The Role of SCL Isoforms in Embryonic Hematopoiesis.

Three waves of hematopoiesis occur in the mouse embryo. The primitive hematopoiesis appears as blood islands in the extra embryonic yolk sac at E7.5. The extra embryonic pro-definitive hematopoiesis launches in late E8 and the embryonic definitive one turns on at E10.5 indicated by the emergence of hemogenic endothelial cells on the inner wall of the extra embryonic arteries and the embryonic aorta. To study the roles of SCL protein isoforms in murine hematopoiesis, the SCL-large (SCL-L) isoform was selectively destroyed with the remaining SCL-small (SCL-S) isoform intact. It was demonstrated that SCL-S was specifically expressed in the hemogenic endothelial cells (HECs) and SCL-L was only detected in the dispersed cells after budding from HECs. The SCLΔ/Δ homozygous mutant embryos only survived to E10.5 with normal extra embryonic vessels and red blood cells. In wild-type mouse embryos, a layer of neatly aligned CD34+ and CD43+ cells appeared on the endothelial wall of the aorta of the E10.5 fetus. However, the cells at the same site expressed CD31 rather than CD34 and/or CD43 in the E10.5 SCLΔ/Δ embryo, indicating that only the endothelial lineage was developed. These results reveal that the SCL-S is sufficient to sustain the primitive hematopoiesis and SCL-L is necessary to launch the definitive hematopoiesis.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis: A case report.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presents with the features of herpes simplex encephalitis (HSE), which is rare and has been described in only a few case reports. Our case describes a 17-year-old female with no significant previous medical history presenting with an acute onset of fever, headache, and epilepsy, similar to HSE. Computed tomography of the brain showed bilateral basal ganglia calcification. Magnetic resonance imaging demonstrated gyriform restricted diffusion with T2-weighted images prolongation. Further investigation showed elevated blood lactate concentration at rest. Hence, MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. The clinical presentation and imaging studies of MELAS are variable and may mimic those of HSE. Infection may have also precipitated MELAS manifestation in this patient. Laboratory features, such as elevated lactate, basal ganglia calcification, and gyriform restricted diffusion may be helpful in identifying patients with MELAS.

Identification of the Framingham Risk Score by an Entropy-Based Rule Model for Cardiovascular Disease.

Since 2001, cardiovascular disease (CVD) has had the second-highest mortality rate, about 15,700 people per year, in Taiwan. It has thus imposed a substantial burden on medical resources. This study was triggered by the following three factors. First, the CVD problem reflects an urgent issue. A high priority has been placed on long-term therapy and prevention to reduce the wastage of medical resources, particularly in developed countries. Second, from the perspective of preventive medicine, popular data-mining methods have been well learned and studied, with excellent performance in medical fields. Thus, identification of the risk factors of CVD using these popular techniques is a prime concern. Third, the Framingham risk score is a core indicator that can be used to establish an effective prediction model to accurately diagnose CVD. Thus, this study proposes an integrated predictive model to organize five notable classifiers: the rough set (RS), decision tree (DT), random forest (RF), multilayer perceptron (MLP), and support vector machine (SVM), with a novel use of the Framingham risk score for attribute selection (i.e., F-attributes first identified in this study) to determine the key features for identifying CVD. Verification experiments were conducted with three evaluation criteria-accuracy, sensitivity, and specificity-based on 1190 instances of a CVD dataset available from a Taiwan teaching hospital and 2019 examples from a public Framingham dataset. Given the empirical results, the SVM showed the best performance in terms of accuracy (99.67%), sensitivity (99.93%), and specificity (99.71%) in all F-attributes in the CVD dataset compared to the other listed classifiers. The RS showed the highest performance in terms of accuracy (85.11%), sensitivity (86.06%), and specificity (85.19%) in most of the F-attributes in the Framingham dataset. The above study results support novel evidence that no classifier or model is suitable for all practical datasets of medical applications. Thus, identifying an appropriate classifier to address specific medical data is important. Significantly, this study is novel in its calculation and identification of the use of key Framingham risk attributes integrated with the DT technique to produce entropy-based decision rules of knowledge sets, which has not been undertaken in previous research. This study conclusively yielded meaningful entropy-based knowledgeable rules in tree structures and contributed to the differentiation of classifiers from the two datasets with three useful research findings and three helpful management implications for subsequent medical research. In particular, these rules provide reasonable solutions to simplify processes of preventive medicine by standardizing the formats and codes used in medical data to address CVD problems. The specificity of these rules is thus significant compared to those of past research.

Correlation of HAMP gene polymorphisms and expression with the susceptibility and length of hospital stays in Taiwanese children with Kawasaki disease.

Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected. Furthermore, we measured plasma hepcidin levels with an enzyme-linked immunosorbent assay. We found that HAMP gene polymorphism (rs7251432, and rs2293689) was significantly correlated with KD risk and that plasma hepcidin levels both before and after IVIG treatment had a significantly positive correlation with length of hospital stays (R = 0.217, p = 0.046 and R = 0.381, p < 0.0001, respectively). In contrast, plasma hepcidin levels has a negative correlation with KD patients' albumin levels (R = -0.27, p < 0.001) prior to IVIG treatment. This study's findings indicate that HAMP might have a role in the disease susceptibility, as well as its expressions correlated length of hospital stays, and albumin levels in Taiwanese children with KD.

Ectopic expression of a tobacco vacuolar invertase inhibitor in guard cells confers drought tolerance in Arabidopsis.

There are several hypotheses that explain stomatal behavior. These include the concept of osmoregulation mediated by potassium and its counterions malate and chlorine and the more recent starch-sugar hypothesis. We have previously reported that the activity of the sucrose cleavage enzyme, vacuolar invertase (VIN), is significantly higher in guard cells than in other leaf epidermal cells and its activity is correlated with stomatal aperture. Here, we examined whether VIN indeed controls stomatal movement under normal and drought conditions by transforming Arabidopsis with a tobacco vacuolar invertase inhibitor homolog (Nt-inhh) under the control of an abscisic acid-sensitive and guard cell-specific promoter (AtRab18). The data obtained showed that guard cells of transgenic Arabidopsis plants had lower VIN activity, stomatal aperture and conductance than that of wild-type plants. Moreover, the transgenic plants also displayed higher drought tolerance than wild-type plants. The data indicate that VIN is a promising target for manipulating stomatal function to increase drought tolerance.

[Study on the status and related socio-psychological factors of maternal depression among high-risk pregnancy women in Harbin city].

OBJECTIVE: This study aimed to investigate the depression status among high-risk pregnancy women, and to analyze its relevant social and psychological factors. METHODS: A total of 42 high-risk pregnancy women and 40 normal pregnancy women in a teaching hospital in Harbin city were followed up at time points of 32 - 36 weeks pregnancy, one week before labor, one week postpartum, and six weeks postpartum, respectively. During follow-up, the basic situation, social psychosocial factors of pregnancy women were collected and the depression of pregnancy women was measured by self-designed questionnaire and self-rating depression scale. The Edinburgh Postnatal Depression Scale (EPDS) was applied at timepoint of one week postpartum. Single factor analysis and the unconditional multivariate logistic regression were applied for analyzing the on the related social-psychosocial factors among high-risk pregnancy women. RESULTS: The age of high-risk pregnancy women was (31.0±5.6), and the age of normal pregnancy women was (30.5±3.8) (t=0.169, P>0.05). The results showed that the depression rate in high-risk pregnancy women was 45.2% (19/42), which was 25.0% (10/40) in normal pregnancy women, the difference was significant (χ2=3.671, P=0.045). The depression rates at different time points were 30.9% (13/42), 42.9% (18/42), 23.8% (10/42), 26.2% (11/42) in high-risk pregnancy women respectively, and 25.0% (10/40), 15.0% (6/40), 20.0% (8/40), 17.5% (7/40) in the control group respectively, the difference of the depression rates among groups at one week before labor was significant (χ2=7.680, P<0.01), the difference among groups at 32-36 weeks pregnancy (χ2=0.133, P=0.80), at one week postpartum (χ2=0.174, P=0.79) and at six weeks postpartum (χ2=0.903, P=0.43) were not significant. At one week postpartum and six weeks postpartum periods, the EPDS depression rate were 12.5% (4/32), 30.4% (7/23) in case group respectively, 8.3% (3/36), 22.9% (8/35) in control group respectively, the difference were not significant (χ2=0.319, 0.416, P=0.573, 0.519). There were significantly associations between the depression mood of one week before labor and the depressive symptoms of six weeks postpartum in both groups (r=0.824, 0.677, both P values were <0.05). The risk factors for maternal depression among high-risk pregnancy women were not ready for production (OR=2.73, P<0.01) and fearing of childbirth safety (OR=2.89, P<0.01). CONCLUSION: The depression date of high-risk pregnancy was high, especially at the time point one week before labor. Risk factors of maternal depression among high-risk pregnancy were "not ready for production" and "fear of childbirth safety".

[Familial aggregation of metabolic syndrome in adolescents with paternal metabolic syndrome].

OBJECTIVE: To analyze the impact of parental Metabolic Syndrome (MS) on adolescents, and to explore the familial aggregation of MS with its components. METHODS: Using a 1:3 case-control familial study design to choose 26 MS male patients as proband and 78 healthy men as controls. Data regarding phenotype of their adolescence offspring were collected. Height, weight, waist circumference (WC), blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were measured or calculated. FPG, TC, TG, HDL-C and LDL-C were detected by automatic biochemical analyzer and hs-CRP was detected. RESULTS: WC, WHtR, WHR, DBP and hs-CRP of those adolescents with paternal MS were significantly higher than in controls (P < 0.05). Rates of MS, Obesity depend WC, low level of HDL-C of adolescent with paternal MS were significantly higher than in controls (P < 0.05). The rate of number on MS was significantly higher in case group than in control (r = 0.231, P < 0.05). CONCLUSION: The phenotypes of MS were different between adolescents with or without parental MS, indicating that the familial aggregation of MS had been existed in their adolescent offspring, and mainly presented in central obesity, increased blood pressure and inflammation.

[Risk factors for emotional abuse in 844 adolescents].

OBJECTIVE: Emotional abuse and neglect is an under-recognized, but is a common form of child abuse. This study aimed to investigate the risk factors for emotional abuse in adolescents. METHODS: A cross-sectional survey on emotional abuse was conducted by anonymous self-administered questionnaire in 865 adolescents randomly sampled from three junior schools in Harbin City. A total of 844 valid questionnaires were received. Risk factors were studied by multivariate non-conditional regression analysis. RESULTS: Over the past year, 47.3% of the 844 respondents suffered from emotional abuse. Monovariate regression analysis indicated that emotional abuse was related to 19 factors, including children's health status, parental marital status, parental educational levels, family rearing patterns, family atmosphere and so on. Multivariate regression analysis showed poor children's health status (OR=1.877, P=0.001), bad parental marital status (OR=1.768, P=0.004), and unjustifiable family rearing patterns [over-interference (OR=3.004, P=0.006) and assentation (OR=5.430, P=0.032)] were risk factors for the occurrence of emotional abuse. The harmonious family atmosphere and the harmonious relations between children and their parents were protective factors for emotional abuse. CONCLUSIONS: The prevalence of emotional abuse is high in adolescents. Poor children's health status, bad parental marital status and unjustifiable family rearing patterns are risk factors for the occurrence of emotional abuse.

Stabilization of hypoxia-inducible factor-1{alpha} by prostacyclin under prolonged hypoxia via reducing reactive oxygen species level in endothelial cells.

Hypoxia-inducible factor-1 (HIF-1) takes part in the transcriptional activation of hypoxia-responsive genes. HIF-1alpha, a subunit of HIF-1, is rapidly degraded under normoxic conditions by the ubiquitin-proteosome system. Hypoxia up-regulates HIF-1alpha by inhibiting its degradation, thereby allowing it to accumulate to high levels with 3-6 h of hypoxia treatment and decreasing thereafter. In vascular tissues, prostacyclin (prostaglandin I(2) (PGI(2))) is a potent vasodilator and inhibitor of platelet aggregation and is known as a vasoprotective molecule. However, the role of PGI(2) in HIF-1 activation has not been studied. In the present study, we investigated the effect of PGI(2) on HIF-1 regulation in human umbilical vein endothelial cells under prolonged hypoxia (12 h). Augmentation of PGI(2) via adenovirus-mediated gene transfer of both cyclooxygenase-1 and PGI(2) synthase activated HIF-1 by stabilizing HIF-1alpha in cells under prolonged hypoxia or the hypoxia-normoxia transition but not under normoxia. Exogenous H(2)O(2) abolished PGI(2)- and catalase-induced HIF-1alpha up-regulation, which suggests that degradation of HIF-1alpha under prolonged hypoxia is through a reactive oxygen species-dependent pathway. Moreover, PGI(2) attenuated NADPH oxidase activity by suppressing Rac1 and p47(phox) expression under hypoxia. These data demonstrate a novel function of PGI(2) in down-regulating reactive oxygen species production by attenuating NADPH oxidase activity, which stabilizes HIF-1alpha in human umbilical vein endothelial cells exposed to prolonged hypoxia.

Seizure, neuron loss, and mossy fiber sprouting in herpes simplex virus type 1-infected organotypic hippocampal cultures.

PURPOSE: Epileptic seizures are frequently seen after viral encephalitis. Herpes simplex virus type 1 (HSV-1) encephalitis is the most common cause of acquired epilepsy in humans. However, little information is available about the neuropathogenesis of HSV-1-associated seizures. We have developed an in vitro HSV-1-infected organotypic hippocampal slice culture to elucidate the underlying mechanisms of HSV-1-associated acute seizure activity. METHODS: Hippocampal slice cultures were prepared from postnatal day 10 to 12 rat pups. Wild-type HSV-1 strain RE (1 x 10(5) PFU) was applied to cultures at 14 days in vitro. The excitability of CA3 pyramidal cells and hippocampal network properties were measured with electrophysiological recordings. Hematoxylin-eosin (H&E) and Timm stains were used. RESULTS: HSV-1 infection induces epileptiform activity, neuron loss, and subsequently a dramatic increase of mossy fiber sprouting in the supragranular area. With intracellular recordings, surviving CA3 pyramidal cells exhibited a more depolarizing resting membrane potential concomitant with an increase in membrane input resistance and had a lower threshold to generate synchronized bursts and a decrease in the amplitude of afterhyperpolarization than did controls. When the antiherpes agent acyclovir was applied with a delay of 1 or 24 h after HSV-1 infection, a dramatic inhibition of HSV-1 replication and protection of the neuron loss were observed. CONCLUSIONS: These results suggest that a direct change in the excitability of the hippocampal CA3 neuronal network and HSV-1-induced neuron loss resulting in subsequent mossy fiber reorganization may play an important role in the generation of epileptiform activity.