Utilizing Patient-Reported Outcome Questionnaires in Standard Practice: A Study from Thoracic Radiation Oncology

https://openworks.mdanderson.org/sumexp22/1059/thumbnail.jp

Interspecies Comparison of Peptide Substrate Reporter Metabolism using Compartment-Based Modeling [post-print]

Peptide substrate reporters are fluorescently labeled peptides that can be acted upon by one or more enzymes of interest. Peptide substrates are readily synthesized and more easily separated than full-length protein substrates; however, they are often more rapidly degraded by peptidases. As a result, peptide reporters must be made resistant to proteolysis in order to study enzymes in intact cells and lysates. This is typically achieved by optimizing the reporter sequence in a single cell type or model organism, but studies of reporter stability in a variety of organisms are needed to establish the robustness and broader utility of these molecular tools. We measured peptidase activity toward a peptide substrate reporter for protein kinase B (Akt) in E. coli, D. discoideum, and S. cerevisiae using capillary electrophoresis with laser-induced fluorescence (CE-LIF). Using compartment-based modeling, we determined individual rate constants for all potential peptidase reactions and explored how these rate constants differed between species. We found the reporter to be stable in D. discoideum (t1/2 = 82–103 min) and S. cerevisiae (t1/2 = 279–314 min), but less stable in E. coli (t1/2 = 21–44 min). These data suggest that the reporter is sufficiently stable to be used for kinase assays in eukaryotic cell types while also demonstrating the potential utility of compartment-based models in peptide substrate reporter design

Respiration rate and volume measurements using wearable strain sensors.

Current methods for continuous respiration monitoring such as respiratory inductive or optoelectronic plethysmography are limited to clinical or research settings; most wearable systems reported only measures respiration rate. Here we introduce a wearable sensor capable of simultaneously measuring both respiration rate and volume with high fidelity. Our disposable respiration sensor with a Band-Aid© like formfactor can measure both respiration rate and volume by simply measuring the local strain of the ribcage and abdomen during breathing. We demonstrate that both metrics are highly correlated to measurements from a medical grade continuous spirometer on participants at rest. Additionally, we also show that the system is capable of detecting respiration under various ambulatory conditions. Because these low-powered piezo-resistive sensors can be integrated with wireless Bluetooth units, they can be useful in monitoring patients with chronic respiratory diseases in everyday settings

Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes

Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different (68)Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin–selective peptide cyclo(FRGDLAFp(NMe)K) via NHS chemistry. Radiolabelling experiments confirmed a high radiochemical yield of the two PET probes. In addition, cellular binding studies showed high binding affinities in the nanomolar range. The two integrin αvβ6-peptide-THP synthesized and radiolabeled in this study will facilitate in vivo monitoring of transmembrane receptor αvβ6 integrin by using the advantage of THP chemistry for rapid, efficient and stable gallium chelation

International capacity building to achieve SDG6 : insights from longitudinal analysis of five water operator partnerships

In pursuit of the United Nations’ Sustainable Development Goal (SDG) 6, water operator partnerships (WOPs) have grown in popularity. However, the literature supporting their effectiveness is lacking. We conducted mid-term interviews and surveys with five participating utilities in a Viet Nam–Australia WOP, followed by post-programme interviews with two managing associations and 10 utilities. We found that while partnerships initially focused on technical training, the need for broader institutional learning emerged as participants gained experience. Communication and relationship-building were consistently reported as success factors for achieving desired outcomes. Expanding the scope to involve governance and policy organizations, together with funding to collaboratively implement upgrades, could enhance future programmes

Methods for generating and colonizing gnotobiotic zebrafish

Vertebrates are colonized at birth by complex and dynamic communities of microorganisms that can contribute significantly to host health and disease. The ability to raise animals in the absence of microorganisms has been a powerful tool for elucidating the relationships between animal hosts and their microbial residents. The optical transparency of the developing zebrafish and relative ease of generating germ-free zebrafish makes it an attractive model organism for gnotobiotic research. Here we provide a protocol for: generating zebrafish embryos; deriving and rearing germ-free zebrafish; and colonizing zebrafish with microorganisms. Using these methods, we typically obtain 80–90% sterility rates in our germ-free derivations with 90% survival in germ-free animals and 50–90% survival in colonized animals through larval stages. Obtaining embryos for derivation requires approximately 1–2 hours with a 3–8 hour incubation period prior to derivation. Derivation of germ-free animals takes 1–1.5 hours, and daily maintenance requires 1–2 hours

All-optical multimode fibre photoacoustic endomicroscopy with scalable spatial resolution and field-of-view

An all-optical, forward-viewing, optical-resolution photoacoustic endomicroscopy probe was developed for guiding minimally invasive procedures. The probe comprises a multimode fibre for the delivery of excitation laser via wavefront shaping, and a fibre-optic ultrasound sensor based on a plane-concave microresonator at the tip of a single-mode fibre. High-resolution photoacoustic microscopy images of mouse red blood cells and mouse ear vasculature were acquired, and the high scalability of the probe in terms of field-of-view and spatial resolution was demonstrated. The ultrathin photoacoustic endomicroscopy probe promises to guide minimally invasive surgery by providing both molecular and microstructural information

Clinical Implications of Combinatorial Pharmacogenomic Tests Based on Cytochrome P450 Variant Selection

Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients’ lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of a given population with an “altered metabolizer” genotype predicted phenotype, where a CPGx test targeted both gene variants a prospective diplotypes. A potential genotype predicted phenotype was considered an altered metabolizer when it resulted in medication therapy modification based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Targeted variant CPGx tests found in the Genetic Testing Registry (GTR), gene selection information, and diplotype frequency data from the Pharmacogenomics Knowledge Base (PharmGKB) were used to determine the detection rate of each CPGx test. Our results indicated that the detection rate of CPGx tests covering CYP2C19, CYP2C9, CYP2D6, and CYP2B6 show significant variation across ethnic groups. Specifically, the Sub-Saharan Africans have 63.9% and 77.9% average detection rates for CYP2B6 and CYP2C19 assays analyzed, respectively. In addition, East Asians (EAs) have an average detection rate of 55.1% for CYP2C9 assays. Therefore, the patient’s ethnic background should be carefully considered in selecting CPGx tests