A physician-scientist refers to a person with dual Medical Doctor (MD) and Doctor of Philosophy (PhD) degrees, i.e., a physician who has acquired medical knowledge and skills as well as scientific knowledge and research abilities. This study examines the background and current status of physician-scientists in Korea and suggests policy directions to foster physician-scientists suitable for Korea.Current Concepts: With the start of the medical graduate school system in 2005, the MD-PhD dual degree program was implemented under the name of “medical scientist”. With the discontinuation of the medical graduate school system, the term “medical scientist” was replaced with “physician-scientist”. The importance of physician-scientists for the development of biomedical research and industry has been consistently emphasized. Therefore, the government has recently initiated a support policy to train physician-scientists.Discussion and Conclusion: To successfully foster physician-scientists in Korea, the following government policy aspects should be strengthened. First, sufficient economic support should be provided so that physician-scientists could immerse themselves in biomedical research. Second, to guarantee stable employment for physician-scientists, a national research institution such as the National Institute of Health in the United States should be established. Finally, the educational programs of the medical schools should be revised to strengthen the research-related knowledge and skills of the medical students.

The Korean Medical Association (KMA) has been working on medical appraisals for the last 30 years. In 2019, the Korean Medical Practice Review Authority (KMPRA) was established to systematically promote medical appraisal. In addition, regulations related to medical appraisals were amended, professional committees of KMPRA established, and medical case management programs developed. This study reviews the history, present challenges, and the future of KMPRA.Current Concepts: The efforts made by KMA for the development of KMPRA have provided evidence of the excellence of medical appraisal system, with a highly professional, fast, and transparent medical practice review system. Nevertheless, KMPRA has not completely resolved the social distrust of fairness and the quickness of medical appraisals. It is necessary to identify the obstacles that exist in the current appraisal system for the continued development of KMPRA. Currently, KMPRA faces several challenges, such as lack of independence, financial constraints, dichotomized process of medical appraisal, and insufficient administrative manpower, in the process of handling thousands of requested cases. To improve the level of expertise of the professional medical appraisal system, independence, fairness, and speed of its process, KMPRA requires more attention and support from KMA and other major professional medical organizations.Discussion and Conclusion: KMPRA is committed to fulfilling the social responsibility of fair medical appraisal, and it will ultimately contribute to resolving social conflicts derived from medical services and further improving trust relationships with the public.

The Korean Medical Association (KMA) has been working on medical appraisals for the last 30 years. In 2019, the Korean Medical Practice Review Authority (KMPRA) was established to systematically promote medical appraisal. In addition, regulations related to medical appraisals were amended, professional committees of KMPRA established, and medical case management programs developed. This study reviews the history, present challenges, and the future of KMPRA.Current Concepts: The efforts made by KMA for the development of KMPRA have provided evidence of the excellence of medical appraisal system, with a highly professional, fast, and transparent medical practice review system. Nevertheless, KMPRA has not completely resolved the social distrust of fairness and the quickness of medical appraisals. It is necessary to identify the obstacles that exist in the current appraisal system for the continued development of KMPRA. Currently, KMPRA faces several challenges, such as lack of independence, financial constraints, dichotomized process of medical appraisal, and insufficient administrative manpower, in the process of handling thousands of requested cases. To improve the level of expertise of the professional medical appraisal system, independence, fairness, and speed of its process, KMPRA requires more attention and support from KMA and other major professional medical organizations.Discussion and Conclusion: KMPRA is committed to fulfilling the social responsibility of fair medical appraisal, and it will ultimately contribute to resolving social conflicts derived from medical services and further improving trust relationships with the public.

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin’s wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin’s wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

OBJECTIVE: The STONE score and modified STONE score are useful clinical prediction rules for ureteral calculi. This study performed an external validation of the STONE score and modified STONE score. The purpose of this study was to minimize the economic cost and radiation exposure of computed tomography. METHODS: The electronic medical records of patients complaining of flank pain from January 2016 to December 2017 at a single emergency department were reviewed retrospectively. The patients were classified into three groups according to the STONE score and modified STONE score. The prevalence of urethral calculi and other important alternative diagnoses were calculated in each group. RESULTS: Out of 561 patients, 266 patients were enrolled in this study, and 222 patients (83.5%) had a ureteral calculus. The same 266 patients were compared using the two clinical decision rule, STONE score, and the modified STONE score. The patients were classified into three groups. The prevalence of ureteral stones in the STONE score was 18.8% in the low-score group, 81.7% in the moderate-score group, and 91.1% in the high-score group. The prevalence of the modified STONE score was 20.0% in the low-score group, 54.1% in the moderate-score group, and 93.0% in the highscore group. The area under the curve of the modified STONE score was 0.779 higher than the area under the STONE score curve 0.73. CONCLUSION The modified STONE score has superior diagnostic specificity to the STONE score.

PURPOSE: Many traumatic patients die from sepsis and multiple organ failure. Early recognition of post-traumatic sepsis in traumatic patients will help improve the prognosis. Recently, procalcitonin (PCT), macrophage migration inhibitory factor (MIF), and lactic acid have emerged as predictive factors. Our study aims to explore the significance of PCT, MIF and lactic acid as a predictor of posttraumatic-sepsis in trauma patients. METHODS: This study was conducted on prospective observational study patients who visited an emergency medical center in a university hospital from March 2014 to February 2016. We measured the white blood cells, c-reactive protein (CRP), lactic acid, PCT, and MIF with serum taken from the patient's blood within 1 hour of the occurrence of the trauma. The definition of post-traumatic sepsis was defined as being part of systemic inflammation response syndrome criteria with infections within a week. RESULTS: A total of 132 patients were analyzed, wherein 74 patients were included in the low injury severity score (ISS) group (ISS < 15) and 58 patients were included in the high ISS group (ISS ≥15). The mean PCT, MIF, and lactic acid levels were higher in the high ISS group (p < 0.05). Meanwhile, 38 patients were included in the early sepsis group and 94 patients were included in the non-sepsis group. The mean MIF levels were higher in the sepsis group than the non-sepsis group (p < 0.05) and there were no significant differences in the initial CRP, lactic acid, and PCT levels in these two groups. CONCLUSIONS MIF may be considered as a predictive factor for sepsis in trauma patients.

Ginseng gintonin is an exogenous ligand of lysophosphatidic acid (LPA) receptors. Accumulating evidence shows LPA helps in rapid recovery of corneal damage. The aim of this study was to evaluate the therapeutic efficacy of gintonin in a rabbit model of corneal damage. We investigated the signal transduction pathway of gintonin in human corneal epithelium (HCE) cells to elucidate the underlying molecular mechanism. We next evaluated the therapeutic effects of gintonin, using a rabbit model of corneal damage, by undertaking histochemical analysis. Treatment of gintonin to HCE cells induced transient increases of [Ca²⁺](i) in concentration-dependent and reversible manners. Gintonin-mediated mobilization of [Ca²⁺](i) was attenuated by LPA1/3 receptor antagonist Ki16425, phospholipase C inhibitor U73122, inositol 1,4,5-triphosphate receptor antagonist 2-APB, and intracellular Ca²⁺ chelator BAPTA-AM. Gintonin facilitated in vitro wound healing in a concentration-dependent manner. When applied as an eye-drop to rabbits with corneal damage, gintonin rapidly promoted recovery. Histochemical analysis showed gintonin decreased corneal apoptosis and increased corneal cell proliferation. We demonstrated that LPA receptor activation by gintonin is linked to in vitro and in vivo therapeutic effects against corneal damage. Gintonin can be applied as a clinical agent for the rapid healing of corneal damage.
Apoptosis ; Cell Proliferation ; Corneal Injuries ; Epithelium, Corneal ; Humans ; In Vitro Techniques ; Inositol 1,4,5-Trisphosphate ; Mortuary Practice ; Panax ; Rabbits ; Receptors, Lysophosphatidic Acid ; Signal Transduction ; Therapeutic Uses ; Type C Phospholipases ; Wound Healing* ; Wounds and Injuries*

Microglia are activated by inflammatory and pathophysiological stimuli in neurodegenerative diseases, and activated microglia induce neuronal damage by releasing cytotoxic factors like nitric oxide (NO). Activated microglia synthesize a significant amount of vitamin D3 in the rat brain, and vitamin D3 has an inhibitory effect on activated microglia. To investigate the possible role of vitamin D3 as a negative regulator of activated microglia, we examined the effect of 25-hydroxyvitamin D3 on NO production of lipopolysaccharide (LPS)-stimulated microglia. Treatment with LPS increased the production of NO in primary cultured and BV2 microglial cells. Treatment with 25-hydroxyvitamin D3 inhibited the generation of NO in LPS-activated primary microglia and BV2 cells. In addition to NO production, expression of 1-alpha-hydroxylase and the vitamin D receptor (VDR) was also upregulated in LPS-stimulated primary and BV2 microglia. When BV2 cells were transfected with 1-alpha-hydroxylase siRNA or VDR siRNA, the inhibitory effect of 25-hydroxyvitamin D3 on activated BV2 cells was suppressed. 25-Hydroxyvitamin D3 also inhibited the increased phosphorylation of p38 seen in LPS-activated BV2 cells, and this inhibition was blocked by VDR siRNA. The present study shows that 25-hydroxyvitamin D3 inhibits NO production in LPS-activated microglia through the mediation of LPS-induced 1-alpha-hydroxylase. This study also shows that the inhibitory effect of 25-hydroxyvitamin D3 on NO production might be exerted by inhibiting LPS-induced phosphorylation of p38 through the mediation of VDR signaling. These results suggest that vitamin D3 might have an important role in the negative regulation of microglial activation.
Animals ; Brain ; Calcifediol* ; Cholecalciferol ; Microglia* ; Negotiating ; Neurodegenerative Diseases ; Neurons ; Nitric Oxide* ; Phosphorylation ; Rats ; Receptors, Calcitriol ; RNA, Small Interfering

Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase alpha1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of alpha1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.
Adenosine Triphosphatases ; Astrocytes ; Brain Injuries ; Glucose ; Ischemia ; L-Lactate Dehydrogenase ; Neuroglia ; Neurons ; RNA, Messenger ; Sodium Azide