Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

The antibacterial activity of date syrup polyphenols against S. aureus and E. coli

Plant-derived products such as date syrup have demonstrated antibacterial activity and can inhibit bacteria through numerous different mechanisms, which may be attributed to bioactive compounds including plant-derived phenolic molecules. Date syrup is rich in polyphenols and this study hypothesized that date syrup polyphenols demonstrate inherent antimicrobial activity, which cause oxidative damage. This investigation revealed that date syrup has a high content of total polyphenols (605 mg/100g), and is rich in tannins (357 mg/100g), flavonoids (40.5 mg/100g) and flavanols (31.7 mg/100g) that are known potent antioxidants. Furthermore, date syrup, and polyphenols extracted from date syrup, the most abundant bioactive constituent of date syrup are bacteriostatic to both Gram positive and Gram negative Escherichia coli and Staphylococcus aureus respectively. It has further been shown that the extracted polyphenols independently suppress the growth of bacteria at minimum inhibitory concentration (MIC) of 30 mg/mL and 20 mg/mL for E. coli and S. aureus, and have observed that date syrup behaves as a prooxidant by generating hydrogen peroxide that mediates bacterial growth inhibition as a result of oxidative stress. At sub-lethal MIC concentrations date syrup demonstrated antioxidative activity by reducing hydrogen peroxide, and at lethal concentrations date syrup demonstrated prooxidant activity that inhibited the growth of E. coli and S. aureus. The high sugar content naturally present in date syrup did not significantly contribute to this effect. These findings highlight that date syrup’s antimicrobial activity is mediated through hydrogen peroxide generation in inducing oxidative stress in bacteria

Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

Implications of new understandings of gliomas in children and adults with NF1: Report of a consensus conference

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade transformed and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and advances in molecularly targeted treatment and potential immunologic treatment of these tumors. Next steps are recommended to advance the management and outcomes for NF1-associated gliomas

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Public health and epidemiology journals published in Brazil and other Portuguese speaking countries

It is well known that papers written in languages other than English have a great risk of being ignored simply because these languages are not accessible to the international scientific community. The objective of this paper is to facilitate the access to the public health and epidemiology literature available in Portuguese speaking countries. It was found that it is particularly concentrated in Brazil, with some few examples in Portugal and none in other Portuguese speaking countries. This literature is predominantly written in Portuguese, but also in other languages such as English or Spanish. The paper describes the several journals, as well as the bibliographic databases that index these journals and how to access them. Most journals provide open-access with direct links in the indexing databases. The importance of this scientific production for the development of epidemiology as a scientific discipline and as a basic discipline for public health practice is discussed. To marginalize these publications has implications for a more balanced knowledge and understanding of the health problems and their determinants at a world-wide level

Update on management of atrial fibrillation in heart failure:a focus on ablation

Atrial fibrillation is increasingly encountered in patients with heart failure. Both diseases have seen tremendous rises in incidence in recent years. In general, the treatment of atrial fibrillation is focused on relieving patients from atrial fibrillation-related symptoms and risk reduction for thromboembolism and the occurrence or worsening of heart failure. Symptomatic relief may be accomplished by either (non-)pharmacological rate or rhythm control in combination with optimal therapy of underlying cardiovascular morbidities and risk factors. Atrial fibrillation ablation has been performed in patients without overt heart failure successfully for many years. However, in recent years, attempts have been made for patients with heart failure as well. In this review, we discuss the current literature describing the treatment of atrial fibrillation in heart failure. We highlight the early rate versus rhythm control studies, the importance of addressing underlying conditions and treatment of risk factors. A critical evaluation will be performed of the catheter ablation studies that have been performed so far in light of larger (post-hoc) ablation studies. Furthermore, we will hypothesise the role of patient selection as next step in optimising outcome for patient with atrial fibrillation and heart failure

Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML

Occurrence of the BCR-ABL[superscript T315I] gatekeeper mutation is among the most pressing challenges in the therapy of chronic myeloid leukemia (CML). Several BCR-ABL inhibitors have multiple targets and pleiotropic effects that could be exploited for their synergistic potential. Testing combinations of such kinase inhibitors identified a strong synergy between danusertib and bosutinib that exclusively affected CML cells harboring BCR-ABL[superscript T315I]. To elucidate the underlying mechanisms, we applied a systems-level approach comprising phosphoproteomics, transcriptomics and chemical proteomics. Data integration revealed that both compounds targeted Mapk pathways downstream of BCR-ABL, resulting in impaired activity of c-Myc. Using pharmacological validation, we assessed that the relative contributions of danusertib and bosutinib could be mimicked individually by Mapk inhibitors and collectively by downregulation of c-Myc through Brd4 inhibition. Thus, integration of genome- and proteome-wide technologies enabled the elucidation of the mechanism by which a new drug synergy targets the dependency of BCR-ABL[superscript T315I] CML cells on c-Myc through nonobvious off targets