445nm Blue Laser for Cricopharyngeal Myotomy/Zenker's Diverticulotomy: Proof of Concept and Use.

OBJECTIVE(S): Treatment for Zenker's diverticulum and cricopharyngeal dysfunction has evolved to include flexible endoscopic approaches. Currently, no flexible modalities combine the precision cutting of CO2 laser and the hemostasis of knife electrocautery. We present the first series describing fiber-based 445nm blue light (BL) laser for endoscopic cricopharyngeal myotomy/Zenker's diverticulotomy. We describe usage characteristics and laser parameters with rigid esophagoscopy to determine the feasibility of use with flexible endoscopy. METHODS: Retrospective review and literature review. RESULTS: The first nine cases of endoscopic diverticulotomy (n = 5) and cricopharyngeal myotomy (n = 4) with BL were reviewed. Rigid exposure was achieved with the Dohlman Slimline diverticuloscope. Mean age was 75.6 years. Average diverticulum depth was 0.89 cm ±1.0 cm. Pulsed mode was used in seven cases with mean of 6.86 W, 54 ms pulse on, and 286 ms pulse pause and overall mean of 6.00 W and 405 J. Complete myotomy with intact buccopharyngeal fascia and without bleeding limiting view was achieved in all patients. One of two patients in whom continuous wave setting was used developed subcutaneous emphysema following vigorous cough on POD0; this resolved after 7 days nothing per oral (NPO). Eight patients were started on oral intake without evidence for leak. Pulsed mode with fiber-to-tissue contact provided effective muscle cutting without disruption of buccopharyngeal fascia. Literature review yielded three articles examining flexible approach with laser for Zenker's and none with BL. CONCLUSION: BL provides safe and effective fiber-based cutting and hemostasis in endoscopic cricopharyngeal myotomy/Zenker's diverticulotomy. Future use in flexible endoscopic approaches appears feasible, though continuous wave should be avoided. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

How Feminist Heterosexual Men Navigate Their Sexual Desire While Following Feminist Principles.

Feminist considerations have influenced how women and men view sex, affecting not only women's perspectives but also men's feelings about sexual desire with regard to gender equity. This might be especially the case among men who self-identify as feminist. However, how men should manage their sexual desire or communicate about it within relationships with women is not always clear in this evolving social climate. Thus, the current study aimed to explore the successes and/or struggles feminist heterosexual men experience while navigating their desires alongside feminist considerations. To explore this, we recruited feminist-identified heterosexual men in long-term relationships. We asked participants (N = 30) a series of questions regarding their sexual desire, considering the context of their long-term relationships and evolving gender norms, during a one-on-one interview via Zoom. Using thematic analysis, we identified 11 themes from the interview data. We found that, though the feminist men in this study were all aware of negative societal perceptions of heterosexual men's sexual desire, most men in this study did not feel conflicts between their feminist principles and their own sexual desires. This is because they reported already following feminist principles; those who felt ambivalent navigated this by communicating with their partners. Findings demonstrate the usefulness and positive impact men report feminism having on them, their sexuality, and their long-term relationships, by allowing them to better engage with their sexuality and partners.

Split-bolus single-phase versus single-bolus split-phase CT acquisition protocols for staging in patients with testicular cancer: A retrospective study.

INTRODUCTION: Computed tomography (CT) imaging has become indispensable in the management of medical oncology patients. Risks associated with high cumulative effective dose (CED) are relevant in testicular cancer patients. Split-bolus protocols, whereby the contrast medium injection is divided into two, followed by combining the required phase images in a single scan acquisition has been shown to provide images of comparable image quality and less radiation dose compared to single-bolus split-phase CT for various indications. We retrospectively evaluated the performance of split-bolus and single-bolus protocols in patients having follow-up CT imaging for testicular cancer surveillance. METHODS: 45 patients with testicular cancer undergoing surveillance CT imaging of the thorax, abdomen, and pelvis who underwent split-bolus and single-bolus protocols were included. Quantitative image quality analysis was conducted by placing region of interests in pre-defined anatomical sub-structures within the abdominal cavity. The signal-to-noise ratio (SNR) and radiation dose in the form of dose length product (DLP) and effective dose (ED) were recorded. RESULTS: The DLP and ED for the single-bolus, split-phase acquisition was 506 ± 89 mGy cm and 7.59 ± 1.3 mSv, respectively. For the split-bolus, single-phase acquisition, 397 ± 94 mGy∗cm and 5.95 ± 1.4 mSv, respectively (p < 0.000). This represented a 21.5 % reduction in radiation dose exposure. The SNR for liver, muscle and fat for the single-bolus were 7.4, 4.7 and 8, respectively, compared to 5.5, 3.8 and 7.4 in the split-bolus protocol (p < 0.001). CONCLUSION: In a testicular cancer patient cohort undergoing surveillance CT imaging, utilization of a split-bolus single-phase acquisition CT protocol enabled a significant reduction in radiation dose whilst maintaining subjective diagnostic acceptability. IMPLICATIONS FOR PRACTICE: Use of split-bolus, single-phase acquisition has the potential to reduce CED in surveillance of testicular cancer patients.

Implementation of the GAA 'healthy clubs project' in Ireland: a qualitative study using the Consolidated Framework for Implementation Research.

The sports clubs' role in promoting health has been acknowledged by policy makers and researchers, but there is little evidence on how sports clubs implement health-related interventions. The present article investigates the Gaelic Athletic Association Healthy Club Project (HCP) implementation process (mechanisms, barriers, leverages) over a 10-year timeframe. A case study design helped to produce and compare a data synthesis for five clubs involved since 2013. A qualitative iterative data collection, including document analysis was conducted through 20 focus groups with Healthy Club Officers, coaches, participants and members. The Consolidated Framework for Implementation Research was used in the deductive analysis process, conducted by the first author. Results have shown the success of the HCP in placing health promotion on the agenda of sports clubs leading to informal policy for health promotion, even if activities and recognition are directed toward and coming from the community. This study also underlines the virtuous cycle of the settings-based approach in enhancing membership and volunteer recognition through health promotion actions, and the importance of social good and corporate social activities for sports clubs. Nevertheless, the HCP still relies on limited human resources, is not recognized by competitive oriented adult playing members. and acknowledged as a resource by some coaches, limiting its rootedness in the core business of sports clubs. Future research should empower the HCP community to focus on organizational changes and develop outcomes for individuals, for the club as a whole as well as for the local community.

Expanding the use of patient-reported outcomes (PROs): Screening youth with type 1 diabetes from underrepresented populations.

AIM: Youth from lower socioeconomic status (SES) have suboptimal type 1 diabetes (T1D) outcomes. Patient reported outcomes (PROs) measure psychosocial states and are associated with T1D outcomes, however are understudied in low SES youth. We aimed to evaluate associations between PROs and public insurance status, a proxy for low SES. METHODS: We analyzed survey data from 129 youth with T1D (age 15.7 ± 2.3 years, 33 % publicly insured) screened with PROMIS Global Health (PGH, measuring global health) and Patient Health Questionnaire (PHQ-9, measuring depressive symptoms) during diabetes appointments. Correlation and regression analyses evaluated differences in PGH and PHQ-9 by insurance status. RESULTS: For youth with public insurance, lower global health correlated with lower self-monitoring blood glucose (SMBG; r = 0.38,p = 0.033) and older age (r = -0.45,p = 0.005). In youth with private insurance, lower global health correlated with lower SMBG (r = 0.27,p = 0.018) and female sex (rho = 0.26,p = 0.015). For youth with private insurance, higher depressive symptoms correlated with higher body mass index (r = 0.22,p = 0.03) and fewer SMBG (r = -0.35,p = 0.04). In multivariate regression analyses, public insurance was inversely associated with global health (p = 0.027). CONCLUSION: PGH is a particularly salient PRO in youth with public insurance. Global health may be an important psychosocial factor to assess in youth with T1D from low SES backgrounds.

Ambient noise limits efficacy of smartphone-based screening for hearing loss in children at risk.

OBJECTIVE: To determine if hearScreen®, a smartphone-based pure tone audiometric screen, serves as an effective hearing screen for identifying hearing loss in children at risk, such as those with chronic otitis media and/or craniofacial anomalies. METHODS: A cross-sectional, single-center, prospective study at an urban tertiary care hospital was completed. From June to October 2019, a total of 208 pediatric ears at risk for hearing loss were evaluated by both hearScreen® and conventional pure tone audiometry. The efficacy of hearScreen® for detecting hearing loss in a pediatric population at risk was determined. RESULTS: A total of 208 pediatric ears at risk for hearing loss were screened. HearScreen® demonstrated a sensitivity of 85%, a specificity of 41%, a positive predictive value of 36%, and a negative predictive value of 87%. Subgroup analysis stratified by hearing loss type showed that hearScreen® screens for conductive hearing loss with increased sensitivity. CONCLUSIONS: This investigation suggests that hearScreen® may serve as a an accessible, low-cost, and sensitive pure tone audiometric screen for hearing loss in children at risk, particularly those with conductive hearing loss, with the caveat that it may generate a high proportion of false positives due to the influence of ambient noise, especially when screening at 500 Hz. Future investigations should weigh the utility of including 500 Hz in the screening protocol as well as assess methods that may mitigate the influence of ambient noise during a pure-tone audiometric screen.

Pneumococcal serotype-specific cut-offs based on antibody responses to pneumococcal polysaccharide vaccination in healthy adults.

Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic tool for humoral immunodeficiencies, part of the larger collection of inborn errors of immunity. Currently, arbitrary criteria, such as a serotype specific titer of >/= 1.3 µg/mL is most often used as a cut-off for interpretation of pneumococcal antibody responses. The magnitude of the antibody response to each of the 23 serotypes in Pneumovax®, and serotype-specific cut-offs in healthy pneumococcal vaccine-naïve adults has not been previously characterized. IgG antibody concentrations were measured prospectively for 23 pneumococcal serotypes pre and 4-6 weeks post-Pneumovax® vaccination in 100 healthy adults, using a multiplex bead-based assay. Antibodies to 19 of 23 serotypes were informative for distinguishing subjects who responded to vaccination, and the serotype threshold was determined to be 9 of 19 serotypes, which characterized an antibody response to pneumococcal vaccination. While this study may facilitate classification of IgG serotype-specific antibody responses post-pneumococcal vaccination in adult patients undergoing diagnostic immunological evaluation for antibody immunodeficiencies or other relevant contexts, additional studies in healthy children and S. pneumoniae protein-conjugate-vaccinated healthy adults will need to be undertaken in the future.

Prophylactic Flexible Bronchoscopy Immediately following Open Airway Reconstruction in Children.

OBJECTIVES: Prophylactic flexible bronchoscopy immediately following open airway reconstruction allows for directed clearance of the distal airways, potentially reducing the rate of certain postoperative respiratory complications. In this investigation, we sought to determine if prophylactic flexible bronchoscopy at the conclusion of pediatric open airway reconstruction has any benefit over blind flexible suctioning of the trachea. METHODS: A retrospective, single-center study at an urban tertiary care hospital was completed. From January 2010 to April 2013, patients underwent open airway reconstruction, immediately followed by blind flexible suctioning of the trachea for distal airway clearance. From May 2013 through December 2016, sequential patients underwent prophylactic flexible bronchoscopy immediately following airway reconstruction. RESULTS: A total of 29 patients (age: 3.6 months-6.2 years) met inclusion criteria. Sixteen sequential patients underwent simple blind flexible suctioning and 13 sequential patients underwent directed, prophylactic flexible bronchoscopy. Demographics and comorbidities between the groups were equivalent other than slightly older age in the prophylactic bronchoscopy group. All clinical outcomes analyzed were equivalent other than faster time to room air (P < .002) and a decrease in the number of chest physical therapy sessions (P < .02) in a subset of patients who did not undergo prophylactic bronchoscopy. CONCLUSION: This investigation suggests that the use of prophylactic flexible bronchoscopy immediately following open airway reconstruction may not be superior to blind flexible suctioning of the trachea in limiting postoperative pulmonary complications. Further studies of greater power are needed to better elucidate any small differences that may exist between these two interventions.

Trends in obstetric management of extreme preterm birth at 23 to 27 weeks' gestation in a tertiary obstetric unit: A 10-year retrospective review.

OBJECTIVE: To evaluate maternal and perinatal outcomes in deliveries from 23 + 0 to 26 + 6 weeks gestation in a tertiary hospital. STUDY DESIGN: A 10-year retrospective analysis was performed which included all women who delivered between 23 + 0 and 26 + 6 weeks gestation in a tertiary obstetric unit from 01/01/2007 to 31/12/2017 inclusive. Data were collected from electronic patient records and individual chart reviews using predetermined variables. RESULTS: 340 women and 402 infants were included. 84 % (282/340) were singleton pregnancy and 17 % (59/340) had multiple pregnancies. 36.8 % (125/340) of women were delivered by Caesarean section, 11.2 % (14/125) had a classical caesarean section. The leading indications for delivery were preterm premature ruptured membranes (PPROM) 28.2 % (96/340), 8.5 % (29/340) severe pre-eclampsia (PET) and 5.6 % (19/340) were delivered for suspected placental abruption. Of all infants (N = 402), 18.9 % (76/402) were stillborn. 300 infants were admitted to the Neonatal Intensive Care Unit (NICU). The NICU survival to discharge rate was 83.7 % (251/300). The overall perinatal mortality rate (PNMR) was 328.4/1000 and a further late neonatal mortality of 47.3/1000 births. Notably, at the 23 week gestation NNDs are the major contributor to the PNMR and at later gestations stillbirths are the largest contributor. CONCLUSION: Pregnant women delivering at extreme preterm gestations are at risk of maternal morbidity. Their infants have high rates of serious morbidity and mortality, with all survivors in this cohort affected by neonatal morbidity. Informed decision-making by providers and parents requires evidence based information on perceived outcomes, ideally individualized to the mother and pregnancy in question. Information from this retrospective cohort study can be used to counsel women and their families on potential morbidity and mortality and to manage expectations.

Electronic cigarettes and obstetric outcomes: a prospective observational study.

OBJECTIVE: To compare the obstetric outcomes and socio-demographic factors in electronic cigarette (EC) users with cigarette smokers and non-smokers in pregnancy. DESIGN: Prospective observational cohort study. SETTING: A large urban maternity hospital delivering almost 8500 infants per year. POPULATION: Pregnant women attending for antenatal care. METHODS: Electronic cigarette users at time of booking history were prospectively identified. Maternal and neonatal outcomes were compared with those of pregnant smokers and non-smokers. Multiple logistic regression analysis was performed to estimate the association between the explanatory variables and birthweight. MAIN OUTCOMES MEASURES: Infant birthweight, gestation at delivery, incidence of low birthweight. RESULTS: A total of 218 women with exclusive EC use and 195 women with dual use of both cigarettes and EC, had a live birth during the study period. EC users were of higher socio-economic status than smokers. Infants born to EC users had a mean birthweight of 3470 g (± 555 g), which was similar to that of non-smokers (3471 ± 504 g, P = 0.97) and significantly greater than that of smokers (3166 ± 502 g, P < 0.001). The mean birth centile of EC users was similar to non-smokers (51st centile versus 47th centile, P = 0.28) and significantly greater than that of smokers (27th centile, P < 0.001). Dual users had a mean birthweight and birth centile similar to that of smokers. CONCLUSION: The birthweight of infants born to EC users is similar to that of non-smokers, and significantly greater than cigarette smokers. Dual users of both cigarettes and EC have a birthweight similar to that of smokers. TWEETABLE EXTRACT: Birthweight of infants born to electronic cigarette users appears to be similar to that of non-smokers.

Parental Perspectives: Identifying Profiles of Parental Attitudes and Barriers Related to Diabetes Device Use.

Background: Despite the demonstrated benefits of diabetes device use, uptake of insulin pumps and continuous glucose monitors (CGMs) remains quite low. The current study aimed to identify profiles of parents of youth with type 1 diabetes based on their attitudes toward diabetes-specific technology and barriers to diabetes technology uptake. Methods: Online survey data were collected from 471 parents in the T1D Exchange Clinic Network (child's age = 12.0 ± 3.2 years; diabetes duration = 7.0 ± 2.9 years; A1c = 8.4% ± 1.3; 75% using insulin pump; 27% using CGM). Results: K-means cluster analyses revealed five parent profiles: Embracers (50.7%), Burdened (15.7%), Hopeful but Hassled (14.2%), Distrusting (12.7%), and Data Minimalists (6.6%). ANOVAs and chi-square tests identified differences between groups based on diabetes distress, worry over hypoglycemia, device use, and demographic characteristics. Conclusions: Providers encouraging device uptake may benefit from tailoring their approaches based on these distinct groups and their corresponding concerns and needs.

Depression in context: Important considerations for youth with type 1 vs type 2 diabetes.

BACKGROUND: Youth with diabetes are at increased risk for depression. However, severity and correlates of depressive symptoms may differ by diabetes type. OBJECTIVE: Associations of depressive symptoms with global health, diabetes duration, and gender were compared between youth with type 1 and type 2 diabetes. METHODS: A sample of 149 youth ages 12 to 21 diagnosed with either type 1 (n = 122) or type 2 (n = 27) diabetes were screened during routine clinic appointments. Regression models were constructed to examine differences by diabetes type. RESULTS: Adolescents with type 2 diabetes had significantly higher depressive symptom scores (4.89 vs 2.99, P = .025) than those with type 1 diabetes. A significant interaction between global health and diabetes type on depressive symptoms revealed inverse associations between global health and depressive symptoms that was stronger among youth with type 2 diabetes (ß = -.98, P < .001) than type 1 (ß = -.48, P < .001). Further probing revealed that among youth with better global health, adolescents with type 1 had more depressive symptoms than those with type 2 diabetes (ß = .33, P = .035). Diabetes duration and depressive symptoms were positively associated among individuals with type 2 (ß = .86, P = .043), but not type 1 diabetes. No gender differences were detected. CONCLUSION: These findings suggest that correlates of depressive symptoms in youth with diabetes differ by diabetes type. Global health appears to be an important correlate among youth with both types, whereas diabetes duration was only a significant factor among those with type 2 diabetes. The current findings can inform future psychosocial intervention efforts within both these populations.

How Much Greater is Obstetric Intervention in Women with Medical Disorders in Pregnancy When Compared to the General Population?

Introduction The purpose of this study was to compare obstetric and neonatal outcomes between women attending a specialised maternal medicine service and the general obstetric population. Methods Women attending from January 2011 to December 2016 were identified from the clinic database. Medical diagnosis, demographics, obstetric and neonatal outcomes were compared with data from hospital annual report 2014. Results 1873 women were compared with 8632 women who delivered at the hospital in 2014. Delivery before 34 weeks [82 (4.5%) vs 189 (2.2%)], induction of labour [761 (40.6%) vs 2664 (30.9%)] and delivery by Caesarean Section (CS) [664 (35%) vs 2479 (29%)] were higher p<0.001; but elective CS [334 (18%) vs 1425 (17%), p=0.18] did not differ between the two groups. Neonatal outcomes were similar. Conclusion Premature delivery, induction of labour and CS rates are higher in women with medical disorders in pregnancy. Encouragingly, 77% of women attempting vaginal birth in this group were successful.

Analgesia, anaesthesia and obstetric outcome in women with inherited bleeding disorders.

OBJECTIVE: Vertebral canal haematoma (VCH) complicates 1 in 168,000 obstetric epidurals (Ruppen et al., 2006). This risk is increased in women with inherited bleeding disorders (IBD). The impact of a contraindication to regional anaesthesia on pain management and obstetric outcome in these women is unknown. The purpose of this study was to determine anaesthetic use and obstetric outcomes in a cohort of women with IBD. STUDY DESIGN: 97 women with IBD that delivered 130 babies at the CWIUH from Jan 2011 to Dec 2016 were identified from a maternal medicine database. Multidisciplinary planning of peripartum care was communicated to labour ward staff using a simple checklist. The primary bleeding disorders were: Von Willebrands disease (VWD) Type 1 27 (27.8%); VWD Type 2A 3 (3.8%); Low VWF 3 (3.8%); Bleeding disorder of unknown aetiology (BDUA) 19 (19.6%); deficiency of Factors VII, VIII, IX, X, and XI 13 (13.4%); Carriers of Factor VIII, IX, X, XIII deficiency 17 (17.5%); 5 had combined deficiencies (5.2%) and there was one platelet function defect. 9 had a family history of a bleeding disorder (9.3%). Haemostatic support, analgesia, mode of delivery and maternal and fetal outcomes were compared between pregnancies where regional anaesthesia was permitted and those that were not using the Chi-squared test. RESULTS: When pregnancies where regional anaesthesia was not recommended (49) were compared with pregnancies where regional anaesthesia was considered safe (81), the women were more likely to see an anaesthetist before labour 46 (94%) vs 46 (61%): p < 0.001; to require prophylactic haemostatic support for delivery 30 (61%) vs 1 (1%): p < 0.001; to use a remifentanil infusion 15 (31%) vs 0: p < 0.001, and have general anaesthesia for Caesarean Section (CS) 10 (20%) vs 1(1%): p < 0.001. Vaginal birth 35 (71%) vs 53(65%): p = 0.4 and CS rates 14 (29%) vs 26 (32%) p = 0.28 were similar. Postpartum haemorrhage (PPH) was more common 11 (24%) vs 9(12%) vs p = 0.07 but not statistically so. There were no cases of neonatal bleeding or VCH. CONCLUSION: Contraindication to neuraxial blockade in labouring women with IBD does not influence mode of delivery. This information is reassuring to these women who may be anxious about delivery without regional anaesthesia.

Optimizing the use of continuous glucose monitoring in young children with type 1 diabetes with an adaptive study design and multiple randomizations.

Parents of young children with type 1 diabetes (T1D) experience unique, developmental challenges in managing their child's T1D, resulting in psychosocial distress. Only a small portion of young children reach glucose goals and adherence to diabetes devices that help improve T1D management have historically been low in this population. The purpose of this study is to test four interventions that couple developmentally tailored behavioral supports with education to optimize use of diabetes devices, improve glucose control, and reduce psychosocial distress for parents of young children with T1D. The study team designed four behavioral interventions, two aimed at improving glucose control and two aimed at optimizing use of diabetes devices. The goal of this paper is to describe the behavioral interventions developed for this study, including the results of a pilot test, and describe the methods and analysis plan to test this intervention strategy with ninety participants in a large-scale, randomized trial using a sequential multiple assignment randomization trial (SMART) design. A SMART design will permit a clinically relevant evaluation of the intervention strategy, as it allows multiple randomizations based on individualized assessments throughout the study instead of a fixed intervention dose seen in most traditional randomized controlled trials.

From Wary Wearers to d-Embracers: Personas of Readiness to Use Diabetes Devices.

BACKGROUND: Diabetes devices such as insulin pumps and continuous glucose monitoring (CGM) are associated with improved health and quality of life in adults with type 1 diabetes (T1D). However, uptake remains low. The aim of this study was to develop different "personas" of adults with T1D in relation to readiness to adopt new diabetes technology. METHODS: Participants were 1498 T1D Exchange participants who completed surveys on barriers to uptake, technology attitudes, and other psychosocial variables. HbA1c data was available from the T1D Exchange for 30% of the sample. K-means cluster analyses grouped the sample by device barriers and attitudes. The authors assigned descriptive labels based on cluster characteristics. ANOVAs and chi-square tests assessed group differences by demographic and psychosocial variables (eg, diabetes duration, diabetes distress). RESULTS: Analyses yielded five distinct personas. The d-Embracers (54% of participants) endorsed few barriers to device use and had the highest rates of device use, lowest HbA1c, and were the least distressed. The Free Rangers (23%) had the most negative technology attitudes. The Data Minimalists (10%) used pumps but had lower CGM use and did not want more diabetes information. The Wary Wearers (11%) had lower overall device use, were younger, more distressed, endorsed many barriers, and had higher HbA1c. The High Distress (3%) group members were the youngest, had the shortest diabetes duration, reported the most barriers, and were the most distressed. CONCLUSION: These clinically meaningful personas of device readiness can inform tailored interventions targeting barriers and psychosocial needs to increase device uptake.

Adipose stromal vascular fraction attenuates TH1 cell-mediated pathology in a model of multiple sclerosis.

BACKGROUND: The therapeutic efficacy of adipose-derived stem cells (ASCs) has been investigated for numerous clinical indications, including autoimmune and neurodegenerative diseases. Less is known using the crude adipose product called stromal vascular fraction (SVF) as therapy, although our previous studies demonstrated greater efficacy at late-stage disease compared to ASCs in the experimental autoimmune encephalomyelitis (EAE) mouse, a model of multiple sclerosis. In this study, SVF cells and ASCs were administered during the pathogenic progression, designated as early disease, to elucidate immunomodulatory mechanisms when high immune cell activities associated with autoimmune signaling occur. These implications are essential for clinical translation when considering timing of administration for cell therapies. METHODS: We investigated the effects of SVF cells and ASCs by analyzing the spleens, peripheral blood, and central nervous system tissues throughout the course of EAE disease following administration of SVF cells, ASCs, or vehicle. In vitro, immunomodulatory potentials of SVF cells and ASCs were measured when exposed to EAE-derived splenocytes. RESULTS: Interestingly, treatment with SVF cells and ASCs transiently enhanced the severity of disease directly after administration, substantiating this critical immunomodulatory signaling. More importantly, it was only the EAE mice treated with SVF cells that were able to overcome the advancing pathogenesis and showed improvements by the end of the study. The frequency of lesions in spinal cords following SVF treatment correlated with diminished activities of the T helper type 1 cells, known effector cells of this disease. Co-cultures with splenocytes isolated from EAE mice revealed transcripts of interleukin-10 and transforming growth factor-ß, known promoters of regulatory T cells, that were greatly expressed in SVF cells compared to ASCs, and expression levels of signaling mediators related to effector T cells were insignificant in both SVF cells and ASCs. CONCLUSION: This is the first evidence, to date, to elucidate a mechanism of action of SVF treatment in an inflammatory, autoimmune disease. Our data supports key immunomodulatory signaling between cell therapies and T cells in this T cell-mediated disease. Together, treatment with SVF mediated immunomodulatory effects that diminished effector cell activities, promoted regulatory T cells, and reduced neuroinflammation.

Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol.

Epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT) promoter via methylation in a glioblastoma (GBM), has been correlated with a more favourable response to alkylating chemotherapeutic agents such as temozolomide. The use of global methylation surrogates such as Long Interspersed Nucleotide Element 1 (LINE1) may also be valuable in order to fully understand these highly heterogeneous tumours. In this study, we analysed both original and recurrent GBMs in 22 patients (i.e. 44 tumours), for both MGMT and LINE1 methylation status. In the 22 patients: 14 (63.6%) displayed MGMT methylation stability in the recurrent GBM versus 8 (36.4%), with instability of methylation status. No significant differences in overall and progression free survival was evident between these two groups. LINE1 methylation status remained stable for 12 (54.5%) of recurrent GBM patients versus 9 (41%) of the patients with instability in LINE1 methylation status (p = 0.02), resulting in an increase in overall survival of the stable LINE1 group (p = 0.04). The results obtained demonstrated major epigenetic instability of GBMs treated with temozolomide as part of the STUPP protocol. GBMs appear to undergo selective evolution post-treatment, and have the ability to recur with a newly reprogrammed epigenetic status. Selective targeting of the altered epigenomes in recurrent GBMs may facilitate the future development of both prognostic biomarkers and enhanced therapeutic strategies.

Implementation of Depression Screening and Global Health Assessment in Pediatric Subspecialty Clinics.

PURPOSE: Adolescents with chronic illness face greater risk of psychosocial difficulties, complicating disease management. Despite increased calls to screen for patient-reported outcomes, clinical implementation has lagged. Using quality improvement methods, this study aimed to investigate the feasibility of standardized screening for depression and assessment of global health and to determine recommended behavioral health follow-up, across three pediatric subspecialty clinics. METHODS: A total of 109 patients aged 12-22 years (median = 16.6) who were attending outpatient visits for treatment of diabetes (80% type 1), inflammatory bowel disease, or cystic fibrosis completed the 9-item Patient Health Questionnaire (PHQ-9) depression and Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health measures on electronic tablets. Patients screening positive on the PHQ-9 received same-day behavioral health assessment and regular phone check-ins to facilitate necessary follow-up care. RESULTS: Overall, 89% of 122 identified patients completed screening during a 6-month window. Patients completed measures in a timely manner (within 3 minutes) without disruption to clinic flow, and they rated the process as easy, comfortable, and valuable. Depression scores varied across disease type. Patients rated lower global health relative to a previously assessed validation cohort. Depression and global health related significantly to certain medical outcomes. Fifteen percent of patients screened positive on the PHQ-9, of whom 50% confirmed attending behavioral health appointments within 6 months of screening. CONCLUSIONS: A standardized depression and global health assessment protocol implemented across pediatric subspecialties was feasible and effective. Universal behavioral health screening for adolescents and young adults living with chronic disease is necessary to meet programmatic needs in pediatric subspecialty clinics.