Human cancer genomes harbor the mutational signature of tobacco-specific nitrosamines NNN and NNK.

Tobacco usage is linked to multiple cancer types and accounts for a quarter of all cancer-related deaths. Tobacco smoke contains various carcinogenic compounds, including polycyclic aromatic hydrocarbons (PAH), though the mutagenic potential of many tobacco-related chemicals remains largely unexplored. In particular, the highly carcinogenic tobacco-specific nitrosamines NNN and NNK form pre-mutagenic pyridyloxobutyl (POB) DNA adducts. In the study presented here, we identified genome-scale POB-induced mutational signatures in cell lines and rat tumors, while also investigating their role in human cancer. These signatures are characterized by T>N and C>T mutations forming from specific POB adducts damaging dT and dC residues. Analysis of 2,780 cancer genomes uncovered POB signatures in ∼180 tumors; from cancer types distinct from the ones linked to smoking-related signatures SBS4 and SBS92. This suggests that, unlike PAH compounds, the POB pathway may contribute uniquely to the mutational landscapes of certain hematological malignancies and cancers of the kidney, breast, prostate and pancreas.

Use of two- and three-dimensional echocardiography for assessment of the left ventricular outflow tract and aortic orifice areas in dogs.

INTRODUCTION/OBJECTIVES: In clinical practice, dogs are screened for subaortic stenosis (SAS) using two-dimensional (2DE) and Doppler echocardiography. There is no accepted antemortem diagnostic criterion to distinguish between mild SAS and unaffected, therefore additional means of evaluating the left ventricular outflow tract (LVOT) and aorta may be desirable. This study sought to determine and compare LVOT and aortic orifice areas using 2DE and three-dimensional echocardiography (3DE) in apparently healthy dogs of various breeds and somatotypes. ANIMALS, MATERIALS, AND METHODS: Sixty-nine healthy, privately-owned dogs. The LVOT and aortic orifice areas were determined using 2DE aortic valve (AV) diameter-derived area; the continuity equation (CE); and 3DE planimetry of the LVOT, AV, sinus of Valsalva, and sinotubular junction. Orifice areas were indexed to body surface area (BSA). RESULTS: Obtaining 3DE images and performing planimetry were feasible in all dogs. The mean indexed area measured using the 2DE AV diameter (2.85 cm2/m2) was significantly lower than that derived from 3DE AV planimetry (3.85 cm2/m2; mean difference, 1.00 cm2/m2; P<0.001). There was poor agreement between the effective area calculated using the CE and the anatomic areas calculated using 2DE AV diameter and 3DE planimetry. The area calculated using the CE was less than all other calculations of area. Interobserver and intraobserver repeatability and reproducibility for 3DE planimetry were excellent. CONCLUSIONS: Methods for determining aortic orifice areas in dogs are not interchangeable, and this must be taken into account if these methods are investigated in the evaluation of dogs with SAS in the future.

Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion.

Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors. SIGNIFICANCE: We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression.

The effect of a hiding space on the behaviour and heart rate variability of dairy calves during temporary separation from the dam.

In natural settings, newborn calves hide for several days before joining the herd. It is unclear whether dairy calves housed indoors would show similar hiding behaviour. This study aimed to describe the use of an artificial hide provided to calves during temporary separation from the dam and assess the effect it has on lying and sleep-like behaviour, as well as heart rate variability (HRV). Twenty-eight cow-calf pairs were randomly assigned to having a hide (n = 14), or no hide (n = 14). Hide use (n = 14), as well as lying and sleep-like behaviour (n = 28), were recorded continuously via video camera during the first hour after the dam was removed for morning milking on day three to seven. Heart rate and R-R intervals were recorded using Polar equine monitors for a subsample of 12 calves (n = 6 per treatment) on day six. Descriptive statistics were calculated for hide use. Wilcoxon Signed Rank tests were used to evaluate whether having a hide affected lying and sleep-like behaviours as well as HRV. Hide use decreased over days and was highly variable between calves. Lying behaviour did not differ between treatments. Duration of sleep-like behaviour was higher for calves without a hide compared to those with a hide. Calves with a hide tended to show signs of higher HRV and parasympathetic activity compared to calves without a hide. Results suggest that providing a hiding space to young calves may be beneficial during periods when the cow is removed from the pen for milking.

Music therapy for supporting informal carers of adults with life-threatening illness pre- and post-bereavement; a mixed-methods systematic review.

BACKGROUND: Music therapy interventions with informal carers of individuals with life-threatening illness at pre- and post-bereavement is an increasingly important clinical area. This systematic review is the first to synthesise and critically evaluate the international evidence associated with music therapy with adult informal carers pre- and post-bereavement. Specifically, the objectives were: i) to describe the characteristics and effectiveness of music therapy interventions which aim to improve health-related outcomes for adult informal carers of adults with life-threatening illness (pre- and post-bereavement), and ii) to describe the experience of music therapy for adult informal carers of adults with life-threatening illness (pre- and post-bereavement). METHODS: Eligibility: adult informal carers of adults at end of life or bereaved; music therapy interventions for improving health-related outcomes; qualitative; mixed-method; and quantitative studies including comparators of any other intervention; published in English from 1998 onwards. Six databases were searched up to July 2022. A JBI mixed-methods systematic review approach was followed throughout, including quality appraisal, data extraction and a convergent segregated approach to synthesis and integration. RESULTS: A total of 34 studies were included, published between 2003 and 2022. Most were conducted in North America (n = 13), Australia (n = 10), or Europe (n = 8). No studies were conducted in low- and middle-income countries or in the UK. The majority were qualitative (n = 17), followed by quasi-experimental (n = 8), mixed-methods (n = 7) and two RCTs. The majority focused on carers of individuals with dementia (n = 21) or advanced cancer (n = 7). Seventeen studies were purely quantitative or included a quantitative component. During meta-synthesis, findings were aligned to core outcomes for evaluating bereavement interventions in palliative care and previously identified risk factors for complicated grief. Commonly targeted outcomes in quantitative studies included quality of life and mental wellbeing, showing equivocal effectiveness of music therapy with significant and non-significant results. Twenty-two studies either purely qualitative or with a qualitative component underwent meta synthesis and suggested a diverse range of improved pre- and post-bereavement outcomes for informal carers across all core outcomes, and across all risk and protective factors, including psychological, spiritual, emotional, and social outcomes. CONCLUSIONS: Qualitative studies provide moderate to strong evidence for improved health-related outcomes for adult informal carers of adults with life-threatening illness pre-bereavement. Limited studies including those bereaved negates conclusions for the bereavement phase. Comparisons and explanations for effectiveness across quantitative and qualitative studies are equivocal, with a high risk of bias and small samples in the limited number of quantitative studies, demonstrating a need for high-quality RCTs. SYSTEMATIC REVIEW PRE-REGISTRATION: PROSPERO [CRD42021244859].

Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma.

Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNß-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNß-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a "tail" of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNß-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.

Effectiveness of adjunctive rifampicin for treatment of Staphylococcus aureus bacteraemia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To assess whether the addition of rifampicin to conventional treatment of Staphylococcus aureus bacteraemia (SAB) reduces bacteriological or clinical failure or death. DATA SOURCES: PubMed, Embase and Cochrane CENTRAL databases were searched from inception to 31 December 2022. Reference lists and PubMed citations of eligible studies were checked. REVIEW METHODS: Two study authors independently identified randomized controlled trials (RCTs) involving adult participants with SAB, in which an intervention group received adjunctive rifampicin and the control group received usual care with or without a placebo. Dichotomous data (bacteriological and clinical failure and deaths) were analysed and pooled across studies using risk ratio (RR) with 95% confidence intervals (CI) using a Mantel-Haenszel random-effect model. The key variable of interest being whether rifampicin was used. RESULTS: Six RCTs including 894 participants-of which 758 (85%) were from one trial-met the inclusion criteria. The addition of rifampicin to conventional treatment of SAB significantly reduced bacteriological failure by 59% (RR 0.41, 95% CI 0.21-0.81, I2 = 0%, number need to treat 27). However, it did not reduce clinical failure (RR 0.70, 95% CI 0.47-1.03, I2 = 0%) or deaths (RR 0.96, 95% CI 0.70-1.32, I2 = 0%). Further, it did not reduce the duration of bacteraemia, or the length of hospital stay. Adjunctive rifampicin reduced SAB recurrences (1% versus 4%, P = 0.01). Emergence of rifampicin resistance during treatment was uncommon (<1%). CONCLUSION: Although adjunctive rifampicin reduced the risk of bacteriological failure and recurrences, we found no mortality benefit to support its use in SAB.

Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma.

Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we described the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic Vesicular stomatitis virus (VSV), VSV-IFNß-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNß-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a 'tail' of long-term survivors (~35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNAseq analysis showed that all the long-term responders had increased expression of a T-cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNß-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.

Surgical procedure prediction using medical ontological information.

BACKGROUND AND OBJECTIVE: Predicting the duration of surgical procedures is an important step in scheduling operating rooms. Many factors have been shown to influence the duration of a procedure, in this research we aim to use medical ontological information to improve the predictions. METHODS: This paper presents two methods for incorporating the medical information about a surgical procedure into the prediction of the duration of the procedure. The first method uses the Systematised Nomenclature of Medicine Clinical Terms to relate different procedures to each other. The second uses simple text fragments. The relationships between types of procedures are included in a regression model for the procedure duration. These methods are applied to data from New Zealand healthcare facilities and the accuracy of the estimations of the durations is compared. In addition a simulation of scheduling the procedures in an operating room is performed. RESULTS: It is shown that both of the methods provide an improvement in the prediction of procedure durations. When compared to a traditional categorical encoding, the ontological information provides an improvement in the continuous ranked probability scores of the prediction of procedure durations from 18.4 min to 17.1 min, and from 25.3 to 21.3 min for types of procedures that are not performed very often. CONCLUSIONS: Different methods for encoding medical ontological information in surgery procedure duration predictions are presented, and show an improvement over traditional models. The improvement in duration prediction is shown to improve the efficiency of scheduling in a simple simulation.

Comparing consumer liking of beef from three feeding systems using a combination of traditional and temporal liking sensory methods.

Research on the effects of animal diet on consumer liking of beef has yielded conflicting results. Currently it is unknown whether dynamic changes occur in liking during consumption of beef. This study applied a combination of traditional and temporal (free and structured) liking methods to determine consumer liking of beef derived from animals that were fed grain (GF), grass silage plus grain (SG) or grazed grass (GG) during finishing. Three separate panels of beef eating consumers (n = 51; n = 52; n = 50) were recruited from Teagasc Food Research Centre, Dublin, Ireland to assess striploin steaks from animals fed either GF, SG, or GG. Using the free temporal liking (TL) method, results revealed that beef from GF animals was liked significantly less (p ≤ 0.05) in terms of overall liking, tenderness and juiciness, when compared to steaks from the SG and GG animals. These effects were not observed using the structured TL or traditional liking methods. Further analysis showed the evolution of scores over time was significant (p ≤ 0.05) for all attributes using the free TL method. Overall, the free TL method yielded more discriminative data and was perceived as easier to perform by consumers compared to the structured TL method. These results show that the free TL method may provide an opportunity to elicit more in-depth information regarding consumer sensory response to meat.

Feline myocardial transcriptome in health and in hypertrophic cardiomyopathy-A translational animal model for human disease.

Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, characterized by primary left ventricular hypertrophy. Feline HCM closely resembles human HCM and is suggested as translational animal model for the human disease. A genetic cause is established in humans and suspected for cats, but little is known about the gene expression and pathways involved in the pathogenesis of HCM. To investigate the myocardial transcriptome changes in HCM, RNA sequencing was conducted on left ventricle (LV) and left atrium (LA) samples of healthy cats and cats with HCM (each n = 5; 20 samples). Ingenuity Pathway Analysis was used to determine functional pathways, regulators, and networks. Distinct gene expression profiles were identified in the LV and LA of the feline healthy and HCM myocardium. Analysis of differentially expressed mRNAs (>2 fold; FDR < 0.01) found chamber-specific (LV vs. LA) expression in both healthy and HCM groups, with higher transcriptional activity in the LA. Genes that contribute to the distinct structure and function of each chamber in health and HCM were identified in the regional comparison. The gene expression profiles of HCM compared to healthy hearts revealed disease related genes, including THBS4 and KLHL33 (LV), FAM177B and THRSP (LA), the latter 3 have not been reported for the myocardium so far, as the top differently expressed genes in the HCM heart. Differently expressed genes and functional pathways found in the HCM heart are associated with cardiac remodeling and fibrosis, inflammation, microvascular changes, calcium signaling and cardiac metabolism, with some regional differences. RhoGDI-RhoGTPase signaling, integrin and ILK signaling pathways, the LXR/RXR pathway in the LA, and the PPARα/RXRα, HIF1α and CXCR4 pathways in the LV might be of particular importance in the HCM disease process. This study identified region-specific myocardial gene transcription patterns as well as novel genes and pathways associated with HCM.

Aroma generation in sponge cakes: The influence of sucrose particle size and sucrose source.

The influence of sucrose source and particle size was investigated in relation to the volatile and aromatic properties of sponge cakes. Six sponge cake formulations were studied using two sucrose sources (sugarbeet and sugarcane), at two particle sizes (large and small) with controls. Volatiles profiles and odour active compounds were identified by gas chromatography mass spectrometry and olfactometry. Sixty two volatile compounds were identified, incorporating twenty five odour active compounds/co-eluting compounds, with 5 odours perceived without any corresponding volatile. Particle size had the greatest impact on volatile abundance, with particle size especially influencing pyrazine abundance. Five odour active volatiles (methional, furfural, 2,3-dimethylpyrazine, heptanal and (E)-2-octenal) contributed most to the aroma of these sponge cakes. Small particle size particularly from sugarbeet yielded higher levels of some Maillard and caramelisation reaction compounds, such as furfural (spicy/ bready), where larger particle size supressed volatile abundance in comparison to the control.

A large outbreak of the Kappa mutation of COVID-19 in Cork, Ireland, April-May 2021.

BACKGROUND: In May 2021, the B.1.617 variant of SARS-CoV-2 emerged in Ireland, and both Delta and Kappa sub-lineages were initially deemed variants of concern (VOCs) on a precautionary basis. We describe a large outbreak of SARS-CoV-2 B.1.617.1 (Kappa mutation) linked to a private gathering among third level students in Cork, Ireland. METHODS: Surveillance data were available from the Health Service Executive COVID Care Tracker. The epidemiological sequence of infection for each new case in this outbreak was tracked and whole genome sequencing was requested on all linked cases. Enhanced public health control measures were implemented by the Department of Public Health HSE-South to contain onward spread of VOCs, including retrospective contact tracing, lengthy isolation and quarantine periods for cases and close contacts. Extensive surveillance efforts were used to describe and control onward transmission. RESULTS: There were 146 confirmed SARS-CoV-2 cases linked to the outbreak. All sequenced cases (53/146; 36%) confirmed Kappa mutation. The median age was 21 years (range 17-65). The majority (88%) had symptoms of SARS-CoV-2 infection. There were 407 close contacts; the median was 3 per case (range 0-14). There were no known hospitalisations, ICU admissions or deaths. Vaccination data was unavailable, but the outbreak pre-dated routine availability of COVID-19 vaccines among younger adults in Ireland. CONCLUSION: Enhanced public health control measures for new and emerging variants of SARS-CoV-2 may be burdensome for cases and close contacts. The overall public health benefit of enhanced controls may only become apparent when evidence on disease transmissibility and severity becomes more complete.

Osteoporotic fracture admissions compared to other major medical admissions in Irish public hospitals.

Multinational reports suggest Ireland has one of the greatest illness burdens related to osteoporosis. Hospital care represents the costliest portion of health services. We found public hospital bed days for fragility fractures in Ireland increased by 43% between 2008 and 2017 which exceeded those for other common diseases. INTRODUCTION: Recent multinational reports suggest Ireland has one of the greatest illness burdens related to osteoporosis, manifesting clinically as fragility fractures (FF). International reports show that FF incidence, rate of hospital admission and cost are similar or greater than those for breast cancer, myocardial infarction and stroke. Studies addressing the illness burden of osteoporosis in Ireland are few, and none compares fragility fractures to other common chronic diseases. METHODS: A retrospective analysis of national administrative data for all public hospital admissions was performed on adults aged 50 years and older from January 2008 to December 2017. RESULTS: In 2017, public hospital bed days for FF totalled 249,887 outnumbering Chronic Obstructive Pulmonary Disease (COPD): 131,897; 6 solid cancers (CA): 118,098; myocardial infarction (MI): 83,477; and diabetes mellitus (DM): 31,044. Bed days for FF increased by 43% between 2008 and 2017, in contrast to a 32%, 28% and 31% reduction for CA, MI and DM, respectively, and a 12% increase for COPD. Public hospital bed days for FF in 2016 were greater than MI, stroke, atrial fibrillation and chest pain combined but less than a combination of COPD, pneumonia and lower respiratory tract infection. CONCLUSION: Osteoporotic fractures represent a large and rapidly increasing illness burden amongst older Irish adults, with substantial care requirements and the resulting onus on our healthcare system. Urgent action is needed to address this public health issue and the services for those at risk of fracture.

Socioeconomic Disadvantage is Associated with Probable Sarcopenia in Community-Dwelling Older Adults: Findings from the English Longitudinal Study of Ageing.

BACKGROUND: Sarcopenia is characterized by the accelerated loss of muscle strength, mass, and function in aging. The disease is a major public health issue with emerging evidence of a disproportionate burden in areas of socioeconomic disadvantage. OBJECTIVES: To estimate the prevalence of probable sarcopenia overall, and according to Socioeconomic Position (SEP). To explore the association between markers of SEP and probable sarcopenia. DESIGN: Cross-sectional analysis of the English Longitudinal Study of Ageing data. SETTING: England, United Kingdom (UK). PARTICIPANTS: This study comprised 6,052 older adult participants from Wave 6 of the English Longitudinal Study of Ageing (ELSA) aged 60 years and older. MEASUREMENTS: Probable sarcopenia was identified by the EWGSOP2 guidelines as low hand grip strength (females <16kg and males <27kg) or poor chair rise test performance (completion of 5 chair rises >15 seconds). Socioeconomic position was defined by educational attainment and subjective social status (SSS). Weighted multivariable regression analysis was employed to identify determinants of probable sarcopenia. RESULTS: Over one-third of older adults met the criteria for probable sarcopenia (33.7%; weighted, 36.1%) in the study population of mean age 70.7 (SD 7.7) years. When examined by SEP, the prevalence of probable sarcopenia was over 2-fold higher in adults in the most vs the least disadvantaged SEP groups (47.0% vs 20.6%, respectively, p<0.001). Multivariable regression analysis identified disadvantaged SEP, as measured by educational attainment and SSS, as independent predictors of probable sarcopenia, along with older age, physical inactivity, underweight BMI, chronic conditions, osteoarthritis, and minority group ethnicity. CONCLUSIONS: Disadvantaged SEP was associated with an increased likelihood of probable sarcopenia when controlled for other known risk factors. The findings suggest a need and opportunity for sarcopenia prevention and treatment strategies to address socioeconomic disadvantage in policies and practice.

National Audit of Criteria For Pre-Operative Sickle Cell Screening in Children.

Aim We set out to identify the current practice in the anaesthesiology departments of Ireland's public hospitals that deliver paediatric anaesthesia with regard to pre-operative screening for sickle cell disease (SCD) and Sickle cell trait (SCT). Methods The Departments of Anaesthesiology at 14 public HSE-funded hospitals that deliver paediatric anaesthesia were contacted over a three month period in 2020. Any existing policies regarding pre-operative screening of paediatric patients for Sickle cell disease or trait were sought. Comparisons were made between any screening policies in place. Results A response was received from 11 of the 14 hospitals. Three out of 11 of the Anaesthesiology Departments have formal policies in place. The ethnicities identified for pre-operative screening varied across these three hospitals. Conclusion Despite a significant increase in the number of people of African, middle Eastern & Indian descent living in Ireland in recent years, no neonatal screening programme for Sickle cell exists here, and no national policy exists with criteria to guide the practice of pre-operative screening of patients for SCD/SCT (trait). Our survey highlights a lack of standardisation in the approach to pre-operative sickle cell screening of children across Ireland's public hospital system. In view of the increasing multiculturalism in Ireland we recommend a national review of the merits of the introduction of developing a targeted national guideline for pre-operative screening for sickle cell in at-risk children.

Cardiac gene activation varies between young and adult cats and in the presence of hypertrophic cardiomyopathy.

Little is known about the difference of myocardial gene transcription in young and adult cats and how transcription is further modified in cats with hypertrophic cardiomyopathy (HCM) and with left atrial (LA) thrombus formation. We hypothesized that selected factors for coagulation, endothelial activation, inflammation, and remodelling are modified with age and are activated in the hearts of cats with HCM. Left atrial and ventricular (LV) samples from 12 cats with HCM (seven without (HCMwoAT] and five with LA thrombi [HCMwAT]), and six young (YC) and six adult (AC) control cats without cardiac disease were investigated for relative expression of the following genes using quantitative polymerase chain reaction: von Willebrand factor, a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13, platelet activating factor, E- and P-selectin, intercellular and vascular adhesion molecules-1, ß2-integrin, vascular endothelial growth factor, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), heat shock protein-70, and myocyte-specific enhancer factor 2C. Significant differences in gene activation were found between YC and AC, and YC and cats with HCM. Compared to AC, MCP-1 and IL-6 were significantly higher in cats with HCM. The presence of an LA thrombus was associated with higher IL-6 expression. These results illustrate the relevance of age and/or lifestyle on gene expression in the feline heart. The gene transcription pattern found in AC hearts might predispose cats to their characteristic cardiac remodelling processes and thrombus formation if disease occurs. It further supports the involvement of inflammation, but not coagulation and endothelial activation, in HCM.

Heart rate distribution in dogs with third degree atrioventricular block and rate responsive pacemakers.

INTRODUCTION: In dogs, single lead ventricular pacing, ventricular sensing, inhibition response, rate adaptive (VVIR) pacemakers are routinely used to treat third degree atrioventricular block. The objectives of this study were to investigate the heart rate distribution in dogs with VVIR pacemakers, and report changes when activity settings were adjusted. ANIMALS: Eighteen client-owned dogs with VVIR pacemakers for third degree atrioventricular block. MATERIALS AND METHODS: This observational study consisted of a review of medical records of dogs with VVIR pacemakers. For dogs with >50% of paced beats at the lower pacing rate, the activity daily living (ADL) and exertion responses were increased. Re-evaluations were performed after 6-12 months. RESULTS: Heart rate distribution similar to healthy dogs was absent for all dogs. In nine dogs, the ADL and exertion responses were increased to the highest level. Of these, three dogs showed no improvement in heart rate distribution; for two dogs, one with an epicardial pacemaker, several activity settings were adjusted and pacing at higher heart rates was observed at re-evaluation. Four dogs died or were lost to follow-up. Clinical signs had resolved for all dogs after pacemaker implantation. CONCLUSION: Default activity settings of VVIR pacemakers do not result in heart rate distribution equivalent to healthy dogs. Increasing the ADL and exertion response settings to the highest levels did not improve the pacemaker rate response. Further investigations into the role of dog size, generator positioning, pacemaker settings, and whether rate responsiveness is required for dogs' quality and quantity of life are warranted.