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Ultrasound echo intensity index for diagnosing amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis, also called Lou Gehrig's disease, is a fatal neurodegenerative disease whereby the upper motor neurons of the central nervous system and the lower motor neurons of the peripheral nervous system are selectively lost. Lou Gehrig's disease leads to muscle weakness affecting the whole body and ultimately resulting in death due to diverse complications usually within three to five years following diagnosis. In the early stages of development, the symptoms are not easy to differentiate from those of other curable diseases, therefore further markers for early detection need to be developed.
Split hand (stronger muscle atrophy on the palm and the back of the hand on the side of the thumb in comparison to that on the side of the little finger) has not yet been fully understood both anatomically and pathophysiologically and has been confirmed unique to Lou Gehrig's disease. Though an index was proposed by using compound muscle action potential to diagnose the presence of split hand at an early stage, this approach is accompanied by uncomfortable pains for patients due to electrical stimuli. Moreover, the sensitivity and specificity of the index are too low for patients whos symptoms have progressed as far as muscle atrophy is too severe to evoke compound muscle action potential.
Prof. Byung-jo Kim's research team in the Department of Neurology at Korea University College of Medicine confirmed an increase in echo intensity and a decrease in volume of denervated muscles in patients with neuropathy using muscle ultrasound. Based on these observations, researchers developed a new ultrasound echo intensity index that can identify the presence of split hand. They then compared the new echo intensity index in three separate groups which includes: patients diagnosed with Lou Gehrig's disease, patients with neuromuscular disorders having similar clinical symptoms accompanied by hand muscle atrophy and a normal healthy control group.
Compared to the existing index using compound muscle action potential, the new index applying ultrasound showed significantly higher sensitivity and specificity for diagnosing Lou Gehrig's disease. Moreover, the new index may also be applied in patients whereby severe muscular atrophy has taken place and for who the conventional index does not apply. Furthermore, no pain is experienced by patients during the new test. The new index has been patented as a diagnostic marker for Lou Gehrig's disease.
A subsequent study is underway to find a pathophysiological mechanism for split hand by combining and analyzing brain MRI data of patients with Lou Gehrig’s disease. Results of the follow-up study are expected to be employed for the development of an advanced diagnostic tool to differentiate patients with curable muscle atrophy in early stage.
pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/29666207
J Neurol Neurosurg Psychiatry. 2018 Sep;89(9):943-948. doi: 10.1136/jnnp-2017-317917. Epub 2018 Apr 17.
The 2019 World Federation for Medical Education World Conference (WFME 2019) was successfully held in Seoul, Korea.
The WFME 2019 was the first and the largest international conference of medical education held in Korea, attracting 800 participants from 56 countries around the world.
The conference provided a meaningful opportunity for exchanging ideas about the future of medical education.
The 2019 World Federation for Medical Education World Conference (WFME 2019) was successfully held in Seoul, co-hosted by Korea University College of Medicine (Dean Hong Sik Lee) and the Korean Council on Medical Education (President Hee Chul Han).
The WFME 2019 was held in the Grand Walkerhill Seoul from April 7th to 10th, joined by 800 experts in medical education and accreditation from 56 countries. The conference program spanned a range of topics including medical education and accreditation for quality assurance, state-run tests and refresher courses in 67 invited lectures and 300 freestyle presentations.
Notably, participants not only shared the current status of medical education in their own countries but discussed the need to establish global standards for medical education, the current records of global accreditation for medical education institutions and future advances in the field, spurred by growing exchanges of medical personnel across countries. In addition, postgraduate medical education that has been rarely touched in the discourse of medical education, i.e., the need for quality improvement and accreditation for medical residency training, was actively discussed in the conference, which was very meaningful considering the reality of residency training in Korea.
Participants also exchanged their ideas on the role of hospitals as training institutions, intensive postgraduate medical education and the improvement options. They agreed that the role of college of medicine needs to be strengthened in the postgraduate medical education as in the US and the UK. Excellent examples were introduced on how to nurture doctors who have deeper understandings of their society and empathy with their patients, drawing a lot of attention from the audience. Moreover, students expressed their own opinions on medical student exchange programs and accreditation for medical education, providing an opportunity to have a grand perspective including views of both providers and consumers of medical education.
The WFME 2019 was very meaningful because it was the first of its kind held in Asia and it provided an opportunity to discuss the goal of current medical education, the limits and issues in different countries from the perspective of followers in medical education, not from the views of advanced runners. Furthermore, the meeting showed that Korea is making efforts to advance medical education based on the global standards free from the existing leadership of advanced countries such as the US and those in Europe, playing a leading role in medical education.
President Hee Chul Han of the Korean Council on Medical Education said "It is a great honor to co-host the WFME World Conference with Korea University College of Medicine in 16 years since the previous one. It is especially meaningful that the 12 members of the Korean Council on Medical Education eagerly cooperated to organize the event including the Korean Medical Association, the Korean Hospital Association, the Korean Academy of Medical Sciences, the Korea Association of Medical Colleges and the Korean Doctors Council." He also added "I hope the government and our society pay attention to our efforts and take measures to promote normalization of medical residency training and advancement of medical education, based on the standards for medical residency training discussed in the WFME 2019."
Prof. Hong Sik Lee, Dean of Korea University College of Medicine, said "It is critical to understand the global trend to advance the medical education in Korea and the government as well as the medical community needs to discuss necessary measures in public about international exchanges of medical students and experts," and he also added "The sustained quality improvement in medical education in Korea requires our society's support and coordination." The Dean finally stated "Above all, I should say that it was a great privilege to host the WFME 2019 for the first time in Asia to discuss the current agenda in medical education with global experts. Korea University College of Medicine will play a leading role in proposing a novel paradigm and setting global standards in medical education to resolve public health issues."
Flubendazole’s anticancer activity and suppression of cancer stem cell properties
The treatment of triple-negative breast cancer (TNBC) remains challenging due to the absence of established molecular targets for the phenotype. These tumors account for 10-15% of all breast cancers and tend to be more aggressive with a higher risk of recurrence and metastasis, leading to poorer clinical outcomes. Evidence from clinical and preclinical studies suggests that the aggressive nature of TNBC may be partially due to the existence of breast cancer stem cells (BCSCs). BCSCs are thought to play a crucial role in promoting tumor initiation, growth and propagation, as well as resistance to chemotherapy.
Prof. Jae Hong Seo's research team in the Department of Hemato-oncology at Korea University Guro Hospital cultivated mammospheres and adherent cells enriched with cancer stem cells using TNBC cell lines, transplanted them into mice respectively, and compared results in tumor growth rate and metastasis. Primary tumors were observed to spread fast to the lungs and the livers of mice grafted with mammospheres, where the ALDH1 activity was higher than in adherent cells, and the metastatic factor STAT3 was activated in the ALDH1+ cell fraction. The study showed that cancer stem cells in TNBC accelerated metastasis and they have a correlation with the STAT3 signaling pathway, a major metastatic factor.
Flubendazole is a widely used anthelmintic agent approved by the FDA and suppresses the multiplication of parasites, faster than normal cells of humans, by acting as a tubulin inhibitor. Though the study of anticancer effects of flubendazole for hematologic malignancy was first published in 2010, there has been no report on the mechanism of its action.
Prof. Jae Hong Seo's research team proposed flubendazole as an agent targeting cancer stem cells and showed reduced cell survival rates and apoptosis in the TNBC cell lines (MDA-MB-231, BT549, HS578T, 4T1) induced by flubendazole. The evidence supporting the mechanism is caspase-3/7 activation and STAT3 suppression. Flubendazole suppressed the expressions of CD24low/CD44high, CD24high/CD49fhigh and ALDH1, which are markers for breast cancer stem cells, through mammoshpere formation. Finally, 4T1 mammospheres were injected into BALB/c mice to prove flubendazole's effects on tumor formation and metastasis by targeting cancer stem cells. Flubendazole significantly inhibited tumor growth as well as lung metastasis induced from primary tumors. In addition, flubendazole also reduced the expressions of STAT3 and Ki-67 in tumor tissues, inducing apoptosis and suppressing cancer stem cell factors.
Therefore, the study showed flubendazole's anticancer effects and inhibition of cancer stem cells in vitro and in vivo, and it suggested flubendazole's potential as a new agent to treat the recurrence and metastasis of TNBC.
pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/29744876
Int J Cancer. 2018 Oct 15;143(8):1978-1993. doi: 10.1002/ijc.31585. Epub 2018 Jul 10.
Romo1 promotes production of reactive oxygen species in tumor cells and development of cancer
Excess amount of reactive oxygen species (ROS) in the body causes diseases such as cancer, diabetes, arthritis and so on. Rising concentration of ROS in the body leads to chronic inflammation and onset of diverse diseases. Mitochondrion is a major cellular organelle generating ROS. Researchers led by Prof. Yoo Young-do in the Graduate School of Medicine at Korea University showed for the first time that a specific protein embedded in the mitochondrial inner membrane promotes generation of ROS and named the protein 'Romo1'. The research team discovered for the first time that Romo1 in mitochondria accelerates production of ROS and development of cancer, and these results will contribute to finding out how to suppress cancer.
Development of new drugs targeting Romo1 requires the knowlege of protein structure of Romo1. However, the existing techniques could not illuminate the protein structure of Romo1 because it is a tiny membrane protein embedded in the inner membrane of mitochondria. The research team used structural bioinformatics to discover the 3D structure of Romo1.
The present study also identified characteristics of Romo1 as a nonselective cation channel in human mitochondria. Moreover, researchers showed that Romo1 is the only protein in the human cell with those features. The 3D structure of Romo1 is expected to be used in developing medicines to treat diseases caused by chronic inflammations.
<Structure of Romo1 embedded in the mitochondrial inner membrane>
pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/29545371
J Cell Biol. 2018 Jun 4;217(6):2059-2071. doi: 10.1083/jcb.201709001. Epub 2018 Mar 15.