Medical research archives最新文献

The Case Comprehensive Cancer Center's Youth Enjoy Science (YES) Program is funded by the National Cancer Institute to promote broad interest in pursuing a career in biomedical research via early intervention strategies that inspire student interest, help envision research as a career path, and strengthen practical research and career skills. A major aspect of the YES program is an 8-week immersion into cancer center faculty laboratories to conduct a cancer research project over the summer. The overall goal is to excite students to consider a future career in biomedical research or healthcare to enhance the future cancer-focused workforce. To ensure the YES program is meeting its goals and providing an exceptional experience for students, an external evaluation team performs an annual evaluation that incorporates a mixed methods approach combining mechanisms for formal and informal feedback. The team shares key insights with program leadership, faculty, and student representatives to ensure that all feedback directly informs program adjustments. This approach emphasizes actionable results rather than passive data collection, reinforcing the program's commitment to continuous quality improvement. Formal surveys suggest the program has been consistently meeting its goals of increasing student understanding of cancer biology and research. However, a recent reduction in survey response rates makes it challenging to determine whether survey respondents are primarily those with the most positive experiences. Integrating both formal and informal feedback mechanisms in program evaluation is essential for capturing the full range of student experiences. Thus, it is critical that training programs provide a channel for informal discussions. The YES program coordinator maintains close relationships with all stakeholders and is deeply familiar with student participants, from the application process to ongoing program activities. As an approachable and engaged leader, the coordinator effectively gathers feedback and implements changes to enhance program performance. In response to formal and informal feedback, the YES program curriculum has been modified to enhance not only student and mentor experiences but also the process for soliciting feedback in the future.

Donor-derived myotubes offer a pre-clinical model for studying muscle biology, the effects of exercise-like electrical stimulation, and assessing drug efficacy and toxicity. We engineered a 3D muscle microphysiological system from myoblasts isolated from vastus lateralis of young and older adults. Over a three-week differentiation process, we applied two cycles of low frequency electrical stimulation daily for seven days generating functional, mature myobundles, as confirmed by gene expression profiling. Both young- and old-derived myobundles showed synchronous contraction in response to electrical stimulation, however, the contraction magnitude was reduced in old-derived myobundles compared to young-derived myobundles. We then assessed the donor-specific response to tomatidine, a steroidal alkaloid found in the skin of green tomatoes, known to inhibit muscle atrophy and promote skeletal muscle hypertrophy. Bioinformatic analyses revealed that infusion of tomatidine during electrical stimulation modulated the IL-6/JAK/STAT3 pathway. The contraction magnitude decreased in the young-derived myobundles treated with tomatidine compared to vehicle-treated controls, while no significant difference was observed in the old-derived myobundles. Secretome analysis revealed age-related changes in secreted proteins linked to inflammation and extracellular matrix remodeling. Notably, tomatidine attenuates the inflammatory and extracellular matrix remodeling responses in the myobundles triggered by electrical stimulation, partially preventing the secretion of proinflammatory proteins. This intervention strategy helps balance muscle adaptation and repair, while limiting excessive proinflammatory responses. Our microphysiological system provides a valuable platform for investigating signaling pathways involved in muscle function, and pharmacological responses, advancing the understanding of age-related muscle biology.

The programming of cardiac implantable electronic devices, such as pacemakers and implantable defibrillators, represents a promising domain for the application of automated learning systems. These systems, leveraging a type of artificial intelligence called reinforcement learning, have the potential to personalize medical treatment by adapting device settings based on an individual's physiological responses. At the core of these self-learning algorithms is the principle of balancing exploration and exploitation. Exploitation refers to the selection of device programming settings previously demonstrated to provide clinical benefit, while exploration refers to the real-time search for adjustments to device programming that could provide an improvement in clinical outcomes for each individual. Exploration is a critical component of the reinforcement learning algorithm, and provides the opportunity to identify settings that could directly benefit individual patients. However, unconstrained exploration poses risks, as an automated change in certain settings may lead to adverse clinical outcomes. To mitigate these risks, several strategies have been proposed to ensure that algorithm-driven programming changes achieve the desired level of individualized optimization without compromising patient safety. In this review, we examine the existing literature on safe reinforcement learning algorithms in automated systems and discuss their potential application to the programming of cardiac implantable electronic devices.

Translocations are rearrangements produced upon erroneous repair of double-strand breaks, fusing segments of non-homologous chromosomes. These events can cause chimeric protein expression and other transcriptional alterations, eventually driving oncogenic transformation. Despite their significance, the factors shaping the heterogeneous translocation landscape in healthy individuals and cancer patients remain incompletely understood. In this review, we focus on genomic content and activation as two fundamental factors associated with translocation formation and selection. While emphasizing the critical role of double-strand breaks and interchromosomal contacts in translocation formation, we discuss that selective advantage is likely the main driver shaping translocation landscapes in health and disease. Finally, we address that it remains difficult to disentangle the effect of translocation formation from the influence of selective pressure, and point out that unraveling their separate contribution in future studies will be key to better understand early tumorigenesis.

Homozygous familial hypercholesterolemia (HoFH) is an autosomal semi-dominant condition characterized by biallelic pathogenic variants impacting low-density lipoprotein receptor (LDLR) function. Affected individuals have severely elevated LDL cholesterol, early onset atherosclerotic heart disease and/or aortic stenosis, and characteristic clinical findings. While the cause is known and diagnosis is relatively simple, real-world HoFH care presents many complexities, including genetic heterogeneity and the diverse personal and social circumstances that influence care. Genetics-informed treatment involves a trial-and-error approach that warrants specific considerations during pregnancy. Thus, HoFH care requires a deep understanding of personal factors, social determinants of health, and a flexible, adaptable approach to treatment, all of which justify the need for personalized care. Framed by complexity theory, this review offers strategies for personalizing HoFH care, including a reconceptualization of the definition of health and implementing a multidisciplinary team approach. We also recommend integrating complexity theory and systems thinking into clinical care. By doing so, we illustrate the advantages of classifying knowledge complexity to inform clinical decision-making. We also demonstrate how openness to relationship-building and time investment is critical to materializing personalized care to HoFH.

Background: Cardiac light-chain amyloidosis represents a critical component of this multi-systemic disease, significantly impacting prognosis. The extent of cardiac free light-chain deposition is the primary determinant of survival.

Case presentation: We report the case of a 67-year-old male with a 10-year history of diabetes mellitus and arterial hypertension who presented with a two-day history of chest discomfort and difficulty lying down or sleeping, along with a two-month history of progressively worsening exertional dyspnea. On examination, the patient exhibited low blood pressure. A 12-lead electrocardiogram revealed poor R-wave progression and left ventricular hypertrophy. Further evaluation using 2D echocardiography demonstrated significant concentric left ventricular hypertrophy, a restrictive filling pattern, and mild pericardial effusion. Cardiac magnetic resonance imaging, nuclear imaging, and biopsy confirmed the diagnosis of cardiac light-chain amyloidosis.

Conclusion: Timely recognition and a high index of suspicion are essential for the early diagnosis of cardiac amyloidosis. Prompt diagnosis enables the initiation of definitive therapy, which may halt disease progression and significantly improve prognosis.

Cardiovascular disease is one of the world's leading causes of natural mortality, taking approximately 18 million lives each year. Dilated cardiomyopathy, a subgroup of cardiac diseases, has an annual incidence of 5 - 8 cases per 100,000 for European and North American populations. Common features of dilated cardiomyopathy include cardiac chamber enlargement, impaired systolic function, reduced ejection fraction, and arrhythmias, with an endpoint of ventricular dilation and heart failure. The focus of this paper is to review the non-genetic and genetic etiologies that lead to dilated cardiomyopathy. The non-genetic causes of dilated cardiomyopathy that are discussed include viruses, cardiotoxicity, recreational drugs, and chemotherapeutic medications. For the genes that lead to dilated cardiomyopathy, the focus of this paper is on cytoskeletal and sarcomeric protein genes. Our scope in defining this area will be to explore numerous mouse models that incorporate mutations found in humans that lead to dilated cardiomyopathy. The purpose of the paper is to define the morphological and physiological consequences of these mutations and how this information has furthered our understanding of the disease. Having gained invaluable knowledge from these animal models, it is hoped that new and improved therapeutic approaches can be developed for the treatment and prevention of dilated cardiomyopathy.

Purpose: To qualitatively assess a novel intervention, the Diabetes Transition of Hospital Care (DiaTOHC) Program, designed to reduce hospital readmissions within 30 days of discharge among people with diabetes.

Methods: In a separately reported randomized controlled trial of the DiaTOHC intervention, hospitalized people with diabetes were identified as high risk for 30-day hospital readmission using the Diabetes Early Readmission Risk Indicator (DERRI^®). Of these, 58 participants were randomized to the intervention. After the 30-day intervention, participants and study staff completed semi-structured interviews until saturation was achieved, yielding 21 participant and 4 staff interviews. Each one underwent thematic analysis.

Results: Four themes were identified: (1) Participants were motivated to make lifestyle changes, (2) Weekly Navigator phone calls were an effective method to support participants, (3) The intervention improved some diabetes knowledge domains but not others, and (4) Perceived lack of control was associated with readmission. Participants with baseline hemoglobin A1C (A1C) ≥8% made more changes to their diabetes management due to the intervention but were less likely to review the educational materials and had more extreme blood glucose levels. Participants who completed fewer post-discharge phone calls were more likely to find the educational booklet helpful than those who completed more calls.

Conclusions: Education, care coordination, and follow up are key components of the DiaTOHC Program that may improve diabetes self-management after a hospitalization and reduce readmission risk.

Background: Ignoring the cultural factors that can affect performance on cognitive tests may result in use of tests that have not been validated for that group. One example is testing of Haitian Creole speaking adults who are increasingly affected by Alzheimer's disease and related dementias, for whom few tests have been validated.

Aims: Our purpose is to describe differences in timed test performance between Haitian Creole and English-speaking participants and explore factors that may account for any differences in results found.

Methods: Data was obtained from an ongoing longitudinal driving and cognition study "In Vehicle Sensors to Detect Cognitive Change in Older Drivers." Two groups consisting of 12 Creole speaking and 12 English speaking older adults were matched by age and gender. Test scores were selected from the battery of tests administered in the parent study. The measures were translated by two bilingual Creole-English researchers. Group performance on five timed cognitive tests commonly used in research was compared.

Results: The English-speaking group's mean scores were significantly higher than the Creole speaking group on the MoCA and the timed Animal category fluency, letter P fluency, Stroop Color Test, and Trail Making Test A and B. The most significant effects were noted in Letter P fluency, Trail Making Test A and B and Animal category fluency where the differences had large effect sizes. However, the Creole speaking group had higher mean scores than the English-Speaking group on the Stroop Color Word Test, although the difference was not statistically significant. It was not feasible to match education levels due to the differences in years of education across the groups. These results highlight the significant role of culture and linguistic context in cognitive task performance.

Conclusions: The results suggest performance in cognitive testing among non-English speaking groups may be impacted by cultural factors related to time perception and the testing approach employed, leading to misinterpretation and misdiagnosis. Future studies should explore the fairness of various cognitive testing approaches with Haitian older adults and other societies with cultures and educational approaches different from those of Western cultures.