Novel second-generation rexinoid induces growth arrest and reduces cancer cell stemness in human neuroblastoma patient-derived xenografts

IntroductionThe poor therapeutic efficacy seen with current treatments for neuroblastoma may be attributed to stem cell-like cancer cells (SCLCCs), a subpopulation of cancer cells associated with poor prognosis and disease recurrence. Retinoic acid (RA) is a differentiating agent used as maintenance therapy for high-risk neuroblastoma but nearly half of children treated with RA relapse. We hypothesized that 6-Methyl-UAB30 (6-Me), a second-generation rexinoid recently developed with a favorable toxicity profile compared to RA, would reduce cancer cell stemness in human neuroblastoma patient-derived xenografts (PDXs).MethodsCells from three neuroblastoma PDXs were treated with 6-Me and proliferation, viability, motility, and cell-cycle progression were assessed. CD133 expression, sphere formation, and mRNA abundance of stemness and differentiation markers were evaluated using flow cytometry, in vitro extreme limiting dilution analysis, and real-time PCR, respectively.ResultsTreatment with 6-Me decreased proliferation, viability, and motility, and induced cell-cycle arrest and differentiation in all three neuroblastoma PDXs. In addition, 6-Me treatment led to decreased CD133 expression, decreased sphere-forming ability, and decreased mRNA abundance of Oct4, Nanog, and Sox2, indicating decreased cancer cell stemness.Conclusions6-Me decreased oncogenicity and reduced cancer cell stemness of neuroblastoma PDXs, warranting further exploration of 6-Me as potential novel therapy for neuroblastoma.     

Safety and Efficacy of a Steroid Avoidance Immunosuppression Regimen in Renal Transplant Patients With De Novo or Preformed Donor-Specific Antibodies: A Single-Center Study

Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection.     

Concurrent hiatal hernia repair and bariatric surgery: outcomes after sleeve gastrectomy and Roux-en-Y gastric bypass

BackgroundHiatal hernias are often repaired concurrently with bariatric surgery to reduce risk of gastroesophageal reflux disease–related complications.ObjectivesTo examine the association between concurrent hiatal hernia repair (HHR) and bariatric outcomes.SettingA 2010–2017 U.S. commercial insurance claims data set.MethodsWe conducted a retrospective cohort study. We identified adults who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) alone or had bariatric surgery concurrently with HHR. We matched patients with and without HHR and followed patients up to 3 years for incident abdominal operative interventions, bariatric revisions/conversions, and endoscopy. Time to first event for each outcome was compared using multivariable Cox proportional hazards modeling.ResultsWe matched 1546 SG patients with HHR to 3170 SG patients without HHR, and we matched 457 RYGB patients with HHR to 1156 RYGB patients without HHR. A total of 73% had a full year of postoperative enrollment. Patients who underwent concurrent SG and HHR were more likely to have additional abdominal operations (adjusted hazard ratio [aHR], 2.1; 95% CI, 1.5–3.1) and endoscopies (aHR, 1.5; 95% CI, 1.2–1.8) but not bariatric revisions/conversions (aHR, 1.7; 95% CI, .6–4.6) by 1 year after surgery, a pattern maintained at 3 years of follow-up. Among RYGB patients, concurrent HHR was associated only with an increased risk of endoscopy (aHR, 1.4; 95% CI, 1.1–1.8)) at 1 year of follow-up, persisting at 3 years.ConclusionsConcurrent SG/HHR was associated with increased risk of some subsequent operative and nonoperative interventions, a pattern that was not consistently observed for RYGB. Additional studies could examine whether changes to concurrent HHR technique could reduce risk.     

Examining how changes in provincial policy on vape marketing impacted the distribution of vaping advertisements near secondary schools in London,Ontario

ObjectivesOn January 1, 2020, the Government of Ontario passed a regulation banning vaping advertisements by retailers, apart from specialty shops. A motivation for this ban was to limit youth exposure to vaping advertisements. The primary goal of this research was to evaluate the impact of this ban on the number and density of vaping advertisements surrounding secondary schools. Additionally, we examined whether the number of vaping advertisements varied by school socio-demographic characteristics.MethodsThis study used a pre-post design. Audits were conducted December 2019 (pre-ban) and again January to February 2020 (post-ban), to identify vaping advertisements within 800 m surrounding secondary schools (n = 18) in London, Ontario.ResultsPrior to the ban, there were 266 vaping advertisements within 800 m of secondary schools. After the ban, this was reduced to 58, a 78.2% reduction. The mean number of vaping advertisements surrounding schools significantly decreased from 18.1 before the ban to 3.6 after the ban (p < 0.001). A significant positive correlation was found, prior to the ban, between the number of vaping advertisements surrounding schools and school-level residential instability (r = 0.42, p = 0.02). After the ban, no significant correlations were found between the number of vaping advertisements and school socio-demographic characteristics.ConclusionThe provincial ban of vaping advertisements in select retail settings significantly reduced the number of vaping advertisements in the areas surrounding secondary schools in London, Ontario. The ban also reduced socio-demographic inequities in youths’ potential exposure to marketing of vaping products. Continued monitoring of the geographic accessibility and promotion of vaping products is warranted.     

Pain syndromes in HIV infection

Pain causes considerable disability and discomfort in HIV (Human Immunodeficiency Virus) infected individuals. A large number of patients infected with HIV suffer from one or more pain-related syndromes. Pain is under-reported and suboptimally managed in these patients. An outline of the different pain syndromes, including headache, oral cavity pain, chest pain, abdominal pain, anorectal pain, musculoskeletal pain and peripheral neuropathic pain, and their aetiologies are discussed. Current pain management modalities, including non-narcotic and narcotic analgesics, tricyclic antidepressants, anticonvulsants, physical therapy and psychological techniques, are outlined. Treatment should be based on the same principles applied to the management of cancer-related pain. A multi-disciplinary, comprehensive approach to pain management will assist these individuals to achieve improved levels of comfort, function and quality of life in this ultimately terminal illness.     

A Correlational Test of the Relationship Between Posttraumatic Growth,Religion, and Cognitive Processing

The present study examined the degree to which event related rumination, a quest orientation to religion, and religious involvement is related to posttraumatic growth. Fifty-four young adults, selected based on prescreening for experience of a traumatic event, completed a measure of event related ruminations, the Quest Scale, an index of religious participation, and the Posttraumatic Growth Inventory. The three subscales of the Quest Scale, the two groups of rumination items (soon after event/within past two weeks), and the index of religious participation were entered in a standard multiple regression with the total score of the Posttraumatic Growth Inventory as the dependent variable. The degree of rumination soon after the event and the degree of openness to religious change were significantly related to Posttraumatic Growth. Congruent with theoretical predictions, more rumination soon after the event, and greater openness to religious change were related to more posttraumatic growth. Present findings offer some confirmation of theoretical predictions, and also offer clear direction for further research on the relationships of religion, rumination, and posttraumatic growth.     

Violence in the Schools: Clinical Issues and Case Analysis for High-Risk Children

School violence in rural communities has gained considerable attention nationally. Examined are theoretical considerations involving escape theory, the risk and protective factors for school violence, case analyses of recent case studies, and discussion of recent school violence involving fatal injuries to others. Also discussed are diagnostic issues in understanding children who are at-risk for school violence and ways school violence maybe managed in the schools. Suggestions and recommendations including recommendations provided by the National School Safety Center for school personnel are offered, as are steps to be taken in creating a safe school environment. This information may be helpful to child psychiatry and clinical personnel who provide services to school aged children.