BACKGROUND: Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. METHODS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. RESULTS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results: of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. CONCLUSION Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

BACKGROUND: Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. METHODS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. RESULTS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results: of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. CONCLUSION Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

Objective: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. Methods Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. Results A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost. Conclusion This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.

Objective: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. Methods Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. Results A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost. Conclusion This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.

As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world. With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.
China ; Coronavirus ; Coronavirus Infections ; Humans ; Kinetics ; Korea ; SARS Virus ; Severe Acute Respiratory Syndrome ; Viral Load

As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world. With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.

PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.
Arm ; Carcinoma, Non-Small-Cell Lung ; Cisplatin ; Disease Progression ; Disease-Free Survival ; Epidermal Growth Factor ; Follow-Up Studies ; Humans ; Korea ; Lung Neoplasms ; Lung ; Pemetrexed ; Protein-Tyrosine Kinases ; Quality of Life ; Receptor, Epidermal Growth Factor ; Tyrosine

BACKGROUND: Efforts for improving surgical outcomes in elderly patients should include the prevention of perioperative complications and proper postoperative pain management. Epidural analgesia is effective in decreasing perioperative stress and postoperative complications, and in improving recovery. Recently, it has been suggested that epidural analgesia may attenuate immune suppression during the perioperative period and lead to reductions in cancer recurrence and improvements in overall survival. Assuming that these effects of epidural analgesia are present in vulnerable elderly patients, we compared the efficacy of epidural patient-controlled analgesia and intravenous patientcontrolled analgesia on postoperative outcomes in elderly patients who had undergone gastrectomy. METHODS: We evaluated 214 elderly patients who had undergone elective open gastrectomy for gastric cancer from 2011 to 2014. The demographic characteristics, analgesic efficacy, complications within the first 30 postoperative days, hospital stay, 24-month postoperative morbidity, cancer recurrence, and mortality were studied retrospectively. RESULTS: Two-hundred and five patients were analyzed. Eighty-five patients received epidural patient-controlled analgesia (EPCA group) and 120 patients received intravenous patient- controlled analgesia (IVPCA group). The maximum pain scores were decreased to a greater extent in the EPCA group on the day of the operation (P < 0.001) and on the first postoperative day (P = 0.001) when compared to the IVPCA group. The patients in the EPCA group also required less analgesics on the day of the operation (P = 0.033) than those in the IVPCA group. The effect of EPCA on complications within the first 30 postoperative days, 24-month postoperative morbidity, cancer recurrence, and mortality were negligible in our study. CONCLUSIONS: EPCA provided more effective pain control than IVPCA in elderly patients who had undergone elective gastric cancer surgery, but did not affect postoperative outcomes.
Aged* ; Analgesia ; Analgesia, Epidural ; Analgesia, Patient-Controlled* ; Analgesics ; Gastrectomy* ; Humans ; Length of Stay ; Mortality ; Pain, Postoperative ; Perioperative Period ; Postoperative Complications ; Recurrence ; Retrospective Studies* ; Stomach Neoplasms

BACKGROUND: Efforts for improving surgical outcomes in elderly patients should include the prevention of perioperative complications and proper postoperative pain management. Epidural analgesia is effective in decreasing perioperative stress and postoperative complications, and in improving recovery. Recently, it has been suggested that epidural analgesia may attenuate immune suppression during the perioperative period and lead to reductions in cancer recurrence and improvements in overall survival. Assuming that these effects of epidural analgesia are present in vulnerable elderly patients, we compared the efficacy of epidural patient-controlled analgesia and intravenous patientcontrolled analgesia on postoperative outcomes in elderly patients who had undergone gastrectomy. METHODS: We evaluated 214 elderly patients who had undergone elective open gastrectomy for gastric cancer from 2011 to 2014. The demographic characteristics, analgesic efficacy, complications within the first 30 postoperative days, hospital stay, 24-month postoperative morbidity, cancer recurrence, and mortality were studied retrospectively. RESULTS: Two-hundred and five patients were analyzed. Eighty-five patients received epidural patient-controlled analgesia (EPCA group) and 120 patients received intravenous patient- controlled analgesia (IVPCA group). The maximum pain scores were decreased to a greater extent in the EPCA group on the day of the operation (P < 0.001) and on the first postoperative day (P = 0.001) when compared to the IVPCA group. The patients in the EPCA group also required less analgesics on the day of the operation (P = 0.033) than those in the IVPCA group. The effect of EPCA on complications within the first 30 postoperative days, 24-month postoperative morbidity, cancer recurrence, and mortality were negligible in our study. CONCLUSIONS: EPCA provided more effective pain control than IVPCA in elderly patients who had undergone elective gastric cancer surgery, but did not affect postoperative outcomes.
Aged* ; Analgesia ; Analgesia, Epidural ; Analgesia, Patient-Controlled* ; Analgesics ; Gastrectomy* ; Humans ; Length of Stay ; Mortality ; Pain, Postoperative ; Perioperative Period ; Postoperative Complications ; Recurrence ; Retrospective Studies* ; Stomach Neoplasms

OBJECTIVE: Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. MATERIALS AND METHODS: This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. RESULTS: A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). CONCLUSION: The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases.
Aged ; Alzheimer Disease* ; Dementia* ; Humans ; Magnetic Resonance Imaging ; Mesencephalon ; Neurodegenerative Diseases ; Parkinson Disease* ; Parkinsonian Disorders ; Retrospective Studies ; Substantia Nigra*