of patients who had 30-day invasive angiography in each group; secondary outcomes included all subsequent 30-day cardiac testing, including nuclear medicine scanning. From July 1, 2012, to June 30, 2014, we collected 1,700 patients: 521 CCTA and 1,179 EST. Demographics and risk factors were similar in both cohorts. In the following 30 days, 30 CCTA (5.8%) and 297 EST (25.2%) patients underwent any type of additional cardiac testing (difference 19.4%, 95% CI 16.0 to 22.6), whereas 12 CCTA (2.3%) and 20 EST patients (1.7%) underwent angiography (difference 0.6%, 95% CI -0.8% to 2.6%). No patients in either group died or had a myocardial infarction within 30 days. For ED patients with chest pain who underwent brief observation, CCTA and EST had similar 30-day angiography rates, but CCTA patients underwent significantly less overall cardiac investigations.

Sequential Right and Left Ventricular Assessment in Posttetralogy of Fallot Patients with Significant Pulmonary Regurgitation.

BACKGROUND: The natural history of right ventricular (RV) and left ventricular (LV) size and function among adults with tetralogy of Fallot (TOF) repair and hemodynamically significant pulmonary regurgitation (PR) is not known. The main aim of this study was to determine changes in RV and LV size and function over time in an adult population with TOF repair and hemodynamically significant pulmonary regurgitation. METHODS: Forty patients with repaired TOF and hemodynamically significant PR were included. These patients were identified on the basis of having more than one CMR between January 2008 and 2015. Patients with a prosthetic pulmonary valve or any cardiac intervention between CMR studies were excluded. Rate of progression (ROP) of RV dilation was determined for both indexed right ventricular end-systolic volume (RVESVi) and indexed right ventricular end-diastolic volume (RVEDVi), and calculated as the difference between the last and first volumes divided by the number of years between CMR#1 and CMR#2. Subjects were also divided into two groups based on the distribution of the ROP of RV dilation: Group I-rapid ROP (>50th percentile) and Group II-slower ROP (≤50th percentile). RESULTS: The interval between CMR#1 and CMR#2 was 3.9 ± 1.7 years (range 1-8 years). We did find a significant change in RVEDVi and RVESVi over this time period, although the magnitude of change was small. Nine patients (23%) had a reduction in right ventricular ejection fraction (RVEF) by greater than 5%, 13 patients (33%) had an increase in RVEDVi by greater than 10 mL/m2 and seven patients (18%) had an increase in RVESVi by greater than 10 mL/m2 . Median ROP for RVEDVi was 1.8 (range -10.4 to 21.8) mL/(m2 year); RVESVi 1.1 (range -5.8 to 24.5) mL/(m2 year) and RVEF -0.5 (range -8 to 4)%/year. Patients with a rapid ROP had significantly larger RV volumes at the time of CMR#1 and lower RVEF as compared to the slow ROP group. There was no overall significant change in LVEDVi, LVESVi, or LVEF over this time period. CONCLUSIONS: We have demonstrated, in a small population of patients with hemodynamically significant PR, that there is a small increase in RV volumes and decrease in RVEF over a mean 4-year period. We believe it to be reasonable practice to perform CMR at least every 4 years in asymptomatic patients with repaired TOF and hemodynamically significant PR. We found that LV volumes and function remained stable during the study period, suggesting that significant progressive LV changes are less likely to occur over a shorter time period. Our results inform a safe standardized approach to monitoring adults with hemodynamically significant PR post TOF repair and assist in planning allocation of this expensive and limited resource.

Comparison of image quality, and diagnostic interpretability of a new volumetric high temporal resolution scanner versus 64-slice MDCT.

We evaluated the performance of a new volume computed tomographic (CT) scanner with regards to image quality and signal homogeneity. Twenty-four subjects were prospectively enrolled. Subjects had prior imaging with rate control. Quantitative analyses performed placing regions of interest in myocardium, blood pool, and aorta. Image quality and diagnostic interpretability were assessed using Likert scales. Median heart rate was 60 and 57 bpm for volume and 64-slice coronary CT angiography (P=.02). Improvement in homogeneity was demonstrated within myocardium (30% improvement), blood pool (73%), and aorta (73%). Improvement in image quality observed at per-patient/per-segment level. Pilot study confirmed improvements in signal homogeneity and diagnostic interpretability, despite imaging at higher heart rates.

Dynamism of the aortic annulus: Effect of diastolic versus systolic CT annular measurements on device selection in transcatheter aortic valve replacement (TAVR).

BACKGROUND: Annular dimensions, including cross-sectional area, perimeter and subsequently derived diameters, are subject to dynamic changes throughout the cardiac cycle. There is ongoing controversy as to whether perimeter measurement changes between systole and diastole are too small to impact on valve sizing. OBJECTIVES: To assess both the variability of aortic annular dimensions throughout the cardiac cycle across a range of sub-annular calcification using computed tomography (CT) and the impact of this variability on device size selection for balloon-expandable valves in a large, all-comer multi-center cohort. METHODS: ECG-gated CT data of 507 patients (mean 81 ± 7.5 years, 60.1% male) were analyzed in this retrospective, multicenter analysis. Aortic annulus dimensions were assessed on pre-specified systolic and diastolic phases by planimetry, yielding both area and perimeter. Contour smoothing was employed to avoid artificial increase in perimeter values by uneven contours. The extent of subannular calcification was graded semi-quantitatively and assessed in relation to the degree of annular dynamism. Hypothetical device sizing was undertaken to assess the impact of using systolic and diastolic measurements on valve selection. RESULTS: Mean annular dimensions were larger during systole than diastole (area: 474.4 ± 87.4 mm(2) vs. 438.3 ± 84.3 mm(2) or 8.23%, p < 0.001; perimeter: 78.5 ± 7.2 mm vs. 75.9 ± 7.2 mm or 3.36%, p < 0.001). The magnitude of annular area and perimeter change (systolic minus diastolic measurement) was greater among patients without calcification compared to patients with grade 3 calcification. Using diastolic rather than systolic data for device sizing resulted in a change of the recommended valve size in nearly half of patients for both annular area and perimeter. CONCLUSIONS: The systematic differences between systolic and diastolic annular measurements for cross-sectional area and perimeter have implications for device sizing with potential for valve under-sizing if diastolic annular dimensions are employed.

Safety and efficiency of outpatient versus emergency department-based coronary CT angiography for evaluation of patients with potential ischemic chest pain.

BACKGROUND: While coronary CT angiography (coronary CTA) may be comparable to standard care in diagnosing acute coronary syndrome (ACS) in emergency department (ED) chest pain patients, it has traditionally been obtained prior to ED discharge and a strategy of delayed outpatient coronary CTA following an ED visit has not been evaluated. OBJECTIVE: To investigate the safety of discharging stable ED patients and obtaining outpatient CCTA. METHODS: At two urban Canadian EDs, patients up to 65 years with chest pain but no findings indicating presence of ACS were further evaluated depending upon time of presentation: (1) ED-based coronary CTA during normal working hours, (2) or outpatient coronary CTA within 72 hours at other times. All data were collected prospectively. The primary outcome was the proportion of patients who had an outpatient coronary CTA ordered and had a predefined major adverse cardiac event (MACE) between ED discharge and outpatient CT; secondary outcome was the ED length of stay in both groups. RESULTS: From July 1, 2012 to June 30, 2014, we enrolled 521 consecutive patients: 350 with outpatient CT and 171 with ED-based CT. Demographics and risk factors were similar in both cohorts. No outpatient CT patients had a MACE prior to coronary CTA. (0.0%, 95% CI 0 to 0.9%) The median length of stay for ED-based evaluation was 6.6 hours (interquartile range 5.4 to 8.3 hours) while the outpatient group had a median length of stay of 7.0 hours (IQR 6.0 to 9.8 hours, n.s.). CONCLUSIONS: In ED chest pain patients with a low risk of ACS, performing coronary CTA as an outpatient may be a safe strategy.

The impact of calcium volume and distribution in aortic root injury related to balloon-expandable transcatheter aortic valve replacement.

BACKGROUND: A detailed assessment of calcium within the aortic root may provide important additional information regarding the risk of aortic root injury during transcatheter heart valve replacement (TAVR). OBJECTIVE: We sought to delineate the effect of calcium volume and distribution on aortic root injury during TAVR. METHODS: Thirty-three patients experiencing aortic root injury during TAVR with a balloon-expandable valve were compared with a control group of 153 consecutive TAVR patients without aortic root injury (as assessed by post-TAVR multidetector CT). Using commercial software to analyze contrast-enhanced pre-TAVR CT scans, calcium volume was determined in 3 regions: (1) the overall left ventricular outflow tract (LVOT), extending 10 mm down from the aortic annulus plane; (2) the upper LVOT, extending 2 mm down from the annulus plane; and (3) the aortic valve region. RESULTS: Calcium volumes in the upper LVOT (median, 29 vs 0 mm(3); P < .0001) and overall LVOT (median, 74 vs 3 mm(3); P = .0001) were higher in patients who experienced aortic root injury compared with the control group. Calcium in the aortic valve region did not differ between groups. Upper LVOT calcium volume was more predictive of aortic root injury than overall LVOT calcium volume (area under receiver operating curve [AUC], 0.78; 95% confidence interval, 0.69-0.86 vs AUC, 0.71; 95% confidence interval, 0.62-0.82; P = .010). Upper LVOT calcium below the noncoronary cusp was significantly more predictive of aortic root injury compared to calcium underneath the right coronary cusp or the left coronary cusp (AUC, 0.81 vs 0.68 vs 0.64). Prosthesis oversizing >20% (likelihood ratio test, P = .028) and redilatation (likelihood ratio test, P = .015) improved prediction of aortic root injury by upper LVOT calcium volume. CONCLUSION: Calcification of the LVOT, especially in the upper LVOT, located below the noncoronary cusp and extending from the annular region, is predictive of aortic root injury during TAVR with a balloon-expandable valve.

Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease.

Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

Diagnostic accuracy and discrimination of ischemia by fractional flow reserve CT using a clinical use rule: results from the Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography study.

BACKGROUND: Fractional flow reserve (FFR) is the gold standard for determining lesion-specific ischemia. Computed FFRCT derived from coronary CT angiography (coronary CTA) correlates well with invasive FFR and accurately differentiates between ischemia-producing and nonischemic lesions. The diagnostic performance of FFRCT when applied in a clinically relevant way to all vessels ≥ 2 mm in diameter stratified by sex and age has not been previously examined. METHODS: Two hundred fifty-two patients and 407 vessels underwent coronary CTA, FFRCT, invasive coronary angiography, and invasive FFR. FFRCT and FFR ≤ 0.80 were considered ischemic, whereas CT stenosis ≥ 50% was considered obstructive. The diagnostic performance of FFRCT was assessed following a prespecified clinical use rule which included all vessels ≥ 2 mm in diameter, not just those assessed by invasive FFR measurements. Stenoses <30% were assigned an FFR of 0.90, and stenoses >90% were assigned an FFR of 0.50. Diagnostic performance of FFRCT was stratified by vessel diameter, sex, and age. RESULTS: By FFR, ischemia was identified in 129 of 252 patients (51%) and in 151 of 407 vessels (31%). Mean age (± standard deviation) was 62.9 ± 9 years, and women were older (65.5 vs 61.9 years; P = .003). Per-patient diagnostic accuracy (83% vs 72%; P < .005) and specificity (54% vs 82%, P < .001) improved significantly after application of the clinical use tool. These were significantly improved over standard coronary CTA values before application of the clinical use rule. Discriminatory power of FFRCT also increased compared with baseline (area under the receiver operating characteristics curve [AUC]: 0.93 vs 0.81, P < .001). Diagnostic performance improved in both sexes with no significant differences between the sexes (AUC: 0.93 vs 0.90, P = .43). There were no differences in the discrimination of FFRCT after application of the clinical use rule when stratified by age ≥ 65 or <65 years (AUC: 0.95 vs 0.90, P = .10). CONCLUSIONS: The diagnostic accuracy and discriminatory power of FFRCT improve significantly after the application of a clinical use rule which includes all clinically relevant vessels >2 mm in diameter. FFRCT has similar diagnostic accuracy and discriminatory power for ischemia detection in men and women irrespective of age using a cut point of 65 years.

Right Ventricular Assessment in Adult Congenital Heart Disease Patients with Right Ventricle-to-Pulmonary Artery Conduits.

BACKGROUND: There is little data on right ventricular (RV) remodeling patterns in complex congenital heart disease (CHD) patients with right ventricle to pulmonary artery (PA) conduits, and novel RV imaging modalities have not been explored in this population. Knowledge of the RV remodeling process is an important first step to future understanding and tracking of the RV response to pressure and volume overload in this diverse population. Three-dimensional knowledge-based reconstruction (3DKBR) derived from two-dimensional transthoracic echocardiography (TTE-3DKBR) is a novel approach to RV assessment. The aims of this study were twofold: (1) to assess the feasibility and accuracy of 3DKBR in patients with CHD with RV to PA conduits and (2) to characterize the three-dimensional shape of the RV across the spectrum of CHD with RV to PA conduits. METHODS: Seventeen patients with tetralogy of Fallot, pulmonary atresia with ventricular septal defect, or truncus arteriosus (mean age, 29 ± 8 years; 24% women) and a conduit referred for cardiac magnetic resonance imaging (CMR) were prospectively recruited and underwent TTE-3DKBR. TTE-3DKBR echocardiographic image acquisition was performed using a standard ultrasound scanner linked to a Ventripoint Medical Systems unit. The surface RV volumetric reconstruction was performed by transmitting two-dimensional data points to an online database and comparing these with a lesion-specific catalog to derive the RV reconstruction. Parameters analyzed were end-diastolic volume (EDV), end-systolic volume, and ejection fraction. Intertechnique agreement was assessed using Pearson's correlation analysis, coefficients of variation, and Bland-Altman analysis. Three-dimensional shape comparisons of RV surface reconstructions were performed via automated validation testing of CMRs from 43 patients (mean age, 30 ± 8 years; 32% women) with RV to PA conduits (tetralogy of Fallot, n = 15; pulmonary atresia, n = 19; and truncus arteriosus, n = 9) distinct from patients in the 3DKBR comparison. RESULTS: There was good correlation and agreement between the two modalities: EDV, R = 0.77, P = .0004; end-systolic volume, R = 0.93, P < .0001; ejection fraction, R = 0.75, P < .0005. On Bland-Altman analyses, CMR EDV was slightly larger TTE-3DKBR, while EF was slightly higher by 3DKBR. Qualitative and quantitative assessment both demonstrated RV shape diversity based on surface reconstructions. CONCLUSION: This study demonstrates that TTE-3DKBR is an alternative technology that can be used to assess the RV in patients with complex CHD with a conduit. A novel method was used to compare RV shapes in this important population, and our results draw specific attention to the fact that the RV both within and outside diagnostic groups has very different unpredictable shapes and should not be treated equally. Our findings should set into motion future work focused on indices of RV shape and their impact on overall RV function and clinical outcomes, hence defining optimal timing of conduit revision, which at the current time is very unclear.

Dental pain among 10-15 year old children attending oral health promoting schools: A cross-sectional study.

INTRODUCTION: Dental pain is a major public health problem and one of the consequences of oral diseases which requires significant adjustments in life management leading to decreased quality of life. OBJECTIVE: To assess prevalence of dental pain and its impact on daily life and to explore its relationship with oral health behavior and clinical oral status among 10-15 year old school children attending oral health promoting schools. METHOD: This cross sectional study was conducted in 6 schools serving low -middle socio economic strata in Bangalore, India. A total of 1237 children were surveyed for history of dental pain during past 3 month. Participants who reported dental pain completed self-reported oral health behaviour and Child dental pain questionnaire. Clinical oral examination included assessment of dental caries, periodontal status. Data was analyzed using t - test, Chi-square test, ANOVA and Regression Analysis. RESULTS: Prevalence of dental pain was 15.6% (n = 194). Among children with pain, 17%, 43% and 40% reported mild, moderate and severe pain. Impact on daily activities was reported by 66%. Mean DMFT and DMFS was 1.80 and 2.11 Mean deft and defs was 2.47 and 3.41. Multiple logistic regression revealed that severity and impact of dental pain was associated with gender, frequency of tooth brushing, consumption of sweets and deciduous dental caries experience. CONCLUSION: Prevalence of Dental pain is associated with brushing behavior, consumption of sweets and deciduous dental caries experience, showing need for further attention to these conditions and a need to strengthen preventive and therapeutic dental services.

Reduced iodine load with CT coronary angiography using dual-energy imaging: a prospective randomized trial compared with standard coronary CT angiography.

BACKGROUND: There is concern regarding the administration of iodinated contrast to patients with impaired renal function because of the increased risk of contrast-induced nephropathy. OBJECTIVE: Evaluate image quality and feasibility of a protocol with a reduced volume of iodinated contrast and utilization of dual-energy coronary CT angiography (DECT) vs a standard iodinated contrast volume coronary CT angiography protocol (SCCTA). METHODS: A total of 102 consecutive patients were randomized to SCCTA (n = 53) or DECT with rapid kVp switching (n = 49). Eighty milliliters and 35 mL of iodinated contrast were administered in the SCCTA and DECT cohorts, respectively. Two readers measured signal and noise in the coronary arteries; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A 5-point signal/noise Likert scale was used to evaluate image quality; scores of <3 were nondiagnostic. Agreement was assessed through kappa analyses. RESULTS: Demographics and radiation dose were not significantly different; there was no difference in CNR between both cohorts (P = .95). A significant difference in SNR between the groups (P = .02) lost significance (P = .13) when adjusted for body mass index. The median Likert score was inferior for DECT for reader 1 (3.6 ± 0.6 vs 4.3 ± 0.6; P < .001) but not reader 2 (4.1 ± 0.6 vs 4.3 ± 0.5; P = .06). Agreement in diagnostic interpretability in the DECT and SCCTA groups was 91% (95% confidence interval, 86%-100%) and 96% (95% confidence interval, 90%-100%), respectively. CONCLUSION: DECT resulted in inferior image quality scores but demonstrated comparable SNR, CNR, and rate of diagnostic interpretability without a radiation dose penalty while allowing for >50% reduction in contrast volume compared with SCCTA.

Recent advances in thoracic x-ray computed tomography for pulmonary imaging.

The present article reviews recent advances in pulmonary computed tomography (CT) imaging, focusing on the application of dual-energy CT and the use of iterative reconstruction. Dual-energy CT has proven to be useful in the characterization of pulmonary blood pool in the setting of pulmonary embolism, characterization of diffuse lung parenchymal diseases, evaluation of thoracic malignancies and in imaging of lung ventilation using inhaled xenon. The benefits of iterative reconstruction have been largely derived from reduction of image noise compared with filtered backprojection reconstructions which, in turn, enables the use of lower radiation dose CT acquisition protocols without sacrificing image quality. Potential clinical applications of iterative reconstruction include imaging for pulmonary nodules and high-resolution pulmonary CT.