South Korea, a relatively collectivistic and homogeneous country with heightened cultural tightness, is believed to have particularly high levels of stigma toward autistic individuals, who sometimes engage in behaviors that diverge from social norms. This study investigated cross-cultural differences in autism stigma (assessed with a Social Distance Scale) in the United States and South Korea. Two-hundred and seventy-six American and 494 Korean participants who completed an online survey were included in the analysis. We conducted a multiple regression predicting autism stigma with variables that were correlated with stigma. Koreans reported greater autism stigma than Americans. Greater vertical individualism, lesser horizontal collectivism, less accurate autism knowledge, less pleasant and frequent previous contact with autism, concerns about the marriageability of family members, and higher cultural tightness predicted greater stigma. Cultural tightness, or an emphasis on social norms, which was heightened among Korean participants, contributed to greater autism stigma in South Korea. Findings highlight the need to increase autism knowledge and foster pleasant and frequent contact with autistic individuals, especially for those who accept inequality as a part of human interactions in both South Korea and the United States. Moreover, interventions that help Koreans understand the relativeness of social appropriateness may reduce autism stigma in South Korea. Lay abstract Misunderstandings about autism may be more common in South Korea than the United States. Koreans often have clear ideas about how people should act. Another way of saying this is that Korea has a tight culture. Americans are looser, meaning people are freer to act as they like. Autistic people often do not act as people expect them to. This makes autistic people stand out. Autistic people may stand out more in tight cultures like South Korea. We studied how people in South Korea and the United States feel about autism. We wanted to see why Korean people might reject autistic people more than people in the United States do. American and Korean people did online surveys. Koreans said they did not want to get close to autistic people more than Americans did. People who understood autism and had met and liked autistic people wanted to get closer to autistic people. We were surprised to learn that Americans said having an autistic brother or sister makes it harder to find a romantic partner more than Korean people did. People who believed that autism makes it harder for family members to find love did not want to get very close to autistic people. Koreans said people should act as expected more than Americans did. People who believed that acting as expected was important did not want to get very close to autistic people. Teaching people that there are many ways of being a good person may help them understand and appreciate autistic people.

SUMMARYCell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1 + pancreatic progenitor cells. Expression of activated Cdk4 R24C kinase leads to increased Nkx2.2 + and Nkx6.1 + cells and a rise in the number and proliferation of Ngn3 + endocrine precursors, resulting in expansion of the  cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes  cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors.KEY WORDS: Cdk4, E2f1, Ngn3 (Neurog3), Pancreas development, Pdx1, Mouse

We explored the barriers to reporting patient safety incidents experienced by nurses and resident physicians while working in tertiary hospitals in South Korea. Sixteen in-depth interviews with 10 nurses and 6 resident physicians, all of whom had experienced patient safety incidents, were conducted. The interviews were analyzed using directed content analysis in accordance with a coding scheme developed in this study, which contains 4 categories (incidents and reporters, reporting procedures and systems, feedbacks, and reporting culture) and 9 subcategories. The barriers to reporting near-misses included the following: characteristics of the incident (eg, nonhazardous and high frequency), reporters' lack of knowledge, uncertainty, fear of blame, lack of role model, and inappropriate responses. Reporting adverse/sentinel events was also prevented by feelings of pressure or guilt, the fact that reporting was nonmandatory, and a belief that reporting was not part of the job. Some other barriers included lack of education, review process after reporting, lack of confidentiality when reporting, absence of feedback for reporting, unfair reporting based on work experience, perception of potential blame, and stigmatization resulting from it. In South Korea, a national system for reporting and learning of patient safety accidents has been operating since July 2016. To fully implement this system, it is necessary to encourage reporting at the institutional level. Our results might help reduce the barriers to patient safety incident reporting among nurses and resident physicians in tertiary hospitals in Korea through informing the development of improvement plans.

Stem cells in adult pancreas and their specific marker are poorly characterized. We hypothesized that pancreatic stem cells could evolve from the duct system in response to neogenic stimulation and may transiently express nestin during tissue regeneration. After partial pancreatectomy (Px), we found extensive formation of ductules consisting of nestin-positive epithelial cells with higher replicating ability in the neogenic foci, particularly at day 3 after Px. Nestin was highly expressed in the earlier stages of ductule morphogenesis and then regressed as the cells evolved toward differentiated pancreatic cell types. The neogenic ductules were isolated for the culture of nestin-positive duct stem cells. These nestin-positive duct cells were numerous and displayed extensive self-replication in the duct cell explants after 2-3 days of culture, thus depicted as nestin-positive duct stem (NPDS) cells. As seen in the tissue of neogenic foci, NPDS cells were negative for cytokeratin-20 and vimentin, the marker for duct epithelial and mesenchymal cells, respectively. Endocrine cells, mostly insulin cells, were present in the explants at day 2 as single cells or as small clusters adjacent to the NPDS cells, and formed islet-like masses at day 3 of culture, suggesting islet cell differentiation from NPDS cells. In addition, insulin secretion from these beta cells responded to glucose stimulation. We found transient up-regulation of PDX-1 expression by reverse transcriptase-polymerase chain reaction at day 3 after Px in pancreatic tissue. Higher expression of PDX-1 was seen in the culture of neogenic ductules than that of ducts isolated from the sham-operated pancreas. In particular, a subpopulation of nestinpositive cells in the duct cell explants formed from the neogenic ductules expressed PDX-1 in their nuclei. Taken together, this information suggests that NPDS cells could be generated from adult pancreas by neogenic motivations and they may differentiate into insulin-secreting cells.

Although research on health information has made significant progress in identifying the antecedents of individuals' information-seeking behavior in the context of the United States, the results have not been generalizable to the contexts of many other countries. Moreover, little is known about how one's information-seeking behavior is connected to actual behavioral outcomes relevant to the search action. The authors conducted an online survey with a stratified random sample of 1,004 mothers to examine the applicability of the comprehensive model of health information seeking in predicting the use of diverse childhood vaccination information sources in South Korea, and to investigate associations between the mothers' engagement with specific vaccine information sources and behavioral intention to immunize their children. Findings indicated that the hierarchical structure and the role of predictors within the comprehensive model of health information seeking provided a valid framework in the context of vaccine information seeking in Korea. In addition, the authors found negative associations between the use of certain types of information sources and mothers' intention to vaccinate. This suggests that the dissemination of critical health information through a variety of available sources does not automatically lead to prudent behavioral decisions when the specific characteristics of the different sources are not considered.

The failure of pancreatic islet β-cells is a major contributor to the etiology of type 2 diabetes. β-Cell dysfunction and declining β-cell mass are two mechanisms that contribute to this failure, although it is unclear whether they are molecularly linked. Here, we show that the cell cycle regulator, cyclin-dependent kinase 2 (CDK2), couples primary β-cell dysfunction to the progressive deterioration of β-cell mass in diabetes. Mice with pancreas-specific deletion of are glucose-intolerant, primarily due to defects in glucose-stimulated insulin secretion. Accompanying this loss of secretion are defects in β-cell metabolism and perturbed mitochondrial structure. Persistent insulin secretion defects culminate in progressive deficits in β-cell proliferation, reduced β-cell mass, and diabetes. These outcomes may be mediated directly by the loss of CDK2, which binds to and phosphorylates the transcription factor FOXO1 in a glucose-dependent manner. Further, we identified a requirement for CDK2 in the compensatory increases in β-cell mass that occur in response to age- and diet-induced stress. Thus, CDK2 serves as an important nexus linking primary β-cell dysfunction to progressive β-cell mass deterioration in diabetes.

Despite the wide and daunting array of cross-cultural obstacles that the formulation of a global policy on advance directives will clearly pose, the need is equally evident. Specifically, the expansion of medical services driven by medical tourism, just to name one important example, makes this issue urgently relevant. While ensuring consistency across national borders, a global policy will have the additional and perhaps even more important effect of increasing the use of advance directives in clinical settings and enhancing their effectiveness within each country, regardless of where that country's state of the law currently stands. One cross-cultural issue that may represent a major obstacle in formulating, let alone applying, a global policy is whether patient autonomy as the underlying principle for the use of advance directives is a universal norm or a construct of western traditions that must be reconciled with alternative value systems that may place lesser significance on individual choice. A global policy, at a minimum, must emphasize respect for patient autonomy, provision of medical information, limits to the obligations for physicians, and portability. And though the development of a global policy will be no easy task, active engagement in close collaboration with the World Health Organization can make it possible.

RB is a key substrate of Cdks and an important regulator of the mammalian cell cycle. RB either represses E2Fs that promote cell proliferation or enhances the activity of cell-specific factors that promote differentiation, although the mechanism that facilitates this dual interaction is unclear. Here, we demonstrate that RB associates with and stabilizes pancreatic duodenal homeobox-1 (Pdx-1) that is essential for embryonic pancreas development and adult b-cell function. Interestingly, Pdx-1 utilizes a conserved RB-interaction motif (RIM) that is also present in E2Fs. Point mutations within the RIM reduce RB-Pdx-1 complex formation, destabilize Pdx-1 and promote its proteasomal degradation. Glucose regulates RB and Pdx-1 levels, RB/Pdx-1 complex formation and Pdx-1 degradation. RB occupies the promoters of b-cell-specific genes, and knockdown of RB results in reduced expression of Pdx-1 and its target genes. Further, RB-deficiency in vivo results in reduced pancreas size due to decreased proliferation of Pdx-1 þ pancreatic progenitors, increased apoptosis and aberrant expression of regulators of pancreatic development. These results demonstrate an unanticipated regulatory mechanism for pancreatic development and b-cell function, which involves RB-mediated stabilization of the pancreas-specific transcription factor Pdx-1.