Search

Mouse molars resemble human teeth, as their roots develop and stop growing. In contrast, mouse incisors grow and erupt continuously due to the presence of a persistent stem cell niche identified as the labial cervical loop, which actively gives rise to dentin-forming odontoblasts to support tooth homeostasis and injury repair. Autophagy (ATG), a cellular degradation process whereby macromolecules and organelles are sequestered to be recycled, has been shown to play a role in mineralized tissue-forming cells including odontoblasts. However, the precise role of ATG in odontoblasts in vivo remains unclear. Beclin1 is an indispensable ATG-related protein involved in ATG initiation. Therefore, we conditionally deleted Beclin1 in odontoblast-specific manner and generated Becn1f/f;Dmp1Cre/+ (Becn1 cKO) mice. From these mice, molars and incisors were evaluated radiographically and histologically. MicroCT scanning was employed to observe dentin formation and measure pulp tissue volume, histological analysis to examine dentin formation and dental pulp cells, and RNAscope in situ hybridization to identify odontoblast differentiation in the incisor stem cell niche and mesenchymal tissue in molars. We further evaluated the mRNA expression of FGF signaling genes in human dental pulp stem cells in vitro using Becn1 knocked down dental pulp cells (DPCs). Becn1 cKO mice were born at the expected Mendalian ratio. However, Becn1 cKO mice at the 6th month mark exhibited increased obliteration of the pulp chamber in both molar and incisors. Interestingly, both Becn1 wildtype (WT) and Becn1 ckO mice a normal laCL histology. When Becn1 was knocked down in DPCs, Etv4, a downstream target gene of FGF signaling pathway, was significantly upregulated. Our study highlights the possible role of Beclin1 in pulp calcification of molars, as Beclin1 KO mice molars were characterized by a completely obliteration and calcification of the pulp space, and suggests that Beclin1 may play a role in develo

Mouse molars resemble human teeth, as their roots develop and stop growing. In contrast, mouse incisors grow and erupt continuously due to the presence of a persistent stem cell niche identified as the labial cervical loop, which actively gives rise to dentin-forming odontoblasts to support tooth homeostasis and injury repair. Autophagy (ATG), a cellular degradation process whereby macromolecules and organelles are sequestered to be recycled, has been shown to play a role in mineralized tissue-forming cells including odontoblasts. However, the precise role of ATG in odontoblasts in vivo remains unclear. Beclin1 is an indispensable ATG-related protein involved in ATG initiation. Therefore, we conditionally deleted Beclin1 in odontoblast-specific manner and generated Becn1f/f;Dmp1Cre/+ (Becn1 cKO) mice. From these mice, molars and incisors were evaluated radiographically and histologically. MicroCT scanning was employed to observe dentin formation and measure pulp tissue volume, histological analysis to examine dentin formation and dental pulp cells, and RNAscope in situ hybridization to identify odontoblast differentiation in the incisor stem cell niche and mesenchymal tissue in molars. We further evaluated the mRNA expression of FGF signaling genes in human dental pulp stem cells in vitro using Becn1 knocked down dental pulp cells (DPCs). Becn1 cKO mice were born at the expected Mendalian ratio. However, Becn1 cKO mice at the 6th month mark exhibited increased obliteration of the pulp chamber in both molar and incisors. Interestingly, both Becn1 wildtype (WT) and Becn1 ckO mice a normal laCL histology. When Becn1 was knocked down in DPCs, Etv4, a downstream target gene of FGF signaling pathway, was significantly upregulated. Our study highlights the possible role of Beclin1 in pulp calcification of molars, as Beclin1 KO mice molars were characterized by a completely obliteration and calcification of the pulp space, and suggests that Beclin1 may play a role in develo

Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.

Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.

Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.

Chapter 12 The following sections are included: Introduction Emerging Powers within the UNFCCC: BRICS, BASIC or just China? Where BASIC Is Challenging the Established Players Own Challenges and Inconsistencies Within the BASIC Group Whither BRICS in the International Climate Negotiations? Convergence, Divergence, and Research Frontiers References

Kyoung Min Kim,1 Haebin Kim,2 Jae-Won Choi,3 Soo Yeon Kim,4 Jun Won Kim5 1Department of Psychiatry, College of Medicine, Dankook University, Cheonan, Republic of Korea; 2Department of Psychiatry, Kyung Hee University Hospital, Seoul, Republic of Korea; 3Department of Psychiatry, Gyeongsang National University Hospital, Jinju, Republic of Korea; 4Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea; 5Department of Psychiatry, Catholic University of Daegu School of Medicine, Daegu, Republic of KoreaCorrespondence: Jun Won KimDepartment of Psychiatry, Catholic University of Daegu School of Medicine, 3056-6 Daemyeong-4 Dong, Nam-gu, Daegu 705-718, Republic of KoreaTel +82 53 650 4332Fax +82 53 623 1694Email f_affection@naver.comPurpose: This study investigated the prevalence and correlates of problematic internet use (PIU) in a large sample of adolescents based on the type of internet service used.Materials and Methods: The study was conducted from 2008 to 2010, and 223,542 adolescents aged 12 to 18 years participated in the study. The participants responded to a self-report questionnaire including items for demographic factors, internet usage time, most used internet service and mental health. The PIU was assessed with the Internet Addiction Proneness Scale for Youth-Short Form.Results: The overall prevalence rate of PIU was 5.2%, and the prevalence rates stratified by sex were 7.7% in boys and 3.8% in girls. The distribution of most used internet services was significantly different across sexes. The most commonly used internet services were gaming (58.1%) in boys and blogging (22.1%) and messenger/chatting (20.3%) in girls. The odds ratio for PIU was significantly different according to the most used internet service; using the internet mostly for pornography compared to information searching had the highest odds ratio (4.526-fold higher). Depressive episodes, suicidal ideation, and suicidal attempts were significantly associated wit

Ho Yub Yoon,1,* In Ho Chang,2,* Yoon Tae Goo,1 Chang Hyun Kim,1 Tae Hoon Kang,1 Soo-Yeon Kim,3 Sang Jin Lee,3 Seh Hyon Song,4 Young Mi Whang,2 Young Wook Choi1 1College of Pharmacy, Chung-ang University, Seoul, Korea; 2College of Medicine, Chung-ang University, Seoul, Korea; 3Research Institute, National Cancer Center, Goyang, Korea; 4College of Pharmacy, Kyungsung University, Busan, Korea*These authors contributed equally to this workPurpose: To develop an intravesical instillation system for the treatment of bladder cancer, rapamycin (Rap) was encapsulated into liposomes and then homogeneously dispersed throughout a poloxamer 407 (P407)-based hydrogel.Methods: Rap-loaded conventional liposomes (R-CL) and folate-modified liposomes (R-FL) were prepared using a film hydration method and pre-loading technique, and characterized by particle size, drug entrapment efficiency, and drug loading. The cellular uptake behavior in folate receptor-expressing bladder cancer cells was observed by flow cytometry and confocal laser scanning microscopy using a fluorescent probe. In vitro cytotoxic effects were evaluated using MTT assay, colony forming assay, and Western blot. For in vivo intravesical instillation, Rap-loaded liposomes were dispersed in P407-gel, generating R-CL/P407 and R-FL/P407. Gel-forming capacities and drug release were evaluated. Using the MBT2/Luc orthotopic bladder cancer mouse model, in vivo antitumor efficacy was evaluated according to regions of interest (ROI) measurement.Results: R-CL and R-FL were successfully prepared, at approximately <160 nm, 42% entrapment efficiency, and 57 μg/mg drug loading. FL cellular uptake was enhanced over 2-fold than that of CL; folate receptor-mediated endocytosis was confirmed using a competitive assay with folic acid pretreatment. In vitro cytotoxic effects increased dose-dependently. Rap-loaded liposomes inhibited mTOR signaling and induced autophagy in urothelial carcinoma cells

Ho Yub Yoon,1,* In Ho Chang,2,* Yoon Tae Goo,1 Chang Hyun Kim,1 Tae Hoon Kang,1 Soo-Yeon Kim,3 Sang Jin Lee,3 Seh Hyon Song,4 Young Mi Whang,2 Young Wook Choi1 1College of Pharmacy, Chung-ang University, Seoul, Korea; 2College of Medicine, Chung-ang University, Seoul, Korea; 3Research Institute, National Cancer Center, Goyang, Korea; 4College of Pharmacy, Kyungsung University, Busan, Korea*These authors contributed equally to this workPurpose: To develop an intravesical instillation system for the treatment of bladder cancer, rapamycin (Rap) was encapsulated into liposomes and then homogeneously dispersed throughout a poloxamer 407 (P407)-based hydrogel.Methods: Rap-loaded conventional liposomes (R-CL) and folate-modified liposomes (R-FL) were prepared using a film hydration method and pre-loading technique, and characterized by particle size, drug entrapment efficiency, and drug loading. The cellular uptake behavior in folate receptor-expressing bladder cancer cells was observed by flow cytometry and confocal laser scanning microscopy using a fluorescent probe. In vitro cytotoxic effects were evaluated using MTT assay, colony forming assay, and Western blot. For in vivo intravesical instillation, Rap-loaded liposomes were dispersed in P407-gel, generating R-CL/P407 and R-FL/P407. Gel-forming capacities and drug release were evaluated. Using the MBT2/Luc orthotopic bladder cancer mouse model, in vivo antitumor efficacy was evaluated according to regions of interest (ROI) measurement.Results: R-CL and R-FL were successfully prepared, at approximately <160 nm, 42% entrapment efficiency, and 57 μg/mg drug loading. FL cellular uptake was enhanced over 2-fold than that of CL; folate receptor-mediated endocytosis was confirmed using a competitive assay with folic acid pretreatment. In vitro cytotoxic effects increased dose-dependently. Rap-loaded liposomes inhibited mTOR signaling and induced autophagy in urothelial carcinoma cells

Soo-Yeon Kim,1,2 Sang-Jin Lee,2 Jin-Ki Kim,3 Han-Gon Choi,3 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, Kwangjin-gu, Seoul, 2Immunotherapeutics Branch, Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 3College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan, Republic of Korea Abstract: Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus–liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that

Soo-Yeon Kim,1,2 Sang-Jin Lee,2 Jin-Ki Kim,3 Han-Gon Choi,3 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, Kwangjin-gu, Seoul, 2Immunotherapeutics Branch, Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 3College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan, Republic of Korea Abstract: Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus–liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that

This paper examines the role of international institutions in preventing the rise of protectionism. We analyze states’ choices in trade policy during the current global economic crisis, a situation likely to exacerbate uncertainty in the conduct of commercial relations and to push countries toward “beggar-thy-neighbor” trade policies. The main argument of the paper is that the numerous international institutions present in the international system during the current economic crisis serve as conveyors of information and mechanisms of commitment and socialization. They mitigate the uncertainty problem that prevails in prisoner’s dilemma settings such as trade. Economic international organizations increase the flow of information about the preferences and behaviors of its members. Non-economic organizations also have a role to play as social environments that encourage cooperation. Specialized international institutions devoted to trade, such as the WTO and preferential trade agreements (PTAs), not only provide monitoring and enforcement functions but also lock in commitments to liberal trade through legal obligations that make defections costly. We test our argument using a dataset of trade policies during the current economic crisis and of membership in international organizations. The paper finds strong support for the role of international institutions as commitment and socialization mechanisms in preventing the rise of protectionism.