Student Perceptions of Superimposed Mixed Reality Anatomy: A Bridge Between the Virtual and Physical.

A prototype mixed reality model was developed in which three-dimensional holograms of musculoskeletal anatomy were superimposed over a physical skeleton model, conferring tactile sensation to the bony attachments of virtually observed muscles. Fifty-three second-year medical students piloted this innovative format and provided feedback on its effectiveness as a learning modality.

The Association of Patient Educational Attainment With Cardiac Rehabilitation Adherence and Health Outcomes.

PURPOSE: Participating in cardiac rehabilitation (CR) after a cardiac event provides many clinical benefits. Patients of lower socioeconomic status (SES) are less likely to attend CR. It is unclear whether they attain similar clinical benefits as patients with higher SES. This study examines how educational attainment (one measure of SES) predicts both adherence to and improvements during CR. METHODS: This was a prospective observational study of 1407 patients enrolled between January 2016 and December 2019 in a CR program located in Burlington, VT. Years of education, smoking status (self-reported and objectively measured), depression symptom level (Patient Health Questionnaire), self-reported physical function (Medical Outcomes Survey), level of fitness (peak metabolic equivalent, peak oxygen uptake, and handgrip strength), and body composition (body mass index and waist circumference) were obtained at entry to, and for a subset (n = 917), at exit from CR. Associations of educational attainment with baseline characteristics were examined using Kruskal-Wallis or Pearson's χ 2 tests as appropriate. Associations of educational attainment with improvements during CR were examined using analysis of covariance or logistic regression as appropriate. RESULTS: Educational attainment was significantly associated with most patient characteristics examined at intake and was a significant predictor of the number of CR sessions completed. Lower educational attainment was associated with less improvement in cardiorespiratory fitness, even when controlling for other variables. CONCLUSIONS: Patients with lower SES attend fewer sessions of CR than their higher SES counterparts and may not attain the same level of benefit from attending. Programs need to increase attendance within this population and consider program modifications that further support behavioral changes during CR.

Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism.

INTRODUCTION: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response. METHODS: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test. RESULTS: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression. CONCLUSIONS: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.

Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations.

BACKGROUND: Estrogen receptor positive breast cancers have high recurrence rates despite tamoxifen therapy. Breast cancer stem/progenitor cells (BCSCs) initiate tumors, but expression of estrogen (ER) or progesterone receptors (PR) and response to tamoxifen is unknown. Interleukin-6 (IL-6) and interleukin-8 (IL-8) may influence tumor response to therapy but expression in BCSCs is also unknown. METHODS: BCSCs were isolated from breast cancer and benign surgical specimens based on CD49f/CD24 markers. CD44 was measured. Gene and protein expression of ER alpha, ER beta, PR, IL-6 and IL-8 were measured by proximity ligation assay and qRT-PCR. RESULTS: Gene expression was highly variable between patients. On average, BCSCs expressed 10-106 fold less ERα mRNA and 10-103 fold more ERß than tumors or benign stem/progenitor cells (SC). BCSC lin-CD49f-CD24-cells were the exception and expressed higher ERα mRNA. PR mRNA in BCSCs averaged 10-104 fold less than in tumors or benign tissue, but was similar to benign SCs. ERα and PR protein detection in BCSCs was lower than ER positive and similar to ER negative tumors. IL-8 mRNA was 10-104 higher than tumor and 102 fold higher than benign tissue. IL-6 mRNA levels were equivalent to benign and only higher than tumor in lin-CD49f-CD24-cells. IL-6 and IL-8 proteins showed overlapping levels of expressions among various tissues and cell populations. CONCLUSIONS: BCSCs and SCs demonstrate patient-specific variability of gene/protein expression. BCSC gene/protein expression may vary from that of other tumor cells, suggesting a mechanism by which hormone refractory disease may occur.

Correlation of breast cancer axillary lymph node metastases with stem cell mutations.

IMPORTANCE: Mutations in oncogenes AKT1, HRAS, and PIK3CA in breast cancers result in abnormal PI3K/Akt signaling and tumor proliferation. They occur in ductal carcinoma in situ, in breast cancers, and in breast cancer stem and progenitor cells (BCSCs). OBJECTIVES: To determine if variability in clinical presentation at diagnosis correlates with PI3K/Akt mutations in BCSCs and provides an early prognostic indicator of increased progression and metastatic potential. DESIGN, SETTING, AND PARTICIPANTS: Malignant (BCSCs) and benign stem cells were collected from fresh surgical specimens via cell sorting and tested for oncogene mutations in a university hospital surgical oncology research laboratory from 30 invasive ductal breast cancers (stages IA through IIIB). MAIN OUTCOMES AND MEASURES: Presence of AKT1, HRAS, and PIK3CA mutations in BCSCs and their correlation with tumor mutations, pathologic tumor stage, tumor histologic grade, tumor hormone receptor status, lymph node metastases, and patient age and condition at the last follow-up contact. RESULTS: Ten tumors had mutations in their BCSCs. In total, 9 tumors with BCSC mutations and 4 tumors with BCSCs without mutations had associated tumor present in the lymph nodes (P = .001). CONCLUSIONS AND RELEVANCE: Tumors in which BCSCs have defects in PI3K/Akt signaling are significantly more likely to manifest nodal metastases. These oncogenic defects may be missed by gross molecular testing of the tumor and are markers of more aggressive breast cancer. Molecular profiling of BCSCs may identify patients who would likely benefit from PI3K/Akt inhibitors, which are being tested in clinical trials.