Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating in vitro disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.

Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating in vitro disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.

Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating in vitro disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.

Background and Objectives: Lymphoblastoid cell lines (LCLs) deposited from disease-affected individuals could be a valuable donor cell source for generating disease-specific induced pluripotent stem cells (iPSCs). However, generation of iPSCs from the LCLs is still challenging, as yet no effective gene delivery strategy has been developed. Methods: and Results: Here, we reveal an effective gene delivery method specifically for LCLs. We found that LCLs appear to be refractory toward retroviral and lentiviral transduction. Consequently, lentiviral and retroviral transduction of OCT4, SOX2, KFL4 and c-MYC into LCLs does not elicit iPSC colony formation. Interestingly, however we found that transfection of oriP/EBNA-1-based episomal vectors by electroporation is an efficient gene delivery system into LCLs, enabling iPSC generation from LCLs. These iPSCs expressed pluripotency makers (OCT4, NANOG, SSEA4, SALL4) and could form embryoid bodies. Conclusions Our data show that electroporation is an effective gene delivery method with which LCLs can be efficiently reprogrammed into iPSCs.

The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has completely changed human life for more than two years. Upon the emergence of this new lethal virus, multiple approaches were utilized to gain basic knowledge about its biology. Moreover, modern technologies, such as the organoid model system and next-generation sequencing, enabled us to rapidly establish strategies to tackle the disease, including vaccines and therapeutics. The recently developed organoid technology reflects human physiology more closely than other model systems. Coupled with its rapidness, high efficiency, and outstanding reliability, it has provided an opportunity to develop new drugs and understand the impact of the viral pathogen on the host. Recent findings using organoids have successfully revealed the cellular tropism of the virus in different organs and identified potential drug candidates that impact the disease. This review will summarize current achievements made with organoids in the fight against COVID-19.

Background: and Purpose Several studies have found that the prevalence of migraine is higher among healthcare professionals than in the general population. Furthermore, several investigations have suggested that the personal experiences of neurologists with migraine can influence their perception and treatment of the disease. This study assessed these relationships in Korea. Methods: A survey was used to investigate the following characteristics among neurologists:1) the prevalence rates of migraine, primary stabbing headache, and cluster headache, and 2) their perceptions of migraine and the pain severity experienced by patients, diagnosing migraine, evaluation and treatment patterns, and satisfaction and difficulties with treatment. Results: The survey was completed by 442 actively practicing board-certified Korean neurologists. The self-reported lifetime prevalence rates of migraine, migraine with aura, primary stabbing headache, and cluster headache were 49.8%, 12.7%, 26.7%, and 1.4%, respectively. Few of the neurologists used a headache diary or validated scales with their patients, and approximately half were satisfied with the effectiveness of preventive medications. Significant differences were observed between neurologists who had and had not experienced migraine, regarding certain perceptions of migraine, but no differences were found between these groups in the evaluation and preventive treatment of migraine. Conclusions The high self-reported lifetime prevalence rates of migraine and other primary headache disorders among Korean neurologists may indicate that these rates are underreported in the general population, although potential population biases must be considered. From the perspective of neurologists, there is an unmet need for the proper application of headache diaries, validated scales, and effective preventive treatments for patients. While the past experiences of neurologists with migraine might not influence how they evaluate or apply preventive treatments to migraine, they may influence certain perceptions of the disease.

The online 2021 Asian-Pacific Heart and Brain Summit was organized to present and discuss experiences within leading Asian-Pacific centers with regard to institutional heart and brain teams managing the diagnosis, treatment, and follow-up of cryptogenic stroke (CS) patients with patent foramen ovale (PFO). This manuscript presents a narrative review of presentations and discussions during the summit meeting. Percutaneous PFO closure is an established therapy for CS patients in whom PFO is considered to be causal. Guidelines and consensus statements emphasize the importance of multidisciplinary clinical decision-making regarding PFO closure with the involvement of several clinical specialties, including neurology, cardiology, and hematology. It is also recommended that the patient be closely involved in this process. The heart and brain team is a collaborative platform that facilitates such a multidisciplinary decision-making process and patient involvement. It also creates opportunities for education and evaluation of the healthcare provided to patients with CS. This review provides insights into the implementation, composition, organization, and operation of a heart and brain team. Methods and metrics are suggested to evaluate the team’s role. We suggest that an efficient heart and brain team can implement guideline-recommended multidisciplinary clinical decision-making with regard to PFO closure in CS patients and play an important role in the management of these patients.

Globally and in Africa specifically, female sex workers (FSWs) are at an extraordinarily high risk of contracting human immunodeficiencyvirus (HIV). Pre-exposure prophylaxis (PrEP) has emerged as an effective and ethical method with which to preventHIV infection among FSWs. PrEP efficacy is, however, closely linked to adherence, and adherence to PrEP among FSWs is a complexand interrelated process that has been shown to be of importance to public health policies and HIV control and interventionprograms. This comprehensive review categorizes barriers to and facilitators of adherence to HIV PrEP for FSWs, and describes fivestrategies for promoting PrEP adherence among FSWs. These strategies encompass 1) a long-term educational effort to decreasethe stigma associated with sex work and PrEP use, 2) education on how PrEP works, 3) lifestyle modification, 4) research on nextgenerationPrEP products to address the inconvenience of taking daily pills, and 5) integration of PrEP into existing services, suchas social services and routine primary care visits, to reduce the economic burden of seeking the medication. Our review is expectedto be useful for the design of future PrEP intervention programs. Multidisciplinary intervention should be considered to promotePrEP adherence among FSWs in order to help control the HIV epidemic.

PURPOSE: The purpose of the present study was to validate an experimental model for assessing tissue integration of titanium and zirconia implants with and without buccal dehiscence defects. METHODS: In 3 dogs, 5 implants were randomly placed on both sides of the mandibles: 1) Z1: a zirconia implant (modified surface) within the bony housing, 2) Z2: a zirconia implant (standard surface) within the bony housing, 3) T: a titanium implant within the bony housing, 4) Z1_D: a Z1 implant placed with a buccal bone dehiscence defect (3 mm), and 5) T_D: a titanium implant placed with a buccal bone dehiscence defect (3 mm). The healing times were 2 weeks (one side of the mandible) and 6 weeks (the opposite side). RESULTS: The dimensions of the peri-implant soft tissue varied depending on the implant and the healing time. The level of the mucosal margin was located more apically at 6 weeks than at 2 weeks in all groups, except group T. The presence of a buccal dehiscence defect did not result in a decrease in the overall soft tissue dimensions between 2 and 6 weeks (4.80±1.31 and 4.3 mm in group Z1_D, and 4.47±1.06 and 4.5±1.37 mm in group T_D, respectively). The bone-to-implant contact (BIC) values were highest in group Z1 at both time points (34.15%±21.23% at 2 weeks, 84.08%±1.33% at 6 weeks). The buccal dehiscence defects in groups Z1_D and T_D showed no further bone loss at 6 weeks compared to 2 weeks. CONCLUSIONS: The modified surface of Z1 demonstrated higher BIC values than the surface of Z2. There were minimal differences in the mucosal margin between 2 and 6 weeks in the presence of a dehiscence defect. The present model can serve as a useful tool for studying peri-implant dehiscence defects at the hard and soft tissue levels.
Animals ; Dental Implants ; Dogs ; Housing ; Mandible ; Models, Theoretical ; Mouth Mucosa ; Osseointegration ; Surface Properties ; Titanium

PURPOSE: To evaluate the impact of postoperative radiotherapy (PORT) on patterns of failure and survivals in uterine carcinosarcoma patients treated with radical surgery. MATERIALS AND METHODS: Between October 1998 and August 2010, 19 patients with stage I-III uterine carcinosarcoma received curative hysterectomy and bilateral salpingo-oophorectomy with or without PORT at Seoul National University Hospital. Their hospital medical records were retrospectively reviewed. PORT and non-PORT groups included 11 and 8 patients, respectively. They were followed for a mean of 22.7 months (range, 7.8 to 126.6 months). RESULTS: At 5 years, the overall survival rates were 51.9% for entire, 61.4% for PORT, and 41.7% for non-PORT groups, respectively. There was no statistical difference between PORT and non-PORT groups with regard to overall survival (p = 0.682). Seven out of 19 (36.8%) patients showed treatment failures, which all happened within 12 months. Although the predominant failures were distant metastasis in PORT group and loco-regional recurrence in non-PORT group, there was no statistically significant difference in loco-regional recurrence-free survival (LRRFS) (p = 0.362) or distant metastasis-free survival (DMFS) (p = 0.548). Lymph node metastasis was found to be a significant prognostic factor in predicting poor LRRFS (p = 0.013) and DMFS (p = 0.021), while the International Federation Gynecology and Obstetrics (FIGO) stage (p = 0.043) was associated with LRRFS. CONCLUSION: Considering that adjuvant radiotherapy after surgical resection was effective to decrease loco-regional recurrence and most treatment failures were distant metastasis, multimodal therapy including surgery, radiotherapy, and chemotherapy might be an optimal treatment for uterine carcinosarcoma patients.
Carcinosarcoma ; Gynecology ; Humans ; Hysterectomy ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Obstetrics ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Failure ; Uterus