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Background: Relatively little is known about how people and groups who function in boundary-spanning positions between different sectors, organisations and professions contribute to improved quality of health care and clinical outcomes. Objectives: To explore whether or not boundary-spanning processes stimulate the creation and exchange of knowledge between sectors, organisations and professions and whether or not this leads, through better integration of services, to improvements in the quality of care. Design: A 2-year longitudinal nested case study design using mixed methods. Setting: An inner-city area in England (‘Coxford’) comprising 26 general practices in ‘Westpark’ and a comparative sample of 57 practices. Participants: Health-care and non-health-care practitioners representing the range of staff participating in the Westpark Initiative (WI) and patients. Interventions: The WI sought to improve services through facilitating knowledge exchange and collaboration between general practitioners, community services, voluntary groups and acute specialists during the period late 2009 to early 2012. We investigated the impact of the four WI boundary-spanning teams on services and the processes through which they produced their effects. Main outcome measures: (1) Quality-of-care indicators during the period 2008–11; (2) diabetes admissions data from April 2006 to December 2011, adjusted for deprivation scores; and (3) referrals to psychological therapies from January 2010 to March 2012. Data sources: Data sources included 42 semistructured staff interviews, 361 hours of non-participant observation, 36 online diaries, 103 respondents to a staff survey, two patient focus groups and a secondary analyses of local and national data sets. Results: The four teams varied in their ability to, first, exchange knowledge across boundaries and, second, implement changes to improve the integration of services. The study setting experienced conditions of flux and uncertainty in which known horizontal and vertical structures underwent considerable change and the WI did not run its course as originally planned. Although knowledge exchanges did occur across sectoral, organisational and professional boundaries, in the case of child and family health services, early efforts to improve the integration of services were not sustained. In the case of dementia, team leadership and membership were undermined by external reorganisations. The anxiety and depression in black and minority ethnic populations team succeeded in reaching its self-defined goal of increasing referrals from Westpark practices to the local well-being service. From October to December 2010 onwards, referrals have been generally higher in the six practices with a link worker than in those without, but the performance of Westpark and Coxford practices did not differ significantly on three national quality indicators. General practices in a WI diabetes ‘cluster’ performed better on three of 17 Quality and Outcomes Framework (QOF) indicators than practices in the remainder of Westpark and in the wider Coxford primary care trust. Surprisingly, practices in Westpark, but not in the diabetes cluster, performed better on one indicator. No statistically significant differences were found on the remaining 13 QOF indicators. The time profiles differed significantly between the three groups for elective and emergency admissions and bed-days. Conclusions: Boundary spanning is a potential solution to the challenge of integrating health-care services and we explored how such processes perform in an ‘extreme case’ context of uncertainty. Although the WI may have been a necessary intervention to enable knowledge exchange across a range of boundaries, it was not alone sufficient. Even in the face of substantial challenges, one of the four teams was able to adapt and build resilience. Implications for future boundary-spanning interventions are identified. Future research should evaluate the direct, measurable and sustained impact of boundary-spanning processes on patient care outcomes (and experiences), as well as further empirically based critiques and reconceptualisations of the socialisation → externalisation → combination → internalisation (SECI) model, so that the implications can be translated into practical ideas developed in partnership with NHS managers. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

The purpose of this study is to evaluate the effectiveness of blended learning on the academic achievement of students in the University of Jordan. To gain in depth understanding of the phenomena under investigation, survey method is employed to collect natural data. For the sake of respondent convince all the questions asked in this survey are directed in Arabic language. Conventional sampling technique is employed due to the subjectivity of the issue. A sample of (427) students from King Abdulla II School for Information Technology at Jordan University are randomly selected. SPSS10 software is used to make statistical analysis. The robust checks of the result are made through arithmetic average, standard deviation statistics and Pearson correlation matrix. Statistical results of the study report that there is a significant and positive impact of blended learning on academic achievement of the students in university of Jordan. [ABSTRACT FROM AUTHOR]

Milk is an essential part of the human diet and is a nutrient-rich food that improves nutrition and food security. The aim of this study was to determine the presence and concentration of aflatoxin M1 (AFM1), adulterants, microbial loads, and physicochemical properties of raw cow's milk (CM) in Nekemte City, Ethiopia. A total of 12 samples of fresh CM were purposefully collected from four kebeles in the city (Bake Jama, Burka Jato, Cheleleki, and Bakanisa Kese) based on the potential of each milk production and distributor site. The AFM1 concentration was determined by high-performance liquid chromatography (HPLC) with a Sigma-Aldrich standard (St. Louis, MO, USA). The concentrations of AFM1 in Bake Jama, Burka Jato, Cheleleki, and Bakanisa Kese were found to be 0.01-0.03 g/L, 0.31-0.35 g/L, 0.19-0.21 g/L, and 0.04-0.07 g/L, respectively. The concentrations of AFM1 in the present study varied significantly ( p < 0.05) and ranged from 0.01 g/L to 0.35 g/L. These results show that of the 12 samples tested, all were positive for AFM1 and contaminated to varying degrees. The results of this study also revealed that the concentration of AFM1 in 7 (58%) of the 12 milk samples was above the European Union's (EU) maximum tolerance limit (0.05 g/L). The present study also revealed that of the investigated adulterants, only the addition of water had positive effects on three milk samples, while the remaining adulterants were not detected in any of the milk samples. The total bacterial count (TBC) and total coliform count (TCC) were significantly ( p < 0.05) different and ranged from 5.53 to 6.82 log 10 cfumL -1 and from 4.21 to 4.74 log 10 cfumL -1 , respectively. The physicochemical properties of the milk samples in the present study were significantly ( p < 0.05) different and ranged from 2.8% to 5.75% fat, 7.03% to 9.75% solid-not-fat (SNF), 2.35% to 3.61% protein, 3.33% to 5.15% lactose, 11.54% to 13.69% total solid, 0.16% to 0.18% titratable acid, 26.7 to 32.1°C, 6.35 to 6.55 pH, and 1.027 to 1.030 specific gravity. The physicochemical parameters of the raw milk in the study area met the required quality standards. Hence, further studies are required to determine the extent of the problem and the factors associated with high levels of AFM1 in raw milk in the study areas, including the detection of aflatoxin B1 (AFB1) in animal feed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Leila Nasir and Habtamu Fekadu Gemede.)

Background: The management of patients in primary care is often complicated by the presence of multiple chronic conditions and psychosocial issues that increase the complexity of the encounter and have important impacts on care. There is a paucity of literature on this subject in the pediatric population., Objectives: The aim of this study was to quantify the burden of chronic conditions in pediatric primary care., Methods: The problem lists of 3995 randomly selected patients from a community pediatric clinic and an academic hospital-based pediatric clinic in the same metropolitan area were analyzed for the presence and number of any chronic condition., Results: In total, 53% of patients suffered from at least one chronic problem, 25% had two or more chronic conditions and 5.1% had four or more conditions. Compared with the community clinic, the academic clinic had significantly more children with catastrophic complex conditions (P<0.001). A regression analysis showed a significant positive correlation between the number of chronic medical conditions and mental health diagnoses., Conclusions: The burden of chronic disease in the pediatric primary care setting may be significantly higher than has been previously suggested. To ensure optimal quality of care, health planners should take into account the high burden of chronic illness, psychosocial issues and multimorbidity among patients in the pediatric primary care setting, as well as the higher complexity profile of patients attending academic clinics.

Objective: To explore in Arab communities the prevalence, dynamics, and resources available to address the physical and psychological consequences that may arise from psychiatric disorders., Methods: An online survey of psychiatrists and primary care physicians from 17 Arab countries was conducted between September 2011 and June 2012. The survey serves as a needs assessment in a scientifically valid and culturally sensitive manner. Additionally, it focuses attention on the clinical strengths and weaknesses of Middle Eastern primary health care and mental health centers in identifying and treating trauma-related health and mental health issues., Results: The 90 survey respondents comprised psychiatrists (n = 53) and primary care physicians (n = 37). They practiced in 3 clinical settings: primary mental health (27%), inpatient mental health (43%), and primary health care (29%). Traumas frequently reported by their patients were attributed to recent death of a close relative or friend (62.3%), domestic violence (41.4%), divorce/separation (72.1%), serious traffic accident (45.6%), sexual assault/rape (20.3%), child abuse (20.3%), psychological effects of war (30.9%), victims of crime (15.9%), refugees/internally displaced persons (20.6%), physical effects of war (19.1%), torture (13.2%), elderly abuse (11.6%), psychological effects of a natural disaster (7.4%), physical effect of a natural disaster (7.2%), and child soldiers (4.3%). Psychiatrists had significantly more patients with the following traumatic experiences: divorce/separation (81.4% vs 57.1%, P = .039), recent death of a close relative or friend (72.7% vs 47.6%, P = .048), and domestic violence (51.1% vs 19.0%, P = .014). Clinical teams comprised substantial numbers of students but small numbers of community volunteers and school counselors., Conclusions: This study highlights the need to develop awareness and training programs in Arab communities to identify and properly treat traumatized individuals in psychiatric and primary care settings., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Bovine papillomavirus (BPV) types 1 and 2 play an important role in the pathogenesis of equine sarcoids (ES), the most common cutaneous tumour affecting horses. MicroRNAs (miRNAs), small non-coding RNAs that regulate essential biological and cellular processes, have been found dysregulated in a wide range of tumours. The aim of this study was to identify miRNAs associated with ES. Differential expression of miRNAs was assessed in control equine fibroblasts (EqPalFs) and EqPalFs transformed with the BPV-1 genome (S6-2 cells). Using a commercially available miRNA microarray, 492 mature miRNAs were interrogated. In total, 206 mature miRNAs were differentially expressed in EqPalFs compared with S6-2 cells. Aberrant expression of these miRNAs in S6-2 cells can be attributed to the presence of BPV-1 genomes. Furthermore, we confirm the presence of 124 miRNAs previously computationally predicted in the horse. Our data supports the involvement of miRNAs in the pathogenesis of ES., (© 2016 John Wiley & Sons Ltd.)

Equine sarcoids develop upon bovine papillomavirus type 1 or 2 (BPV1, BPV2) infection in conjunction with trauma and represent the most common tumour disease in horses and other equids, including donkeys. In face of a sarcoid outbreak involving 12 of 111 donkeys and mules at the 'Rifugio degli Asinelli', a subsidiary charity organization of The Donkey Sanctuary, non-invasively collected sample material including crusts, dandruff, swabs and hair roots was collected from sarcoid-affected and 26 healthy donkeys, as well as dandruff from a grooming kit and tabanids caught from or in the vicinity of sarcoid patients. In addition five previously collected sarcoids stored in formalin were provided. DNA isolated from collected material was tested for the presence of the BPV1/2 E5 oncogene using PCR. Positive samples were further analysed by E2/E4 and LCR PCR and amplicon sequencing to determine a possible common source of infection via comparative alignment of intralesional BPV1/2 gene variants. IC/PCR was used to assess sample aliquots for the presence of BPV1/2 virions, and IHC to analyse five tumours for BPV1 E5 and L1 protein expression. All sarcoid-affected donkeys, two of 55 tabanids and dandruff from a curry comb tested positive for BPV1/2 E5, yet negative by IC/PCR. Healthy animals were BPV1/2-free. IHC revealed different levels of intralesional E5 and L1 expression. A series of BPV1 E5, E2, and LCR variants and BPV2 E5 were detected from donkeys, indicating that they had accidently developed sarcoids at about the same time rather than having acquired disease from each other., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The common equine skin tumors known as sarcoids have been causally associated with infection by bovine papillomavirus (BPV). Additionally, there is evidence for host genetic susceptibility to sarcoids. We investigated the genetic basis of susceptibility to sarcoid tumors on a cohort of 82 affected horses and 270 controls genotyped on a genome-wide platform and two custom panels. A Genome Wide Association Study (GWAS) identified candidate regions on six chromosomes. Bayesian probability analysis of the same dataset verified only the regions on equine chromosomes (ECA) 20 and 22. Fine mapping using custom-produced SNP arrays for ECA20 and ECA22 regions identified two marker loci with high levels of significance: SNP BIEC2-530826 (map position 32,787,619) on ECA20 in an intron of the DQA1 gene in the Major Histocompatibility Complex (MHC) class II region (p = 4.6e-06), and SNP BIEC2-589604 (map position 25,951,536) on ECA22 in a 200 kb region containing four candidate genes: PROCR, EDEM2, EIF6 and MMP24 (p = 2.14e-06). The marker loci yielded odds ratios of 5.05 and 4.02 for ECA20 and ECA22, respectively. Associations between genetic MHC class II variants and papillomavirus-induced tumors have been reported for human papillomavirus and cottontail rabbit papillomavirus infections. This suggests a common mechanism for susceptibility to tumor progression that may involve subversion of the host immune response. This study also identified a genomic region other than MHC that influenced papillomavirus-induced tumor development in the studied population., (© 2016 UICC.)

Most physicians who work in the United Nations Relief and Works Agency (UNRWA) infant and child health programme in Jordan are general practitioners with no postgraduate training in paediatrics. Furthermore, in resource-poor or remote settings, the ability to deliver live continuing medical education (CME) is often limited. A questionnaire exploring the resources available for accessing CME, preferences for types of CME, current sources of CME and topics of interest in the field of paediatric care was sent to all 92 physicians practising in UNRWA clinics in Jordan. Of the 89 respondents 80% had attended live medical lectures for CME and 70% CME meetings. Despite most physicians having access to the Internet only 52.8% were interested in Internet-based courses for accessing CME. There was a statistically significant relationship between year of graduation from medical school and preference for Internet-based CME. Implications for CME participation and paediatric CME topics are discussed.

Family physicians are often a source of information and advice on early childhood concerns regarding sleep, thumb-sucking/pacifier use, picky eating, school readiness, and oral health. Evidence indicates that family variables are important in the genesis of sleep difficulties, and that traditional behavioral methods are not as effective as previously thought. Attention to family psychosocial well-being, especially maternal functioning, is important in addressing childhood sleep difficulties. Thumb-sucking and pacifier use may be associated with negative consequences if they persist, and referral is recommended after four years of age if appropriate behavioral interventions are ineffective. Picky eating is heavily influenced by environmental factors, and food neophobia is a normal stage of development. The main approaches to childhood eating problems include social modeling of normal eating behaviors, repeated exposures to new foods, and positive mealtime experiences. School readiness focuses on supporting the psychosocial variables that are associated with school success. Reading with the child enhances literacy skills. Quality early childhood education programs are also effective in enhancing school success. Delaying school entry is not beneficial and may be detrimental. School readiness includes the schools' role in supporting the learning needs of all children regardless of their abilities and skills. Oral health is increasingly recognized as an important contributor to overall health. Oral health should be incorporated into well-child visits beginning at the eruption of the first tooth.

Papillomaviruses are a family of slowly evolving DNA viruses and their evolution is commonly linked to that of their host species. However, whilst bovine papillomavirus-1 (BPV-1) primarily causes warts in its natural host, the cow, it can also cause locally aggressive and invasive skin tumours in equids, known as sarcoids, and thus provides a rare contemporary example of cross-species transmission of a papillomavirus. Here, we describe the first phylogenetic analysis of BPV-1 in equine sarcoids to our knowledge, allowing us to explore the evolutionary history of BPV-1 and investigate its cross-species association with equids. A phylogenetic analysis of the BPV-1 transcriptional promoter region (the long control region or LCR) was conducted on 15 bovine and 116 equine samples from four continents. Incorporating previous estimates for evolutionary rates in papillomavirus implied that the genetic diversity in the LCR variants was ancient and predated domestication of both equids and cattle. The phylogeny demonstrated geographical segregation into an ancestral group (African, South American and Australian samples), and a more recently derived, largely European clade. Whilst our data are consistent with BPV-1 originating in cattle, we found evidence of multiple, probably relatively recent, cross-species transmission events into horses. We also demonstrated the high prevalence of one particular sequence variant (variant 20), and suggest this may indicate that this variant shows a fitness advantage in equids. Although strong host specificity remains the norm in papillomaviruses, our results demonstrate that exceptions to this rule exist and can become epidemiologically relevant., (© 2014 The Authors.)

This is a baseline of published research in the trauma field by Arab researchers. It highlights groundbreaking attempts by Arab researchers to investigate the mental health impact of violence in their countries before the Arab Spring. Peer-reviewed articles (N = 157) were identified through computerized searches in PubMed, PsycINFO, Google Scholar, and Pilots Database, 1995 to 2012. A synopsis of the published research included (a) country, (b) screening instruments, (c) sample size, (d) methods, and (e) results. The findings reveal that domestic violence attracted most attention after civil strife in Palestine and Lebanon. Torture survivors and victims of sexual violence received little attention. Study instruments were borrowed from Western researchers without being validated within local Arab cultures. No clinical outcome studies were found. In light of the Arab Spring, it is urgent that Arab researchers conduct studies that are evidence based and culturally valid addressing the mental health care of all traumatized citizens.

The Papillomaviridae family comprises a large number of viruses that can infect a broad range of hosts including mammals, birds and reptiles giving rise to benign lesions of the skin or mucosal membranes. They are characterized by great genetic diversity yet adhere to common biological principles. In this review, we first describe the structure and function of the viral proteins encoded by papillomaviruses (PVs), with a particular emphasis on bovine papillomaviruses (BPV). We then discuss the role of BPV types 1 and 2 in the pathogenesis of equine sarcoids and present recent evidence implicating a novel equine papillomavirus (EcPV-2) in the pathogenesis of equine genital cancers., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We describe how the formation of Health Networks in Ealing leads to improved outcomes for patients by the coordination of the care they receive by health and social care professionals.

We describe four stages of an initiative to co-create a shared care system to treat patients with diabetes out of hospital and in the community.

Equine sarcoids are skin tumours of fibroblastic origin affecting equids worldwide. Bovine papillomavirus type-1 (BPV-1) and, less commonly, type-2 are recognized as etiological factors of sarcoids. The transforming activity of BPV is related to the functions of its major oncoprotein E5 which binds to the platelet-derived growth factor β receptor (PDGFβR) causing its phosphorylation and activation. In this study, we demonstrate, by coimmunoprecipitation and immunoblotting, that in equine sarcoid derived cell lines PDGFβR is phosphorylated and binds downstream molecules related to Ras-mitogen-activated protein kinase-ERK pathway thus resulting in Ras activation. Imatinib mesylate is a tyrosine kinase receptors inhibitor which selectively inhibits the activation of PDGFβR in the treatment of several human and animal cancers. Here we show that imatinib inhibits receptor phosphorylation, and cell viability assays demonstrate that this drug decreases sarcoid fibroblasts viability in a dose-dependent manner. This study contributes to a better understanding of the molecular mechanisms involved in the pathology of sarcoids and paves the way to a new therapeutic approach for the treatment of this common equine skin neoplasm.

Bovine papillomavirus type 1 infects not only cattle but also equids and is a causative factor in the pathogenesis of commonly occurring equine sarcoid tumours. Whilst treatment of sarcoids is notoriously difficult, cisplatin has been shown to be one of the most effective treatment strategies for sarcoids. In this study we show that in equine fibroblasts, BPV-1 sensitises cells to cisplatin-induced and UVB-induced apoptosis, a known cofactor for papillomavirus associated disease, however BPV-1 transformed fibroblasts show increased clonogenic survival, which may potentially limit the therapeutic effects of repeated cisplatin treatment. Furthermore we show that BPV-1 increases p53 expression in sarcoid cell lines and p53 expression can be either nuclear or cytoplasmic. The mechanism and clinical significance of increase/abnormal p53 expression remains to be established.

We describe how the formation of Health Networks in Ealing leads to improved outcomes for patients by the coordination of the care they receive by health and social care professionals.

We describe four stages of an initiative to co-create a shared care system to treat patients with diabetes out of hospital and in the community.

Papillomaviruses (PVs) are established agents of human and animal cancers. They infect cutaneous and mucous epithelia. High Risk (HR) Human PVs (HPVs) are consistently associated with cancer of the uterine cervix, but are also involved in the etiopathogenesis of other cancer types. The early oncoproteins of PVs: E5, E6 and E7 are known to contribute to tumour progression. While the oncogenic activities of E6 and E7 are well characterised, the role of E5 is still rather nebulous. The widespread causal association of PVs with cancer makes their study worthwhile not only in humans but also in animal model systems. The Bovine PV (BPV) system has been the most useful animal model in understanding the oncogenic potential of PVs due to the pivotal role of its E5 oncoprotein in cell transformation. This review will highlight the differences between HPV-16 E5 (16E5) and E5 from other PVs, primarily from BPV. It will discuss the targeting of E5 as a possible therapeutic agent.

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type 1 (BPV-1) activity is necessary for the transformation phenotype of equine fibroblasts. Among the many changes induced by BPV-1, matrix metalloproteinase 1 (MMP-1) upregulation contributes to the invasiveness of equine fibroblasts. However, it is not yet known how BPV-1 proteins regulate equine MMP-1 expression. To elucidate this mechanism, the equine MMP-1 promoter was cloned and analysed. A putative activator protein-1 (AP-1)-binding site was demonstrated to be crucial for upregulated MMP-1 promoter activity by BPV-1. BPV-1 E6 and E7 proteins increased MMP-1 promoter activity, and inhibition of BPV-1 gene expression by small interfering RNA significantly reduced the promoter activity. c-Jun and Fra-1, two components of the AP-1 transcription factor complex, were overexpressed and activated by BPV-1 in equine fibroblasts. Finally, BPV-1 E5, E6 and E7 proteins increased MMP-1 mRNA and protein expression. In conclusion, the expression of MMP-1 can be enhanced by BPV-1 oncoproteins E6 and E7 through the AP-1 transcription factor and by E5 via an indirect mechanism. These findings shed light on the mechanism of BPV-1-mediated equine fibroblast infiltration and indicate that both BPV-1 oncoproteins and AP-1 could be potential targets for equine sarcoid therapy.

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type-1 (BPV-1) and less commonly BPV-2 are the causative agents of the diseases. It has been demonstrated that BPV-1 viral gene expression is necessary for maintaining the transformation phenotype. However, the underlying mechanism for BPV-1 transformation remains largely unknown, and the cellular factors involved in transformation are not fully understood. Previously mitogen-activated protein kinase (MAPK) signalling pathway has been shown to be important for cellular transformation. This study investigated the role of p38 MAPK (p38) in the transformation of equine fibroblasts by BPV-1. Elevated expression of phosphorylated p38 was observed in BPV-1 expressing fibroblasts due to the expression of BPV-1 E5 and E6. The phosphorylation of the MK2 kinase, a substrate of p38, was also enhanced. Inhibition of p38 activity by its selective inhibitor SB203580 changed cell morphology, reduced the proliferation of sarcoid fibroblasts and inhibited cellular invasiveness, indicating the indispensable role of p38 in BPV-1 transformation of equine fibroblasts. These findings provide new insights into the pathogenesis of equine sarcoids and suggest that p38 could be a potential target for equine sarcoid therapy.

In equids, bovine papillomaviruses of type 1 (BPV-1) and less frequently type 2 induce common, locally aggressive skin tumours termed sarcoids. Whereas BPV infection in cattle usually involves the epidermis and is productive in this skin layer, infection in equids is currently thought to be abortive, with virus solely residing as multiple episomes in dermal fibroblasts. Based on recent observations that do not agree with this assumption, we hypothesised that BPV also infects equid epidermis and is active in this skin layer. To test this hypothesis, we conducted a proof-of-principle study on eight distinct sarcoids. Presence of viral DNA was addressed by qualitative and quantitative BPV-1 PCR from microdissected sarcoid epidermis, and by subsequent amplicon sequencing. Viral activity was assessed by screening sarcoid epidermis for BPV-1 protein expression using immunohistochemistry (IHC) or immunofluorescence (IF). Virus-free equine skin served as negative control throughout the assays. BPV-1 DNA was demonstrated in all sarcoid epidermis samples, with viral DNA loads ranging between 2 and 195 copies/cell. Identical BPV-1 E5 genes were identified in epidermis and dermis of each of two sarcoids, yet different E5 variants were found in individual lesions. IHC/IF revealed the presence of E5 and E7 protein in sarcoid epidermis, and L1 capsomers in the squamous layer of one lesion. These findings indicate that BPV infection also involves the epidermis, where it may occasionally be productive., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by localized invasion, rare regression and high recurrence following surgical intervention. Bovine papillomavirus type 1 (BPV-1) and less commonly BPV-2 are now widely recognized as the causative agents of the disease. Fibroblasts isolated from sarcoids are highly invasive. Invasion is associated with a high level of viral gene expression and matrix metalloproteinase upregulation. However, it remains unclear to what extent BPV-1 proteins are involved in the transformation of equine cells. To address this question, the individual viral genes E5, E6 and E7 were overexpressed in normal equine fibroblasts (EqPalF cells) and in the immortal but not fully transformed sarcoid-derived EqS02a cell line. The proliferation and invasiveness of these cell lines were assessed. E5 and E6 were found to be responsible for the enhanced cell proliferation and induction of increased invasion in EqS02a cells, whilst E7 appeared to enhance cell anchorage independence. Knockdown of BPV-1 oncogene expression by small interfering RNA reversed the transformed phenotype of sarcoid fibroblasts. Together, these observations strongly suggest that BPV-1 proteins play indispensable roles in the transformation of equine fibroblasts. These data also suggest that BPV-1 proteins are potential drug targets for equine sarcoid therapy.

Telomerase targeted cancer gene therapy is being exploited for treatment of human cancer. The high incidence and many comparative aspects of human and canine cancer and the compliance and dedication of dog owners to treat cancer makes the canine pet population a good clinical model for investigating and developing new cancer therapeutics. Here, we report that the human telomerase promoter operates in canine cells, suggesting that human telomerase promoter-driven cancer therapy can be used to treat cancer in canines. Therefore, the canine pet population can act as a clinical model for new drug development based on telomerase therapeutics., (© 2010 Blackwell Publishing Ltd.)

BPV-1 and less commonly BPV-2 are associated with the pathogenesis of equine skin tumours termed sarcoids. We recently documented the transcriptional changes that are induced by BPV-1 in equine fibroblasts using microarray analyses. TLR4 expression was found to be significantly down-regulated by BPV-1. In the present study, we show that TLR4 expression is significantly decreased following the exogenous expression of BPV-1 E2 and E7 in primary equine fibroblasts. The results were confirmed by the demonstration of increased TLR4 expression following siRNA suppression of BPV-1 E2 and E7 viral gene expression. These data imply that BPV-1 is able to subvert the innate immune response by downregulation of TLR4., (Copyright 2010 Elsevier B.V. All rights reserved.)