Equine and human mutual welfare: a whole subject? Critical aspects and possible strategies in equine-assisted activities and therapies

General aim of the study is equine welfare, particularly concerning different husbandry methodic and inter-specific relational factors. Specific aim is the evaluation of possible mutual (to humans and to equines) benefits and the analysis of critical factors/strength points, of human-horse relationship within Therapeutic Riding context (TR). The peculiarities of human-horse relationship (compared to the bond with “Pet”) are analyzed, concerning their socio-anthropological, psychological, psycho-dynamic distinctive characteristics. 8 European representative therapeutic riding centers (TRC) were therefore selected (on the basis of their different animals’ husbandry criteria, and of the different rehabilitative methodologies adopted). TRC were investigated through 2 different questionnaires, specifically settled to access objective/subjective animal welfare parameters; the quality of human-horse relationship; technicians’ emotional experienced. 3 Centers were further selected, and behavioral (145 hours of behavioral recording) and physiological parameters (heart rate and heart rate variability) were evaluated, aimed to access equine welfare and horses’ adaptive responses/coping (towards general environment and towards TR job). Moreover a specific “handling-task” was ideated and experimented, aimed to measure the quality of TR technicians-horses relationship. We did therefore evaluate both the individual horses’ responses and the possible differences among Centers. Data collected highlight the lack of univocal standardized methodic, concerning the general animals’ management and the specific methodologies (aimed to improve animal welfare and to empower TR efficacy). Some positive and some critical aspects were detected concerning TR personnel-horse relationship. Another experimental approach did evaluate the efficacy (concerning the mutual benefits’ empowerment) of an “ethologically-fitted” TR intervention, aimed to educate children to and through the relationship with horses. Our data evidenced that the improvement of human horse relationship, through structured educational programs for TR personnel might have important consequences both to human and equine welfare.

Generation and characterization of mouse models of Small cell lung cancer and Basal cell carcinoma for the preclinical evaluation of new therapies

Background. Human small cell lung cancer (SCLC) accounting for approximately 15-20% of all lung cancers, is an aggressive tumor with high propensity for early regional and distant metastases. Although the initial tumor rate response to chemotherapy is very high, SCLC relapses after approximately 4 months in ED and 12 months in LD. Basal cell carcinoma (BCC) is the most prevalent cancer in the western world, and its incidence is increasing worldwide. This type of cancer rarely metastasizes and the death rate is extraordinary low. Surgery is curative for most of the patients, but for those that develop locally advanced or metastatic BCC there is currently no effective treatment. Both types of cancer have been deeply investigated and genetic alterations, MYCN amplification (MA) among the most interesting, have been found. These could become targets of new pharmacological therapies. Procedures. We created and characterized novel BLI xenograft orthotopic mouse models of SCLC to evaluate the tumor onset and progression and the efficacy of new pharmacological strategies. We compared an in vitro model with a transgenic mouse model of BCC, to investigate and delineate the canonical HH signalling pathway and its connections with other molecular pathways. Results and conclusions. The orthotopic models showed latency and progression patterns similar to human disease. Chemotherapy treatments improved survival rates and validated the in vivo model. The presence of MA and overexpression were confirmed in each model and we tested the efficacy of a new MYCN inhibitor in vitro. Preliminar data of BCC models highlighted Hedgehog pathway role and underlined the importance of both in vitro and in vivo strategies to achieve a better understanding of the pathology and to evaluate the applicability of new therapeutic compounds

Improving adoptive T cell therapies of cancer by ectopic expression of miR181a to repress inhibitory phosphatases

Adoptive T cell therapy using antigen-specific T lymphocytes is a powerful immunotherapeutic approach against cancer. Nevertheless, many T cells against tumor-antigens exhibit only weak anti-tumoral response. To overcome this barrier it is necessary to improve the potency and anti-tumoral efficacy of these T cells. Activation and activity of T cells are tightly controlled to inhibit unwanted T cell responses and to reduce the risk of autoimmunity. Both are regulated by extrinsic signals and intrinsic mechanisms which suppress T cell activation. The intrinsic mechanisms include the expression of phosphatases that counteract the activation-inducing kinases. Modifying the expression of these phosphatases allows the targeted modulation of T cell reactivity. MicroRNAs (miRNAs) are regulatory small noncoding RNA molecules that control gene expression by targeting messenger RNAs in a sequence specific manner. Gene-specific silencing plays a key role in diverse biological processes, such as development, differentiation, and functionality. miR181a has been shown to be highly expressed in immature T cells that recognize low-affinity antigens.rnThe present study successfully shows that ectopic expression of miR181a is able to enhance the sensitivity of both murine and human T cells. In CD4+ T helper cells as well as in CD8+ cytotoxic T cells the overexpression of miR181a leads to downregulation of multiple phosphatases involved in the T cell receptor signaling pathway. Overexpression of miR181a in human T cells achieves a co-stimulatory independent activation and has an anti-apoptotic effect on CD4+ T helper cells. Additionally, increasing the amount of miR181a enhances the cytolytic activity of murine CD8+ TCRtg T cells in an antigen-specific manner.rnTo test miR181a overexpressing T cells in vivo, a mouse tumor model using a B cell lymphoma cell line (A20-HA) expressing the Influenza hemagglutinin (Infl.-HA) antigen was established. The expression of model antigens in tumor cell lines enables targeted elimination of tumors using TCRtg T cells. The transfer of miR181a overexpressing Infl.-HA TCRtg CD8+ T cells alone has no positive effect neither on tumor control nor on survival of A20-HA tumor-bearing mice. In contrast, the co-transfer of miR181a overexpressing Infl.-HA TCRtg CD8+ and CD4+ T cells leads to improved tumor control and prolongs survival of A20-HA tumor-bearing mice. This effect is characterized by higher amounts of effector T cells and the expansion of Infl.-HA TCRtg CD8+ T cells.rnAll effects were achieved by changes in expression of several genes including molecules involved in T cell differentiation, activation, and regulation, cytotoxic effector molecules, and receptors important for the homing process of T cells in miR181a overexpressing T cells. The present study demonstrates that miR181a is able to enhance the anti-tumoral response of antigen-specific T cells and is a promising candidate for improving adoptive cell therapy.

Revisioning a Japanese Spiritual Recovery Through Manga: Kobayashi Yoshinori’s ‘Gōmanism’ as Aesthetics and Ideology

This essay provides a critical analysis of the aesthetic ideology of “Gomanism” in the manga of Kobayashi Yoshinori (b. 1953), particularly Yasukuniron (On Yasukuni, 2005) and Tennōron (On the Emperor, 2009), in order to flesh out the implications of the author’s “revisionist” approach to Japanese religion, politics and history.

Cell therapies for heart function recovery: focus on myocardial tissue engineering and nanotechnologies

Cell therapies have gained increasing interest and developed in several approaches related to the treatment of damaged myocardium. The results of multiple clinical trials have already been reported, almost exclusively involving the direct injection of stem cells. It has, however, been postulated that the efficiency of injected cells could possibly be hindered by the mechanical trauma due to the injection and their low survival in the hostile environment. It has indeed been demonstrated that cell mortality due to the injection approaches 90%. Major issues still need to be resolved and bed-to-bench followup is paramount to foster clinical implementations. The tissue engineering approach thus constitutes an attractive alternative since it provides the opportunity to deliver a large number of cells that are already organized in an extracellular matrix. Recent laboratory reports confirmed the interest of this approach and already encouraged a few groups to investigate it in clinical studies. We discuss current knowledge regarding engineered tissue for myocardial repair or replacement and in particular the recent implementation of nanotechnological approaches.

First-line therapies in inflammatory bowel disease

Medical therapy of inflammatory bowel disease (IBD) is becoming more complex, given the increasing choice of drugs to treat Crohn's disease (CD) and ulcerative colitis (UC). We aimed to summarize the current guidelines for first-line treatments in IBD.

Novel targeted therapies for eosinophilic disorders

Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders.

[Arterial Hypertension - when are which combination therapies useful?]

Arterial hypertension is a widely prevalent risk factor for cardiovascular diseases with well documented harmful effects on the heart and the vascular system. Despite a broad antihypertensive drug armamentarium control of hypertension is worldwide suboptimal. Daily practice as well as large intervention trials show that single-drug therapy often fails to adequately control blood pressure (BP). Therefore, the early introduction of a combination therapy may lead to a better and more rapid BP lowering effect, particularly in patients with more than stage I hypertension or in patients with mild hypertension and high cardiovascular risk. In addition, side effects of an antihypertensive drug can be prevented by a meaningful (low dose) combination with a second antihypertensive agent. Moreover, combination of antihypertensive drugs, especially if provided fixed, may substantially improve compliance. However, the choice of the drug combination primarily relates on the demographic features and co-morbidities of the patient. Although BP lowering is the main determinant of cardiovascular risk reduction in the treatment of hypertension, some antihypertensive drugs may exhibit protective effects beyond BP reduction that have to be considered when antihypertensive drugs are combined. In recent large intervention studies, the combination of an ACE inhibitor with a calcium channel blocker was especially advantageous in high risk hypertensive patients. The addition of a thiazide type diuretic to a blocker of the renin-angiotensin system is also sensible and popular with numerous available fixed combinations.

Mother-Child Spiritual Discourse: A Mixed Methods Study

Parents and children, starting at very young ages, discuss religious and spiritual issues¿where we come from, what happens to us after we die, is there a God, and so on. Unfortunately, few studies have analyzed the content and structure of parent-child conversation about religion and spirituality (Boyatzis & Janicki, 2003; Dollahite & Thatcher, 2009), and most studies have relied on self-report with no direct observation. The current study examined mother-child (M-C) spiritual discourse to learn about its content, structure, and frequency through a survey inventory in combination with direct video observation using a novel structured task. We also analyzed how mothers¿ religiosity along several major dimensions related to their communication behaviors within both methods. Mothers (N = 39, M age = 40) of children aged 3-12 completed a survey packet on M-C spiritual discourse and standard measures of mothers¿ religious fundamentalism, intrinsic religiosity, sanctification of parenting (how much the mother saw herself as doing God¿s work as a parent), and a new measure of parental openness to children¿s spirituality. Then, in a structured task in our lab, mothers (N = 33) and children (M age = 7.33) watched a short film or read a short book that explored death in an age-appropriate manner and then engaged in a videotaped conversation about the movie or book and their religious or spiritual beliefs. Frequency of M-C spiritual discourse was positively related to mothers¿ religious fundamentalism (r = .71, p = .00), intrinsic religiosity (r = .77, p = .00), and sanctification of parenting (r = .79, p = .00), but, surprisingly, was inversely related to mothers¿ v openness to child¿s spirituality (r = -.52, p = .00). Survey data showed that the two most common topics discussed were God (once a week) and religion as it relates to moral issues (once a week). According to mothers their children¿s most common method of initiating spiritual discourse was to repeat what he or she has heard parents or family say about religious issues (M = 2.97; once a week); mothers¿ most common method was to describe their own religious/spiritual beliefs (M = 2.92). Spiritual discourse most commonly occurred either at bedtime or mealtime as reported by 26% of mothers, with the most common triggers reported as daily routine/random thoughts (once a week) and observations of nature (once a week). Mothers¿ most important goals for spiritual discourse were to let their children know that they love them (M = 3.72; very important) and to help them become a good and moral person (M = 3.67; very important). A regression model showed that significant variance in frequency of mother-child spiritual discourse (R2 = .84, p = .00) was predicted by the mothers¿ importance of goals during discourse (ß = 0.46, p = .00), frequency that the mother¿s spirituality was deepened through spiritual discourse (ß = 0.39, p = .00), and the mother¿s fundamentalism (ß = 0.20, p = .05). In a separate regression, the mother¿s comfort in the structured task (ß = 0.70, p = .00), and the number of open-ended questions she asked (ß = -0.26, p = .03) predicted the reciprocity between mother and child (R2 = .62, p = .00). In addition, the mother¿s age (ß = 0.22, p = .059) and comfort during the task (ß = 0.73, p = .00) predicted the child¿s engagement within the structured task. Other findings and theoretical and methodological implications will be discussed.