Search

A 12-year-old boy developed acute headache and vomiting. MRI brain showed a partially cystic suprasellar mass. He underwent cyst fenestration, but the cyst regrew, so he underwent transcranial subtotal resection of the mass. The pathologic diagnosis was adamantinomatous craniopharyngioma. Residual tumor was treated with proton beam radiation therapy, and panhypopituitarism was treated with hormone replacement therapy, including growth hormone. Serial brain MRI scans over several years showed no evidence of tumor recurrence. But at four years after radiation, surveillance MRI showed a new focus of nonenhancing FLAIR hyperintensity in the left basal ganglia attributed to gliosis caused by radiotherapy. Seven months later, he developed progressive right hemiparesis, expressive aphasia, and blurred vision, prompting reevaluation. MRI brain showed new enhancing and T2/FLAIR hyperintense lesions in the midbrain, basal ganglia, thalamus, anterior temporal lobe, and optic tract. The abnormal regions showed low diffusivity and relatively high regional blood flow. Stereotactic biopsy disclosed a WHO Grade 4 astrocytoma, likely radiation-induced. A germline ataxia telangiectasia mutation was found in the tumor tissue. The risk of radiation-induced pediatric brain malignancies is low but may have been increased by the mutation. [ABSTRACT FROM AUTHOR]

Pediatric and adult high-grade gliomas (HGGs) frequently harbor PDGFR[alpha] alterations. We hypothesized that cotreatment with everolimus may improve the efficacy of dasatinib in PDGFR[alpha]-driven glioma through combinatorial synergism and increased tumor accumulation of dasatinib. We performed dose-response, synergism, P-glycoprotein inhibition, and pharmacokinetic studies in in vitro and in vivo human and mouse models of HGG. Six patients with recurrent PDGFR[alpha]-driven glioma were treated with dasatinib and everolimus. We found that dasatinib effectively inhibited the proliferation of mouse and human primary HGG cells with a variety of PDGFR[alpha] alterations. Dasatinib exhibited synergy with everolimus in the treatment of HGG cells at low nanomolar concentrations of both agents, with a reduction in mTOR signaling that persisted after dasatinib treatment alone. Prolonged exposure to everolimus significantly improved the CNS retention of dasatinib and extended the survival of PPK tumor-bearing mice (mutant TP53, mutant PDGFR[alpha], H3K27M). Six pediatric patients with glioma tolerated this combination without significant adverse events, and 4 patients with recurrent disease (n = 4) had a median overall survival of 8.5 months. Our results show that the efficacy of dasatinib treatment of PDGFR[alpha]-driven HGG was enhanced with everolimus and suggest a promising route for improving targeted therapy for this patient population., Introduction High-grade gliomas (HGGs) are common and aggressive pediatric and adult brain tumors. The median overall survival (OS) of adult patients diagnosed with glioblastoma (GBM), grade IV glioma, is 12.6 [...]

Undergraduate students at a large, public, southeastern university enrolled in one of two independent, fully-online courses were released from the instructor-regulated structure mid-semester. Subsequently, the course was structured as student-regulated and students self-managed pace of study and timing of assessments for the remainder of the course. The objective of the research is to assess student preferences in learning structure (instructor-regulated versus student-regulated) in order to inform effective course design options in the online learning environment. At the end of each semester included in the study, a survey was administered to ascertain students' perceptions of the student-regulated (self-paced) learning environment. After analyzing the survey results, but before drawing final conclusions, it was acknowledged that student preferences might be skewed if coupled with altered performance in the course, real or perceived. Therefore, student performance was evaluated to ensure neutrality in this component. To this end, exam grades were collected over multiple semesters based on the original instructor-regulated structure (control group) together with the student-regulated structure (study group) and analyzed to compare mean grade performance between the two learning formats. Results indicated that the slight decline in grades for the self-paced students were not statistically significant. Given the benign performance results, the survey results were analyzed for statistical reliability and revealed a strong student preference for the self-paced online structure. The survey and grade performance results were compared against other research literature on online learning. Issues relating to incompatibility of student-paced flexibility and group-based assignments are also presented. Implications and opportunities for increasing student-regulated learning in online course design are addressed.

ObjectiveTo assess the influence of genetic and environmental risk factors upon postpartum depression.DesignCase-control, prospective study.SettingThe University of California at San Francisco Obstetric and Gynecology Clinic.ParticipantsMothers screened for postpartum depression six weeks after delivery with the Edinburgh Postnatal Depression Scale and recruited as cases and controls.MeasurementsEligible subjects completed a series of assessments and a structured clinical interview to confirm diagnosis of depression. Deoxyribonucleic acid was obtained for genotyping of 81 single nucleotide polymorphisms in 12 genes hypothesized to be postpartum depression-related.ResultsTwenty-four cases and 24 controls were eligible for analysis. Three single necleotide polymorphisms in the serotonin 2A receptor (HTR2A) gene were associated with postpartum depression. The strongest association at a functional promoter polymorphism (rs6311), a functional promoter single nucleotide polymorphisms (p=0.002, odds ratio 0.25, 95% confidence interval:0.10-0.63), was a finding robust to population stratification. Gene-wide association was significant for HTR2A (permuted p=0.008), but not when corrected for all 12 genes. Analysis of demographic and psychosocial risk factors identified distressed relationship, unplanned pregnancy, and a previous history of depression as significant predictive variables (p≤0.05).ConclusionsThis pilot data suggests deoxyribonucleic acid variations in HTR2A may be associated with postpartum depression. Psychosocial variables were also identified as risk factors. The relative influence of these variables on the manifestation of postpartum depression is yet to be determined.

ObjectiveTo assess the frequency and associations of barrier protection use during sexual activity in a population of women who have sex with women (WSW).MethodsWSW were invited to participate in an international internet-based survey. Information regarding ethnodemographics, sexual health, and barrier use during sexual activities was collected.ResultsThe study cohort comprised 1557 participants. Barrier use was least prevalent during digital genital stimulation (11.3% ever used barriers) and most prevalent during stimulation with a sex toy (34.4% ever used barriers). Univariate analysis revealed that women in non-monogamous relationships were more likely than monogamous women to always use barrier protection for sexual activity (14.3% vs 3.5%). On multivariate analysis, there was no association between barrier use and frequency of casual sexual activity or history of sexually transmitted infection. Small associations were noted between barrier use and certain sexual activities, age, race, and number of partners.ConclusionMany WSW do not use barrier protection during sexual activity, even in the context of potentially risky sexual behaviors. Safer-sex practices among WSW merit increased attention from healthcare providers and public health researchers.

In 2005, medical educators at the University of California, San Francisco (UCSF), began developing the Parnassus Integrated Student Clinical Experiences (PISCES) program, a year-long longitudinal integrated clerkship at its academic medical center. The principles guiding this new clerkship were continuity with faculty preceptors, patients, and peers; a developmentally progressive curriculum with an emphasis on interdisciplinary teaching; and exposure to undiagnosed illness in acute and chronic care settings. Innovative elements included quarterly student evaluation sessions with all preceptors together, peer-to-peer evaluation, and oversight advising with an assigned faculty member. PISCES launched with eight medical students for the 2007/2008 academic year and expanded to 15 students for 2008/2009. Compared to UCSF's traditional core clerkships, evaluations from PISCES indicated significantly higher student satisfaction with faculty teaching, formal didactics, direct observation of clinical skills, and feedback. Student performance on discipline-specific examinations and United States Medical Licensing Examination step 2 CK was equivalent to and on standardized patient examinations was slightly superior to that of traditional peers. Participants' career interests ranged from primary care to surgical subspecialties. These results demonstrate that a longitudinal integrated clerkship can be implemented successfully at a tertiary care academic medical center.

Background: Magnetic Resonance Imaging is used for evaluation of bone in Gaucher disease (GD), but a widely available quantitative scoring method remains elusive. Aims: The study purpose was to assess the reproducibility of the LiverLab tool for assessing bone marrow fat fraction (FF) and determine whether it could differentiate GD patients from healthy subjects. Methods: Ten healthy volunteers and 18 GD patients were prospectively recruited. FF was calculated at L3, L4 and L5. GD patient bone marrow burden (BMB) score assessed by one observer. Inter and intra‐rater agreement assessed with Bland–Altman data plots. Differences in FF between healthy volunteers versus GD patients and between subjects treated versus not treated assessed using two‐sample t‐tests. In GD patients, the relationship between FF, BMB and glucosylsphingosine was determined using the Pearson's correlation coefficient. Results: Healthy volunteer mean FF was 0.36, standard deviation (SD) 0.10 (range 0.20–0.57). Intra and inter‐rater SD were both 0.02. GD patient mean FF was 0.40, SD 0.13 (range 0.09–0.57). No statistical difference was shown between healthy volunteers and GD patients (P = 0.447) or between GD patients whether on enzyme replacement therapy or not (P = 0.090). No significant correlation between mean FF and total BMB (r = −0.525, P = 0.253) or between FF and glucosylsphingosine levels (r = 0.287, P = 0.248). Conclusion: Excellent reproducibility of LiverLab FF measurements across studies and observers is comparable to Dixon quantitative chemical shift imaging (QCSI). Lack of statistical difference between GD patients and controls may be explained by limited patient numbers, active treatment or mild disease severity in untreated patients. [ABSTRACT FROM AUTHOR]

Three separate baseline decisions are recommended when designing an undergraduate course prior to considering any course content. The "Three S" course design decisions include determining (1) the "setting" (on-campus, online or hybrid), (2) the learning "style" (passive or active), and (3) the learning "structure" (instructor-regulated or student-regulated). This theoretical paper identifies connections within and among these interrelated decisions and illustrates the compatible course design combinations. The paper finds that the online setting has the fewest compatible "Three S" combinations and the hybrid setting has the most compatible combinations.

In the current era of limited funding, researchers need strategic alliances to launch or sustain programs of research to significantly impact the nation's health. This article presents a collaborative model, the Scholar Award Model, which is based on a strategic alliance between a College of Nursing in a research-intensive university and a pediatric campus of a local 22 hospital system. The conceptualization, marketing, and implementation of the Scholar Award Model are described and three examples of the model in action are illustrated. Features that have contributed to the success of the model include mutual goals with clearly defined outcomes, codified operating rules and procedures, and shared resources that differentially capitalize on the strengths and expertise of everyone involved. It is recommended that research directors in academic and healthcare organizations who are seeking ways to promote health research use the model to develop similar alliances.

Definitional Ceremonies are used as a forum for integrating members of diverse cultures into multicultural counseling sessions. The authors provide a philosophical foundation, implementation process, and excerpts from a typescript of a recent definitional ceremony involving a women and her mother, both recently in the United States from Panama.