Initial phase establishment of an in vitro method for developmental neurotoxicity test using Ki-67 in human neural progenitor cells.

Building a precise alternative neurotoxicological test is of great importance to respond to societal and ethical requirements. In this study, a new developmental neurotoxicity test (DNT) was established with the human neural progenitor cell line. ReNcell CX cells were exposed to neurotoxic chemicals (aphidicolin, hydroxyurea, cytosine arabinoside, 5-fluorouracil, and ochratoxin A) or non-neurotoxic chemicals (sodium gluconate, sodium bicarbonate, penicillin G, and saccharin). Propidium iodide (PI) was used to evaluate cell viability. BrdU and Ki-76 were employed to determine cell proliferation. Based on the cell viability and proliferation, mathematical models were built by linear discriminant analysis. Furthermore, the neurotoxic-considered chemicals inhibited cell cycle progression at the protein level, supporting the biomolecular rationale for the predictive model. Overall, these results show that the new test method can be used to determine the potential developmental neurotoxicants or new drug candidates.

Multimodality imaging appearance of intrapericardial paragangliomas.

Paragangliomas are neuroendocrine tumours of the sympathetic and parasympathetic nervous systems originating from neural crest cells. Less than 1% of paragangliomas in the heart originate from intrinsic cardiac ganglia cells in the posterior wall of the atria, atrioventricular groove, and along the root of the great vessels. We describe the tumour characteristics, patient demographics, presentation, means of diagnosis, pathology correlation, management, and outcome in 11 patients with intrapericardial paragangliomas. To the authors' knowledge, this is the largest case series reported, with emphasis on multimodality imaging findings.

Unconventional supercurrent phase in Ising superconductor Josephson junction with atomically thin magnetic insulator.

In two-dimensional (2D) NbSe2 crystal, which lacks inversion symmetry, strong spin-orbit coupling aligns the spins of Cooper pairs to the orbital valleys, forming Ising Cooper pairs (ICPs). The unusual spin texture of ICPs can be further modulated by introducing magnetic exchange. Here, we report unconventional supercurrent phase in van der Waals heterostructure Josephson junctions (JJs) that couples NbSe2 ICPs across an atomically thin magnetic insulator (MI) Cr2Ge2Te6. By constructing a superconducting quantum interference device (SQUID), we measure the phase of the transferred Cooper pairs in the MI JJ. We demonstrate a doubly degenerate nontrivial JJ phase (ϕ), formed by momentum-conserving tunneling of ICPs across magnetic domains in the barrier. The doubly degenerate ground states in MI JJs provide a two-level quantum system that can be utilized as a new dissipationless component for superconducting quantum devices. Our work boosts the study of various superconducting states with spin-orbit coupling, opening up an avenue to designing new superconducting phase-controlled quantum electronic devices.

Second-phase validation study of an alternative developmental toxicity test using mouse embryonic stem cell-derived embryoid bodies.

The embryoid body test (EBT) is a developmental toxicity test method that measures the size of embryoid bodies (EBs) and the viability of mouse embryonic stem cells (mESCs) and fibroblasts (3T3 cells). The previous pre-validation study confirmed the high accuracy (above 80%) of EBT using 26 coded test chemicals. This second-phase validation study assessed the inter-laboratory reproducibility (5 chemicals in common) and predictive capacity (10 chemicals in each laboratory) test using the coded test chemicals at three laboratories. For the prediction model, the accuracy is increased when more data is accumulated. Therefore, we updated the prediction model and analyzed the results of the second year with the newly created-prediction model. Statistical analysis of the inter-laboratory reproducibility test results indicated that accuracy, sensitivity, and specificity were 87%, 78%, and 100%, respectively. The results of the statistical analysis of the predictive capacity test showed an accuracy of 80%, sensitivity of 78%, and specificity of 81%. In conclusion, the EBT can accurately classify various embryotoxicants within a short period and with relatively little effort. Therefore, EBT can be used as a good way to test developmental toxicity.

[Child Abuse - Interdisciplinary Collaboration and Child Protection]. / Kindesmisshandlung: interdisziplinärer Kinderschutz.

In Germany, the increasing focus on child abuse led to remarkable changes in recent years. The latest child protection laws (Kinderschutzgesetz, 2012) and the new medical guideline (AWMF S3+ Kinderschutzleitlinie, 2019) provide effective means for child protection services. Sound knowledge of the clinical manifestations, the parties involved, and the legal situation are required in order to provide effective child protection interventions. This article presents an update of the epidemiology, the legal situation, and the clinical manifestations concerning child abuse. With this information it foremost adresses medical professionals seeing children regularly without having a child protection team at disposal.

Study and evaluation of physical activity of youth from the Visegrad countries in relation to the WHO recommendations

Background: In recent years, the subject literature has provided concrete recommendations concerning health with regard to specific parameters. Therefore, it is necessary to indicate appropriate physical activity standards for proper development at various stages of human ontogenesis. Objective: The aim of the work was knowledge of the level of physical activity of high school youth in the Visegrad countries, including gender indications, to demonstrate whether the WHO recommendations are fulfilled. Material and methods: The research was conducted in students from four Visegrad countries: the Czech Republic, Poland, Slovakia and Hungary. As the research method, the International Physical Activity Questionnaire − IPAQ in the extended version was used. Results: Boys seem to do much better and have largely fulfilled the WHO recommendation for high-intensity efforts performed 3 times for 20 minutes, and medium and high efforts − 7 times for 60 minutes, which is particularly crucial for the effectiveness of the level of physical activity. Conclusions: It is indispensable to continue monitoring the physical activity of young people using modern research techniques. It seems intentional to intensify promotion and educational activities, which should be aimed at motivating young people to undertake physical activity in accordance with world-wide recommendations.

Fathers' Perceived Reasons for Their Underrepresentation in Child Health Research and Strategies to Increase Their Involvement.

Purpose Examine fathers' perceived reasons for their lack of inclusion in pediatric research and strategies to increase their participation. Description We conducted expert interviews with researchers and practitioners (N = 13) working with fathers to inform the development of an online survey. The survey-which measured fathers' perceived reasons for their underrepresentation in pediatric research, recommended recruitment venues, and research personnel and study characteristics valued by fathers-was distributed online and in-person to fathers. Assessment Respondents included 303 fathers. Over 80 % of respondents reported that fathers are underrepresented in pediatric research because they have not been asked to participate. Frequently recommended recruitment venues included community sports events (52 %), social service programs (48 %) and the internet (60 %). Compared with white fathers, more non-white fathers recommended public transit (19 % vs. 10 %, p = .02), playgrounds (16 % vs. 6 %, p = .007) and barber shops (34 % vs. 14 %, p < .0001) and fewer recommended doctors' offices (31 % vs. 43 %, p = .046) as recruitment venues. Compared with residential fathers (100 % resident with the target child), more non-residential fathers recommended social services programs (45 % vs. 63 %, p = .03) and public transit (10 % vs. 27 %, p = .001) and fewer recommended the workplace (17 % vs. 40 %, p = .002) as recruitment venues. Study brevity, perceived benefits for fathers and their families, and the credibility of the lead organization were valued by fathers. Conclusion Fathers' participation in pediatric research may increase if researchers explicitly invite father to participate, target father-focused recruitment venues, clearly communicate the benefits of the research for fathers and their families and adopt streamlined study procedures.

The Effect of 3-Isocyanato-1-Propene on Adhesive Properties of UV-Curing Urethane/Siloxane Acrylate Resin.

We synthesized the urethane/siloxane acrylate oligomer from isophorone diisocyanate (IPDI), hydroxyl alkyl terminated polydimethylsiloxane and 2-hydroxyethyl acrylate (2-HEA). UV-curable resins were formulated from the synthesized oligomer, ethylene glycol phenyl ether acrylate (PHEA), 1,6-hexanediol diacrylate (HDDA), trimethylolpropane triacrylate (TMPTA) as a reactive diluent, 3-isocyanato-1-propene as an adhesion promoter and photoinitiators. The PET film was treated with plasma in order to introduce the functional group on the PET surface and the functional group was observed through X-ray photoelectron spectroscopy (XPS) and the Fourier transform infrared (FT-IR). The adhesion strength between the PET film and the UV-cured resin were increased by using the adhesion promoter. Also, the thermal stability, the modulus and surface hardness were increased, as the adhesion promoter was added.

Effect of vaccination against foot-and-mouth disease on growth performance of Korean native goat (Capra hircus coreanae).

The objectives of this study were 1) to evaluate the effects of vaccination against foot-and-mouth disease (FMD) on growth performance, nutrient digestibility, hematological parameters, and behavior in a ruminant animal and 2) to investigate a possible strategy for reducing its adverse effect. A total of 12 Korean native goats (Capra hircus coreanae; 19.8 ± 2.9 kg) were used in a crossover design with 3 experimental periods and 3 treatments, randomized and balanced for counteracting possible carry-over effects. The treatments were 1) control, 2) co-injection with a commercially available dipyrone (CADI), and 3) supplementation with γ-amino butyric acid (GABA) at 10 g/kg in concentrate mix. Each period lasted 4 wk, and the vaccination against FMD was performed at 2 wk after the start of each period. The goats were individually housed in a metabolic cage and fed ad libitum with a diet consisting of bermuda grass and commercial concentrate mix (6:4, wt/wt). Dry matter intake, ADG, nutrients digestibility, hematological parameters, and behavioral activities of the goats were measured before and after vaccination. Although DMI was not decreased (P > 0.05), ADG was decreased by the vaccination to the goats (P < 0.01). The total number of leukocytes was increased while that of erythrocytes was decreased by the FMD vaccination (P < 0.01). The vaccination shortened standing time while extended lying time and the time spent in drinking (P < 0.05). The treatment by CADI reduced the adverse effect of vaccination on ADG and goat behavior compared with control and GABA treatment (P < 0.05). We concluded that the FMD vaccination decreased ADG of the goats without depression of diet intake, and CADI may attenuate the adverse effect of the FMD vaccination.

Impact of sex incompatibility on the outcome of single-unit cord blood transplantation for adult patients with hematological malignancies.

Donor-recipient sex incompatibility has been associated with transplant outcomes in allogeneic hematopoietic SCT. Such outcomes might be because mHA encoded by Y chromosome genes could be immunological targets for allogeneic T cells and B cells to induce GVHD, GVL effect and graft failure. However, its effect on the outcome of cord blood transplantation (CBT) is yet to be clarified. We retrospectively analyzed 191 adult patients who received single-unit CBT after myeloablative conditioning for malignant disease in our institute. In multivariate analysis, male recipients with female donors had a higher incidence of extensive chronic GVHD (hazard ratio (HR) 2.97, P=0.02), and female recipients with male donors had a lower incidence of platelet engraftment (HR 0.56, P=0.02) compared with female recipients with female donors as the reference. Nevertheless, there was no increase in mortality following sex-incompatible CBT. These data suggested that donor-recipient sex compatibility does not have a significant impact on survival after myeloablative CBT for hematological malignancies.

Capillary regeneration in scleroderma: stem cell therapy reverses phenotype?

BACKGROUND: Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS: We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue), antiangiogenic interferon alpha (overexpressed in the scleroderma dermis) and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon alpha and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. CONCLUSION/SIGNIFICANCE: These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have implications for other diseases characterized by loss of capillaries including hypertension, congestive heart failure and scar formation.

Application of the solid-phase Julia-Lythgoe olefination in vitamin D side-chain construction.

An example of the Julia-Lythgoe attachment of the vitamin D side chain to a solid-phase linked Inhoffen-Lythgoe diol derived CD-ring fragment is reported.

Upregulation of pigment epithelium-derived factor after laser photocoagulation.

PURPOSE: To determine the changes in the expression of pigment epithelium-derived factor in cultured human retinal pigment epithelial cells and rat retinas after laser photocoagulation. METHODS: Experimental study of laser photocoagulation on human retinal pigment epithelial cells in culture and on adult rats. Reverse transcription-polymerase chain reaction and semiquantitative polymerase chain reaction analysis were used. RESULTS: After photocoagulation, the mRNA expression of pigment epithelium-derived factor was upregulated in human retinal pigment epithelial cells at 6 hours and then gradually decreased. Compared with controls, significantly higher levels of pigment epithelium-derived factor were observed in rat retinas from 6 to 24 hours after laser photocoagulation (P <.005), and they were still higher than before photocoagulation at 2 weeks. CONCLUSION: An upregulation of pigment epithelium-derived factor in retinal pigment epithelial cells and in the retina after photocoagulation suggests that pigment epithelium-derived factor plays a role in inhibiting neovascularization by its antiangiogenic activity.

Inhibition of neointimal formation after balloon injury by cilostazol, accompanied by improvement of endothelial dysfunction and induction of hepatocyte growth factor in rat diabetes model.

AIMS/HYPOTHESIS: Cilostazol, a well-known phosphodiesterase type 3 (PDE3) inhibitor for the treatment of peripheral arterial disease, has vasodilator properties and an anti-proliferative action on the growth of vascular smooth muscle cells. In this study, we tested whether cilostazol inhibits neointimal formation and improves endothelial dysfunction after balloon injury in non-diabetic and diabetic rats. METHODS: Cilostazol or vehicle was administered to non-diabetic and streptozotocin-induced diabetic rats from 7 days before to 14 days after balloon injury of the carotid artery. We focused on the expression of hepatocyte growth factor to explore how cilostazol improved endothelial dysfunction. Also, we studied the effects of cilostazol on hepatocyte growth factor production in in vitro experiments. RESULTS: At 14 days after injury, the ratio of neointimal to medial area was decreased in rats treated with cilostazol in non-diabetic and diabetic animals. The impaired response to acetylcholine in balloon injured vessels was improved by cilostazol in non-diabetic and diabetic rats (p < 0.05). Vascular hepatocyte growth factor concentration was decreased in injured vessels of non-diabetic rats compared to uninjured vessels. Moreover, hepatocyte growth factor was further decreased in injured vessels of diabetic rats as compared to those of non-diabetic rats (p < 0.05). Of note, administration of cilostazol attenuated the decrease in hepatocyte growth factor concentration in injured vessels of both non-diabetic and diabetic rats (p < 0.01). Increase in vascular hepatocyte growth factor by cilostazol was confirmed by in vitro experiments showing that cilostazol increased hepatocyte growth factor concentration in cultured human vascular smooth muscle cells, accompanied by cAMP accumulation. CONCLUSION/INTERPRETATION: Our study shows that the increase in vascular hepatocyte growth factor by cilostazol could improve abnormal growth of vascular smooth muscle cells and endothelial dysfunction through rapid regeneration of endothelial cells.

Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury.

PURPOSE: Pigment epithelium-derived factor (PEDF) is a protein shown to have neurotrophic activity. The purpose of this study was to determine whether PEDF is neuroprotective of retinal neurons that are exposed to transient ischemia-reperfusion. METHODS: Transient retinal ischemia was produced by increasing the intraocular pressure for 45 min in albino rats eyes. Immediately after reperfusion, PEDF was injected intravitreally into the experimental eyes. Injury was evaluated morphologically and by measuring the thickness of the inner retinal layers (IRL) and by counting the number of retinal ganglion cells (RGC) in epon embedded sections. RESULTS: Morphologic and morphometric analysis of the thickness of the IRL and the counting of RGC demonstrated that PEDF injected immediately after reperfusion protected the eyes partially but significantly from the ischemic injury. CONCLUSIONS: Intravitreal injection of PEDF even after the ischemia can ameliorate retinal injury. PEDF may be useful in preventing neuronal degeneration in the inner retina resulting from ischemia.

Community-based rehabilitation in South Korea.

This paper gives a brief introduction to the geography and demography of the Republic of South Korea. Since 1988 South Korea has been actively legislating and implementing welfare policy for the disabled of the Republic. An overview of these policy changes is presented. The extent to which the policy has been implemented using community-based rehabilitation (CBR) is illustrated using an example from the North Wanju Project. Finally, there is a discussion of the future of CBR in South Korea and the means whereby there can be more social integration of the disabled.

The difference of means of two indirect unpaired groups in receptor autoradiography.

We present an approximate method to compare the difference of the means of two groups of populations by indirect unpaired data. This indirect data structure occurs in receptor autoradiography, where the tissue distribution of receptors is visualized in the form of ligand bindings. This visualization is indirect because we can only observe and measure nonspecific bindings in one autoradiograph and total bindings in another autoradiograph. The distribution of receptors is obtained by subtracting the nonspecific bindings from the total bindings. Besides the reasoning of our method, an example is given using our experimental data.

In vivo microradioautographic study of insulin binding in the skin of normal and NIDDM mice: with special reference to acanthosis nigricans.

Insulin bindings in the tissues and cells in the skin of non-diabetic (control) and genetically diabetic db/db (NIDDM) mice were investigated by in vivo microradioautography at 3 and 15 min. after intravenous injection of 125I-insulin. Specific insulin bindings were observed in the interfollicular epidermis, infundibulum, dermis, outer root sheath, sebaceous glands and blood vessels, but not in the hair shaft of the control mice. Although the specific bindings were seen in the interfollicular epidermis, infundibulum, outer root sheath and blood vessels in the NIDDM mice, the bindings were much less than those of the control mice at both 3 and 15 min. after 125I-insulin injection with an exception of the blood vessels at 3 min. The possible relationships between NIDDM and acanthosis nigricans from the viewpoint of insulin binding are considered.

Epidermal growth factor binding sites in the mouse exocrine and endocrine pancreas shown by in vivo quantitative microautoradiography and confocal laser scanning microscopy.

Microautoradiography at 3, 6 and 15 min after intravenous injection of 125I-EGF was used to investigate the distribution of epidermal growth factor (EGF) binding sites in the pancreas of normal male mice. The autoradiographs were observed by confocal laser microscopy, which allows the quantification of silver grains. The results demonstrated that both endocrine and exocrine pancreatic cells exhibited substantial specific binding of 125I-EGF. The highest level of EGF binding was found in the duct cells of the exocrine pancreas followed by the acinar cells. The cells of the islets of Langerhans also showed substantial specific binding of 125I-EGF though the binding level was lower than that of the exocrine pancreas. In the control experiments, mice were injected with 125I-EGF and various amounts of unlabeled EGF.

Distribution of [1,2-3H]taurine in the skin of adult and newborn mice studied by microradioautography.

In vivo light microscopic radioautography was used to demonstrate the distribution of taurine in adult and newborn mice at 30 min. and 3 hrs. after the injection of 3H-taurine. This study showed that the injected taurine was present in free form in the skin. Radioautographically, it was found that in the adult a very high density of taurine was found over the epidermis and external root sheaths near the opening of the hair follicles. The external root sheath just below the insertion of the sebaceous glands and the peripheral part of the sebaceous glands showed a high taurine distribution. Connective tissue in the dermis, however, showed low uptake of taurine. In the neonate mouse, the density of injected taurine in both the epidermis and the external root sheath was lower than that the density in the connective tissue in the dermis. We report these findings in detail and discuss some of the functional roles of taurine in the skin.