Cardiovascular disease is the leading cause of global mortality. Among the many risk factors for cardiovascular disease, it's long been known that high cholesterol increases the risk for heart attacks and stroke. In today's episode of Beyond the Abstract, Derek and Dan discuss two new papers that challenge commonly held beliefs about the way in which cholesterol increases the risk for cardiovascular disease. They finish by talking about a new type of genetic medicine to lower cholesterol and reduce the risk for cardiovascular disease.

Papers discussed

Alternating high-fat diet enhances atherosclerosis by neutrophil reprogramming, Lavillegrand et al 2024 Nature

https://www.nature.com/articles/s41586-024-07693-6

Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis, Takaoka et al 2024 Nature

https://www.nature.com/articles/s41586-024-07993-x

Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia, Rosenson et al 2024 NEJM

http://nejm.org/doi/full/10.1056/NEJMoa2404147

Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia, Ballantyne et al 2024 NEJM

https://www.nejm.org/doi/full/10.1056/NEJMoa2404143

Humans have long sought the fountain of youth, and recently scientists have explored the biological basis of aging and potential strategies to reverse the process. Along with groundbreaking discoveries that have enabled extending the lifespan of model organisms, the anti-aging movement has spurred an entire industry focused on stopping the biological clock. In today's episode of Beyond the Abstract, Derek and Dan discuss recent studies about the aging process and debate the promises and pitfalls of this fast-moving field.

This episode is sponsored by Proteintech Group, a company that creates reagents for the biomedical sciences so scientists can conduct groundbreaking science. Visit them at www.ptglab.com to find out more.

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Articles Discussed

Abad et al. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature, 2013.

Ross et al. Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity. Nature, 2024.

Ocampo et al. In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Cell, 2016.

Wang et al. In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. Nature Communications, 2021.

Browder et al. In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice. Nature Aging, 2022.

Weindruch et al. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. Journal of Nutrition, 1986.

Lu et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature, 2020.

Yucel and Gladyshev. The long and winding road of reprogramming-induced rejuvenation. Nature Communications, 2024.

Lopez-Otin et al. The Hallmarks of Aging. Cell, 2013.

Choudhury et al. Proline restores mitochondrial function and reverses aging hallmarks in senescent cells. Cell Reports, 2024.

Zeng et al. Restoration of CPEB4 prevents muscle stem cell senescence during aging. Developmental Cell, 2023.

Disorders of the brain are among the most challenging to treat in all of medicine. Among the challenges is access: the brain is locked away in the skull, preventing medicines from reaching their destination. To deal with this difficulty, researchers are turning to an unexpected access point to the brain: the eye. In today's episode of Beyond the Abstract, Derek and Dan discuss new papers that demonstrate neural and immune links between the eye and the brain that could soon help doctors treat diseases ranging from Alzheimer's to cancer.

Articles discussed

Murdock et al., Multisensory gamma stimulation promotes glymphatic clearance of amyloid. Nature. 2024 (https://www.nature.com/articles/s41586-024-07132-6)

Yin et al., Compartmentalized ocular lymphatic system mediates eye-brain immunity. Nature. 2024 (https://www.nature.com/articles/s41586-024-07130-8)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Food allergies are a major problem – common, potentially deadly, and without effective medicines to prevent them from occurring. But earlier this year, researchers and doctors published a clinical trial reporting an effective new treatment for preventing allergic food reactions. In today’s episode of Beyond the Abstract, Derek and Dan dive into the science behind the new treatment and what it might mean for the future of combating a deadly disease.

Article discussed

Wood et al., Omalizumab for the Treatment of Multiple Food Allergies. New England Journal of Medicine. 2024 (https://www.nejm.org/doi/full/10.1056/NEJMoa2312382)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Thousands of patients in the US die every year waiting for an organ transplant, often because there are not enough human organ donors. Xenotransplantation — transplantation from another species to humans — could solve this problem, but has remained the realm of science fiction given many technical obstacles. Now, with advances in gene editing, this pipe dream is becoming reality. In today's episode of Beyond the Abstract, Dan and Derek explore xenotransplantation, tell the stories of the few humans who have received pig organs, and explain why this may herald a new era in transplant medicine.

Articles discussed

Griffith et al. Genetically modified porcine-to-human cardiac xenotransplantation. New England Journal of Medicine. 2022. (https://www.nejm.org/doi/full/10.1056/NEJMoa2201422)

Anand et al. Design and testing of a humanized porcine donor for xenotransplantation. Nature. 2023. (https://www.nature.com/articles/s41586-023-06594-4)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

While almost all women experience nausea and vomiting during pregnancy, few are debilitated by severe symptoms: a condition known as hyperemesis gravidarum (HG). HG has been stigmatized and neglected by the biomedical community, with limited research funding for developing effective treatments. In this episode of Beyond the Abstract, Derek and Dan tell the remarkable story of one scientist who experienced HG herself, and her decades-long journey to find a cure.

Articles discussed

Her Doctor Said Her Illness Was All in Her Head. This Scientist Was Determined to Find the Truth. Alice Callahan. New York Times, 2023. (https://www.nytimes.com/2023/03/14/well/marlena-fejzo-hyperemesis-gravidarum.html)

GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Fejzo et al. 2023. Nature. (https://www.nature.com/articles/s41586-023-06921-9).

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Fejzo et al. 2018. Nature Communications. (https://www.nature.com/articles/s41467-018-03258-0)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

A new class of medicines has transformed the treatment of obesity -- Wegovy and Ozempic have become household names. While we discussed these GLP-1 medicines on an episode of Beyond the Abstract less than a year ago, the field has progressed so quickly we thought it was already time to review many of these recent developments. In today's episode, Derek and Dan first discuss improved versions of these medicines on the horizon for the treatment of obesity. Derek and Dan then talk about how these medicines are being studied to treat a wide range of diseases outside of obesity, ranging from cardiovascular disease to substance use disorder.

Articles discussed

Jastreboff et al 2023 NEJM, Triple-Hormone Receptor Agonist Retatrutide for Obesity -- A Phase 2 Trial (https://www.nejm.org/doi/full/10.1056/NEJMoa2301972)

Wharton et al 2023 NEJM, Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity (https://www.nejm.org/doi/full/10.1056/NEJMoa2302392)

Lincoff et al 2023 NEJM, Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (https://www.nejm.org/doi/full/10.1056/NEJMoa2307563)

Kosiborod et al 2023 NEJM, Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (https://www.nejm.org/doi/full/10.1056/NEJMoa2306963)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Debates around artificial intelligence are everywhere: will ChatGPT usher in a new era of productivity and creativity? Or will advanced AI replace millions of workers? Doctors have similar questions about how AI may influence medicine. In today's episode of Beyond the Abstract, Dan and Derek take a deep dive into all things AI and health. They discuss the current role of AI in medicine and the promises and perils of potential new applications made possible because of ChatGPT and other emerging AI technologies.

Moor et al., Foundational models for generalist medical artificial intelligence, Nature, 2023 (https://www.nature.com/articles/s41586-023-05881-4).

He et al., Blinded, randomized trial of sonographer versus AI cardiac function assessment, Nature, 2023 (https://www.nature.com/articles/s41586-023-05947-3).

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.