YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling.

Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the first time that VEGF-C signaling is necessary for valve morphogenesis. We have also discovered that the transcriptional co-activators YAP and TAZ are required to maintain PROX1 expression in LVs and LVVs in response to VEGF-C signaling. Deletion of Yap and Taz in the lymphatic vasculature of mouse embryos did not affect the formation of LVs or LVVs, but resulted in the degeneration of these structures. Our results have identified VEGF-C, YAP and TAZ as a crucial molecular pathway in valve development.

Soft Pneumatic Gripper With a Tendon-Driven Soft Origami Pump.

In this study, we propose a soft pneumatic gripper that uses a tendon-driven soft origami pump. The gripper consists of three pneumatic soft actuators that are controlled by a tendon-driven origami pump. An external air compressor that supplies air to the pneumatic actuator is replaced by an origami pump. The soft actuator is composed of silicone (Ecoflex 00-30) with a chamber-based structure, which is fabricated using a mold, and the origami pump is fabricated by folding a Kresling patterned polypropylene film. In addition, we conduct a series of experiments to evaluate the performance of the pneumatic actuator with a tendon-driven origami pump. Specifically, movement characteristics, frequency response, blocking force, and the relation between bending angle and pressure are analyzed from the results of the experiments. Furthermore, we understand the entire operation mechanism from the deformation of the origami pump to bending through pressure. Finally, we demonstrate the grasping of objects with diverse shapes and materials, and indicate the feasibility of the pneumatic gripper as an independent module without an external compressor.

Complementary Wnt Sources Regulate Lymphatic Vascular Development via PROX1-Dependent Wnt/ß-Catenin Signaling.

Wnt/ß-catenin signaling is necessary for lymphatic vascular development. Oscillatory shear stress (OSS) enhances Wnt/ß-catenin signaling in cultured lymphatic endothelial cells (LECs) to induce expression of the lymphedema-associated transcription factors GATA2 and FOXC2. However, the mechanisms by which OSS regulates Wnt/ß-catenin signaling and GATA2 and FOXC2 expression are unknown. We show that OSS activates autocrine Wnt/ß-catenin signaling in LECs in vitro. Tissue-specific deletion of Wntless, which is required for the secretion of Wnt ligands, reveals that LECs and vascular smooth muscle cells are complementary sources of Wnt ligands that regulate lymphatic vascular development in vivo. Further, the LEC master transcription factor PROX1 forms a complex with ß-catenin and the TCF/LEF transcription factor TCF7L1 to enhance Wnt/ß-catenin signaling and promote FOXC2 and GATA2 expression in LECs. Thus, our work defines Wnt sources, reveals that PROX1 directs cell fate by acting as a Wnt signaling component, and dissects the mechanisms of PROX1 and Wnt synergy.

Secondary Traumatic Stress and Burnout of North Korean Refugees Service Providers.

OBJECTIVE: The current study investigated the burnout and secondary traumatic stress of service providers for North Korean (NK) refugees based on the conceptual framework of theJob Demands-Resources (JD-R) model of workplace burnout. METHODS: A cross-sectional self-administered survey was conducted with a national sample consisting of all 63 organizations in direct services to North Korean refugees. Of the estimated total number of 230 service providers comprising of social workers, psychotherapists, job counselors and paraprofessional counselors, 179 completed the survey, a 77.8% return rate. RESULTS: While job resources such as personal commitment to work and organizational support indicated inverse relations to burnout, job demands such as workload, work environment and secondary traumatic stress (STS) showed a positive relationship to worker burnout. The STS were present in more than half of the respondents (51.3%), of which 20.7% of them indicating a severe level of STS. The STS proved to be the most significant risk to worker burnout as it showed strong relations to all three dimensions of burnout. CONCLUSION: Structural issues of chronic work overload and poor work environment need to be addressed to reduce staff burnout. STS is a serious occupational hazard in working with North Korean refugees.

Comparing Inpatient Falls Guidelines to Develop an ICNP.

This study compared and synthesized clinical guidelines for inpatient falls with the aim of developing an ICNP®-based nursing catalogue for use in electronic nursing records. The identified content will influence nursing services provided to patients and the associated documentation.

Mechanotransduction activates canonical Wnt/ß-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves.

Lymphatic vasculature regulates fluid homeostasis by returning interstitial fluid to blood circulation. Lymphatic endothelial cells (LECs) are the building blocks of the entire lymphatic vasculature. LECs originate as a homogeneous population of cells predominantly from the embryonic veins and undergo stepwise morphogenesis to become the lymphatic capillaries, collecting vessels or valves. The molecular mechanisms underlying the morphogenesis of the lymphatic vasculature remain to be fully understood. Here we show that canonical Wnt/ß-catenin signaling is necessary for lymphatic vascular morphogenesis. Lymphatic vascular-specific ablation of ß-catenin in mice prevents the formation of lymphatic and lymphovenous valves. Additionally, lymphatic vessel patterning is defective in these mice, with abnormal recruitment of mural cells. We found that oscillatory shear stress (OSS), which promotes lymphatic vessel maturation, triggers Wnt/ß-catenin signaling in LECs. In turn, Wnt/ß-catenin signaling controls the expression of several molecules, including the lymphedema-associated transcription factor FOXC2. Importantly, FOXC2 completely rescues the lymphatic vessel patterning defects in mice lacking ß-catenin. Thus, our work reveals that mechanical stimulation is a critical regulator of lymphatic vascular development via activation of Wnt/ß-catenin signaling and, in turn, FOXC2.

Posttraumatic Stress Disorder as a Mediator Between Trauma Exposure and Comorbid Mental Health Conditions in North Korean Refugee Youth Resettled in South Korea.

A structural equation model was used to investigate the relationship between trauma exposure and comorbid mental health problems and the mediation effect of posttraumatic stress disorder (PTSD) between trauma and mental health variables. The research model is based on the stress-vulnerability conceptual framework in which PTSD as a comorbid disorder mediates the relationship between trauma exposure and mental health problems. A self-administered survey was administered to 144 North Korean refugee youth residing in South Korea. Trauma exposure, both interpersonal and noninterpersonal, had no direct relationship with comorbid mental health problems. However, interpersonal trauma contributed to comorbid mental health problems through PTSD, demonstrating the mediation effect of PTSD and supporting the stress-vulnerability hypothesis of the current research model. Clinical implications of the study and future direction for research are discussed.

Reliability of self-administered Work Ability Index questionnaire among Korean workers.

Although the Work Ability Index (WAI) has been used in many countries, its reliability is yet to be validated in Korea. In our study, test-retest results of WAI total score, WAI category and seven subscales were compared. The correlation coefficients of WAI total score and subscales 1 and 2 between test and retest were 0.70, 0.80 and 0.63, respectively. The κ values on WAI category, subscales 4, 5, 6 and 7 were 0.52, 0.32, 0.31, 0.48 and 0.85, respectively. The results of our reliability test show that WAI scores of female, younger and private company workers were found to be higher than those of male, older and public company workers, respectively. We conclude that overall test-retest reliability of WAI in Korea is acceptable. Another notable observation from our study is that work ability dimension (subscales 1, 2 and 7) had a higher reliability, whereas health dimension (subscales 3-6) had a lower reliability.

Subsequent afebrile seizure in children who have a first seizure with fever after 6 years of age.

The objective was to evaluate the risk and the risk factors associated with subsequent afebrile seizures in 31 children who experienced their first seizure with fever after 6 years of age. The children were classified into two groups. Group I comprised children with their first seizure with fever after 6 years of age (n = 15). Group II comprised children who had febrile seizures before 5 years of age and who had recurrent seizures with fever after 6 years of age (n = 16). Of these 31 children, 7 (22.5%) had subsequent afebrile seizure. The cumulative probability of subsequent afebrile seizure was 13.3% at 6 months and 36 months in group I; in group II, the cumulative probability was 12.5% at 6 months, 18.8% at 18 months, 25% at 24 months, and 31.3% at 36 months. There was no significant difference in the risk for subsequent afebrile seizures between the two groups. There were no risk factors associated with an increased risk of subsequent afebrile seizures. If the first seizure with fever occurred after 6 years of age, this was a significant risk for subsequent afebrile seizure; the risk of seizure recurrence in this group appears to be similar to children who have persistent febrile seizures after 6 years of age, but far below that of children with first epileptic seizure.

Polymorphism of haptoglobin in patients with premature rupture of membrane.

PURPOSE: To investigate whether allelic polymorphism of haptoglobin (Hp) is associated with premature rupture of membrane (PROM), the Hp phenotypes of pregnant women with PROM were analyzed. PATIENTS AND METHODS: The Hp phenotypes of 221 pregnant Korean women (187 control and 34 PROM patients) were determined by benzidine/hydrogen peroxide staining, following native polyacrylamide gel electrophoresis of hemoglobin-mixed sera. The Hp allele frequencies were calculated from the data of Hp phenotypes, and overall association with PROM was evaluated using Pearson Chi-Square test. RESULTS: The polymorphic distribution of the patients cohort who underwent a normal delivery (control group) was similar to that of healthy Koreans. In contrast, however, patients with PROM showed significantly higher occurrence of the Hp 1-1 phenotype than control group (23.5% vs 8.0%). Hp 2-2 phenotype was lower in PROM cohort (38.2%) than in the control group (48.7%). The Hp(1) allele frequency in PROM group was significantly higher than that in the control group (0.426 vs 0.297, p = 0.034) with odds ratio of 1.762 (95% CI: 1.038 - 2.991). CONCLUSION: These findings suggest that pregnant Korean women who possess Hp(1) allele (expressed as Hp 1-1 phenotype) have higher incidence of PROM than women with Hp(2) allele (expressed as Hp 2-2 phenotype). This is the first study that evaluated the significance of Hp polymorphism with respect to the development of PROM.

Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog.

Spermatogonial stem cell transplantation (SSCT) offers unique approaches to investigate SSC and to manipulate the male germline. We report here the first successful performance of this technique in the dog, which is an important model of human diseases. First, we investigated an irradiation protocol to deplete endogenous male germ cells in recipient testes. Histologic examination confirmed >95% depletion of endogenous spermatogenesis, but retention of normal testis architecture. Then, 5-month-old recipient dogs (n=5) were focally irradiated on their testes prior to transplantation with mixed seminiferous tubule cells (fresh (n=2) or after 2 weeks of culture (n=3)). The dogs receiving cultured cells showed an immediate allergic response, which subsided quickly with palliative treatment. No such response was seen in the dogs receiving fresh cells, for which a different injection medium was used. Twelve months post-injection recipients were castrated and sperm was collected from epididymides. We performed microsatellite analysis comparing DNA from the epididymal sperm with genomic DNA from both the recipients and the donors. We used six markers to demonstrate the presence of donor alleles in the sperm from one recipient of fresh mixed tubule cells. No evidence of donor alleles was detected in sperm from the other recipients. Using quantitative PCR based on single nucleotide polymorphisms (SNPs), about 19.5% of sperm were shown to be donor derived in the recipient. Our results demonstrate the first successful completion of SSCT in the dog, an important step toward transgenesis through the male germline in this valuable biomedical model.

Parturition prediction and timing of canine pregnancy.

An accurate method of predicting the date of parturition in the bitch is clinically useful to minimize or prevent reproductive losses by timely intervention. Similarly, an accurate method of timing canine ovulation and gestation is critical for development of assisted reproductive technologies, e.g. estrous synchronization and embryo transfer. This review discusses present methods for accurately timing canine gestational age and outlines their use in clinical management of high-risk pregnancies and embryo transfer research.

Effect of donor age on success of spermatogenesis in feline testis xenografts.

Ectopic xenografting of 'donor' feline testicular tissue into a 'recipient' immunodeficient mouse is a promising tool to preserve the male genome from genetically valuable felids. To define parameters under which the technique can succeed, we compared the effect of donor age on xenograft spermatogenesis among four age groups of domestic cats (Felis catus; age range 8 weeks to 15 months). In all cases, fresh tissue was grafted into castrated mice and collected 10, 30 and 50 weeks later. The percentage of xenografts recovered decreased as donor age increased. Mature testicular spermatozoa were observed in xenografts from the 8 and 9-16 week age groups; only a single 7-month-old donor produced elongating spermatids and xenografts from donors >/= 8 months of age degenerated. Seminal vesicle weight, an indicator of bioactive testosterone, was not significantly different between donors aged 8 weeks to 7 months and controls, suggesting that xenograft Leydig cells were ultimately functional even in the 5-7 month age group. Regardless of donor age, production of mature spermatozoa from xenografts was markedly delayed compared with controls. Comparison of xenografts that produced sperm with normal controls revealed a decrease in tubule cross-sections having post-meiotic germ cells. Together, these results indicate that the maximum practical donor age was just before the onset of puberty and that even successful xenografts had abnormalities in spermatogenesis.

Recipient preparation and mixed germ cell isolation for spermatogonial stem cell transplantation in domestic cats.

The loss of genetic diversity poses a serious threat to the conservation of endangered species, including wild felids. We are attempting to develop spermatogonial stem cell transplantation in the cat as a tool to preserve and propagate male germ-plasm from genetically valuable animals, be they threatened wild species or lines of cats used as models for inherited diseases. In this study, we investigated the use of local external beam radiation treatment to deplete the endogenous germ cells of male domestic cats, a step necessary to prepare them for use as recipients for transplantation. Testes of 5-month-old domestic cats were irradiated with a fractionated dose of 3 Gy per fraction for 3 consecutive days. These cats were castrated at 2, 4, 8, 16, and 32 weeks posttreatment, and progress of spermatogenesis was evaluated histologically and compared against age-matched controls. Even at the latest time points, less than 10% of tubules contained germ cells at any stage of meiosis, showing the efficacy of this protocol. In addition, male germ cells were isolated from the testes of domestic cats using a 2-step enzymatic dissociation to establish a protocol for the preparation of donor cells. The presence and viability of spermatogonia within this population were demonstrated by successful transplantation into, and colonization of, mouse seminiferous tubules. The success of these protocols provides a foundation to perform spermatogonial stem cell transplantation in the domestic cat.

Atractylodes japonica suppresses lipopolysaccharide-stimulated expressions of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages.

Atractylodes japonica has traditionally been used for the treatment of pain and arthritis. The effect of Atractylodes japonica against lipopolysaccharide-induced inflammation was investigated using reverse transcription-polymerase chain reaction (RT-PCR), nitric oxide detection, and prostaglandin E2 (PGE2) immunoassay in mouse RAW 264.7 macrophages. The aqueous extract of Atractylodes japonica suppressed nitric oxide production and PGE2 synthesis by inhibition of the lipopolysaccharide-stimulated enhancement of inducible nitric oxide synthase and cyclooxygenase-2 mRNAs expressions in RAW 264.7 macrophages. These results suggest that Atractylodes japonica exerts anti-inflammatory and analgesic effects probably by suppression of the inducible nitric oxide synthase and cyclooxygenase-2 expressions.

Effects of Puerariae radix on cell proliferation and nitric oxide synthase expression in dentate gyrus of alcohol-intoxicated Sprague-Dawley rats.

Traditionally, Puerariae radix had been used for the treatment of alcohol-related problems. In this study, effects of Puerariae radix on cell proliferation and nitric oxide synthase expression in the dentate gyrus of alcohol-intoxicated Sprague-Dawley rats were investigated via 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Alcohol administration was shown to inhibit the numbers of both BrdU-positive and NADPH-d-positive cells, while Puerariae radix treatment was shown to increase those numbers. It is possible that nitric oxide, which might play an important role in the regulation of cell proliferation, is a major target of the toxic effects of alcohol.