Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humans.

Since the inception of the IARC Monographs Programme in the early 1970s, this Programme has developed 119 Monograph Volumes on more than 1000 agents for which there exists some evidence of cancer risk to humans. Of these, 120 agents were found to meet the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs, compiled in 2008-2009 and published in 2012, provided a review and update of the 107 Group 1 agents identified as of 2009. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. The Group I agents reviewed in Volume 100, as well as five additional Group 1 agents defined in subsequent Volumes of the Monographs, were used to assess the degree of concordance between sites where tumors originate in humans and experimental animals including mice, rats, hamsters, dogs, and non-human primates using an anatomically based tumor nomenclature system, representing 39 tumor sites and 14 organ and tissue systems. This evaluation identified 91 Group 1 agents with sufficient evidence (82 agents) or limited evidence (9 agents) of carcinogenicity in animals. The most common tumors observed in both humans and animals were those of the respiratory system including larynx, lung, and lower respiratory tract. In humans, respiratory system tumors were noted for 31 of the 111 distinct Group 1 carcinogens identified up to and including Volume 109 of the IARC Monographs, comprising predominantly 14 chemical agents and related occupations in category VI; seven arsenic, metals, fibers, and dusts in category III, and five personal habits and indoor combustions in category V. Subsequent to respiratory system tumors, those in lymphoid and hematopoietic tissues (26 agents), the urothelium (18 agents), and the upper aerodigestive tract (16 agents) were most often seen in humans, while tumors in digestive organs (19 agents), skin (18 agents), and connective tissues (17 agents) were frequently seen in animals. Exposures to radiation, particularly X- and γ-radiation, and tobacco smoke were associated with tumors at multiple sites in humans. Although the IARC Monographs did not emphasize tumor site concordance between animals and humans, substantial concordance was detected for several organ and tissue systems, even under the stringent criteria for sufficient evidence of carcinogenicity used by IARC. Of the 60 agents for which at least one tumor site was identified in both humans and animals, 52 (87%) exhibited tumors in at least one of the same organ and tissue systems in humans and animals. It should be noted that some caution is needed in interpreting concordance at sites where sample size is particularly small. Although perfect (100%) concordance was noted for agents that induce tumors of the mesothelium, only two Group 1 agents that met the criteria for inclusion in the concordance analysis caused tumors at this site. Although the present analysis demonstrates good concordance between animals and humans for many, but not all, tumor sites, limitations of available data may result in underestimation of concordance.

Interatrial block and interatrial septal thickness in patients with paroxysmal atrial fibrillation undergoing catheter ablation: Long-term follow-up study.

BACKGROUND: Interatrial block (IAB) is a strong predictor of recurrence of atrial fibrillation (AF). IAB is a conduction delay through the Bachman region, which is located in the upper region of the interatrial space. During IAB, the impulse travels from the right atrium to the interatrial septum (IAS) and coronary sinus to finally reach the left atrium in a caudocranial direction. No relation between the presence of IAB and IAS thickness has been established yet. OBJECTIVE: To determine whether a correlation exists between the degree of IAB and the thickness of the IAS and to determine whether IAS thickness predicts AF recurrence. METHODS: Sixty-two patients with diagnosis of paroxysmal AF undergoing catheter ablation were enrolled. IAB was defined as P-wave duration ≥120 ms. IAS thickness was measured by cardiac computed tomography. RESULTS: Among 62 patients with paroxysmal AF, 45 patients (72%) were diagnosed with IAB. Advanced IAB was diagnosed in 24 patients (39%). Forty-seven patients were male. During a mean follow-up period of 49.8 ± 22 months (range 12-60 months), 32 patients (51%) developed AF recurrence. IAS thickness was similar in patients with and without IAB (4.5 ± 2.0 mm vs. 4.0 ± 1.4 mm; p = .45) and did not predict AF. Left atrial size was significantly enlarged in patients with IAB (40.9 ± 5.7 mm vs. 37.2 ± 4.0 mm; p = .03). Advanced IAB predicted AF recurrence after the ablation (OR: 3.34, CI: 1.12-9.93; p = .03). CONCLUSIONS: IAS thickness was not significantly correlated to IAB and did not predict AF recurrence. IAB as previously demonstrated was an independent predictor of AF recurrence.

The atrial T wave: The elusive electrocardiographic wave exposed by a case of shifting atrial pacemaker.

The atrial T wave (Ta wave) is the body surface manifestation of atrial repolarisation and, unlike the P wave (atrial depolarisation), is little recognised. We report the case of a patient with shifting pacemaker which clearly demonstrates the effect of the Ta wave on ST segment and T wave. A simple conceptual model is used to explain the observed phenomenon. The case serves as a reminder of this often forgotten ECG wave and its potential effects on other ECG features.

Failed anti-tachycardia pacing can be used to differentiate atrial arrhythmias from ventricular tachycardia in implantable cardioverter-defibrillators.

BACKGROUND: Atrial fibrillation/tachycardia (AF/AT) may result in inappropriate therapies in implantable cardioverter-defibrillators (ICDs). The post-pacing interval (PPI) and tachycardia cycle length difference (PPI - TCL) has been previously demonstrated to indicate the proximity of the pacing site to a tachycardia origin. AIMS: We postulated that the PPI and PPI - TCL would be greater in AT/AF vs. ventricular tachycardia (VT) after episodes of failed anti-tachycardia pacing (ATP). METHODS AND RESULTS: This was a single-centre, retrospective study evaluating consecutive patients implanted with dual (DR)/biventricular (BIV) ICDs. Stored electrograms were used to determine whether the ATP captured the arrhythmia and the arrhythmia did not present with primary or secondary termination. Measurements were done using manual calipers. A total of 155 patients were included. There were 79 BIV and 76 DR devices. In total, 39 episodes were identified in 20 patients over a 23-month follow-up period. A total of 76 sequences of ATP (burst/ramp) were delivered, 28 (37%) of them inappropriate. Fifty-one events (18 AT/AF and 33 VT) were compared. The mean PPI was 693 ± 96 vs. 512 ± 88 ms (P < 0.01) and the mean PPI - TCL was 330 ± 97 vs. 179 ± 103 ms (P < 0.01) for AT/AF and VT, respectively. Cut-offs of 615 ms for the PPI [area under curve (AUC) 0.93; 95% confidence interval (CI): 0.84-1.00; P < 0.01] and 260 ms for PPI - TCL (AUC 0.86; 95% CI: 0.74-0.98; P < 0.01) were identified. CONCLUSION: The PPI and PPI - TCL after failed ATP differs significantly between AF/AT and VT and are therefore useful indices to discriminate between supraventricular tachycardia and VT in ICDs.

Pectinatus sottacetonis sp. nov., isolated from a commercial pickle spoilage tank.

A strictly anaerobic, Gram-stain-negative, non-spore-forming, motile bacterium, designated strain FSRU B0405(T), was isolated from a commercial pickle spoilage tank and characterized by biochemical, physiological and molecular biological methods. Analyses of the 16S rRNA gene sequence of strain FSRU B0405(T) showed affiliation to the class Negativicutes in the phylum Firmicutes, with the closest relatives being the type strains of Pectinatus haikarae (96 %) and Pectinatus brassicae (95 %). In maximum-likelihood and neighbour-joining phylogenetic trees, strain FSRU B0405(T) clustered definitively (in 100 % of bootstrapped trees) within the genus Pectinatus, but not specifically with any characterized species within this genus. Strain FSRU B0405(T) was a slightly curved rod, varying from 3 to 30 µm in length, motile with a distinctive X-wise movement, having flagella only on the concave side of the cell. The isolate produced acetate and propionate from fructose and glucose as major metabolites similar to type strains of species of the genus Pectinatus. The major fatty acids were C11 : 0, C13 : 0, C15 : 0, C13 : 0 3-OH, C17 : 1 and C18 : 1ω11t. Strain FSRU B0405(T) differed from the pickle wastewater strain, Pectinatus brassicae TY(T), due to its lack of susceptibility to vancomycin, acetoin production, growth temperature range, acid production from adonitol, erythritol, glycerol, inositol, lactose, maltose, mannose, ribose, salicin, sorbitol, trehalose and xylitol and lack of hydrolysis of milk. Strain FSRU B0405(T) could be differentiated from other species of the genus Pectinatus both phenotypically and genetically. The results indicate that strain FSRU B0405(T) represents a novel species of the genus Pectinatus, for which the name Pectinatus sottacetonis sp. nov. is proposed. The type strain is FSRU B0405(T) ( = ATCC BAA-2501(T) = VTT E-113163(T)). An emended description of the genus Pectinatus is also provided.

Atrioventricular Nodal Re-entry Tachycardia in Identical Twins: A Case Report and Literature Review.

This report details the case of 17 year old identical twins who both presented with paroxysmal supraventricular tachycardia (PSVT). Electrophysiological studies revealed atrioventricular nodal reentry tachycardia (AVNRT) in both twins. Successful but technically challenging slow pathway ablation was performed in both twins. This is the first reported case of confirmed AVNRT in identical twins which adds strong evidence to heritability of the dual AV node physiology and AVNRT. A review of the current literature regarding PSVT in monozygotic twins is provided.

The link in Linking.

We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block.

Feasibility of linking universal child and family healthcare and financial counselling: findings from the Australian Healthier Wealthier Families (HWF) mixed-methods study.

OBJECTIVES: 'Healthier Wealthier Families' (HWF) seeks to reduce financial hardship in the early years by embedding a referral pathway between Australia's universal child and family health (CFH) services and financial counselling. This pilot study investigated the feasibility and short-term impacts of HWF, adapted from a successful Scottish initiative. METHODS: Setting: CFH services in five sites across two states, coinciding with the COVID-19 pandemic. PARTICIPANTS: Caregivers of children aged 0-5 years experiencing financial hardship (study-designed screen). DESIGN: Mixed methods. With limited progress using a randomised trial (RCT) design in sites 1-3 (March 2020-November 2021), qualitative interviews with service providers identified implementation barriers including stigma, lack of knowledge of financial counselling, low financial literacy, research burden and pandemic disruption. This informed a simplified RCT protocol (site 4) and direct referral model (no randomisation, pre-post evaluation, site 5) (June 2021-May 2022). INTERVENTION: financial counselling; comparator: usual care (sites 1-4). Feasibility measures: proportions of caregivers screened, enrolled, followed up and who accessed financial counselling. Impact measures: finances (quantitative) and other (qualitative) to 6 months post-enrolment. RESULTS: 355/434 caregivers completed the screen (60%-100% across sites). In RCT sites (1-4), 79/365 (19%-41%) reported hardship but less than one-quarter enrolled. In site 5, n=66/69 (96%) caregivers reported hardship and 44/66 (67%) engaged with financial counselling; common issues were utility debts (73%), and obtaining entitlements (43%) or material aid/emergency relief (27%). Per family, financial counselling increased income from government entitlements by an average $A6504 annually plus $A784 from concessions, grants, brokerage and debt waivers. Caregivers described benefits (qualitative) including reduced stress, practical help, increased knowledge and empowerment. CONCLUSIONS: Financial hardship screening via CFH was acceptable to caregivers, direct referral was feasible, but individual randomisation was infeasible. Larger-scale implementation will require careful, staged adaptations where CFH populations and the intervention are well matched and low burden evaluation. TRIAL REGISTRATION NUMBER: ACTRN12620000154909.

Simplified electrocardiogram sampling maintains high diagnostic capability for atrial fibrillation: implications for opportunistic atrial fibrillation screening in primary care.

AIMS: Atrial fibrillation (AF) is a major cause of morbidity, mortality, and health resource consumption. However, as many patients with chronic AF are asymptomatic, rapid, accurate opportunistic screening is needed in primary care to detect AF. Conventional electrocardiogram (ECG) technology is too clumsy and time consuming for mass opportunistic screening, thus technology that allows easy, rapid, yet accurate AF screening is required. To address this requirement a prototype hand-held electrode assembly was developed. We hypothesized that a 6-lead frontal-plane ECG acquired from this apparatus in a seated, clothed patient would be as accurate at detecting AF as conventional 12-lead ECG in the undressed, supine patient (the 'gold standard'). METHODS AND RESULTS: Electrocardiograms were obtained from 78 patients with AF and 79 with sinus rhythm (SR). All had a conventional 12-lead ECG, a 6-lead ECG from conventionally positioned limb electrodes, a supine 6-lead recording using the prototype recorder placed on the lower thorax/upper abdomen, and a 6-lead prototype recording in the seated patient, the latter with loosened clothing only. Electrocardiograms were randomly and blindly assessed by two cardiologists for (i) diagnosis of AF vs. SR and (ii) tracing quality (subjectively assessed as good, adequate, or bad). Compared with conventional 12-lead ECG recordings, all 'new' recording methods performed satisfactorily with sensitivities ≥90% (90-99%), specificities ≥94% (94-100%), positive predictive values ≥94% (94-100%), negative predictive values ≥90% (90-99%), and accuracies ≥93% (93-99%). Tracing quality was higher in conventional 12-lead recordings (71 and 80% were assessed as good by the two observers) compared with conventional 6-lead (57 and 59%), supine prototype (41 and 31%), and sitting prototype (39 and 19%). CONCLUSIONS: Despite inferior electrocardiographic quality a 6-lead frontal plane ECG acquired by a simple prototype hand-held electrode assembly allowed reliable differentiation of AF from SR compared with standard 12-lead ECG.

Ventricular fibrillation following successful DC cardioversion for atrial fibrillation.

Cardioversion remains an important therapy in the management of atrial fibrillation. Here, we report a case where direct current cardioversion resulted in a sudden dramatic change of heart rate that was associated with multiple ventricular fibrillation arrests in a manner akin to that previously observed post-atrioventricular node ablation.

DEHP: genotoxicity and potential carcinogenic mechanisms-a review.

Di(ethylhexyl) phthalate (DEHP) is a manufactured chemical commonly added to plastics: it is a ubiquitous environmental contaminant to which humans are exposed through multiple routes. DEHP is a rodent carcinogen with an extensive data base on genotoxicity and related effects spanning several decades. Although DEHP has been reported to be negative in most non-mammalian in vitro mutation assays, most studies were performed under conditions of concurrent cytotoxicity, precipitation, or irrelevant metabolic activation. However, a number of in vitro rodent tissue assays have reported DEHP to be positive for effects on chromosomes, spindle, and mitosis. A robust database shows that DEHP increases transformation and inhibits apoptosis in Syrian hamster embryo cells. In a transgenic mouse assay, in vivo DEHP exposure increased the mutation frequency only in the liver, which is the target organ for cancer. In vitro exposure of human cells or tissues to DEHP induced DNA damage; altered mitotic rate, apoptosis, and cell proliferation; increased proliferation, tumor mobility, and invasiveness of tumor cell lines; and activated a number of nuclear receptors. DEHP has been shown to be an agonist for CAR2, a novel constitutive androstane receptor occurring only in humans. Environmental exposures of humans to DEHP have been associated with DNA damage. After taking into account study context and relevant issues affecting interpretation, in vitro studies reported that a similar DEHP concentration range induced both mutagenic and non-mutagenic effects in human tissues and, using a much more limited rodent database, transformation of embryonic rodent tissues. The human and rodent data suggest that DEHP induces cancer through multiple molecular signals, including DNA damage. The analyses presented here may provide guidance for similar data sets used in structure-activity relationships, computational-toxicology extrapolations, and attempts to extrapolate in vitro results to predict in vivo effects for hazard characterization.

Unusual signals in a halo catheter: what is the mechanism?

In this "featured arrhythmia" article we present a set of unusual intracardiac electrode tracings that were recorded in a patient with typical clockwise flutter but a very dilated right atrium. The potential mechanism underlying this phenomenon is discussed with reference to the current literature.

Rationale and study design of the MINERVA study: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction-UK multicentre collaboration.

INTRODUCTION: The purpose of this study is to assess the ability of two new ECG markers (Regional Repolarisation Instability Index (R2I2) and Peak Electrical Restitution Slope) to predict sudden cardiac death (SCD) or ventricular arrhythmia (VA) events in patients with ischaemic cardiomyopathy undergoing implantation of an implantable cardioverter defibrillator for primary prevention indication. METHODS AND ANALYSIS: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction is a prospective, open label, single blinded, multicentre observational study to establish the efficacy of two ECG biomarkers in predicting VA risk. 440 participants with ischaemic cardiomyopathy undergoing routine first time implantable cardioverter-defibrillator (ICD) implantation for primary prevention indication are currently being recruited. An electrophysiological (EP) study is performed using a non-invasive programmed electrical stimulation protocol via the implanted device. All participants will undergo the EP study hence no randomisation is required. Participants will be followed up over a minimum of 18 months and up to 3 years. The first patient was recruited in August 2016 and the study will be completed at the final participant follow-up visit. The primary endpoint is ventricular fibrillation or sustained ventricular tachycardia >200 beats/min as recorded by the ICD. The secondary endpoint is SCD. Analysis of the ECG data obtained during the EP study will be performed by the core lab where blinding of patient health status and endpoints will be maintained. ETHICS AND DISSEMINATION: Ethical approval has been granted by Research Ethics Committees Northern Ireland (reference no. 16/NI/0069). The results will inform the design of a definitive Randomised Controlled Trial (RCT). Dissemination will include peer reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries. TRIAL REGISTRATION NUMBER: NCT03022487.

Multifunctional ZnO/Nylon 6 nanofiber mats by an electrospinning-electrospraying hybrid process for use in protective applications.

ZnO/Nylon 6 nanofiber mats were prepared by an electrospinning-electrospraying hybrid process in which ZnO nanoparticles were dispersed on the surface of Nylon 6 nanofibers without becoming completely embedded. The prepared ZnO/Nylon 6 nanofiber mats were evaluated for their abilities to kill bacteria or inhibit their growth and to catalytically detoxify chemicals. Results showed that these ZnO/Nylon 6 nanofiber mats had excellent antibacterial efficiency (99.99%) against both the Gram-negative Escherichia coli and Gram-positive Bacillus cereus bacteria. In addition, they exhibited good detoxifying efficiency (95%) against paraoxon, a simulant of highly toxic chemicals. ZnO/Nylon 6 nanofiber mats were also deposited onto nylon/cotton woven fabrics and the nanofiber mats did not significantly affect the moisture vapor transmission rates and air permeability values of the fabrics. Therefore, ZnO/Nylon 6 nanofiber mats prepared by the electrospinning-electrospraying hybrid process are promising material candidates for protective applications.

Exercise-induced ventricular arrhythmia in coronary cameral fistula: A manifestation of reperfusion injury.

Presentation, Investigation and Management of Coronary fistula and its arrhythmic complications.

Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease.

BACKGROUND: The sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases. METHODS: A goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques. RESULTS: When the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT). CONCLUSIONS: SAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker.

What are the thromboembolic risks of heart failure combined with chronic or paroxysmal AF?

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks. METHODS AND RESULTS: Current guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF. CONCLUSIONS: An area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF.

Should sevoflurane be used in the electrophysiology assessment of accessory pathways?

Sevoflurane has been shown to significantly prolong the action potential duration and the QTc interval. Despite this, clinical studies have shown only minor clinical effects on accessory pathway properties under general anaesthesia with sevoflurane compared with conscious sedation with midazolam. This case demonstrates significant prolongation of accessory pathway effective refractory period (APERP) under general anaesthetic with sevoflurane compared with propofol.