Murine Hind Limb Explant Model for Studying the Mechanobiology of Achilles Tendon Impingement.

Tendon impingement upon bone generates a multiaxial mechanical strain environment with markedly elevated transverse compressive strain, which elicits a localized fibrocartilage phenotype characterized by accumulation of glycosaminoglycan (GAG)-rich matrix and remodeling of the collagen network. While fibrocartilage is a normal feature in impinged regions of healthy tendons, excess GAG deposition and disorganization of the collagen network are hallmark features of tendinopathy. Accordingly, impingement is clinically recognized as an important extrinsic factor in the initiation and progression of tendinopathy. Nevertheless, the mechanobiology underlying tendon impingement remains understudied. Prior efforts to elucidate the cellular response to tendon impingement have applied uniaxial compression to cells and excised tendon explants in vitro. However, isolated cells lack a three-dimensional extracellular environment crucial to mechanoresponse, and both in vitro and excised explant studies fail to recapitulate the multiaxial strain environment generated by tendon impingement in vivo, which depends on anatomical features of the impinged region. Moreover, in vivo models of tendon impingement lack control over the mechanical strain environment. To overcome these limitations, we present a novel murine hind limb explant model suitable for studying the mechanobiology of Achilles tendon impingement. This model maintains the Achilles tendon in situ to preserve local anatomy and reproduces the multiaxial strain environment generated by impingement of the Achilles tendon insertion upon the calcaneus during passively applied ankle dorsiflexion while retaining cells within their native environment. We describe a tissue culture protocol integral to this model and present data establishing sustained explant viability over 7 days. The representative results demonstrate enhanced histological GAG staining and decreased collagen fiber alignment secondary to impingement, suggesting elevated fibrocartilage formation. This model can easily be adapted to investigate different mechanical loading regimens and allows for the manipulation of molecular pathways of interest to identify mechanisms mediating phenotypic change in the Achilles tendon in response to impingement.

Pediatric Chronic Critical Illness, Prolonged ICU Admissions, and Clinician Distress.

To gain an in-depth understanding of the experience of pediatric intensive care unit (PICU) clinicians caring for children with chronic critical illness (CCI), we conducted, audiotaped, and transcribed in-person interviews with PICU clinicians. We used purposive sampling to identify five PICU patients who died following long admissions, whose care generated substantial staff distress. We recruited four to six interdisciplinary clinicians per patient who had frequent clinical interactions with the patient/family for interviews. Conventional content analysis was applied to the transcripts resulting in the emergence of five themes: nonbeneficial treatment; who is driving care? Elusive goals of care, compromised personhood, and suffering. Interventions directed at increasing consensus, clarifying goals of care, developing systems allowing children with CCI to be cared for outside of the ICU, and improving communication may help to ameliorate this distress.

Stabilization of Damaged Articular Cartilage with Hydrogel-Mediated Reinforcement and Sealing.

Cartilage injuries and subsequent tissue deterioration impact millions of patients. Since the regeneration of functional hyaline cartilage remains elusive, methods to stabilize the remaining tissue, and prevent further deterioration, would be of significant clinical utility and prolong joint function. Finite element modeling shows that fortification of the degenerate cartilage (Reinforcement) and reestablishment of a superficial zone (Sealing) are both required to restore fluid pressurization within the tissue and restrict fluid flow and matrix loss from the defect surface. Here, a hyaluronic acid (HA) hydrogel system is designed to both interdigitate with and promote the sealing of the degenerated cartilage. Interdigitating fortification restores both bulk and local pericellular tissue mechanics, reestablishing the homeostatic mechanotransduction of endogenous chondrocytes within the tissue. This HA therapy is further functionalized to present chemo mechanical cues that improve the attachment and direct the response of mesenchymal stem/stromal cells at the defect site, guiding localized extracellular matrix deposition to "seal" the defect. Together, these results support the therapeutic potential, across cell and tissue length scales, of an innovative hydrogel therapy for the treatment of damaged cartilage.

A Systematic Review and Guide to Mechanical Testing for Articular Cartilage Tissue Engineering.

Articular cartilage is integral to the mechanical function of many joints in the body. When injured, cartilage lacks the capacity to self-heal, and thus, therapies and replacements have been developed in recent decades to treat damaged cartilage. Given that the primary function of articular cartilage is mechanical in nature, rigorous physical evaluation of cartilage tissues undergoing treatment and cartilage constructs intended for replacement is an absolute necessity. With the large number of groups developing cartilage tissue engineering strategies, however, a variety of mechanical testing protocols have been reported in the literature. This lack of consensus in testing methods makes comparison between studies difficult at times, and can lead to misinterpretation of data relative to native tissue. Therefore, the purpose of this study was to systematically review mechanical testing of articular cartilage and cartilage repair constructs over the past 10 years (January 2009-December 2018), to highlight the most common testing configurations, and to identify key testing parameters. For the most common tests, key parameters identified in this systematic review were validated by characterizing both cartilage tissue and hydrogels commonly used in cartilage tissue engineering. Our findings show that compression testing was the most common test performed (80.2%; 158/197), followed by evaluation of frictional properties (18.8%; 37/197). Upon further review of those studies performing compression testing, the various modes (ramp, stress relaxation, creep, dynamic) and testing configurations (unconfined, confined, in situ) are described and systematically reviewed for parameters, including strain rate, equilibrium time, and maximum strain. This systematic analysis revealed considerable variability in testing methods. Our validation testing studies showed that such variations in testing criteria could have large implications on reported outcome parameters (e.g., modulus) and the interpretation of findings from these studies. This analysis is carried out for all common testing methods, followed by a discussion of less common trends and directions in the mechanical evaluation of cartilage tissues and constructs. Overall, this work may serve as a guide for cartilage tissue engineers seeking to rigorously evaluate the physical properties of their novel treatment strategies. Impact Statement Articular cartilage tissue engineering has made significant strides with regard to treatments and replacements for injured tissue. The evaluation of these approaches typically involves mechanical testing, yet the plethora of testing techniques makes comparisons between studies difficult, and often leads to misinterpretation of data compared with native tissue. This study serves as a guide for the mechanical testing of cartilage tissues and constructs, highlighting recent trends in test conditions and validating these common procedures. Cartilage tissue engineers, especially those unfamiliar with mechanical testing protocols, will benefit from this study in their quest to physically evaluate novel treatment and regeneration approaches.

Role of behavioral health in management of pediatric atopic dermatitis.

OBJECTIVE: To describe the behavioral components and complications in treating pediatric patients with atopic dermatitis (AD) and the critical role of behavioral health professionals in addressing disease impact and behavioral aspects of disease management for these patients and families. DATA SOURCES: Studies and review articles were selected from medical and psychology databases for relevance to pertinent topics. RESULTS: AD has significant negative effects in affected individuals and their families on quality of life, behavioral, emotional, and sleep disturbances, and family functioning. Effective treatment strategies for AD are available, but the challenges for children and parents in coping with disease-related concerns and in following through with the multiple aspects of treatment are considerable. A biopsychosocial model, which incorporates the interplay among biological, psychological, and social dimensions of medical care, can be implemented in various treatment settings to achieve an integrated medical and behavioral health care approach. By sharing a family orientation, using a stress and coping model, and taking into account children's developmental capabilities and concerns, medical and behavioral health care providers are equipped to bring an in-depth understanding and different evidence-based therapeutic tools to address emotional, behavioral, and interpersonal challenges imposed by moderate to severe AD in children and families. CONCLUSION: Behavioral health and medical providers working together to provide integrated care play a critical role in helping children and families cope with the burdens imposed by AD, successfully manage the disease, and achieve optimal quality of life for affected children and their families.

A social-ecological framework: A model for addressing ethical practice in nursing.

AIMS AND OBJECTIVES: To develop a framework to enable discussion, debate and the formulation of interventions to address ethical issues in nursing practice. BACKGROUND: Social, cultural, political and economic drivers are rapidly changing the landscape of health care in our local environments but also in a global context. Increasingly, nurses are faced with a range of ethical dilemmas in their work. This requires investigation into the culture of healthcare systems and organisations to identify the root causes and address the barriers and enablers of ethical practice. The increased medicalisation of health care; pressures for systemisation; efficiency and cost reduction; and an ageing population contribute to this complexity. Often, ethical issues in nursing are considered within the abstract and philosophical realm until a dilemma is encountered. Such an approach limits the capacity to tangibly embrace ethical values and frameworks as pathways to equitable, accessible, safe and quality health care and as a foundation for strengthening a supportive and enabling workplace for nurses and other healthcare workers. DESIGN: Conceptual framework development. METHODS: A comprehensive literature review was undertaken using the social-ecological framework as an organising construct. RESULTS: This framework views ethical practice as the outcome of interaction among a range of factors at eight levels: individual factors (patients and families); individual factors (nurses); relationships between healthcare professionals; relationships between patients and nurses; organisational healthcare context; professional and education regulation and standards; community; and social, political and economic. CONCLUSIONS: Considering these elements as discrete, yet interactive and intertwined forces can be useful in developing interventions to promote ethical practice. We consider this framework to have utility in policy, practice, education and research. RELEVANCE TO CLINICAL PRACTICE: Nurses face ethical challenges on a daily basis, considering these within a social-ecological framework can assist in developing strategies and resolutions.

What is the relationship between free flow and pressure flow studies in women?

INTRODUCTION AND HYPOTHESIS: The relationship between free flow (FFS) and pressure flow (PFS) voiding studies remains uncertain and the effect of a urethral catheter on flow rates has not been determined. The relationship between residuals obtained at FF and PFS has yet to be established. METHODS: This was a prospective cohort study based on 474 consecutive women undergoing cystometry using different sized urethral catheters at different centres. FFS and PFS data were compared for different conditions and the relationship of residuals analysed for FFS and PFS. The null hypothesis was that urethral catheters do not produce an alteration in maximum flow rates for PFS and FF studies. RESULTS: Urethral catheterisation results in lower flow rates (p < 0.01) and this finding is confirmed when flows are corrected for voided volume (p < 0.01). FFS and PFS maximum flow rates are lower in women with DO than USI (p < 0.01). A 6-F urethral catheter does not have a significantly greater effect than a 4.5-F urethral catheter. A mathematical model can be applied to transform FFS to PFS flow rates and vice versa. There was no significant difference between the mean residuals of the two groups (FFS vs PFS-two-tailed t = 0.54, p = 0.59). Positive residuals in FFS showed a good association with positive residuals in the PFS (r = 0.53, p < 0.01) CONCLUSIONS: Urethral catheterisation results in lower maximum flow rates. The relationship can be compared mathematically. The null hypothesis can be rejected.

Urgency resolution following prolapse surgery: is voiding important?

INTRODUCTION AND HYPOTHESIS: The objective of this study was to assess whether resolution of urgency symptoms in women undergoing surgical repair of pelvic organ prolapse (POP) is associated with any measurable change in voiding parameters. METHODS: This was a prospective observational study. Women with symptomatic POP stage 2 or greater requiring surgery and who had concurrent urinary urgency and/or urinary urgency incontinence (UUI) were eligible for inclusion. Uroflowmetry data was collected from eligible women with urgency who underwent POP repair both preoperatively and at 10 weeks postoperative. Previously published preliminary data were used for an a priori power calculation. Urgency was assessed pre- and postoperatively with the Urgency Perception Scale (UPS). Participants were divided into those who experienced urgency resolution and those with persistent urgency. Differences in voiding parameters were evaluated at baseline and postoperatively in the two groups. The primary outcome measures were change in maximum flow rate and presence of urgency symptoms as determined by the UPS 10 weeks postoperatively. A paired Student's t test was used to evaluate whether there was any significant difference in uroflowmetry parameters between the two groups postoperatively, with an unpaired Student's t test test being used to evaluate any differences in these parameters at baseline. Discrete data were evaluated using Fisher's exact test. RESULTS: One hundred and twenty-eight women were recruited to the study. Urgency resolved in 61.7 % of participants, with resolution being associated with a significant increase in maximum flow rate from 11.2 [confidence interval (CI) 3.4-20.1] to 26.9 (CI 17.1-35.2) (p = 0.03), even when corrected for voiding volume. CONCLUSION: This large prospective study indicates that urgency resolution after prolapse repair is associated with an increase in urinary flow rate, indicating a possible aetiological role for voiding in women with POP and urgency.

Psychopharmacological treatment for very young children: contexts and guidelines.

Systematic research and practice guidelines addressing preschool psychopharmacological treatment in very young children are limited, despite evidence of increasing clinical use of medications in this population. The Preschool Psychopharmacology Working Group (PPWG) was developed to review existing literature relevant to preschool psychopharmacology treatment and to develop treatment recommendations to guide clinicians considering psychopharmacological treatment in very young children. This article reviews the developmental considerations related to preschool psychopharmacological treatment, presents current evidence bases for specific disorders in early childhood, and describes the recommended algorithms for medication use. The purpose of this effort is to promote responsible treatment of young children, recognizing that this will sometimes involve the use of medications.

Abdominal sacrocolpopexy for vault prolapse without burial of mesh: a case series.

OBJECTIVES: To audit the clinical outcome of abdominal vault suspension (sacrocolpopexy, hysteropexy or cervicopexy) using non-absorbable mesh, without burial by closure of the peritoneum. DESIGN: A case series. SETTING: Urogynaecology units of four hospitals. POPULATION: One hundred and twenty-eight women having open or laparoscopic sacrocolpopexy (121), hysteropexy (6) or cervicopexy (1) using non-absorbable mesh for vault prolapse. METHODS: Patients had suspension of the vault, uterus or cervix from the sacral promontory using a monofilament polypropylene mesh. The pelvic peritoneum was not closed over the mesh. Patients were followed up every six months. MAIN OUTCOME MEASURES: Incidence of bowel complications as a consequence of the mesh; cure rate of prolapse and incidence of other post-operative complications; rate of re-operation for prolapse or incontinence. RESULT: After a median follow up of 19 months (1.5-62), there were no bowel complications as a result of non-burial of mesh. Three patients had asymptomatic vaginal mesh erosion, which required minor surgical intervention. Ninety percent of patients had good resolution of their prolapse symptoms while 10% of patients required further surgery. CONCLUSION: Leaving the mesh uncovered by the pelvic peritoneum was not associated with complications. It appears safe to perform vault suspension without closing the peritoneum.

William Osler and Basil Gildersleeve on Plato's Eryximachus.

Basil Lanneau Gildersleeve was a colleague of Sir William Osler at the Johns Hopkins University. Gildersleeve was a classicist who praised Osler in public but who also took him to task for his high opinion of Eryximachus, a character in Plato's Symposium. The present paper reviews this dispute between two colleagues and explores its origins.