High energy requirements and water throughput of adult Shuar forager-horticulturalists of Amazonian Ecuador.

OBJECTIVES: We measured total energy expenditure (TEE; kcal/d) and water throughput (L/d) among Shuar forager-horticulturalists from Amazonian Ecuador to compare their daily energy and water demands to adults in other small-scale and industrialized populations. METHODS: TEE and water throughput were measured using the doubly labeled water method among 15 Shuar adults (eight women, seven men; age range 18-60 years) living in a relatively remote village. We used multiple regression to assess the effects of anthropometric variables (body size, fat free mass, age, and sex) on TEE and water throughput. We also compared Shuar TEE and water throughput to those of other small-scale and industrialized societies. RESULTS: TEE among Shuar adults (men: 4141 ± 645 kcal/d, women: 2536 ± 281 kcal/d) was most strongly correlated with fat free mass. Estimated physical activity levels (PAL) calculated as (TEE/estimated BMR), were greater for men (2.34 ± 0.29) than women (1.83 ± 0.14, P < 0.001). Water throughput was also greater among Shuar men (9.37 ± 2.34 L/d) than women (4.76 ± 0.36 L/d, P < 0.001). Shuar TEE and water throughput were elevated compared to adults in industrialized populations. DISCUSSION: TEE and PAL of Shuar men are among the highest recorded during normal daily life, and likely reflect both high levels of physical activity and cultural dietary practices. Drinking large amounts of chicha, a traditional carbohydrate-rich drink made from manioc, likely contributes to the high levels of water throughput among Shuar men, and may contribute to elevated TEE.

PNOC015: Repeated convection-enhanced delivery of MTX110 (aqueous panobinostat) in children with newly diagnosed diffuse intrinsic pontine glioma.

BACKGROUND: The objective of this study was to determine the safety, tolerability, and distribution of MTX110 (aqueous panobinostat) delivered by convection-enhanced delivery (CED) in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) who completed focal radiation therapy (RT). METHODS: Patients with DIPG (2-21 years) were enrolled after RT. CED of MTX110 combined with gadoteridol was completed across 7 dose levels (DL) (30-90 µM; volumes ranging from 3 mL to 2 consecutive doses of 6 mL). An accelerated dose escalation design was used. Distribution of infusate was monitored with real-time MR imaging. Repeat CED was performed every 4-8 weeks. Quality-of-life (QoL) assessments were obtained at baseline, every 3 months on therapy, and end of therapy. RESULTS: Between May 2018 and March 2020, 7 patients who received a total of 48 CED infusions, were enrolled (median age 8 years, range 5-21). Three patients experienced dose-limited toxicities. Four grade 3 treatment-related adverse events were observed. Most toxicities were transient new or worsening neurologic function. Median overall survival (OS) was 26.1 months (95% confidence interval: 14.8-not reached). Progression-free survival was 4-14 months (median, 7). Cumulative percentage of tumor coverage for combined CED infusions per patient ranged from 35.6% to 81.0%. Increased CED infusions were negatively associated with self-reported QoL assessments. CONCLUSION: Repeat CED of MTX110 with real-time imaging with gadoteridol is tolerable for patients with DIPG. Median OS of 26.1 months compares favorably with historical data for children with DIPG. The results support further investigation of this strategy in a larger cohort.

Wild Dictyostelium discoideum social amoebae show plastic responses to the presence of nonrelatives during multicellular development.

When multiple strains of microbes form social groups, such as the multicellular fruiting bodies of Dictyostelium discoideum, conflict can arise regarding cell fate. Both fixed and plastic differences among strains can contribute to cell fate, and plastic responses may be particularly important if social environments frequently change. We used RNA-sequencing and photographic time series analysis to detect possible conflict-induced plastic differences between wild D. discoideum aggregates formed by single strains compared with mixed pairs of strains (chimeras). We found one hundred and two differentially expressed genes that were enriched for biological processes including cytoskeleton organization and cyclic AMP response (up-regulated in chimeras), and DNA replication and cell cycle (down-regulated in chimeras). In addition, our data indicate that in reference to a time series of multicellular development in the laboratory strain AX4, chimeras may be slightly behind clonal aggregates in their development. Finally, phenotypic analysis supported slower splitting of aggregates and a nonsignificant trend for larger group sizes in chimeras. The transcriptomic comparison and phenotypic analyses support discoordination among aggregate group members due to social conflict. These results are consistent with previously observed factors that affect cell fate decision in D. discoideum and provide evidence for plasticity in cAMP signaling and phenotypic coordination during development in response to social conflict in D. discoideum and similar microbial social groups.

Future directions in 3-dimensional imaging and neurosurgery: stereoscopy and autostereoscopy.

Recent advances in 3-dimensional (3-D) stereoscopic imaging have enabled 3-D display technologies in the operating room. We find 2 beneficial applications for the inclusion of 3-D imaging in clinical practice. The first is the real-time 3-D display in the surgical theater, which is useful for the neurosurgeon and observers. In surgery, a 3-D display can include a cutting-edge mixed-mode graphic overlay for image-guided surgery. The second application is to improve the training of residents and observers in neurosurgical techniques. This article documents the requirements of both applications for a 3-D system in the operating room and for clinical neurosurgical training, followed by a discussion of the strengths and weaknesses of the current and emerging 3-D display technologies. An important comparison between a new autostereoscopic display without glasses and current stereo display with glasses improves our understanding of the best applications for 3-D in neurosurgery. Today's multiview autostereoscopic display has 3 major benefits: It does not require glasses for viewing; it allows multiple views; and it improves the workflow for image-guided surgery registration and overlay tasks because of its depth-rendering format and tools. Two current limitations of the autostereoscopic display are that resolution is reduced and depth can be perceived as too shallow in some cases. Higher-resolution displays will be available soon, and the algorithms for depth inference from stereo can be improved. The stereoscopic and autostereoscopic systems from microscope cameras to displays were compared by the use of recorded and live content from surgery. To the best of our knowledge, this is the first report of application of autostereoscopy in neurosurgery.

Bayesian image analysis of dexamethasone and shear stress-induced glucocorticoid receptor intracellular movement.

Endothelial cells are continuously exposed to hemodynamic shear stress, which has been shown to induce an array of physiological responses at the cellular and molecular levels. Uniform high shear stress is protective against vascular diseases such as atherosclerosis which preferentially occur at regions of disturbed flow and low shear. The glucocorticoid receptor (GR), a member of the steroid nuclear receptors with anti-inflammatory functions, has been shown to be activated by shear stress. Using a unique expectation-maximization (EM) algorithm based on Bayesian statistics, we have developed an image analysis algorithm to quantitatively assess GR nuclear translocation based on time-lapse images of green fluorescence protein-tagged GR (GFP-GR) under continuous exposure to a shear stress of 10 or 25 dynes/cm(2) as well as to Dexamethasone, a GR agonist. Average fluorescence brightness is generated for nucleus and cytoplasm. Real-time imaging of sheared cells revealed a steady and significant nuclear GFP-GR increase of approximately 20% within 2 h, compared to a rapid 60% increase in Dexamethasone-treated cells within 30 min. Furthermore, we found that that GFP-GR nuclear translocation under shear is not dependent on an intact cytoskeleton. Our image analysis algorithm provides a novel quantitative method to further study shear-sensitive mechanotransduction pathways in endothelial cells.