New insights into signal transduction pathways in adrenal steroidogenesis: role of mitochondrial fusion, lipid mediators, and MAPK phosphatases.

Hormone-receptor signal transduction has been extensively studied in adrenal gland. Zona glomerulosa and fasciculata cells are responsible for glucocorticoid and mineralocorticoid synthesis by adrenocorticotropin (ACTH) and angiotensin II (Ang II) stimulation, respectively. Since the rate-limiting step in steroidogenesis occurs in the mitochondria, these organelles are key players in the process. The maintenance of functional mitochondria depends on mitochondrial dynamics, which involves at least two opposite events, i.e., mitochondrial fusion and fission. This review presents state-of-the-art data on the role of mitochondrial fusion proteins, such as mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), in Ang II-stimulated steroidogenesis in adrenocortical cells. Both proteins are upregulated by Ang II, and Mfn2 is strictly necessary for adrenal steroid synthesis. The signaling cascades of steroidogenic hormones involve an increase in several lipidic metabolites such as arachidonic acid (AA). In turn, AA metabolization renders several eicosanoids released to the extracellular medium able to bind membrane receptors. This report discusses OXER1, an oxoeicosanoid receptor which has recently arisen as a novel participant in adrenocortical hormone-stimulated steroidogenesis through its activation by AA-derived 5-oxo-ETE. This work also intends to broaden knowledge of phospho/dephosphorylation relevance in adrenocortical cells, particularly MAP kinase phosphatases (MKPs) role in steroidogenesis. At least three MKPs participate in steroid production and processes such as the cellular cycle, either directly or by means of MAP kinase regulation. To sum up, this review discusses the emerging role of mitochondrial fusion proteins, OXER1 and MKPs in the regulation of steroid synthesis in adrenal cortex cells.

An Ex Vivo Tissue Culture Method for Discovering Cell Dynamics Involved in Stromal Vascular Fraction Vasculogenesis Using the Mouse Mesentery.

Stromal vascular fraction (SVF), isolated from adipose tissue, identifies as a rich cell source comprised of endothelial cells, endothelial progenitor cells, pericytes, smooth muscle cells, fibroblasts, and immune cells. SVF represents a promising therapeutic heterogonous cell source for growing new blood microvessels due to its rich niche of cells. However, the spatiotemporal dynamics of SVF within living tissues remain largely unknown. The objective of this chapter is to describe a protocol for culturing SVF on mouse mesentery tissues in order to aid in the discovery of SVF dynamics and associated vessel growth over time. SVF was isolated from the inguinal adipose from adult mice and seeded onto mesentery tissues. Tissues were then cultured for up to 5 days and labeled with endothelial cell and pericyte markers. Representative results demonstrate the observation of SVF-derived vasculogenesis characterized by de novo vessel formation and subsequent vessel connection.

Assessing Interpersonal Relationships in Medical Education: the Connection Index.

OBJECTIVE: The relationship between a resident physician and his/her supervising attending is foundational to graduate medical education and may impact the clinical learning environment and resident well-being. This paper focuses on how to measure connection between a resident and their clinical supervisor. Connection includes the subdomains of psychological safety, empathy, educational alliance, and feedback. METHODS: After reviewing the literature, the authors designed the 12-item, 7-point Connection Index (CI12) to quantitatively measure connections between a resident and his/her supervisor during a 6-month period (supervision dyad), and based on educational alliance, empathy, psychological safety, and effective feedback. A 9-criteria evaluation framework was applied to assess its reliability and validity on a sample of psychiatry residents at a residency program, July 2016 through June 2018. RESULTS: Out of a total possible number of 50 residents, 100% participated to rate 41 supervisors over 201 supervision dyads; the CI12 satisfied all eight of the eight testable criteria, including high scalability (H = 0.78), consistency (alpha = 0.98), test-retest validity (ICC = 0.95), and construct validity where CI12 was found to have statistically significant correlations with outcomes measures (greater connection was associated with less negative emotional experiences, less mistreatment or bias, less burnout, and higher attendance to supervision sessions). CONCLUSION: The authors showed the CI12 can be a valid and reliable instrument to quantify whether a resident and his/her supervisor connects during a 6-month supervision with respect to empathy, psychological safety, educational alliance, and feedback. We recommend assessing connections as part of the overall evaluation of a resident's experience with the clinical learning environment.

Experimental and numerical investigation of standing-wave thermoacoustic instability under transcritical temperature conditions.

This manuscript describes an experimental and numerical investigation of transcritical thermoacoustic instability in a standing-wave setup using the refrigerant octafluoropropane (R-218) as the working fluid. Thermoacoustic instability is excited by two microtube heat exchangers separated by a vacuum-jacketed microtube stack. R-218 is allowed to flow axially through the microtubes into a closed resonator while heating and cooling fluids flow radially over the microtubes to create a temperature gradient. The fluid achieved pressure amplitudes up to 669 kPa (97 psi) at a temperature difference ΔT=Thot-Tcold of 150 K and a base pressure, P0, of 1.3 times the critical pressure (3.43 MPa). The high pressure amplitudes obtained are attributed to the strong density variations near the critical point of the working fluid. The thermoacoustic response was characterized in a set of parametric studies in which ΔT, base pressure, and resonator length were varied. A modeling approach based on linearized Navier-Stokes equations reproduces the experimental results with fair agreement. This work demonstrates promising application of transcritical working fluids to thermoacoustic engines as devices for energy extraction and waste heat removal.

Mucositis periimplantaria asociada a ortodoncia correctiva / Peri-implant mucositis associated to corrective orthodontics

Introducción: Los minitornillos de ortodoncia son dispositivos temporales de anclaje utilizados ampliamente en ortodoncia correctiva. Sin embargo, se ha reportado en la literatura que su tasa clínica de éxito no es completa debido a que pueden existir fallas relacionadas con la pérdida de su estabilidad. Varios factores pueden comprometer el anclaje y están relacionados con el tipo de implante, su manejo quirúrgico y el hospedero. Dentro de este último, se encuentra la inflamación del tejido periimplantario o mucositis que, aunque reversible, es necesario su tratamiento temprano para evitar su progresión a la afectación de tejido duro (periimplantitis). Objetivo: Describir un caso clínico de mucositis periimplantaria asociada a un dispositivo de anclaje ortodóntico temporal. Presentación del caso: Paciente femenina que acudió a la consulta por presentar dolor en la zona anterior del maxilar superior. Durante el examen intraoral se observó que usaba aparatos de ortodoncia con mecanismo de anclaje: dos minitornillos de ortodoncia ubicados al nivel de los caninos superiores. Se realizó la remoción quirúrgica de los minitornillos de ortodoncia, se le indicó el uso de antibióticos y se realizó estudio histopatológico para descartar malignidad. Se diagnosticó con mucositis periimplantaria. Conclusiones: La remoción quirúrgica de los minitornillos de ortodoncia es una excelente alternativa para evitar la progresión de la lesión hacia los tejidos duros. A través de esta técnica lograron eliminar signos de dolor, enrojecimiento y sangrado(AU)

Introduction: Orthodontic miniscrews are temporary anchorage devices widely used in corrective orthodontics. However, it has been reported in the literature that their clinical success rate is not high, due to failures related to the loss of stability. Anchorage may be affected by factors associated to the type of implant, its surgical management and the host. Host-related factors include peri-implant tissue inflammation or mucositis, which though reversible, its early treatment is necessary to prevent expansion into and damage to the hard tissue (peri-implantitis). Objective: Describe a clinical case of peri-implant mucositis associated to a temporary orthodontic anchorage device. Case presentation: A female patient attends clinical consultation with pain in the anterior zone of her upper maxilla. Intraoral examination revealed the presence of orthodontic appliances with an anchorage mechanism: two orthodontic miniscrews located at the level of the upper canines. Surgical removal was performed of the orthodontic miniscrews, antibiotics were indicated and histopathological testing was conducted to rule out malignancy. The patient was diagnosed with peri-implant mucositis. Conclusions: Surgical removal of orthodontic miniscrews is an excellent alternative to prevent the progress of the lesion into hard tissues. Pain signs, reddening and bleeding were all eliminated with the technique applied(AU)

Alteración del colágeno en la Hipertrofia Gingival en pacientes con ortodoncia: caracterización histológica e inmunohistoquímica / Collagen alteration in gingival hypertrophy in orthodontic patients: histological and immunohistochemical characterization

Resumen Introducción: La hipertrofia gingival (HG) es el aumento del volumen de la encía asociado a ciertas enfermedades sistémicas, hereditarias (idiopático), ingesta de algunos medicamentos o a factores locales como el tratamiento ortodóntico, capaz de provocar cambios histológicos en el tejido conectivo gingival. Objetivo: Describir las características histológicas e identificar el colágeno tipo I y tipo III en tejidos gingivales de sujetos con hipertrofia gingival portadores de ortodoncia. Materiales y método: Se diseñó un estudio de casos y controles que incluyó el análisis de biopsias de tejido gingival de 12 pacientes sometidos a cirugías periodontales. La muestra se dividió en dos grupos: individuos sanos (control; n= 6) y pacientes con HG portadores de ortodoncia (pacientes; n= 6). Las muestras fueron procesadas e incluidas en parafina. Las tinciones Masson-Goldner y rojo sirius/verde rápido fueron empleadas. El colágeno tipo I y tipo III fueron identificados mediante inmunohistoquímica con anticuerpos monoclonales. Resultado: En los pacientes con HG portadores de ortodoncia se observó un epitelio hiperplásico y tejido conectivo denso con abundantes fibras de colágeno distribuidos aleatoriamente. La inmunodetención de colágeno tipo I indicó la presencia de abundantes fibras desorganizadas y el colágeno tipo III fue inmunolocalizado subyacente a la membrana basal, vasos sanguíneos y toda la extensión del tejido conectivo de los pacientes con HG con tratamiento ortodóntico. Conclusión: La acumulación de fibras de colágeno, particularmente del colágeno tipo I y tipo III, son hallazgos histológicos que caracterizan la HG en pacientes portadores de ortodoncia. Futuros estudios son necesarios para dilucidar el fenotipo de los fibroblastos gingivales y la probable pérdida homeostática entre la producción y degradación de colágeno en esta patología.

Abstract Introduction: Gingival hypertrophy (GH) is the increase in the volume of the gingiva associated with certain systemic, hereditary (idiopathic) diseases, the intake of some medications or local factors such as orthodontic treatment, capable of causing histological changes in the gingival connective tissue. Objective: To describe the histological characteristics and identify type I and type III collagen in gingival tissues of subjects with gingival hypertrophy wearing orthodontics. Method: A case-control study was designed that included the analysis of gingival tissue biopsies from 12 patients submitted to periodontal surgeries. The sample was divided into two groups: healthy individuals (Control; n= 6) and patients with GH wearing orthodontics (Patients; n= 6). The samples were processed and embedded in paraffin. Masson-goldner and sirius red/fast green stains were used. Type I and type III collagen were identified by immunohistochemistry with monoclonal antibodies. Result: A hyperplastic epithelium and dense connective tissue with abundant randomly distributed collagen fibers were observed in patients with orthodontic GH. Immunodetention of type I collagen indicated the presence of abundant disorganized fibers and type III collagen was inmunolocalized underlying the basement membrane, blood vessels and the entire extension of the connective tissue of patients with GH orthodontic. Conclusion: The accumulation of collagen fibers, particularly type I and type III collagen, are histological findings that characterize GH in orthodontic wearers. Future studies are necessary to elucidate the phenotype of gingival fibroblasts and the probable homeostatic loss between collagen production and degradation in this pathology.

Pericyte migration and proliferation are tightly synchronized to endothelial cell sprouting dynamics.

Pericytes are critical for microvascular stability and maintenance, among other important physiological functions, yet their involvement in vessel formation processes remains poorly understood. To gain insight into pericyte behaviors during vascular remodeling, we developed two complementary tissue explant models utilizing 'double reporter' animals with fluorescently-labeled pericytes and endothelial cells (via Ng2:DsRed and Flk-1:eGFP genes, respectively). Time-lapse confocal imaging of active vessel remodeling within adult connective tissues and embryonic skin revealed a subset of pericytes detaching and migrating away from the vessel wall. Vessel-associated pericytes displayed rapid filopodial sampling near sprouting endothelial cells that emerged from parent vessels to form nascent branches. Pericytes near angiogenic sprouts were also more migratory, initiating persistent and directional movement along newly forming vessels. Pericyte cell divisions coincided more frequently with elongating endothelial sprouts, rather than sprout initiation sites, an observation confirmed with in vivo data from the developing mouse brain. Taken together, these data suggest that (i) pericyte detachment from the vessel wall may represent an important physiological process to enhance endothelial cell plasticity during vascular remodeling, and (ii) pericyte migration and proliferation are highly synchronized with endothelial cell behaviors during the coordinated expansion of a vascular network.

Bioprinting on Live Tissue for Investigating Cancer Cell Dynamics.

A challenge in cancer research is the lack of physiologically responsive in vitro models that enable tracking of cancer cells in tissue-like environments. A model that enables real-time investigation of cancer cell migration, fate, and function during angiogenesis does not exist. Current models, such as 2D or 3D in vitro culturing, can contain multiple cell types, but they do not incorporate the complexity of intact microvascular networks. The objective of this study was to establish a tumor microvasculature model by demonstrating the feasibility of bioprinting cancer cells onto excised mouse tissue. Inkjet-printed DiI+ breast cancer cells on mesometrium tissues from C57Bl/6 mice demonstrated cancer cells' motility and proliferation through time-lapse imaging. Colocalization of DAPI+ nuclei confirmed that DiI+ cancer cells remained intact postprinting. Printed DiI+ 4T1 cells also remained viable after printing on Day 0 and after culture on Day 5. Time-lapse imaging over 5 days enabled tracking of cell migration and proliferation. The number of cells and cell area were significantly increased over time. After culture, cancer cell clusters were colocalized with angiogenic microvessels. The number of vascular islands, defined as disconnected endothelial cell segments, was increased for tissues with bioprinted cancer cells, which suggests that the early stages of angiogenesis were influenced by the presence of cancer cells. Bioprinting cathepsin L knockdown 4T1 cancer cells on wild-type tissues or nontarget 4T1 cells on NG2 knockout tissues served to validate the use of the model for probing tumor cell versus microenvironment changes. These results establish the potential for bioprinting cancer cells onto live mouse tissues to investigate cancer microvascular dynamics within a physiologically relevant microenvironment. Impact statement To keep advancing the cancer biology field, tissue engineering has been focusing on developing in vitro tumor biomimetic models that more closely resemble the native microenvironment. We introduce a novel methodology of bioprinting exogenous cancer cells onto mouse tissue that contains multiple cells and systems within native physiology to investigate cancer cell migration and interactions with nearby microvascular networks. This study corroborates the manipulation of different exogenous cells and host microenvironments that impact cancer cell dynamics in a physiologically relevant tissue. Overall, it is a new approach for delineating the effects of the microenvironment on cancer cells and vice versa.

Microvascular dysfunction and kidney disease: Challenges and opportunities?

Kidneys are highly vascular organs that despite their relatively small size receive 20% of the cardiac output. The highly intricate, delicately organized structure of renal microcirculation is essential to enable renal function and glomerular filtration rate through the local modulation of renal blood flow and intraglomerular pressure. Not surprisingly, the dysregulation of blood flow within the microvessels (abnormal vasoreactivity), fibrosis driven by disordered vascular-renal cross talk, or the loss of renal microvasculature (rarefaction) is associated with kidney disease. In addition, kidney disease can cause microcirculatory dysfunction in distant organs such as the heart and brain, mediated by mechanisms that remain to be elucidated. The objective of this review is to highlight the role of renal microvasculature in kidney disease. The overview will outline the impetus to study renal microvasculature, the bidirectional relationship between kidney disease and microvascular dysfunction, the key pathways driving microvascular diseases such as vasoreactivity, the cell dynamics coordinating fibrosis, and vessel rarefaction. Finally, we will also briefly highlight new therapies targeting the renal microvasculature to improve renal function.

A clinical perspective on adipose-derived cell therapy for enhancing microvascular health and function: Implications and applications for reconstructive surgery.

Restoration of form and function requires apposition of tissues in the form of flaps to reconstitute local perfusion. Successful reconstruction relies on flap survival and its integration with the recipient bed. The flap's precariously perfused hypoxic areas undergo adaptive microvascular changes both internally and in connection with the recipient bed. A cell-mediated, coordinated response to hypoxia drives these adaptive processes, restoring a tissue's normoxic homeostasis via de novo vasculogenesis, sprouting angiogenesis, and stabilizing arterialization. As cells exert prolonged and coordinated effects on site, their use as biological agents merit translational consideration of sourcing angio-competent cells and delivering them to territories enduring microcirculatory acclimatization. Angio-competent cells abound in adipose tissue: a reliable, accessible, and expendable source of adipose-derived cells (ADC). When subject to enzymatic digestion and centrifugation, adipose tissue separates its various ADC: A subset of buoyant oil-dense adipocytes (the tissue's parenchymal component) accumulates on a supra-natant layer, whereas the mesenchymal component remains in the infra-natant sediment, containing the tissue's stromal vascular fraction (SVF), where angio-component cells abound. The SVF can be further manipulated, selected, or culture expanded into more specific stromal subsets (herein defined as adipose stromal cells, ASC). While promising clinical applications for ADC await clinical proof and regulatory authorization, basic science investigation is needed to elucidate the specific ADC mechanisms that influence microvascular growth, remodeling, and function following flap surgery. The objective of this article is to share the clinical perspectives of reconstructive plastic surgeons regarding the use of ADC-based therapies to help with flap tissue integration, revascularization, and wound healing. Specifically, the focus will be on considering the potential for ADC as therapeutic agents and how their clinical application motivates basic science opportunities.

Vaginal residence and pharmacokinetic preclinical study of topical vaginal mucoadhesive W/S emulsions containing ciprofloxacin.

The aim of this work is to test the in vivo behavior of a mucoadhesive vaginal emulsion resistant to the clearance of vaginal fluids using ciprofloxacin (CPX) as an anti-infective model of drug. CPX is a broad-spectrum antibiotic used in the treatment of sexual tissues infections, as intravenous injection in a dose of 20 mg every 12 h. In this study, CPX was incorporated in water in silicone (W/S) mucoadhesive emulsions and the in vivo residence time and the CPX in vivo absorption and distribution to the sexual organs was studied using the rat as animal model. W/S emulsion shows excellent in vitro bioadhesion having high resistance to the vaginal fluids clearance. The drug release profiles show a constant release of CPX during at least 6 h according to a zero-order kinetics. In vivo computerized PET/CT Image Analysis after intravaginal administration to rats indicates that W/S emulsions remain in the vaginal area for a long time and shows a good absorption of the radiotracers used as markers through the vaginal mucosa. Ciprofloxacin pharmacokinetic studies developed after the single intravaginal administration of W/S emulsion shows a good absorption and distribution of CPX on the uterus and ovarian tissue. A significant concentration of CPX in the sexual tissues was observed after 24 h of administration of W/S emulsion. Therefore, W/S emulsions have a good in vivo residence and drug release in the vaginal mucosae showing a great potential for the treatment of sexual tissues infections, as vaginal bioadhesive delivery systems of antinfectious drugs.

Induction of microvascular network growth in the mouse mesentery.

OBJECTIVE: Motivated by observations of mesenteries harvested from mice treated with tamoxifen dissolved in oil for inducible gene mutation studies, the objective of this study was to demonstrate that microvascular growth can be induced in the avascular mouse mesentery tissue. METHODS: C57BL/6 mice were administered an IP injection for five consecutive days of: saline, sunflower oil, tamoxifen dissolved in sunflower oil, corn oil, or peanut oil. RESULTS: Twenty-one days post-injection, zero tissues from saline group contained branching microvascular networks. In contrast, all tissues from the three oils and tamoxifen groups contained vascular networks with arterioles, venules, and capillaries. Smooth muscle cells and pericytes were present in their expected locations and wrapping morphologies. Significant increases in vascularized tissue area and vascular density were observed when compared to saline group, but sunflower oil and tamoxifen group were not significantly different. Vascularized tissues also contained LYVE-1-positive and Prox1-positive lymphatic networks, indicating that lymphangiogenesis was stimulated. When comparing the different oils, vascularized tissue area and vascular density of sunflower oil were significantly higher than corn and peanut oils. CONCLUSIONS: These results provide novel evidence supporting that induction of microvascular network growth into the normally avascular mouse mesentery is possible.

Improving Children's cancer pain management in the home setting: Development and formative evaluation of a web-based program for parents.

BACKGROUND AND METHODS: Despite advances in health care, the majority of children undergoing cancer treatment experience pain, particularly in the home setting. Mobile health tools provide a promising avenue to deliver pain management education and information to parents of children receiving cancer treatment. The current study describes the development and formative evaluation of a novel intervention, Cancer-Tailored Intervention for Pain and Symptoms (C-TIPS), which provides empirically-based pharmacological and non-pharmacological pain management information and coping skills training to parents of pediatric cancer patients. C-TIPS is a web-based application including a tailoring algorithm, customization tools, guided diaphragmatic breathing training, relaxation practice, and educational material (COPE modules). Thirty parents of children undergoing chemotherapy treatment for cancer participated in this initial mixed methods pilot study. Participants completed quantitative measures assessing their stress and relaxation ratings and satisfaction with C-TIPS. Formative evaluation and qualitative data were collected using individual and group interviews. RESULTS: Parents reported high satisfaction with both the educational and skills training modules of C-TIPS (ps < 0.001). Parent self-reported stress significantly reduced (p = 0.004) and relaxation increased (p = 0.05) following participation with the skills training module. CONCLUSIONS: C-TIPS is a feasible and well-received web-based intervention that promises to improve pain management in children undergoing cancer treatment, improve stress management in parents, and increase parents' knowledge and understanding of their child's cancer treatment. Results from the current study will help make improvements to C-TIPS in preparation for a randomized-controlled trial of this innovative program.

Cold Pressor Pain Response in Children With Cancer.

OBJECTIVE: The goal of this study was to examine pain responses in pediatric patients with cancer. METHOD: Children (ages 6 to 18) undergoing treatment for cancer (N=68) completed the cold pressor task. RESULTS: Average pain tolerance was 118.22 seconds (SD=101.18) and 40% of the children kept their hand in the water the entire 4-minute ceiling. On a 0 to 10 numeric rating scale, children reported a pain severity of 5.07 (SD=3.47) at their first report of pain, a pain severity of 5.94 (SD=3.54) at their maximum report of pain, and a pain severity of 5.33 (SD=3.72) at the time they reached pain tolerance. Children receiving chemotherapy agents (N=56) with possible neuropathic effects exhibited higher pain tolerance compared with children not receiving such treatments (N=10), ß=0.84, SE=0.38, Wald χ1=4.88, P=0.027, hazard ratio=2.33, 95% confidence interval (1.10-4.92). CONCLUSIONS: This study provides data on experimental pain responses in a sample of children undergoing cancer treatment and suggests that pain experience may be moderated by cancer treatment type.

A Novel ex vivo Mouse Mesometrium Culture Model for Investigating Angiogenesis in Microvascular Networks.

BACKGROUND: The development of models that incorporate intact microvascular networks enables the investigation of multicellular dynamics during angiogenesis. Our laboratory introduced the rat mesentery culture model as such a tool, which would be enhanced with mouse tissue. Since mouse mesentery is avascular, an alternative is mouse mesometrium, the connective tissue of uterine horns. The study's objective was to demonstrate that mouse mesometrium contains microvascular networks that can be cultured to investigate multicellular dynamics during angiogenesis. METHODS: Harvested mesometrium tissues from C57Bl/6 female mice were cultured in media with serum for up to 7 days. PECAM, NG2, αSMA, and LYVE-1 labeling identified endothelial cells, pericytes, smooth muscle cells, and lymphatic endothelial cells, respectively. RESULTS: These cells comprised microvascular networks with arterioles, venules, and capillaries. Compared to day 0, capillary sprouts per vascular length were increased by 3 and 5 days in culture (day 0, 0.08 ± 0.01; day 3, 3.19 ± 0.78; day 5, 2.49 ± 0.05 sprouts/mm; p < 0.05). Time-lapse imaging of cultured tissues from FlkEGFP mice showcases the use of the model for lineage studies. The impact is supported by the identification of endothelial cell jumping from one sprout to another. CONCLUSION: These results introduce a novel culture model for investigating multicellular dynamics during angiogenesis in real-time ex vivo microvascular networks.

Understanding angiogenesis during aging: opportunities for discoveries and new models.

Microvascular network growth and remodeling are common denominators for most age-related pathologies. For multiple pathologies (myocardial infarction, stroke, hypertension), promoting microvascular growth, termed angiogenesis, would be beneficial. For others (cancer, retinopathies, rheumatoid arthritis), blocking angiogenesis would be desirable. Most therapeutic strategies, however, are motivated based on studies using adult animal models. This approach is problematic and does not account for the impaired angiogenesis or the inherent network structure changes that might result from age. Considering the common conception that angiogenesis is impaired with age, a need exists to identify the causes and mechanisms of angiogenesis in aged scenarios and for new tools to enable comparison of aged versus adult responses to therapy. The objective of this article is to introduce opportunities for advancing our understanding of angiogenesis in aging through the discovery of novel cell changes along aged microvascular networks and the development of novel ex vivo models.

Emotion regulation and positive affect in the context of salivary alpha-amylase response to pain in children with cancer.

BACKGROUND: Children with cancer routinely undergo painful medical procedures invoking strong physiological stress responses. Resilience to this pain may be conferred through resources such as emotion regulation strategies and positive affect. PROCEDURE: This study measured dispositional positive affect in children with cancer (N = 73) and randomly assigned participants to one of three emotion regulation strategy conditions (distraction, reappraisal, or reassurance). Children applied their assigned strategy during an experimental pain procedure (the cold pressor task [CPT]) and provided saliva samples before, immediately after, and 15 min after the CPT. Saliva samples were later assayed for salivary alpha amylase (sAA)-a surrogate marker for autonomic/sympathetic nervous system activity and regulation. RESULTS: Children in the reassurance group had sAA levels that continued to rise after completion of the CPT compared to children in the distraction (b = -1.68, P = 0.021) and reappraisal conditions (b = -1.24, P = 0.084). Furthermore, dispositional positive affect moderated the effect of condition such that children in the reassurance group with lower levels of positive affect had sAA levels that continued to rise after completion of the CPT (dy/dx = 1.56, P = 0.027), whereas children in the reassurance condition with higher levels of positive affect did not exhibit this rise (P > 0.05). CONCLUSIONS: Specific emotion regulation strategies, such as distraction and reappraisal, may attenuate the stress response to pain in pediatric patients with cancer, and positive affect may confer resilience in response to pain even with use of less effective coping strategies such as reassurance.

Community-based participatory research: an innovative approach for improving perioperative care of underserved children.

Pediatric disparities disproportionately affect Latino youth undergoing surgery and their families. As such, there is a critical need for culturally relevant frameworks that can advance perioperative intervention approaches in this population and reduce these disparities. In the following article, we first describe the methodological process of community-based participatory research (CBPR) and next report the results of the CBPR process that was conducted in this population. An interdisciplinary group of investigators, Latina mothers, and various other stakeholders met for a series of CBPR-based structured meetings. Qualitative data collection and analyses of the CBPR process were guided by principles of grounded theory that employs inductive techniques and constant comparison analyses until reaching saturation of data. Barriers identified in the process can be grouped within the following domains: child-related factors, family-related factors, health care provider factors, and hospital system factors. Family system factors category (coded references = 136) had the highest number of coded references; this category was found to be best described by the value of familismo or familism, including a duty to help family members when in need. The health care provider category (coded references = 42) was ranked second by frequency. Within this category, two major themes surfaced: health care provider cultural competence and overestimating health literacy. All barriers identified will be next incorporated in an innovative behavioral intervention that is currently being developed. We conclude that the model of CBPR can be used within the context of perioperative care of children and their families.

Aging is associated with impaired angiogenesis, but normal microvascular network structure, in the rat mesentery.

A big problem associated with aging is thought to be impaired microvascular growth or angiogenesis. However, to link the evidence for impaired angiogenesis to microvascular dysfunction in aged tissues, we must compare adult vs. aged microvascular networks in unstimulated scenarios. The objective of this study was to test the hypothesis that aged microvascular networks are characterized by both fewer vessels and the impaired ability to undergo angiogenesis. Mesentery tissues from adult (9-mo) and aged (24-mo) male Fischer 344 rats were harvested and immunolabeled for platelet/endothelial cell adhesion molecule (an endothelial cell marker) according to two scenarios: unstimulated and stimulated. For unstimulated groups, tissues harvested from adult and aged rats were compared. For stimulated groups, tissues were harvested 3 or 10 days after compound 48/80-induced mast cell degranulation stimulation. Unstimulated aged microvascular networks displayed larger mean vascular area per tissue area compared with the unstimulated adult networks. The lack of a decrease in vessel density was supported at the gene expression level with RNA-Seq analysis and with comparison of vessel densities in soleus muscle. Following stimulation, capillary sprouting and vessel density were impaired in aged networks at 3 and 10 days, respectively. Our results suggest that aging associated with impaired angiogenesis mechanisms might not influence normal microvascular function, since unstimulated aged microvascular networks can display a "normal adult-like" vessel density and architecture. NEW & NOTEWORTHY: Using a multidimensional approach, we present evidence supporting that aged microvascular networks display vessel density and patterning similar to adult networks despite also being characterized by a decreased capacity to undergo angiogenesis. Thus, vessel loss is not necessarily a characteristic of aging.

Pain buddy: A novel use of m-health in the management of children's cancer pain.

BACKGROUND: Over 12,000 children are diagnosed with cancer every year in the United States. In addition to symptoms associated with their disease, children undergoing chemotherapy frequently experience significant pain, which is unfortunately often undertreated. The field of m-Health offers an innovative avenue for pain assessment and intervention in the home setting. The current study describes the development and initial evaluation of a tablet-based program, Pain Buddy, aimed to enhance pain management and foster improved quality of life in children ages 8-18 years undergoing cancer treatment. METHODS: An animated avatar-based tablet application was developed using state-of-the-art software. Key aspects of Pain Buddy include daily pain and symptom diaries completed by children, remote monitoring of symptoms by uploading patient's data through internet to a cloud server, cognitive and behavioral skills training, interactive three-dimensional avatars that guide children through the program, and an incentive system to motivate engagement. Twelve children between the ages of 8 and 18 participated in a pilot study of Pain Buddy. RESULTS: Children were highly satisfied with the program. Pain and appetite disturbances were most frequently endorsed. Symptom trigger alerts to outside providers were largely related to clinically significant pain. Children infrequently used analgesics, and reported using some non-pharmacological pain management strategies. CONCLUSION: Pain Buddy appears to be a promising tool to improve pain and symptom management in children undergoing cancer treatment. Results from the current study will inform future improvements to Pain Buddy, in preparation for a randomized controlled trial to assess the efficacy of this innovative treatment.