Embryonic stem cell gene expression signatures in the canine mammary tumor: a bioinformatics approach

Canine breast cancer was considered as an ideal model of comparative oncology for the human breast cancer, as there is significant overlap between biological and clinical characteristics of the human and canine breast cancer. We attempt to clarify expression profile of the embryonic stem cell (ES) gene signatures in canine breast cancer. Using microarray datasets (GSE22516 and GSE20718), expression of the three major ES gene signatures (modules or gene‐sets), including Myc, ESC‐like, and PRC modules, was primarily analyzed through Gene‐Set Enrichment Analysis (GSEA) method in tumor and healthy datasets. For confirmation of the primary results, an additional 13 ES gene‐sets which were categorized into four groups including ES expressed (ES exp1 and ES exp2), NOS targets (Nanog targets, Oct4 targets, Sox2 targets, NOS targets, and NOS TFs), Polycomb targets (Suz12 targets, Eed targets, H3K27 bound, and PRC2 targets), and Myc targets (Myc targets1, and Myc targets2) were tested in the tumor and healthy datasets. Our results revealed that there is a valuable overlap between canine and human breast cancer ES gene‐sets expression profile, where Myc and ESC‐like modules were up‐regulated and PRC module was down‐regulated in metastatic canine mammary gland tumors. Further analysis of the secondary gene‐sets indicated overexpression of the ES expressed, NOS targets (Nanog targets, Oct4 targets, Sox2 targets, and NOS targets), and Myc targets and underexpression of the Polycomb targets in metastatic canine breast cancer.     

Participatory action inquiry using baccalaureate nursing students: The inclusion of integrative health care modalities in nursing core curriculum

Nurses, nursing educators and students support the inclusion of integrative health care (IHC) into nursing core curriculum as a way to create nurses who deliver nursing care to the full extent of their scope of practice and advance evidenced based IHC. Because of the holistic nature of IHC modalities, research to investigate appropriate teaching strategies and potential efficacy of learning IHC in the baccalaureate core curriculum requires a holistic approach. Therefore a phenomenological exploration using participatory action inquiry was conducted at a large Midwestern university. Eighteen first year nursing students were selected as co-researchers. Their experiences in learning and delivering three 15 min IHC interventions (foot reflexology, lavender aromatherapy and mindful breathing) in an acute care setting were captured using reflexive journaling and participation in structured and organic communicative spaces. Of the patients approached, 67% accepted to receive one or more IHC modalities (147/219). Using van Manen's model for holistic data reduction three themes emerged: The experience of presence, competency and unexpected results. Learning IHC modalities is best supported by a self-reflective process that is constructed and modeled by a nurse faculty member with experience in delivering IHC modalities.     

颅颌面创伤多功能面套的研制和初步应用

目的：研制一种新型多功能面套,应用于颅颌面创伤患者,以达到快速、简便、通用、舒适、牢固和安全的对患者进行包扎.方法：42例患者包括额部、颏部、人中、面颊部、头顶部损伤及合并伤,使用颅颌面创伤多功能面套对其进行包扎治疗.结果：颅颌面创伤多功能面套对42例患者均一次性包扎成功,且提高了包扎的效果.结论：该多功能面套可快速、简便、通用、舒适、牢固和安全的对患者进行包扎,是一种新型的颅颌面创伤包扎面套.     

Head-out immersion in hot water increases serum BDNF in healthy males

Purpose: Brain-derived neurotrophic factor (BDNF) is an important neurotrophin. The present study investigated the effects of head-out water immersion (HOI) on serum BDNF concentrations.

Methods: Eight healthy men performed 20?min head-out water immersion at 42?°C (hot-HOI) and 35?°C (neutral-HOI). These experimental trials were administered in a randomised order separated by at least 7?days. Venous blood samples were withdrawn at rest, immediately after the 20-min HOI, as well as at 15 and 30?min after the end of the HOI. Serum BDNF and S100β, plasma cortisol, platelet and monocyte counts, and core body temperature (T_cb) were measured.

Results: T_cb was higher at the end of the hot-HOI and 15?min after hot-HOI (p?T_cb was recorded during neutral-HOI. BDNF level was higher (p?Conclusions: The present findings suggested that the increase in BDNF during 20-min hot-HOI was induced by hyperthermia through enhanced production, rather than by changes in permeability of the blood–brain barrier (BBB), platelet clotting mechanisms or secretion from monocytes.     

Affective core consciousness and the instroke

Solms and Panksepp have revolutionised concepts of consciousness and unconsciousness. Consciousness is generated by the id, in the brainstem, arises endogenously and is affective. Subjectivity is not corticocentric but located in the upper brainstem. Cortical consciousness is built upon this subjectivity and could not exist without brainstem consciousness. But the reverse is possible. The classical body representation in the cortex is an object representation located in brain areas that create all representations but an internal subjective body exists in the brainstem as the subject of perception. The author reviews 35 years of working with the instroke of the pulsation, which leads to two further developments: the endo self-state and the understanding that the relationship with the self is the most primary relationship. Solms and Panksepp’s work supports both developments grounding these in the functioning of a brainstem subjectivity. In addition, there is encouragement for Reich’s model of the importance of the body, the vegetative system and working with primary emotions.     

Core–shell nanocarriers for cancer therapy. Part I: biologically oriented design rules

Introduction: The application of nanotechnologies to the cancer field for therapeutic, imaging or diagnostic purposes represents an advanced and very attractive approach to overcome the main limits related to conventional chemotherapy. In particular, core–shell nanocarriers can be engineered to provide adequate features to overcome the main biological barriers encountered by free anti-cancer drugs.

Areas covered: This review will try to summarise the design rules – as dictated by biological requirements – to take into account for proper nanocarrier design and to highlight the potential of administration routes other than intravenous.

Expert opinion: Although intravenous injection remains the most investigated route of administration for ‘nanoncologicals', research interest towards less explored administration routes allowing localised chemotherapy or delivery in close proximity to the tumour site might change the way cancer is treated in the near future. Nevertheless, an experimental set-up more biologically oriented taking into account an in-depth evaluation of stability in complex media, protein interaction, and cell interaction of novel nanoconstructs could allow their successful translation in pre-clinical and clinical settings.     

Modeling of activity landscapes for drug discovery

Introduction: Activity landscapes (ALs) are graphical representations that integrate compound structure and potency relationships. These computer-generated models enable the interactive large-scale analysis of structure–activity relationships (SARs) and complement traditional approaches to study SARs of individual compound series in a qualitative or quantitative manner. A variety of AL designs have been reported.

Areas covered: The concept of activity landscapes is introduced and different methodologies to represent 2D or 3D AL representations of large compound data sets are described on the basis of original literature references. Several AL variants and extensions have been generated for special applications in medicinal chemistry. These include, for example, AL views of evolving data sets with constant topology, selectivity landscapes and multi-target ALs, or molecular mechanism and multi-property maps. Furthermore, the applicability domain of the AL concept is discussed including specific requirements for practical utility in medicinal chemistry opportunities for further developments.

Expert opinion: AL modeling has substantially extended conventional ways to study SARs. The AL concept is inseparable from the notion of activity cliffs that are of high interest in SAR analysis. AL design is an area of active research at the interface between chemoinformatics and medicinal chemistry with potential for further growth. Special emphasis must be put on increasing the usability of AL models for practicing medicinal chemists.     

Experimental Methods for Improved Spatial Control of Thermal Lesions in Magnetic Resonance-Guided Focused Ultrasound Ablation

Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU, or MRgFUS) is a hybrid technology that was developed to provide efficient and tolerable thermal ablation of targeted tumors or other pathologic tissues, while preserving the normal surrounding structures. Fast 3-D ablation strategies are feasible with the newly available phased-array HIFU transducers. However, unlike fixed heating sources for interstitial ablation (radiofrequency electrode, microwave applicator, infra-red laser applicator), HIFU uses propagating waves. Therefore, the main challenge is to avoid thermo-acoustical adverse effects, such as energy deposition at reflecting interfaces and thermal drift of the focal lesion toward the near field. We report here our investigations on some novel experimental solutions to solve, or at least to alleviate, these generally known tolerability problems in HIFU-based therapy. Online multiplanar MR thermometry was the main investigational tool extensively used in this study to identify the problems and to assess the efficacy of the tested solutions. We present an improved method to cancel the beam reflection at the exit window (i.e., tissue-to-air interface) by creating a multilayer protection, to dissipate the residual HIFU beam by bulk scattering. This study evaluates selective de-activation of transducer elements to reduce the collateral heating at bone surfaces in the far field, mainly during automatically controlled volumetric ablation. We also explore, using hybrid US/MR simultaneous imaging, the feasibility of using disruptive boiling at the focus, both as a far-field self-shielding technique and as an enhanced ablation strategy (i.e., boiling core controlled HIFU ablation).