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OBJECTIVE: The objectives of this topical review are to (1) increase understanding of pediatric medical traumatic stress (PMTS) in pediatric urology populations through literature review, (2) identify a theoretical model to guide prevention of PMTS in this population, and (3) provide clinical care recommendations based on the model identified. Authors introduce a new term "uropsychology" to describe psychological practice that specializes in the treatment of urology patients. METHODS: Pediatric uropsychologists from 5 pediatric medical care centers gathered to discuss their experience with treating PMTS in their settings and to review existing literature related to PMTS in pediatric urology, PMTS in other populations, and established models for prevention. Authors provide recommendations based on literature review for preventing PMTS in a pediatric urology population. RESULTS: Gaps in the evidence base for preventing PMTS in this population are identified. Authors provide a series of clinical care recommendations, utilizing clinical experience, and the Pediatric Psychosocial Preventative Health Model (PPPHM) as a framework. CONCLUSIONS: While there is limited research on PMTS in pediatric urology populations, urologic interventions can be perceived as invasive, painful, distressing, and traumatic. Application of the PPPHM can guide prevention and intervention efforts. Future research is needed to characterize PMTS in this population, evaluate the efficacy of trauma-informed prevention and intervention practices, and develop screening measures that accurately identify at-risk patients. Authors recommend intradisciplinary collaboration among uropsychologists, urology specialists, and patients and families to create formal standards of care, avenues for other future research, and equitable access to uropsychology care.

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A growing number of individuals with type 1 diabetes are choosing to use "do-it-yourself" artificial pancreas systems (DIY APS) to support their diabetes self-management. Observational and self-report data of glycemic benefits of DIY APS are promising; however, without rigorous clinical trials or regulation from governing bodies, liability and user safety continue to be central concerns for stakeholders. Despite DIY APS having been used for several years now, there are no guidelines to assist users and healthcare professionals in addressing DIY APS use in routine clinical care. This commentary reports key stakeholders' perspectives presented at the annual Advanced Technologies and Treatments in Diabetes conference in February 2020. Important considerations to inform the development of clinical care guidelines are also presented to generate further debate.

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PURPOSE: Depression is one of the most prevalent psychiatric comorbidities in epilepsy. This quality improvement project compared a standardized rating scale, the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y), with physician opinion to see if it improved sensitivity to depressive symptoms. RESULTS: A convenience sample of thirty adolescents with epilepsy ages 12-17 (mean [M] = 15.02, standard deviation [SD] = 1.81; 53% female) participated in the screening. Thirteen percent of the sample scored in the Elevated range on the NDDI-E-Y (exceeded cutoff). Seven percent of the sample were rated by the physician as definitely showing signs of depression. There were two false negatives when the NDDI-E-Y score exceeded the established cutoff, but physician rating was negative for depressive symptoms. CONCLUSION: This pilot project shows that the NDDI-E-Y is a convenient clinical tool with the potential to improve sensitivity in the detection of depressive symptoms in adolescents with epilepsy.

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Lower urinary tract dysfunction in children is a common multifactorial functional problem that often correlates with bowel dysfunction and behavioral disorders. Ideal management combines integrative therapies that optimize bladder and bowel habits, address behavioral issues, foster mind-body connection, and improve pelvic floor muscle dysfunction. Movement therapies that teach diaphragmatic breathing and relaxation, mind-body awareness, and healthy pelvic floor muscle function are vital for long-term symptom improvement in children. This paper outlines recommendations for integrative management of these patients and discusses a recently developed interprofessional clinic that aims to better meet these patients' complex needs and to provide patients with an integrated holistic plan of care. Additional work is needed to scientifically assess these treatment models and educate providers across the various disciplines that evaluate and treat these patients.

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OBJECTIVE: The objective was to investigate the relationship of body mass index (BMI) to differing glycemic responses to psychological stress in patients with type 1 diabetes. METHODS: Continuous blood glucose monitor (CGM) data were collected for 1 week from a total of 37 patients with BMI ranging from 21.5-39.4 kg/m2 (mean = 28.2 ± 4.9). Patients reported daily stress levels (5-point Likert-type scale, 0 = none, 4 = extreme), physical activity, carbohydrate intake, insulin boluses and basal rates. Daily reported carbohydrates, total insulin bolus, and average blood glucose (BG from CGM) were compared among patients based on their BMI levels on days with different stress levels. In addition, daily averages of a model-based "effectiveness index" (quantifying the combined impact of insulin and carbohydrate on glucose levels) were defined and compared across stress levels to capture meal and insulin independent glycemic changes. RESULTS: Analyses showed that patient BMI likely moderated stress related glycemic changes. Linear mixed effect model results were significant for the stress-BMI interaction on both behavioral and behavior-independent glycemic changes. Across participants, under stress, an increase was observed in daily carbohydrate intake and effectiveness index at higher BMI. There was no significant interactive effect on daily insulin or average BG. CONCLUSION: Findings suggest that (1) stress has both behavioral and nonbehavioral glycemic effects on T1D patients and (2) the direction and magnitude of these effects are potentially influenced by level of stress and patient BMI. Possibly responsible for these observed effects are T1D/BMI related alterations in endocrine response.

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AIMS: To test the accuracy of Diabetes Alert Dogs (DADs) by comparing recorded alerts to continuous glucose monitoring (CGM) device readings during waking and sleeping hours. METHODS: 14 individuals (7 adults with type 1 diabetes and 7 youth with type 1 diabetes/parents) who owned DADs for ≥6 mos wore masked CGM devices over a several-week period while recording DAD alerts electronically and in paper diaries. RESULTS: During waking hours, sensitivity scores across participants were 35.9% for low BG events and 26.2% for high BG events. DAD accuracy was highly variable with 3/14 individual dogs performing statistically higher than chance. Sensitivity scores were lower during sleep hours of the person with diabetes (22.2% for low BG events and 8.4% for high BG events). DAD accuracy during sleeping hours was also highly variable, with 1/11 individual dogs performing statistically better than chance. Rate of change analyses indicated that DADs were responding to absolute BG level, rather than rapid shifts in glucose levels. CONCLUSIONS: In this study the majority of DADs did not demonstrate accurate detection of low and high BG events. However, performance varied greatly across DADs and additional studies are needed to examine factors contributing to this variability. Additionally, more research is needed to investigate the significant gap between the positive experiences and clinical outcomes reported by DAD owners and the mixed research findings on DAD accuracy.

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BACKGROUND: Diabetes alert dogs (DADs) are growing in popularity as an alternative method of glucose monitoring for individuals with type 1 diabetes (T1D). Only a few empirical studies have assessed DAD accuracy, with inconsistent results. The present study examined DAD accuracy and variability in performance in real-world conditions using a convenience sample of owner-report diaries. METHOD: Eighteen DAD owners (44.4% female; 77.8% youth) with T1D completed diaries of DAD alerts during the first year after placement. Diary entries included daily BG readings and DAD alerts. For each DAD, percentage hits (alert with BG ≤ 5.0 or ≥ 11.1 mmol/L; ≤90 or ≥200 mg/dl), percentage misses (no alert with BG out of range), and percentage false alarms (alert with BG in range) were computed. Sensitivity, specificity, positive likelihood ratio (PLR), and true positive rates were also calculated. RESULTS: Overall comparison of DAD Hits to Misses yielded significantly more Hits for both low and high BG. Total sensitivity was 57.0%, with increased sensitivity to low BG (59.2%) compared to high BG (56.1%). Total specificity was 49.3% and PLR = 1.12. However, high variability in accuracy was observed across DADs, with low BG sensitivity ranging from 33% to 100%. Number of DADs achieving ≥ 60%, 65% and 70% true positive rates was 71%, 50% and 44%, respectively. CONCLUSIONS: DADs may be able to detect out-of-range BG, but variability across DADs is evident. Larger trials are needed to further assess DAD accuracy and to identify factors influencing the complexity of DAD accuracy in BG detection.

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Pediatric elimination disorders are common in childhood, yet psychosocial correlates are generally unclear. Given the physiological concomitants of both enuresis and encopresis, and the fact that many children with elimination disorders are initially brought to their primary care physician for treatment, medical evaluation and management are crucial and may serve as the first-line treatment approach. Scientific investigation on psychological and behavioral interventions has progressed over the past couple of decades, resulting in the identification of effective treatments for enuresis and encopresis. However, the body of literature has inherent challenges, particularly given the multicomponent nature of many of the treatment packages. This review identified 25 intervention studies-18 for nocturnal enuresis and 7 for encopresis-over the past 15 years and classified them according to the guidelines set forth by the Task Force on the Promotion and Dissemination of Psychological Procedures. For nocturnal enuresis, the urine alarm and dry-bed training were identified as well-established treatments, Full Spectrum Home Therapy was probably efficacious, lifting was possibly efficacious, and hypnotherapy and retention control training were classified as treatments of questionable efficacy. For encopresis, only two probably efficacious treatments were identified: biofeedback and enhanced toilet training (ETT). Best practice recommendations and suggestions for future research are provided to address existing limitations, including heterogeneity and the multicomponent nature of many of the interventions for pediatric elimination disorders.

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Use of technology in diabetes management is rapidly advancing and has the potential to help individuals with diabetes achieve optimal glycemic control. Over the past 40 years, several devices have been developed and refined, including the blood glucose meter, insulin pump, and continuous glucose monitor. When used in tandem, the insulin pump and continuous glucose monitor have prompted the Artificial Pancreas initiative, aimed at developing control system for fully automating glucose monitoring and insulin delivery. In addition to devices, modern technology, such as the Internet and mobile phone applications, have been used to promote patient education, support, and intervention to address the behavioral and emotional challenges of diabetes management. These state-of-the-art technologies not only have the potential to improve clinical outcomes, but there are possible psychological benefits, such as improved quality of life, as well. However, practical and psychosocial limitations related to advanced technology exist and, in the context of several technology-related theoretical frameworks, can influence patient adoption and continued use. It is essential for future diabetes technology research to address these barriers given that the clinical benefits appear to largely depend on patient engagement and consistence of technology use. (PsycINFO Database Record

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OBJECTIVE: Fear of hypoglycemia (FoH) can be a significant barrier to glycemic control in pediatric type 1 diabetes (T1D). This study aimed to explore underlying constructs of the Hypoglycemia Fear Survey (HFS) for parents (PHFS) and children (CHFS). METHODS: Data were aggregated from five studies of 259 youth with T1D and 250 parents. Exploratory Factor Analysis was used to determine the underlying factors of the CHFS and PHFS. RESULTS: Similar four-factor solutions were found for the CHFS and PHFS. Both subscales consisted of two factors: Behavior Subscale (1) behaviors used to keep blood glucose (BG) high to prevent hypoglycemia (Maintain High BG) and (2) other actions to avoid hypoglycemia (Avoidance); Worry Subscale (1) concerns about helplessness (Helplessness) and (2) negative social consequences associated with hypoglycemia (Social Consequences). CONCLUSIONS: These constructs provide a more comprehensive understanding of pediatric FoH and have implications for interventions aimed at reducing FoH in this population.

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INTRODUCTION: Gene delivery from hydrogel biomaterials provides a fundamental tool for a variety of clinical applications including regenerative medicine, gene therapy for inherited disorders and drug delivery. The high water content and mild gelation conditions of hydrogels support their use for gene delivery by preserving activity of lentiviral vectors and acting to shield vectors from any host immune response. AREAS COVERED: Strategies to control lentiviral entrapment within and retention/release from hydrogels are reviewed. The authors discuss the ability of hydrogel design parameters to control the transgene expression profile and the capacity of hydrogels to protect vectors from (and even modulate) the host immune response. EXPERT OPINION: Delivery of genetic vectors from scaffolds provides a unique opportunity to capitalize on the potential synergy between the biomaterial design for cell processes and gene delivery. Hydrogel properties can be tuned to directly control the events that determine the tissue response to controlled gene delivery, which include the extent of cell infiltration, preservation of vector activity and vector retention. While some design parameters have been identified, numerous opportunities for investigation are available in order to develop a complete model relating the biomaterial properties and host response to gene delivery.

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Cells respond to changes in the physical properties of the extracellular matrix with altered behavior and gene expression, highlighting the important role of the microenvironment in the regulation of cell function. In the current study, culture of epithelial ovarian cancer cells on three-dimensional collagen I gels led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with a concomitant increase in nuclear ß-catenin and enhanced ß-catenin/Tcf/Lef transcriptional activity. Increased three-dimensional collagen gel invasion was accompanied by transcriptional up-regulation of the membrane-tethered collagenase membrane type 1 matrix metalloproteinase, and an inverse relationship between dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human epithelial ovarian cancer specimens. Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling.

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BACKGROUND: Diabetes technology is rapidly advancing toward fully automated glucose control systems, but little is known about patient perspectives on these systems. This study aimed to gather qualitative and quantitative data on patient attitudes and concerns about using a personalized glucose advisory system (PGASystem) for diabetes management. SUBJECTS AND METHODS: Fifty-six adults with type 1 diabetes on insulin pump therapy participated in focus group interviews following use of an insulin pump and continuous glucose monitoring for 4 weeks in a parent study to develop a PGASystem. Focus groups were transcribed and coded for thematic content. RESULTS: All participants endorsed the desire to use a PGASystem, and the majority wanted advice from the system on all aspects of insulin delivery. However, participants indicated that they might be reluctant to follow such advice because of the following concerns: how the advice was generated, relinquishing control to automated technology, and inadequate personalization of the system. Participants believed the system would need to consider numerous factors related to their food, activities, and other personal information to provide optimally individualized advice. The majority also reported difficulties with behavioral event recording on their insulin pumps, and approximately one-third endorsed difficulty with accurate carbohydrate counting. CONCLUSIONS: Adults with type 1 diabetes appear to be enthusiastic about using a PGASystem system for their diabetes management but also have significant concerns affecting their overall willingness to follow such a system's advice. Addressing these concerns will be crucial in the future development of glucose advisory and control technology.

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The utility of hydrogels for regenerative medicine can be improved through localized gene delivery to enhance their bioactivity. However, current systems typically lead to low-level transgene expression located in host tissue surrounding the implant. Herein, we investigated the inclusion of macropores into hydrogels to facilitate cell ingrowth and enhance gene delivery within the macropores in vivo. Macropores were created within PEG hydrogels by gelation around gelatin microspheres, with gelatin subsequently dissolved by incubation at 37 °C. The macropores were interconnected, as evidenced by homogeneous cell seeding in vitro and complete cell infiltration in vivo. Lentivirus loaded within hydrogels following gelation retained its activity relative to the unencapsulated control virus. In vivo, macroporous PEG demonstrated sustained, elevated levels of transgene expression for 6 weeks, while hydrogels without macropores had transient expression. Transduced cells were located throughout the macroporous structure, while non-macroporous PEG hydrogels had transduction only in the adjacent host tissue. Delivery of lentivirus encoding for VEGF increased vascularization relative to the control, with vessels throughout the macropores of the hydrogel. The inclusion of macropores within the hydrogel to enhance cell infiltration enhances transduction and influences tissue development, which has implications for multiple regenerative medicine applications.

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Driving is a dangerous activity for adolescents, perhaps being even more precarious for adolescents with type 1 diabetes due to the possibility of extreme blood glucose (BG). There is no available data on adolescent driving safety concerns and type 1 diabetes. To begin addressing this issue, we surveyed parents regarding their observations and concerns. Seventy-two parents (87.5% mothers) of adolescent drivers aged 16-19 with type 1 diabetes provided analyzable data. Females comprised 36% of their adolescents, with 74% using pump therapy. In the past year, 13 and 84% of parents reported that their adolescent had experienced severe or moderate disruptive hypoglycemia, respectively. Over half (56%) of the parents reported moderate to extreme worry about how diabetes impacted their adolescent's driving, while only 21% of parents thought their adolescents had similar concerns (p = 0.037). Almost one third (31%) of parents thought their adolescent need not treat low BG until it fell below 70 mg/dL, 13% thought their adolescent could safely drive with BG below 65 mg/dL. And, 31 and 14% of parents, respectively, reported their adolescent had been in a collision or stopped by the police in the past year, which they attributed to both hypo- and hyperglycemia. Adolescents reportedly took steps to prevent hypo- and hyperglycemia while driving, but more aggressively avoided hypoglycemia (p < 0.001). While this data is limited, lacking a non-diabetic control group and randomized sample, it does suggest that driving and adolescent type 1 diabetes deserve further attention and investigation.

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Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration.

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This article summarizes the literature on fear of hypoglycemia in pediatric Type 1 diabetes and the assessment of this fear in both children with Type 1 diabetes and their parents. The most common instrument for assessing fear of hypoglycemia in this population is the children's and parent's versions of the Hypoglycemia Fear Survey (HFS), although studies using other assessment measures are also reviewed. Studies using this survey have identified variables contributing to fear of hypoglycemia in children with Type 1 diabetes and their parents, such as history of frequent or traumatic hypoglycemia, as well as trait anxiety. In addition to this summary of the literature, new data are presented supporting the reliability of hypoglycemic fear assessment in younger children and comparing fear of hypoglycemia in children in different age groups (6-18 years old) and their parents. Also reviewed are studies investigating the relationship between fear of hypoglycemia and diabetes control, which have yielded inconsistent results. Given the potential importance of fear of hypoglycemia in pediatric diabetes, there has been limited research in this area.