Psycho-oncology in Korea: Past, present and future

Background: Psycho-oncology in Korea was introduced among the circle of consultation-liaison psychiatrists, in the 1990s. For almost 25 years, the field has been developing at a steady pace as the psychosocial needs of patients with cancer continue to increase. In this study, we review the history of psycho-oncology in Korea, in a chronological order, within the domains of clinical practice, research activity, training, and public policy. Main body: Before the 1990s, patients with cancer with psychiatric comorbidities were usually taken care of by consultation-liaison psychiatrists in general hospitals. In 1993, psycho-oncology was first introduced by psychiatrists. Psychologists, nurses, and social workers have also been increasingly involved in providing psychosocial care for patients with cancer. Professionals from various disciplines began to communicate, and agreed to found the Korean Psycho-Oncology Study Group (KPOSG) in 2006, the first academic society in this field. In 2009, National Cancer Center published the Recommendations for Distress Management in Patients with Cancer, which are consensus-based guidelines for Korean patients. In 2014, the KPOSG was dissolved and absorbed into a new organization, the Korean Psycho-Oncology Society (KPOS). It functions as a center of development of psycho-oncology, publishing official journals, and hosting annual conferences. There are many challenges, including, low awareness of psycho-oncology, presence of undertreated psychiatric disorders in patients with cancer, shortage of well-trained psycho-oncologists, stigma, and suicide risk. It is important to improve the cancer care system to the extent that psycho-oncology is integrated with mainstream oncology. Considering the socio-cultural characteristics of Korean cancer care, a Korean model of distress management is being prepared by the KPOS. Conclusion: This article provides an overview of the development, current issues, and future challenges of psycho-oncology in Korea. Through its long journey to overcome the many barriers and stigmas of cancer and mental illnesses, psycho-oncology is now acknowledged as an essential part of integrated supportive care in cancer. Active research and international cooperation can gradually shape the Korean model of distress management.ope

Osteoblast-Osteoclast Communication and Bone Homeostasis

Bone remodeling is tightly regulated by a cross-talk between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoblasts and osteoclasts communicate with each other to regulate cellular behavior, survival and differentiation through direct cell-to-cell contact or through secretory proteins. A direct interaction between osteoblasts and osteoclasts allows bidirectional transduction of activation signals through EFNB2-EPHB4, FASL-FAS or SEMA3A-NRP1, regulating differentiation and survival of osteoblasts or osteoclasts. Alternatively, osteoblasts produce a range of different secretory molecules, including M-CSF, RANKL/OPG, WNT5A, and WNT16, that promote or suppress osteoclast differentiation and development. Osteoclasts also influence osteoblast formation and differentiation through secretion of soluble factors, including S1P, SEMA4D, CTHRC1 and C3. Here we review the current knowledge regarding membrane bound- and soluble factors governing cross-talk between osteoblasts and osteoclasts

A RUNX2 stabilization pathway mediates physiologic and pathologic bone formation

The osteoblast differentiation capacity of skeletal stem cells (SSCs) must be tightly regulated, as inadequate bone formation results in low bone mass and skeletal fragility, and over-exuberant osteogenesis results in heterotopic ossification (HO) of soft tissues. RUNX2 is essential for tuning this balance, but the mechanisms of posttranslational control of RUNX2 remain to be fully elucidated. Here, we identify that a CK2/HAUSP pathway is a key regulator of RUNX2 stability, as Casein kinase 2 (CK2) phosphorylates RUNX2, recruiting the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which stabilizes RUNX2 by diverting it away from ubiquitin-dependent proteasomal degradation. This pathway is important for both the commitment of SSCs to osteoprogenitors and their subsequent maturation. This CK2/HAUSP/RUNX2 pathway is also necessary for HO, as its inhibition blocked HO in multiple models. Collectively, active deubiquitination of RUNX2 is required for bone formation and this CK2/HAUSP deubiquitination pathway offers therapeutic opportunities for disorders of inappropriate mineralization

The ERK MAPK Pathway Is Essential for Skeletal Development and Homeostasis

Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that function as key signal transducers of a wide spectrum of extracellular stimuli, including growth factors and pro-inflammatory cytokines. Dysregulation of the extracellular signal-regulated kinase (ERK) MAPK pathway is associated with human skeletal abnormalities including Noonan syndrome, neurofibromatosis type 1, and cardiofaciocutaneous syndrome. Here, we demonstrate that ERK activation in osteoprogenitors is required for bone formation during skeletal development and homeostasis. Deletion of Mek1 and Mek2, kinases upstream of ERK MAPK, in osteoprogenitors (Mek1(Osx)Mek2(-/-)), resulted in severe osteopenia and cleidocranial dysplasia (CCD), similar to that seen in humans and mice with impaired RUNX2 function. Additionally, tamoxifen-induced deletion of Mek1 and Mek2 in osteoprogenitors in adult mice (Mek1(Osx-ERT)Mek2(-/-)) significantly reduced bone mass. Mechanistically, this corresponded to decreased activation of osteoblast master regulators, including RUNX2, ATF4, and beta-catenin. Finally, we identified potential regulators of osteoblast differentiation in the ERK MAPK pathway using unbiased phospho-mass spectrometry. These observations demonstrate essential roles of ERK activation in osteogenesis and bone formation

Numerical study on CO2 absorption efficiency by using aqueous monoethanolamine solution in CO2 absorber column

Paper presented at the 8th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Mauritius, 11-13 July, 2011.In this study, the one-dimensional rate based model is developed for predicting the performance of the CO2 absorber column using aqueous monoethanolamine (MEA) solution. To determine the concentration of each species and temperature distribution along the column height, mass and heat balance equations of vapor and liquid phase are coupled with chemical reactions in MEA-CO2-H2O system. The two-film model is applied to estimate the mass transfer in the vapour and liquid film. To calculate the enhancement factor, three types of reaction rate coefficient of the CO2/aqueous MEA reaction are considered. The mathematical and reaction kinetics models used in this study are validated in the comparison of simulation results with experimental data given in the literature. The simulation results are in good agreement with the data in the literature. In addition, three types of reaction rate coefficient suggested by Hikita et al., Versteeg et al. and Aboudheir et al. are considered. The performance of CO2 absorber column with respect to the reaction rate coefficients is compared with experimental data.mp201

Capric Acid Inhibits NO Production and STAT3 Activation during LPS-Induced Osteoclastogenesis

Capric acid is a second medium-chain fatty acid, and recent studies have shown that fatty acids are associated with bone density and reduce bone turnover. In this study, we investigated the effects of capric acid on lipopolysaccharide (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, an osteoclast differentiation marker, without inhibiting cell viability. LPS strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA expression. Subsequently, we investigated various intracellular signaling proteins, including nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 1 (STAT1) and STAT3 associated with osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the NF-κB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited LPS-induced phosphorylation of Ser727 in STAT3. Additionally, stattic (a STAT3 inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by suppressing NO production via the STAT3 pathway. These results suggest that capric acid has important therapeutic implications for treating bone diseases associated with excessive osteoclastogenesis

Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis

RNAi-based bone anabolic gene therapy has demonstrated initial success, but many practical challenges are still unmet. Here, we demonstrate that a recombinant adeno-associated virus 9 (rAAV9) is highly effective for transducing osteoblast lineage cells in the bone. The adaptor protein Schnurri-3 (SHN3) is a promising therapeutic target for osteoporosis, as deletion of shn3 prevents bone loss in osteoporotic mice and short-term inhibition of shn3 in adult mice increases bone mass. Accordingly, systemic and direct joint administration of an rAAV9 vector carrying an artificial-microRNA that targets shn3 (rAAV9-amiR-shn3) in mice markedly enhanced bone formation via augmented osteoblast activity. Additionally, systemic delivery of rAAV9-amiR-shn3 in osteoporotic mice counteracted bone loss and enhanced bone mechanical properties. Finally, we rationally designed a capsid that exhibits improved specificity to bone by grafting the bone-targeting peptide motif (AspSerSer)6 onto the AAV9-VP2 capsid protein. Collectively, our results identify a bone-targeting rAAV-mediated gene therapy for osteoporosis

Eosinophilic gastroenteritis in an 18-year-old male with prolonged nephrotic syndrome

Eosinophilic gastroenteritis is a rare disease characterized by prominent eosinophilic tissue infiltration of the gastrointestinal tract. Here, we report a case of eosinophilic gastroenteritis in an 18-year-old patient with prolonged nephrotic syndrome who presented with abdominal pain and peripheral hypereosinophilia. During the previous 2 years, he had visited local Emergency Department several times because of epigastric pain and nausea. He had been treated with steroid-dependent nephrotic syndrome since 3 years of age. Tests ruled out allergic and parasitic disease etiologies. Gastroduodenoscopy with biopsy revealed marked eosinophilic infiltration in the duodenum. Renal biopsy findings indicated minimal change disease spectrum without eosinophilic infiltration. The oral deflazacort dosage was increased, and the patient was discharged after abdominal pain resolved. To our knowledge, this is the first report of eosinophilic gastroenteritis in a patient with minimal change disease

Predictors of cervical myelopathy and hydrocephalus in young children with achondroplasia

Background Cervical myelopathy and hydrocephalus occasionally occur in young children with achondroplasia. However, these conditions are not evaluated in a timely manner in many cases. The current study presents significant predictors for cervical myelopathy and hydrocephalus in young children with achondroplasia. Methods A retrospective analysis of 65 patients with achondroplasia who visited Seoul National University Childrens Hospital since 2012 was performed. The patients were divided into groups according to the presence of cervical myelopathy and hydrocephalus, and differences in foramen magnum parameters and ventricular parameters by magnetic resonance imaging between groups were analyzed. Predictors for cervical myelopathy and hydrocephalus were analyzed, and the cut-off points for significant ones were calculated. Results The group with cervical myelopathy showed foramen magnum parameters that indicated significantly lower cord thickness than in the group without cervical myelopathy, and the group with hydrocephalus showed significantly higher ventricular parameters and Posterior indentation grade than the group without hydrocephalus. Cord constriction ratio (OR 5199.90, p = 0.001) for cervical myelopathy and Frontal horn width (OR 1.14, p = 0.001) and Posterior indentation grade (grade 1: OR 9.25, p = 0.06; grade 2: OR 18.50, p = 0.01) for hydrocephalus were significant predictors. The cut-off points for cervical myelopathy were Cord constriction ratio of 0.25 and FM AP of 8 mm (AUC 0.821 and 0.862, respectively) and Frontal horn width of 50 mm and Posterior indentation grade of 0 (AUC 0.788 and 0.758, respectively) for hydrocephalus. Conclusion Cord constriction ratio for cervical myelopathy and Frontal horn width and Posterior indentation grade for hydrocephalus were significant predictors and may be used as useful parameters for management. Posterior indentation grade may also be used to determine the treatment method for hydrocephalus