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Intervertebral disc (IVD) degeneration is a common pathological condition associated with low back pain. Recent evidence suggests that mesenchymal signaling cells (MSCs) promote IVD regeneration, but underlying mechanisms remain poorly defined. One postulated mechanism is via modulation of macrophage phenotypes. In this manuscript, we tested the hypothesis that MSCs produce trophic factors that alter macrophage subsets. To this end, we collected conditioned medium from human, bone marrow-derived STRO3 + MSCs. We then cultured human bone marrow-derived macrophages in MSC conditioned medium (CM) and performed single cell RNA-sequencing. Comparative analyses between macrophages cultured in hypoxic and normoxic MSC CM showed large overlap between macrophage subsets; however, we identified a unique hypoxic MSC CM-induced macrophage cluster. To determine if factors from MSC CM simulated effects of the anti-inflammatory cytokine IL-4, we integrated the data from macrophages cultured in hypoxic MSC CM with and without IL-4 addition. Integration of these data sets showed considerable overlap, demonstrating that hypoxic MSC CM simulates the effects of IL-4. Interestingly, macrophages cultured in normoxic MSC CM in the absence of IL-4 did not significantly contribute to the unique cluster within our comparison analyses and showed differential TGF-β signaling; thus, normoxic conditions did not approximate IL-4. In addition, TGF-β neutralization partially limited the effects of MSC CM. In conclusion, our study identified a unique macrophage subset induced by MSCs within hypoxic conditions and supports that MSCs alter macrophage phenotypes through TGF-β-dependent mechanisms., Competing Interests: Authors BR and TB were employed by Medtronic. Authors KC and NS were employed by Medtronic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Koroth, Chitwood, Kumar, Lin, Reves, Boyce, Reineke, Ellingson, Johnson, Stone, Chaffin, Simha, Ogle and Bradley.)

Objectives: To evaluate facility postoperative opioid prescribing patterns in comparison to published guidelines and adherence to opioid safety mandates., Methods: This quality analysis was performed between November 2019 and March 2020. Patients were identified to have been opioid naïve prior to receiving a new opioid prescription postoperatively during the study period. Patient charts were reviewed, and patients were contacted to collect desired data. Statistical analysis was performed to evaluate distributions of morphine equivalent daily dose and opioid day supply prescribed across study subpopulations., Results: Ninety-four of 100 prescriptions evaluated were determined to be within quantity or duration recommendations of the selected guideline. Statistical analysis found no significantly different distributions between the duration and quantity of opioid prescribed at discharge and patient-specific risk factors. Forty-eight patients did not use the entire quantity of the initial opioid prescription dispensed. Of those patients, 26 still had opioids within the home. Opioid risk review documentation was completed in 19 of 65 patients indicated for documentation., Conclusion: Most opioid prescriptions provided within the study period aligned with recommendations from author-selected guidelines. However, a review of risk prior to opioid prescribing frequently was not performed. The number of patients utilizing less than 50% of prescribed opioids, and few refills indicate that reductions in opioids prescribed would improve safety for both patients and the surrounding community without increasing the risk for the under-treatment of postoperative pain. Improved prescribing habits and patient safety will be targeted through provider education regarding risk review documentation in opioid naïve patients., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Selective autophagy is a conserved subcellular process that maintains the health of eukaryotic cells by targeting damaged or toxic cytoplasmic components to the vacuole/lysosome for degradation. A key player in the initiation of selective autophagy in S. Cerevisiae (baker's yeast) is a large adapter protein called Atg11. Atg11 has multiple predicted coiled-coil domains and intrinsically disordered regions, is known to dimerize, and binds and organizes other essential components of the autophagosome formation machinery, including Atg1 and Atg9. We performed systematic directed mutagenesis on the coiled-coil 2 domain of Atg11 in order to map which residues were required for its structure and function. Using yeast-2-hybrid and coimmunoprecipitation, we found only three residues to be critical: I562, Y565, and I569. Mutation of any of these, but especially Y565, could interfere with Atg11 dimerization and block its interaction with Atg1 and Atg9, thereby inactivating selective autophagy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Meyer, Winzeler, Taylor, Kilgore, Edicha, Chitwood, Spearin, Silvia, Chakraborty, Smith, Kennedy, Zois, Cawthon, Gilruth and Backues.)

Introduction: Worldwide, commercially available waterpipes vary widely in design and durability, including differences in fabrication materials, degree of leak-tight fit, and flow path diameter. Little is known about how the components of the waterpipe may influence puffing behavior and user's exposure to toxins. To systematically evaluate exposure, it is necessary to use a standardized research-grade waterpipe (RWP) when conducting clinical and laboratory-based trials., Methods: We developed a RWP that is configured with an in-line topography system which allows real-time measurement and recording of the smoke volume drawn through the RWP. The RWP was calibrated across the flow rate range expected for waterpipe tobacco smoking and the calibration was verified for known puff volumes using a smoking machine. Operation of the RWP was qualified in a cohort of experienced waterpipe smokers, each smoker using the RWP ad libitum in a laboratory setting while smoker topography and subjective effects data were collected., Results: RWP machine smoking was highly reproducible and yielded puff volumes that agreed well with true values. User acceptance was comparable, and puffing behavior was similar in pattern, with more frequent puffing in the beginning of the session, but significantly different in intensity from that used to estimate the majority of toxicant exposure reported in the literature., Conclusions: The RWP operates with known precision and accuracy and is well accepted by experienced smokers. This tool can be used to determine the extent to which puffing behaviors are affected by the waterpipe design, components, and/or accessories, tobacco nicotine content, sweet flavorings and/or additives known to increase addictiveness., Implications: This study describes a standardized RWP, equipped with a puffing topography analyzer, which can operate with known precision and accuracy, and is well-accepted by experienced smokers in terms of satisfaction and reward. The RWP is an important tool for determining if puffing behaviors, and thus estimated toxin exposures, are affected by the waterpipe design, components, and/or accessories, tobacco nicotine content, sweet flavorings, and/or additives that are known to increase addictiveness., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A mailed survey of 239 Texas physicians selected by a stratified random sample was completed in 1990 (response ratio = 39.5%) concerning physician's background in nutrition, nutrition knowledge, and recommended treatments to patients with hypercholesterolemia. Twenty-one percent reported taking a nutrition seminar and 41 percent read a nutrition text during the past year. Less than a third had taken a nutrition course after medical school; half had taken such a course during medical school. Over 46 percent achieved a perfect score on nine knowledge questions regarding dietary fat. Only 35 percent identified the latest American Heart Association nutrition education effort. Seventy-four percent said they ate chicken or fish instead of red meat three or more times a week. Over 80 percent selected exercise, weight reduction, and low fat diets as the most important treatment types. Physicians continue to have limited knowledge of nutrition and should be encouraged to make greater use of dietitians as consultants.