Project description:BackgroundMitochondrial dysfunction results in poor organ quality, negatively affecting the outcomes of lung transplantation. Whether hydrogen benefits mitochondrial function in cold-preserved donors remain unclear. The present study assessed the effect of hydrogen on mitochondrial dysfunction in donor lung injury during cold ischemia phase (CIP) and explored the underlying regulatory mechanism.MethodsLeft donor lungs were inflated using 40% oxygen + 60% nitrogen (O group), or 3% hydrogen + 40% oxygen + 57% nitrogen (H group). Donor lungs were deflated in the control group and were harvested immediately after perfusion in the sham group (n = 10). Inflammation, oxidative stress, apoptosis, histological changes, mitochondrial energy metabolism, and mitochondrial structure and function were assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also analyzed.ResultsCompared with the sham group, inflammatory response, oxidative stress, histopathological changes, and mitochondrial damage were severe in the other three groups. However, these injury indexes were remarkably decreased in O and H groups, with increased Nrf2 and HO-1 levels, elevated mitochondrial biosynthesis, inhibition of anaerobic glycolysis and restored mitochondrial structure and function compared with the control group. Moreover, inflation using hydrogen contributed to stronger protection against mitochondrial dysfunction and higher levels of Nrf2 and HO-1 when comparing with O group.ConclusionsLung inflation using hydrogen during CIP may improve donor lung quality by mitigating mitochondrial structural anomalies, enhancing mitochondrial function, and alleviating oxidative stress, inflammation, and apoptosis, which may be achieved through activation of the Nrf2/HO-1 pathway.
Project description:In 2023, Korea had 104953 diagnostic radiological devices installed across 43529 medical institutions, with 398947394 examinations performed. The number of devices and examinations rank among the highest by OECD standards. The average medical radiation dose per individual was 3.13 mSv, representing an increase of approximately 27.2% compared to 2020, contrary to the global trend of decreasing radiation exposure. This study aimed to review various research activities by the Korean Society of Radiology, its members, and other researchers to reduce radiation exposure and explore additional strategies to further mitigate this issue.
Project description:Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
Project description:Through a combination of a controlled experiment and a survey, we examine the effect of voting power on shareholders' voting behavior at general meetings. To avoid a selection bias, common in archival voting data, we exogenously manipulate shareholders' power to affect the outcome. Our findings suggest that, when it comes to corporate decisions involving conflicts of interest, voting power nudges shareholders to oppose management and to choose the "right" alternative, that is, vote against a proposal which prima facie does not serve the company's best interest. This effect obtained even when the dissenting vote contravened the choices of all other voters. Furthermore, the drive "to do the right thing" was established as significant, above and beyond the size of the economic stake. We also demonstrate that strategic voting among institutional investors is contingent on voting power: when in a position to affect the outcome of a vote, institutional investors tend to eschew strategic considerations and display fewer consistent patterns in their voting, compared to situations in which their ability to make a difference is limited. In anticipation of a "bad" proposal to be put to vote at the general shareholder meeting, institutional investors prefer to negotiate terms with management beforehand, and vote against it only after such negotiations fail. Our results shed new light on the "behind the scenes" processes in shareholder voting and underscore the importance of institutional investor agency to corporate governance, accountability, and minority shareholder representation.Supplementary informationThe online version contains supplementary material available at 10.1007/s10551-022-05108-y.
Project description:ObjectivesWhile there has been increasing awareness of the importance of social determinants of health (SDOH) learning for internal medicine residents and physicians, only a few residency programs have incorporated training into their curricula. For those who did, the curricula were often didactic and lacked action-driven components or community partnership. Therefore, we built an experiential SDOH curriculum with an action-driven element and emphasis on community partnerships in a newly established residency program in rural New York.MethodsOver 24 months, 22 internal medicine residents were engaged in SDOH lectures, workshops, and action-driven learning through implementing screening tools in residency clinics and working with community partners. After the curriculum, residents' competency in addressing SDOH needs was assessed through Likert-scale questionnaires. Focused interviews were conducted among participating residents and faculty to obtain qualitative feedback on the curriculum.ResultsParticipating resident physicians demonstrated competency in recognizing and addressing SDOH needs after curriculum completion (mean competency score = 4.04). A significant increase in residents' self-rated confidence in addressing SDOH was observed after training (P = .002). Residents reported enhanced relationships with patients, effective utilization of community resources, and readiness to apply SDOH knowledge and skills to their future practice. Residents and faculty also discussed the SDOH challenges unique to rural primary care through their experiences.ConclusionThis curriculum provides insights into an educational framework that improves residents' SDOH awareness, integrates SDOH into resident physicians' daily practice, and facilitates community collaboration. While challenges unique to rural primary care exist, this curriculum demonstrated the feasibility of longitudinal, action-driven, and community-centered SDOH education in rural areas that may inform future programs' curricular design.
Project description:Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants.
Project description:In vitro drug release kinetics studies are routinely performed to examine the ability of new drug formulations to modulate drug release. The underlying assumption is that the studies are performed in a sufficiently dilute solution, where the drug release is not limited by the solubility and the difference in release kinetics profile reflects the performance of a drug carrier in vivo. This condition is, however, difficult to meet with poorly water-soluble drug formulations, as it requires a very large volume of release medium relative to the formulation mass, which makes it challenging to measure the drug concentration accurately. These difficulties are aggravated with nanoparticle (NP) formulations, which are hard to separate from the release medium and thus require a dialysis bag or repeated high-speed centrifugation for sampling. Perhaps for these reasons, drug release kinetics studies of NPs of poorly water-soluble drugs are often performed in suboptimal conditions in which the NPs are not sufficiently diluted. However, such a practice can potentially underestimate drug release from NPs, leading to an inaccurate prediction that the NPs will attenuate the drug activity in vivo. Here we perform release kinetics studies of two different NP formulations of paclitaxel, a representative poorly water-soluble drug, according to common practices in the literature. We find that the drug release from NPs can be substantially underestimated depending on the choice of the release medium, NP/medium ratio, and handling of release samples. We discuss potential consequences of underestimating drug release, ending with suggestions for future studies with NP formulations of poorly water-soluble drugs.
Project description:BackgroundCardiopulmonary assessment for lung resection is important for risk stratification, and the American College of Chest Physicians (ACCP) guidelines provide decision support. We ascertained the cardiopulmonary assessment practices of thoracic surgeons and determined whether they are guideline concordant.MethodsAn anonymous survey was emailed to 846 thoracic surgeons who participate in The Society of Thoracic Surgeons General Thoracic Surgery Database. We analyzed survey responses by practice type (general thoracic [GT] versus cardiothoracic [CT]) and years in practice (0-9, 10-19, and ≥20) with the use of contingency tables. We compared adherence of survey responses with the guidelines.ResultsThe response rate was 24.0% (n = 203). Most surgeons (n = 121, 59.6%) cited a predicted postoperative forced expiratory volume in 1 second or diffusing capacity of lung for carbon monoxide threshold of 40% for further evaluation. Experienced surgeons (≥20 years) were more likely to have a threshold that varies by surgical approach (31.3% versus 23.5% with 10-19 years of experience and 15.9% for 0-9 years of experience, P = .007). Overall, 52.2% refer patients with cardiovascular risk factors to cardiology and 42.9% refer patients with abnormal stress testing. CT surgeons were more likely to refer all patients to cardiology than GT surgeons (17.6% versus 2.4%, P < .001). Only one respondent (0.5%) was 100% adherent to the ACCP guidelines, and 4.4% and 45.8% were 75% and 50% adherent, respectively.ConclusionsAmong thoracic surgeons, there is variation in preoperative cardiopulmonary assessment practices, with differences by practice type and years in practice, and marked discordance with the ACCP guidelines. Further study of guideline adherence linked to postoperative morbidity and mortality is warranted to determine whether adherence affects outcomes.