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Background: Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful. Aim: Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS. Method: A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming. Results: 39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies. Conclusions: The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation. Keywords: Implantable cardioverter-defibrillator (ICDs), Inappropriate therapies, Standardized programming

Summary: Alpha-1 adrenergic receptors (α1-ARs) play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, the authors administered dabuzalgron to mice treated with doxorubicin (DOX), a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to heart failure (HF). Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF. Key Words: alpha adrenergic receptors, anthracyclines, cardioprotection, catecholamines, heart failure

The authors used 52 nonfailing and failing human hearts to develop a simple, high throughput left ventricular myocardial slice model that is stable by ATP and viability assays for at least 3 days. The model supports studies of signaling, contraction, and viral transduction. They use the model to show for the first time that the alpha-1A-adrenergic receptor, which is present at very low abundance in the human myocardium, activates cardioprotective ERK with nanomolar EC50 in failing heart slices and stimulates a positive inotropic effect. This model should be useful for translational studies, to test whether molecules discovered in basic experiments are functional in the human heart.

The ultimate goal of world crop production is to produce more with less to meet the growing population demands. However, concentrating solely on increased quantity of production often impacts the quality of produce. Consumption of crops or foods that do not meet nutritional or dietary needs can lead to malnutrition. Malnutrition and undernutrition are prevalent in a significant portion of the population. Agronomic biofortification of minerals and vitamins in horticultural crops has emerged as a promising approach to address nutrient deficiencies and enhance the nutritional quality of food. Despite numerous research papers on plant nutrient biofortification, there remains a lack of systematic reviews that comprehensively summarize the latest knowledge on this topic. Herein we discuss different agronomic ways to biofortify several horticultural crops over the past decade. This systematic review aims to fill this gap by presenting various methodologies and comparing the outcomes of these methods in respect to nutrient content in plant parts. The review focuses on original research papers collected from various scientific databases including Scopus and Web of Knowledge, covering the most recent literature from the last ten years (2012-2022) for specific studies on the agronomic biofortification macronutrients, micronutrients, and vitamins in horticultural plants with exclusion of certain criteria such as 'genetic,' 'breeding,' and 'agronomic crops.' This review critically analyzes the current state of research and explores prospects for the future in this field. The biofortification of various minerals and vitamins, including calcium, selenium, iodine, B vitamins, vitamin A, and vitamin C, are examined, highlighting the achievements and limitations of existing studies. In conclusion, agronomic biofortification of minerals and vitamins in horticultural crops with further research offers a promising approach to address nutrient deficiencies and improve the nutritional quality of food., Competing Interests: Declaration of competing interest The authors declare that they have no known conflicting financial or personal interests that influenced the work reported in this paper., (Published by Elsevier B.V.)

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is currently diagnosed using a combination of clinical features, imaging, electrocardiography, and genetic investigations. An abnormal signal-averaged electrocardiogram (SAECG) is defined as a minor diagnostic criterion by the 2010 Task Force Criteria, but doubts remain about the value of this investigation., Objective: We evaluated the utility of the SAECG in diagnosing ARVC using the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry, a population representative registry of probands with ARVC and relatives, less influenced by referral bias., Methods: Probands with ARVC and family members from the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry underwent phenotype review. SAECG parameters were compared individually and in combination between those with varying degrees of ARVC severity and healthy controls (family members of probands with ARVC and unexplained sudden death, free of evidence of cardiac disease)., Results: A total of 196 patients with ARVC and 205 controls were included (mean age 44 ± 15 years; 186 of 401 men [46%]). SAECG abnormalities were seen in 83 of 205 controls (40%), 33 of 68 patients with ARVC and mild disease (51%), and 31 of 42 with severe disease (74%). The SAECG associated strongly with imaging abnormalities (major: odds ratio 3.0, 95% confidence interval 1.3-6.9; minor: odds ratio 3.5, 95% confidence interval 0.7-16.5) but not with other aspects of phenotype. Patients carrying pathogenic variants but with minimal phenotype had similar SAECGs to healthy controls (filtered QRS duration 111.2 ± 11.2 ms vs 111 ± 7.6 ms, P = .93; duration of low amplitude signals < 40 μV 32.3 ± 8.9 ms vs 34.2 ± 7.2 ms, P = .32; root mean square of the terminal 40 ms of the filtered QRS complex 43.1 ± 25.2 ms vs 38.2 ± 20.2 ms, P = .38)., Conclusion: The SAECG appears to be a surrogate marker for structural abnormalities seen on imaging in those with ARVC. Great caution is required in interpreting SAECG findings in those without other corroborating evidence of an ARVC phenotype., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Lyme disease is the most reported tick-borne illness in North America. Lyme carditis (LC) is an early-disseminated manifestation of Lyme disease, most commonly presenting as symptomatic high-degree atrioventricular block (AVB) which resolves with appropriate antibiotic therapy. However, long-term outcomes of treated LC have not previously been described. We present a series of 7 patients (median 28 years, 6 male) with serologically confirmed LC treated with a standard protocol developed at our center including antibiotics and pre-discharge stress test to assess AV node stability. At a mean follow-up of 20.8 months, all patients were asymptomatic, had resumed normal activities, and were free of conduction abnormalities. None required permanent pacing. Our study supports avoidance of permanent pacing for LC if conduction is stable at discharge., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Percutaneous endoscopic gastrostomy (PEG) placement is essential for the provision of enteral nutrition in select head and neck cancer (HNC) patients. Minimally invasive tube placement is facilitated through one of two techniques, push or pull, but there have been conflicting results regarding safety profiles of these procedures. The objectives of this study were to determine the association of PEG insertion technique with gastrostomy tube complications, including stomal metastases., Methods: A multi-institutional retrospective cohort study of patients with HNC undergoing PEG insertion by either the pull (gastroscope assisted) or push (fluoroscopy assisted) technique was performed. Tube-related complications included infection, dislodgement, deterioration, leak, and other. Adjusted analysis was performed via a multivariable logistic regression model., Results: 1,575 patients were included across three institutions. Tube-related complications occurred in 36% of patients, the most common being peristomal leak (13%) and infection (16%). The push technique (OR 2.66, 95% CI: 1.42-4.97), and the presence of T4 disease (OR 4.62, 95% CI: 1.58-13.51), were associated with a greater risk of developing any tube-related complication. Infection rates were similar between pull and push cohorts. All detected stoma metastases occurred with the pull technique, with an overall prevalence of 0.32% amongst the cohort., Conclusions: The push technique is associated with a greater risk of developing any tube-related complication, but the rate of stomal metastases may be higher with the pull technique. There is potential for quality improvement measures to improve tube-related complications associated with either technique., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The conduction delay and block that compose the critical isthmus of macroreentrant ventricular tachycardia (VT) is partly "functional" in that they only occur at faster cycle lengths. Close-coupled pacing stresses the myocardium's conduction capacity and may reveal late potentials (LPs) and fractionation. Interest has emerged in targeting this functional substrate., Objective: The purpose of this study was to assess the feasibility and efficacy of a functional substrate VT ablation strategy., Methods: Patients with scar-related VT undergoing their first ablation were recruited. A closely coupled extrastimulus (ventricular effective refractory period + 30 ms) was delivered at the right ventricular apex while mapping with a high-density catheter. Sites of functional impaired conduction exhibited increased electrogram duration due to LPs/fractionation. The time to last deflection was annotated on an electroanatomic map, readily identifying ablation targets., Results: A total of 40 patients were recruited (34 [85%] ischemic). Median procedure duration was 330 minutes (interquartile range [IQR] 300-369), and ablation time was 49.4 minutes (IQR 33.8-48.3). Median functional substrate area was 41.9 cm 2 (IQR 22.1-73.9). It was similarly distributed across bipolar voltage zones. Noninducibility was achieved in 34 of 40 patients (85%). Median follow-up was 711 days (IQR 255.5-972.8), during which 35 of 39 patients (89.7%) did not have VT recurrence, and 3 of 39 (7.5%) died. Antiarrhythmic drugs were continued in 53.8% (21/39)., Conclusion: Functional substrate ablation resulted in high rates of noninducibility and freedom from VT. Mapping times were increased considerably. Our findings add to the encouraging trend reported by related techniques. Randomized multicenter trials are warranted to assess this next phase of VT ablation., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Drivers at risk of sudden incapacitation from syncope pose a potential threat to themselves and to society. The purpose of this systematic review is to synthesize the risk of motor vehicle collisions (MVCs) for patients with a history of syncope., Methods: We systematically searched Medline (1946-2019) as well as Cinahl, Embase, Psychinfo, and the Transportation Research Information Documentation (1806-2017) for articles on MVCs and drivers with vasovagal syncope (VVS), arrhythmic syncope, or syncope not yet diagnosed (NYD). Quality ratings were assigned by team consensus., Results: Eleven studies of moderate quality were included (n = 42,972). Compared with the general populations of Canada, the United States, and the United Kingdom (0.49%-2.29% per driver-year), the prospective MVC risk was lower for VVS (0.0%-0.31% per driver-year; 3 studies; n = 782) and higher for arrhythmic syncope (1.9%-3.4% per driver-year; 2 studies; n = 730). The results were more variable for syncope NYD (0.0%-6.9% per driver-year prospectively; 6 studies; n = 41,460). Patients with syncope NYD had an almost 2-fold increased MVC risk in the largest study, although the smaller studies showed contradictory findings., Conclusions: VVS patients appear to be at very low risk for MVCs, supporting current guidelines which do not recommend driving suspension for these patients in most cases. Although the data for other forms of syncope are too limited for definitive conclusions and must be improved, arrhythmic syncope appears to be associated with nontrivial risk., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Antibiotics are widely prescribed for acute bronchitis in the UK. Herbal medicine could be used instead to provide symptom relief., Aim: To explore the views of patients and health professionals on using herbal medicine for acute bronchitis instead of antibiotics., Design and Setting: This was a nested qualitative study, conducted alongside a feasibility randomised clinical trial which ran from July 2018 to May 2019 in 20 GP practices in Wessex, UK., Method: We conducted telephone semi-structured interviews with patients and with health professionals. The interview data were transcribed and analysed thematically., Results: Overall, 40 interviews were conducted with 29 patients, six GPs and five nurses. While some patients believed antibiotics are more effective, most were aware of resistance and were keen to try an alternative, including herbal medicine. Several patients believed herbals would be "less intrusive" than antibiotics, whereas a few disliked the taste or experienced side-effects after taking a herbal. Professionals were concerned about potential interactions with conventional medicines. Many patients trusted herbals because of their long history of use, while some did not understand them. Availability of herbals without a prescription enables patients to use them for self-care, but their cost was a barrier for some. Many patients were willing to take a herbal if advised by their GP. Most GPs were happy to recommend a herbal, if endorsed by evidence-based guidelines., Conclusion: Many patients and health professionals would consider using herbal medicine for acute bronchitis, if based on trustworthy advice and evidence-based guidelines respectively., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: Bowel cancer screening home-testing kits are offered every two years to individuals aged 60-74 years in the United Kingdom (UK), with prisoners eligible for screening in the same way as the general population. There are currently major changes planned to the bowel cancer screening programme in England, with the transition to the single-sample faecal immunochemical test (FIT) and the planned lowering of the age limit from 60 to 50 years. In this project, we aimed to explore processes and beliefs around bowel cancer screening in an English prison., Study Design: This is a qualitative study., Methods: Semistructured qualitative interviews were conducted with eight prisoners and four staff members in a male prison in North West England. Data were analysed via thematic analysis., Results: Promoting and impeding factors to screening were identified. There was high willingness amongst prisoners to be screened for bowel cancer, with screening seen as important and having benefits for the individual and healthcare system. However, there was often low awareness of screening and there were psychological challenges associated with screening. Prison healthcare staff were widely respected and were a motivator to accept screening, with prisoners viewing prison as a good opportunity to access health care. Despite this, prison life was characterised by competing priorities, with security taking precedence, and screening sometimes a low priority for staff and prisoners. There were also considerable logistical challenges to delivering bowel cancer screening in a prison, and the system was not comparable with that in the community. Providing good-quality understandable information, though challenging, was key., Conclusions: This is the first project to explore entering the bowel cancer screening programme in UK prisons, and promoting and impeding factors to the take-up of screening have been identified. This information could be practically used by local commissioners and policymakers to aid the design of staff and prisoner interventions to maximise uptake of bowel cancer screening in prisons. As the planned changes to bowel cancer screening in England are likely to increase the number of eligible prisoners, this work could also be used to inform any service reconfiguration required to accommodate these changes., (Copyright © 2019 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI)., Methods: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016)., Results: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded., Conclusions: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Three dimensional (3D) surface imaging is a viable alternative to traditional body morphology measures, but the feasibility of using this technique with people with obesity has not been fully established. Therefore, the aim of this study was to investigate the validity, repeatability and acceptability of a consumer depth camera 3D surface imaging system in imaging people with obesity., Methods: The concurrent validity of the depth camera based system was investigated by comparing measures of mid-trunk volume to a gold-standard. The repeatability and acceptability of the depth camera system was assessed in people with obesity at a clinic., Results: There was evidence of a fixed systematic difference between the depth camera system and the gold standard but excellent correlation between volume estimates (r 2 =0.997), with little evidence of proportional bias. The depth camera system was highly repeatable - low typical error (0.192L), high intraclass correlation coefficient (>0.999) and low technical error of measurement (0.64%). Depth camera based 3D surface imaging was also acceptable to people with obesity., Conclusion: It is feasible (valid, repeatable and acceptable) to use a low cost, flexible 3D surface imaging system to monitor the body size and shape of people with obesity in a clinical setting., (Copyright © 2018 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Cardiac implantable electrical devices (CIEDs) are subject to advisories and complications that can result in morbidity and mortality for patients; there is currently no system in Canada to track these., Methods: This was a multicenter, prospective cohort study conducted at 5 centers to determine feasibility. Patients with a de novo high-voltage (HV) lead implantation were included and followed for a minimum of 1 year., Results: There were 611 leads enrolled into the registry over 18 months. The mean age was 62.4 ± 12.8 years; 144 (23.6%) women were enrolled. The indication for lead implantation was for primary prevention in 65.5%. There were 497 (82.1%) de novo devices (single chamber: 54.5%, dual chamber: 20.5%, cardiac resynchronization therapy [CRT] 25.0%); the remainder of the procedures was a system revision for either upgrade (8.1%) or lead revision (9.8%). The lead revision rate at 1 year was 3.4%, with the primary reason being lead dislodgements. Mortality rate was 3.8% at 1 year. The rate of any device-related complication was 2.0% at 30 days, with the highest rate in CRT implants (4.9%, P = 0.0105). At 1 year, the complication rate was 4.5%, with no significant difference among device types., Conclusions: This study demonstrates that device surveillance is feasible and highlights (1) the need for CIED surveillance to track device-related complications, (2) the scope of this should be larger, and (3) mandatory participation should be considered. This system could predict CIEDs that may be susceptible to higher than usual rates of failure, mitigating adverse outcomes in patients., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Despite improving algorithms, inappropriate shocks for supraventricular tachycardia (SVT) still occur in a significant number of patients with implantable cardioverter-defibrillators (ICDs). This makes the discovery of novel discriminators that use existing ICD hardware an attractive proposition., Objective: We hypothesized that the delay of activation onset from the device-detected, far-field electrogram (EGM) to the near-field, bipole EGM would allow the differentiation of ventricular tachycardias (VTs) from SVTs., Methods: Proof of principle was demonstrated by rapid pacing in the right atrium, right ventricle, and left ventricle in healthy patients undergoing atrial fibrillation ablation procedures (n = 17). Using real-life ICD recordings, the equivalent measurements were made in a derivation cohort (n = 26) and cutoff predictive values obtained. Finally, the selected values were validated in a separate group of recordings (n = 82)., Results: In healthy patients, significant differences in the far-field to near-field EGM activation onsets were observed between right atrial (14.7 ± 2.7 ms), right ventricular (36.3 ± 8 ms), and left ventricular (57.8 ± 10.3 ms; P < .001) pacing. In the derivation ICD cohort, the median far-field to near-field onset delay was significantly shorter in SVT (24.5 ms; interquartile range, 15.3-47.5 ms) than in VT (118.5 ms; interquartile range, 102.5-131.5 ms) (P < .001). Using a cutoff of 100 ms in the validation cohort, SVT was successfully discriminated from VT with a sensitivity and specificity of 88% and a negative predictive value of 94.2%., Conclusion: The delay between far-field and near-field EGMs offers a potential new discrimination tool to reduce inappropriate ICD therapies and aid interpretation of single-lead device tracings., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Trisomy 18 (T18) is a genetic disorder with cardiac lesions in up to 90% of patients. Cardiac surgery is not frequently offered because of the overall poor prognosis, although this has recently been challenged. Our study aimed to explore the practices and attitudes of Canadian pediatric cardiologists managing T18 patients. We administered a survey to pediatric cardiologists attending the Canadian Cardiovascular Congress, Canadian Pediatric Cardiology Association Business Meeting. There were 30 respondents. Most (67%) supported comfort care for affected patients with a heart lesion. None supported palliative surgery for those with complex heart lesions. Of 30 respondents, 16 (53%) counsel families prenatally, and none would present the option of a single ventricle surgical track for complex heart disease. In a hypothetical situation in which their own child was born with T18, 67% would choose comfort care with medical treatment of heart failure, and none would choose palliative surgery. Being a parent was associated with a higher likelihood of choosing termination (14 of 20 vs 6 of 9; P = 0.046) or comfort care (14 of 20 vs 6 of 9; P = 0.036). Qualitative data suggest support for comfort care, while recognizing the need for individualization and shared decision-making, within the context of institution-specific policies. Canadian pediatric cardiologists surveyed support comfort care and medical treatment but not surgical treatment for T18 patients with cardiac lesions. They place primacy on nonmaleficence, yet also recognize the emerging need for individualized shared decision-making in these cases., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Increasing evidence suggests an inverse association between cadmium (Cd) and size at birth, potentially greatest among female neonates. We evaluated whether greater maternal body burden of Cd is associated with reduced neonatal anthropometry (birthweight, birth length, head circumference, and ponderal index) and assessed whether these associations differ by infant sex. The analytic sample for the present study (n=396) was derived from a subcohort of 750 women randomly drawn from among all participants (N=4344) in the Omega Study, a prospective pregnancy cohort. Creatinine-corrected Cd in maternal clean-catch spot urine samples (U-Cd) was quantified by inductively coupled plasma mass spectrometry. Continuous log2-transformed Cd (log2-Cd) and U-Cd tertiles (low<0.29μg/g creatinine, middle 0.29-0.42μg/g creatinine, high≥0.43μg/g creatinine) were used in multivariable linear regression models. Females had reduced birth length with greater U-Cd tertile, whereas males birth length marginally increased [β(95% CI) females: low=reference, middle=-0.59cm (-1.37, 0.19), high=-0.83cm (-1.69, 0.02), p-trend=0.08; males: low=reference, middle=0.18cm (-0.59, 0.95), high=0.78cm (-0.04, 1.60), p-trend=0.07; p for interaction=0.03]. The log2-Cd by infant sex interaction was statistically significant for ponderal index [p=0.003; β(95% CI): female=0.25kg/m(3) (-0.20, 0.70); male=-0.63kg/m(3) (-1.01, -0.24)] and birth length [p<0.001; β(95% CI): female=-0.47cm (-0.74, -0.20), male=0.32cm (0.00, 0.65)]. Our findings suggest potential sex-specific reversal of Cd's associations on birth length and contribute to the evidence suggesting Cd impairs fetal growth., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Identification and appropriate management of patients with atrial fibrillation (AF) is critical to mitigate the consequences of the disease. We sought to assess the frequency and pattern of the emergency department (ED) use by patients who presented with AF and/or atrial flutter (AFL) in a midsized Canadian hospital., Methods: We conducted a retrospective cohort analysis of patients who presented to the ED with AF and/or AFL during the calendar years 2010-2012. Patients were identified using the MUSE (General Electric Healthcare, Bucks, United Kingdom) electrocardiogram database and matched with the National Ambulatory Care Reporting System and Discharge Abstract Database up to and including December 31, 2013, a follow-up period of 12 months. The number of presentations and time between visits was assessed. Admissions were identified and lengths of stay and reason for admission were recorded., Results: We identified 1361 patients who represented a total of 4783 visits to the ED, a mean of 2.8 ± 2.9 visits per patient with 949 (69.7%) who returned for a subsequent ED visit in the subsequent 12 months. Mean time between base and subsequent visits was 136.8 ± 114.2 days. ED visits generated 1462 admissions (63.0% at repeat ED visits); mean length of stay was 9.7 ± 16.0 days. Stroke or transient ischemic attack accounted for 80 return visits and 8 deaths in 77 patients, 74% of whom with subtherapeutic or no anticoagulation medication., Conclusions: Presentation to the ED with AF and/or AFL, either as a primary reason for consultation or as a secondary diagnosis, was associated with a high risk of subsequent re-presentation and hospital admission., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: The association between smoking-induced chronic obstructive pulmonary disease (COPD) and lung cancer (LC) is well documented. Recent genome-wide association studies (GWAS) have identified 28 susceptibility loci for LC, 10 for COPD, 32 for smoking behavior, and 63 for pulmonary function, totaling 107 nonoverlapping loci. Given that common variants have been found to be associated with LC in genome-wide association studies, exome sequencing of these high-priority regions has great potential to identify novel rare causal variants., Methods: To search for disease-causing rare germline mutations, we used a variation of the extreme phenotype approach to select 48 patients with sporadic LC who reported histories of heavy smoking-37 of whom also exhibited carefully documented severe COPD (in whom smoking is considered the overwhelming determinant)-and 54 unique familial LC cases from families with at least three first-degree relatives with LC (who are likely enriched for genomic effects)., Results: By focusing on exome profiles of the 107 target loci, we identified two key rare mutations. A heterozygous p.Arg696Cys variant in the coiled-coil domain containing 147 (CCDC147) gene at 10q25.1 was identified in one sporadic and two familial cases. The minor allele frequency (MAF) of this variant in the 1000 Genomes database is 0.0026. The p.Val26Met variant in the dopamine β-hydroxylase (DBH) gene at 9q34.2 was identified in two sporadic cases; the minor allele frequency of this mutation is 0.0034 according to the 1000 Genomes database. We also observed three suggestive rare mutations on 15q25.1: iron-responsive element binding protein neuronal 2 (IREB2); cholinergic receptor, nicotinic, alpha 5 (neuronal) (CHRNA5); and cholinergic receptor, nicotinic, beta 4 (CHRNB4)., Conclusions: Our results demonstrated highly disruptive risk-conferring CCDC147 and DBH mutations., (Copyright © 2015 International Association for the Study of Lung Cancer. All rights reserved.)

Background: Varenicline is an effective pharmacotherapy to aid smoking cessation. However, its use is limited by continuing concerns about possible associated risks of serious adverse cardiovascular and neuropsychiatric events. The aim of this study was to investigate whether use of varenicline is associated with such events., Methods: In this retrospective cohort study, we used data from patients included in the validated QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients aged 18-100 years (registered for longer than 12 months before data extraction) who received a prescription of nicotine replacement treatment (NRT; reference group), bupropion, or varenicline. We excluded patients if they had used one of the drugs during the 12 months before the start date of the study, had received a prescription of a combination of these drugs during the follow-up period, or were temporary residents. We followed patients up for 6 months to compare incident cardiovascular (ischaemic heart disease, cerebral infarction, heart failure, peripheral vascular disease, and cardiac arrhythmia) and neuropsychiatric (depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders (primary outcomes)., Findings: We identified 164,766 patients who received a prescription (106,759 for nicotine replacement treatment; 6557 for bupropion; 51,450 for varenicline) between Jan 1, 2007, and June 30, 2012. Neither bupropion nor varenicline showed an increased risk of any cardiovascular or neuropsychiatric event compared with NRT (all hazard ratios [HRs] less than 1. Varenicline was associated with a significantly reduced risk of ischaemic heart disease (HR 0.80 [95%CI 0.72-0.87]), cerebral infarction (0.62 [0.52-0.73]), heart failure (0.61 [0.45-0.83]), arrhythmia (0.73 [0.60-0.88]), depression (0.66 [0.63-0.69]), and self-harm (0.56 [0.46-0.68])., Interpretation: Varenicline does not seem to be associated with an increased risk of documented cardiovascular events, depression, or self-harm when compared with NRT. Adverse events that do not come to attention of general practitioners cannot be excluded. These findings suggest an opportunity for physicians to prescribe varenicline more broadly, even for patients with comorbidities, thereby helping more smokers to quit successfully than do at present., Funding: Egton Medical Information Systems, University of Nottingham, Ministry of Innovation, Science and Research of the German Federal State of North Rhine-Westphalia, Cancer Research UK, Medical Research Council, Commonwealth Fund., (Copyright © 2015 Kotz et al. Open Access article published under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Bipolar voltage mapping is useful to delineate post-infarct endocardial scar and guide ablation of ischemic VT. The role of unipolar mapping is not yet well defined. The aim of this study was to assess the correlation between electrophysiological findings in patients with ischemic VT and unipolar voltage maps using different cut-offs., Methods: We included 10 patients (age 67 ± 7 years, ejection fraction 33 ± 10%) with ischemic cardiomyopathy undergoing catheter ablation for recurrent VT. Patients with right-sided VTs were excluded. In all patients a unipolar voltage map was constructed during right ventricular pacing. Ablation was performed guided by activation and entrainment mapping in hemodynamically stable VTs and by pace-mapping and abnormal (late/split/fractionated) potentials in unstable VTs. Subsequently, the unipolar voltage maps were analyzed off-line using cutoffs from 1.0 to 8.0 mV and correlated with the isthmus sites., Results: A total of 17 sustained VTs were induced in the 10 patients and non-inducibility of the clinical VT was achieved in 90% of patients by endocardial ablation. The optimal cutoff was 5.0 mV. By using this value, the mean surface area of abnormal unipolar voltage was 43.8% and 95% of all VT isthmuses were located within the area of scar, as well as 81% of abnormal potentials. In addition, 71% of isthmuses were at less than 1cm from the scar border., Conclusion: Unipolar voltage mapping showed good correlation with areas of isthmuses and abnormal electrograms in patients with scar-related VT, with a cut-off of 5.0 mV allowing the best delineation of ablation targets., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Organic thiols (R-SH) are known to react and form complexes with some toxic soft metals such as mercury (Hg) in both biotic and abiotic systems. However, a clear understanding of these interactions is currently limited because quantifying thiols in environmental matrices is difficult due to their low abundance, susceptibility to oxidation, and measurement interference by non-thiol compounds in samples. Here, we report a fluorescence-labeling method using a maleimide containing probe, ThioGlo-1 (TG-1), to determine total thiols directly on bacterial cells and natural organic matter (NOM). We systematically evaluated the optimal thiol labeling conditions and interference from organic compounds such as disulfide, methionine, thiourea, and amine, and inorganic ions such as Na(+), K(+), Ca(2+), Fe(2+), Cl(-), SO4(2-), HCO3(-), and SCN(-), and found that the method is highly sensitive and selective. Only relatively high levels of sulfide (S(2-)) and sulfite (SO3(2-)) significantly interfere with the thiol analysis. The method was successful in determining thiols in a bacterium Geobacter sulfurreducens PCA and its mutants in a phosphate buffered saline solution. The measured value of ~2.1 × 10(4) thiols cell(-1) (or ~0.07 µmol g(-1) wet cells) is in good agreement with that observed during reactions between Hg and PCA cells. Using the standard addition, we determined the total thiols of two reference NOM samples, the reduced Elliot soil humic acid and Suwanee River NOM, to be 3.6 and 0.7 µmol g(-1), respectively, consistent with those obtained based on their reactions with Hg., (© 2013 Published by Elsevier B.V.)

Background: A community around a chemical plant was exposed to perfluorooctanoic acid (PFOA) for over 50 years, primarily through drinking water. One cohort study of PFOA-exposed workers found a positive trend with stroke mortality. Other, cross-sectional, studies have found positive associations between serum PFOA and risk factors for stroke, including cholesterol, uric acid, and hypertension., Objectives: We examined the relation between PFOA exposure and incident strokes (including transient ischemic attacks) in community members, including plant workers., Methods: Participants completed surveys in 2008-2011 regarding medical history, health-related behaviors, and demographics. Cox proportional hazards models were used to compare the hazard of stroke in relation to time-varying estimated cumulative PFOA serum levels, adjusting for confounders., Results: Of 32,254 survey participants with exposure estimates, 1596 self-reported stroke, of whom 919 had their self-report validated by medical records review. After excluding subjects with strokes before age 20 and subjects born before 1920 or with missing covariate data, 825 cases remained. Compared with the lowest quintile of cumulative exposure, subsequent quintiles in the retrospective analysis had hazard ratios of 1.39 [95% confidence interval, 1.11-1.76], 1.36 [1.08-1.71], 1.45 [1.15-1.82], and 1.13 [0.90-1.44]. Tests for trend with linear or log-transformed cumulative dose were not significant (p=0.52 and 0.59, respectively). Neither an analysis with a 5-year lag, nor prospective analyses restricted to 2005-2011 (302 cases) found positive trends (p=0.44, positive trend; p=0.28, negative trend, respectively)., Conclusions: Overall, our data provide only modest evidence of an association between PFOA and stroke incidence., (© 2013 Published by Elsevier Inc.)

Sleep disruption in childhood is associated with clearly defined deficits in neurocognition and behaviour. Childhood eczema is also a potent cause of sleep disruption though it is unknown whether it too results in neurocognitive deficits. To test this hypothesis, neurocognitive (WISC-IV), parental-reported sleep quality (Sleep Disturbance Scale of Children (SDSC)) and overnight polysomnographic (PSG) data were collected in 21 children with eczema and 20 healthy controls (age range 6-16 years). Children with eczema had worse sleep quality on both PSG (notably increased nocturnal wakefulness, a higher number of stage shifts and a longer latency to REM onset) and parental report. In addition, they demonstrated significant neurocognitive deficits (especially verbal comprehension, perceptual reasoning and to a lesser extent working memory) with a composite Full Scale IQ 16 points lower than controls. Parental reported sleep problems but not PSG parameters were correlated with reduced neurocognitive performance. However, hierarchical regression analyses revealed that eczema status was predictive while sleep fragmentation (parental or PSG) was not predictive of neurocognitive performance. As this is the first study to systematically examine neurocognitive functioning in children with eczema and given the finding of significant deficits it merits replication especially given the prevalence of the condition. The unanswered question is whether these cognitive deficits normalise with effective eczema treatment and if this is mediated by improvements in sleep architecture., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

The FDI World Dental Federation has defined a strategy for the development of oral health in Africa during the "African Summit" held in Cape Town, South Africa. The summit gathered presidents from 16 African National Dental Associations, FDI stakeholders, the World Health Organisation and government delegates. The outcomes of this summit were stated in a Declaration, defining the functional principles of the African strategy as three priorities: To establish and reinforce the credibility of NDAs To acquire and develop leadership and management skills Effective peer-to-peer exchange of information., (© 2013 FDI World Dental Federation.)

Background: A unique form of lead failure has been described in the Riata (8-F) and Riata ST (7-F) silicone defibrillation lead degradation of the outer insulation, resulting in the externalization of conductor cables., Objective: To assess rates of lead revision due to lead failure in Riata leads affected by the Riata advisory., Methods: Nineteen implantable cardioverter-defibrillator implant and follow-up centers were surveyed., Results: As of March 1, 2012, there were 5043 known affected leads implanted in Canada. Data on 4358 (86.4%) leads were obtained; 65.3% of these were Riata (8-F) and 32.4% were Riata ST (7-F) leads. The median time from implant to last follow-up was 5 years. Electrical abnormalities were reported in 4.6% of the affected leads; 8.0% of these were found to have concomitant radiographic evidence of externalization. The rate of electrical failure was higher in the 8-F (5.2%) vs 7-F (3.3%) leads (P = .007). Oversensing with or without inappropriate shocks was reported in 39.8% of the leads with confirmed failure. Abnormally high or low impedance values (29.9%) and elevated pacing capture thresholds (43.8%) were frequently reported. One death (0.5%) attributed to lead failure was reported. Among the leads that were replaced, 21% were extracted. Two major complications (1.0%) were attributed to extraction of these leads., Conclusions: The overall rate of lead failure in the Riata (8-F) and Riata ST (7-F) leads is higher than previously reported by using passive surveillance data. The impact of recent advisories related to these leads is not yet apparent., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

There are more than 200,000 Canadians living with permanent pacemakers or implantable defibrillators, many of whom will require surgery or invasive procedures each year. They face potential hazards when undergoing surgery; however, with appropriate planning and education of operating room personnel, adverse device-related outcomes should be rare. This joint position statement from the Canadian Cardiovascular Society (CCS) and the Canadian Anesthesiologists' Society (CAS) has been developed as an accessible reference for physicians and surgeons, providing an overview of the key issues for the preoperative, intraoperative, and postoperative care of these patients. The document summarizes the limited published literature in this field, but for most issues, relies heavily on the experience of the cardiologists and anesthesiologists who contributed to this work. This position statement outlines how to obtain information about an individual's type of pacemaker or implantable defibrillator and its programming. It also stresses the importance of determining if a patient is highly pacemaker-dependent and proposes a simple approach for nonelective evaluation of dependency. Although the document provides a comprehensive list of the intraoperative issues facing these patients, there is a focus on electromagnetic interference resulting from electrocautery and practical guidance is given regarding the characteristics of surgery, electrocautery, pacemakers, and defibrillators which are most likely to lead to interference. The document stresses the importance of preoperative consultation and planning to minimize complications. It reviews the relative merits of intraoperative magnet use vs reprogramming of devices and gives examples of situations where one or the other approach is preferable., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Reports of clinical rickets are particularly evident in minority infants and children, but only limited analyses of vitamin D are available in this demographic group., Objective: We sought to characterize circulating 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and their determinants, including circulating parathyroid hormone (PTH), total alkaline phosphatase activity (ALP), calcium, and phosphorus, in minority infants and children., Design: We obtained demographic information and blood samples for measurement of PTH, ALP, 25(OH)D, and 1,25(OH)(2)D in >750 6-mo- to 3-y-old children. Dietary intake data were obtained and analyzed., Results: The mean (±SD) 25(OH)D concentration was 66 ± 22 nmol/L (26.3 ± 8.7 ng/dL). A total of 15% of children had 25(OH)D concentrations less than the recommended target threshold of 50 nmol/L. Combined elevations of PTH and ALP occurred in only 2.5% of children. Determinants of 25(OH)D included vitamin D intake, age (decreasing with age), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), formula use (higher intakes), season (greater concentrations in the summer and fall than in the winter and spring), and, inversely, PTH. The mean 1,25(OH)(2)D concentration was 158 ± 58 pmol/L (60.6 ± 22.5 pg/mL), which was consistent with a reference range of 41-274 pmol/L or 15.7-105.5 pg/mL. Determinants for 1,25(OH)(2)D were age (decreasing with age), sex (greater concentrations in girls than in boys), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), and, inversely, serum calcium and phosphorus., Conclusions: Although 15% of subjects were vitamin D insufficient, only 2.5% of subjects had elevations of both PTH and ALP. The greater 25(OH)D concentrations observed with formula use confirm that dietary vitamin D fortification is effective in this demographic group. Circulating 1,25(OH)(2)D is higher in infants than in older children and adults and, in contrast to 25(OH)D, is not directly correlated with nutrient intakes.

Little information is available regarding the fate of Listeria monocytogenes during freezing, thawing and home storage of frankfurters even though recent surveys show that consumers regularly store unopened packages in home freezers. This study examined the effects of antimicrobials, refrigerated storage, freezing, thawing method, and post-thawing storage (7 degrees C) on L. monocytogenes on frankfurters. Inoculated (2.1 log CFU/cm(2)) frankfurters formulated without (control) or with antimicrobials (1.5% potassium lactate plus 0.1% sodium diacetate) were vacuum-packaged, stored at 4 degrees C for 6 or 30 d and then frozen (-15 degrees C) for 10, 30, or 50 d. Packages were thawed under refrigeration (7 degrees C, 24 h), on a countertop (23 +/- 2 degrees C, 8 h), or in a microwave oven (2450 MHz, 1100 watts, 220 s followed by 120 s holding), and then stored aerobically (7 degrees C) for 14 d. Bacterial populations were enumerated on PALCAM agar and tryptic soy agar plus 0.6% yeast extract. Antimicrobials completely inhibited (p < 0.05) growth of L. monocytogenes at 4 degrees C for 30 d under vacuum-packaged conditions, and during post-thawing aerobic storage at 7 degrees C for 14 d. Different intervals between inoculation and freezing (6 or 30 d) resulted in different pathogen levels on control frankfurters (2.1 or 3.9 log CFU/cm(2), respectively), while freezing reduced counts by <1.0 log CFU/cm(2). Thawing treatments had little effect on L. monocytogenes populations (<0.5 log CFU/cm(2)), and post-thawing fate of L. monocytogenes was not influenced by freezing or by thawing method. Pathogen counts on control samples increased by 1.5 log CFU/cm(2) at d-7 of aerobic storage, and reached 5.6 log CFU/cm(2) at d-14. As indicated by these results, consumers should freeze frankfurters immediately after purchase, and discard frankfurters formulated without antimicrobials within 3 d of thawing and/or opening.

This study investigated metaphor comprehension in the broader context of task-difference effects and manipulation of processing difficulty. We predicted that right hemisphere recruitment would show greater specificity to processing difficulty rather than metaphor comprehension. Previous metaphor processing studies have established that the left inferior frontal gyrus strongly correlates with metaphor comprehension but there has been controversy about whether right hemisphere (RH) involvement is specific for metaphor comprehension. Functional MRI data were recorded from healthy subjects who read novel metaphors, conventional metaphors, definition-like sentences, or literal sentences. We investigated metaphor processing in contexts where semantic judgment or imagery modulates linguistic judgment. Our findings support the position that the type of task rather than figurative language processing per se modulates the left inferior gyrus (LIFG). RH involvement was more influenced by processing difficulty and less by the novelty or figurativity of linguistic expressions. Our results suggest that figurative language processing depends upon the effects of task-type and processing difficulty on imaging results.

Background: Implantable cardioverter defibrillator (ICD) generator advisories present management dilemmas for physicians regarding competing risks of ICD failure and replacement-related complications. There is currently a paucity of long-term data concerning the complications associated with advisory ICD replacement., Objective: In a large multicenter advisory ICD generator replacement cohort followed for 12 months, we aimed to assess replacement-related complications by performing a case-control determination of complication risk factors to identify characteristics that could assist with advisory ICD replacement decision making., Methods: Twelve large ICD implanting centers reviewed the 1-year follow-up outcome of advisory ICDs replaced between October 2004 and October 2005. The complication cohort was characterized and compared in a nested case-control analysis with age- and gender-matched controls without complications from the same replacement population., Results: At the 12 participating institutions, 451 of 2635 advisory ICD devices were replaced (17.1%). Over 355 +/- 204 days of follow-up, there were 41 (9.1%) complications; 27 (5.9%) required reoperation and included two deaths. There were 14 minor complications (3.1%). Multivariate analysis demonstrated that the number of previous pocket procedures was associated with an increase in complications and that combined consultant and fellow operators was associated with a decrease in complications compared with a single operator alone., Conclusions: Complications from advisory ICD generator replacement are frequent and include infection and, rarely, death. The risk of replacement is increased in patients with multiple previous pocket procedures.

Background: Defibrillation threshold (DFT) testing has traditionally been a routine part of implantable cardioverter-defibrillator (ICD) implantation, despite a lack of compelling evidence that it predicts or improves outcomes. In the past, when devices were much less reliable, DFT testing seemed prudent; however, modern ICD systems have such a high rate of successful defibrillation that many electrophysiologists now question whether DFT testing is still worthwhile, particularly since DFT testing may now be the highest acute risk component of ICD implantation., Objective: The purpose of this study was to systematically document complications directly attributable to intraoperative DFT testing., Methods: We obtained data on DFT-related complications from all 21 adult ICD implant centers in Canada, covering the period from January 1, 2000, to September 30, 2006., Results: There were a total of 19,067 ICD implants in Canada during the study period. There were three DFT testing-related deaths, five DFT testing-related strokes, and 27 episodes that required prolonged resuscitation. Two patients had significant clinical sequelae after prolonged resuscitation., Conclusions: The risk of severe complications from intraoperative DFT testing appears small, even allowing for the underestimation of its true rate with the current study methodology. These slight but measurable risks must be considered when assessing the risk-benefit ratio of the procedure. Additional data from ongoing prospective ICD registries and/or clinical trials are required.

The transcription factor NF-kappaB plays a central role in regulating inflammation and apoptosis, making it a compelling target for drug development. We identified a small molecule inhibitor (ML120B) that specifically inhibits IKKbeta, an Ikappa-B kinase that regulates NF-kappaB. IKKbeta and NF-kappaB are required in vivo for prevention of TNFalpha-mediated apoptosis. ML120B sensitized mouse bone marrow progenitors and granulocytes, but not mature B cells to TNFalpha killing in vitro, and induced apoptosis in vivo in the bone marrow and spleen within 6 hours of a single oral dose. In vivo inhibition of IKKbeta with ML120B resulted in depletion of thymocytes and B cells in all stages of development in the bone marrow but did not deplete granulocytes. TNF receptor-deficient mouse thymocytes and B cells were resistant to ML120B-induced depletion in vivo. Surprisingly, surviving bone marrow granulocytes expressed TNFR1 and TNFR2 after dosing in vivo with ML120B. Our results show that inhibition of IKKbeta with a small molecule in vivo leads to rapid TNF-dependent depletion of T and B cells. This observation has several implications for potential use of IKKbeta inhibitors for the treatment of inflammatory disease and cancer.

In 2005, an unprecedented number of recalls were issued on pacemakers and implantable cardioverter defibrillators. While recalls in the cardiac rhythm device industry are not new, the sheer magnitude of potentially affected patients in 2005 led to a great deal of concern, frustration, and even anger. Physicians have, in many instances, been uncertain when (or if) to recommend device replacement in an environment where the magnitude of the risk and the potential consequences of device failure have not been well defined in a timely way. Doctors and patients are now calling for reform of postmarket analysis and reporting mechanisms. The present article provides a uniquely Canadian perspective on this international issue. Potential solutions include the development of a set of realistic and common expectations, a restoration of confidence in postmarket analysis and reporting mechanisms, increased data transparency, and an increased role for patient and physician groups.

Background: The discrimination of side population (SP) cells is a useful flow cytometric tool for the study of putative stem cells in many tissue types. Previous studies on murine bone marrow (BM) SP cells and concurrent surface immunophenotyping provide a good model for comparing Hoechst bivariate profiles. Here we compare the results of SP cells from the same specimens generated on three different instruments., Methods: Concurrent SP analysis and immunophenotyping was performed on murine BM. The data acquisition was performed on a DakoCytomation MoFlo, a Becton Dickinson LSR and a Becton Dickinson FACSAria to compare the ability of each instrument to discriminate putative stem cells. Further experiments examined the effect of apoptotic changes, assessed by Annexin V binding, and the presence of nucleated erythroid precursors on the Hoechst profile., Results: Identifiable and equivalent side populations were generated on all three instruments despite differences in appearance of the Hoechst profiles. Differences in laser type, collection filter combinations and the presence of erythroid precursors and apoptotic cells all contributed to this effect., Conclusions: In our hands, murine SP cells with the expected surface immunophenotype can be identified on a MoFlo, LSR and a factory standard FACSAria.