The chemotherapeutic drug cisplatin, which targets DNA, serves as one of the main staples in cancer treatment. Yet, the therapeutic application of cisplatin is limited by two major challenges: the occurrence of reversible and irreversible side effects due to non-specific toxicity, and the intrinsic or developing resistance of tumor cells toward cisplatin. Here we demonstrate that cancer cells respond to cisplatin treatment with the nucleolar accumulation of inorganic polyphosphate (polyP), a universally conserved high-energy compound. PolyP accumulation positively correlates with the levels of activated caspase-3, suggesting a novel role of polyP in cisplatin-mediated apoptosis. In support of this finding, we discovered that administration of exogenous polyP increases cisplatin-induced toxicity in select cancer cell lines, raising the exciting possibility that enhancing endogenous polyP levels might be a novel mechanism to sensitize cancer cells to cisplatin treatment.

Background: Amid the COVID-19 pandemic, medical education and residency application have faced unprecedented changes. This has forced residency directors to alter their selection criteria in the absence of away rotations and the implementation of nationwide virtual interviews. Purpose: The purpose of this study was to assess how residency directors have adapted their selection criteria in light of this unique application cycle and to look at the effect, and future, of the different changes. Methods: A 16-question online survey was disseminated to 31 residency programs gathering data about new opportunities offered this cycle, changes to selection criteria, match outcomes, as well as the number of applicants to their program. Results: Twenty-nine respondents completed the survey (94% response rate). There was a significant rise in the number of applications received by programs this cycle (p < 0.05). Programs have unanimously altered their selection processes. The biggest changes in selection criteria were putting more weight into communication from mentors, emails from the applicants, home applicant status, and virtual information session attendance. Some programs used additional application requirements beyond Electronic Residency Application Service, which were often uncompleted, and cut the number of eligible applications by up to 46%. Among the new opportunities offered this cycle, virtual information sessions and social media platforms seem to be the most commonly offered and are anticipated to grow. Discussion and Conclusion: Orthopaedic surgery residency continues to become more competitive with a significant rise in the number of applications during the COVID-19 pandemic. Amid this increasingly demanding virtual application cycle, a holistic application review was more challenging. More weight was put that cycle into communication from faculty mentors, emails from the applicants, home applicant status, and virtual information session attendance. Supplementary applications and virtual informative opportunities are likely to last and change the future of the orthopaedic surgery residency application process.Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A380).

Lifespan in poikilothermic organisms, such as Caenorhabditis elegans, can be substantially increased simply by decreasing growth temperature. To gain insights into the mechanistic underpinnings of this effect, we investigated the effects of temperature in development and adulthood on C. elegans lifespan. We found that worms exposed to 25 °C during development and shifted to 15 °C in adulthood exhibited an even longer lifespan than animals constantly kept at 15 °C. Analysis of the in vivo redox status demonstrated that at 25 °C, C. elegans larvae have a more reduced redox state and higher Prdx-2 expression levels than animals raised at 15 °C. Worms lacking prdx-2 fail to show the additional lifespan extension upon shift from 25 °C to 15 °C and reveal a lifespan similar to prdx-2 worms always kept at 15 °C. These results suggest that transiently altering the in vivo redox state during development can have highly beneficial long-term consequences for organisms.

BackgroundIt is generally believed that trauma to fat grafts is detrimental and affects the survival of the graft. In addition, it has been shown that smaller fat particle size corresponds to better survival; however, smaller cannula openings correspond to slower and more difficult fat graft harvesting. ObjectivesThis study documents the relationship between cannula size, harvested fat cell size, and injection needle size. A means of reducing fat particle size following aspiration with larger diameter cannulas is also discussed. MethodsFat was harvested from five patients undergoing elective liposuction. Each fat sample was placed in a syringe and injected through progressively smaller needles until obstruction under low pressure was obtained. The minimal needle size was documented for each sample. ResultsFat harvested with a liposuction cannula results in different size fat particles ranging up to the size of the cannula. Particles obtained from 3-and 4-mm cannulas can be injected without obstruction through a 16-gauge needle. Particles obtained from a 2-mm cannula can be injected without obstruction through an 18-gauge needle. Particles obtained from a 1-mm cannula can be injected without obstruction through a 20-gauge needle. Particles obtained from a 1-mm cannula could not be injected without obstruction through a 22-gauge needle. ConclusionsThere is a relationship between cannula opening size and the resultant fat graft size. Fat particles are somewhat compressible but should not be forced through needles or cannulas that are too narrow. It may be beneficial to harvest fat with larger cannulas and cut the particles to smaller sizes for injection.

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