[Analysis of genotype and hematological phenotype of 14 patients with coinheritance HKαα and South-East deletion thalassemia].

Objective: To analyze the genotype-phenotype correlations among those thalassemia samples with the presence of -α(3.7,) --(SEA) and normal α(2) alleles on their α-globin gene clusters. Methods: Fourteen patients(including 1fetus, 4 males and 9 females, aged 0- 56 years old)who were suspected diagnosed by hematologic analysis and genetic testing among 16 080 participants in our laboratory since from August 2011 to August 2016, were enrolled. Complete blood cell count was performed on XE4000i automatic hemocyte analyzer. HbA0, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was adopted to detect three common deletional thalassemia deletions. Reverse dot-blot (RDB) assay was applied for detecting 17 common ß-globin gene mutations and three common non-deletional α(2) gene mutations. Two-round nested PCR assay was established to detect the genotype of HKαα in α-thalassemia. Results: Fourteen cases were identified as HKαα/--(SEA) (14/16 080), including a pedigree and a rare case of HKαα/--(SEA) co-inheritance with IVS-Ⅱ-654(C→T) heterozygote. In HKαα/--(SEA) thalassemia group, mean cell volume(MCV) was (69.54±5.92)fl, and mean cell hemoglobin(MCH) was(22.11±2.22)pg and hemoglobin(Hb) was (117.64±18.14) g/L. Compared with normal group, MCV, MCH and Hb in HKαα/--(SEA) thalassemia group, was significantly decreased(P<0.05). There were no significant differences between α-thalassemia control group(--(SEA) /αα) in most hematological parameters (P>0.05). Conclusion: The two-round nested PCR could effectively detect the HKαα/--(SEA) genotype. The hematologic characteristics changed significantly in HKαα/--(SEA) group compared with HbH thalassemia and normal group. The genotype and phenotype non-correlation in patients with α-thalassemia should especially be causious to avoid a misdiagnosis of genetic tests, especially in prenatal diagnosis.

A longitudinal study of the association between the GNB3 C825T polymorphism and metabolic disturbance in bipolar II patients treated with valproate.

This longitudinal study aimed to investigate the associations between the polymorphisms of guanine nucleotide-binding protein subunit ß-3 (GNB3) C825T and metabolic disturbance in bipolar II disorder (BP-II) patients being treated with valproate (VPA). A 100 BP-II patients received a 12-week course of VPA treatment, and their body weight and metabolic indices were measured. At baseline, the GNB3 C825T polymorphisms were associated with the triglyceride level (P=0.032) in BP-II patients. During the VPA treatment course, the polymorphisms were not only associated with body mass index (BMI) and waist circumference (P-values=0.009 and 0.001, respectively), but also with total cholesterol, triglyceride, low-density lipoprotein and leptin levels (P-values=0.004, 0.002, 0.031 and 0.015, respectively). Patients with the TT genotype had a lower BMI, smaller waist circumference, and lower levels of lipids and leptin than those with the CT or CC genotypes undergoing the VPA treatment course.

[Analysis of haematological phenotype and mutation spectrum of δ-globin gene from Guangdong area in Chinese Han prenatal population].

Objective: To analyze the genotype-phenotype correlations among southern Chinese Han prenatal population in Guangdong area with δ-globin gene mutation, so as to enrich the delta-thalassemia gene mutations data. Methods: A total of 33 cases were selected in 7 580 patients during prenatal thalassemia trait screening, from January 2012 to May 2015(including 10 males and 23 females, aged 22-48 years old). Complete blood cell count was performed on a XE 4000i automatic hemocyte analyzer. Hb, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Genomic DNA was extracted from whole blood samples using a whole blood genomic DNA extraction kit. Polymerase chain reaction (PCR) was used to amplify three different fragments corresponding to the exons and the regulatory sequences using three different couples of primers for the δ-globin gene. Results: Twenty one of the 33 samples were positive for the δ-globin gene defects. Four previously known mutations were detected: including 12 cases for -77(T>C)[HBD c. -127 (T>C)](57.14%), 4 cases for -30 (T>C)[HBD c. -80 (T>C)](19.05%), 1 case for codon 10 (-G) (HBD c. 31delG)(4.76%), and 1 case for HBD c. 244 C>T(4.76%). Three new δ-globin gene defects which had not yet been reported in database were detected, including 1 case for HBD c. 22_24delGAG(4.76%), 1 case for HBD c. 347 C>T(4.76%), and one case for HBD c. 349 C>G(4.76%). Conclusions: -77 (T>C) is the most common mutation in Chinese southern prenatal population. Three new HBD gene mutations are referred in this report, which provide the valuable information for genetic counseling and prenatal diagnosis in Guangdong area.

[Beneficial effects of Schisandrin B on the cardiac structure and function in a mice model of myocardial infarction].

Objective: To investigate whether Schisandrin B (Sch B) could improve cardiac structure and function in myocardial infarction (MI) mice and related mechanisms. Methods: Male C57BL/6J mice were randomized into sham (n=8), MI+ Sch B (n=24, 80 mg·kg(-1)·d(-1) per gavage) or MI+ vehicle (n=24, equal volume). After treatment for 3 weeks, cardiac function was detected by echocardiography measurement.Infarction size was measured by Evans blue and TTC staining.HE and Masson trichrome staining were used to observe the myocardial inflammation, structure and fibrosis.TNF-α, TGF-ß, IL-1ß were detected by ELISA. The apoptosis index of ischemic myocardial cells was detected by immunofluorescence. NF-κB, Bcl-2, Bax, Akt phosphorylated Akt(p-Akt), eNOS, phosphorylated eNOS (p-eNOS) were detected by Western blot. Results: Three weeks after operation, survival rate (83.33% vs. 54.17%, P<0.05), LVEF((51.77±8.50)% vs.(40.23±8.30)%, P<0.05), LVFS((26.44±5.15)% vs. (19.53±4.56)%, P<0.05)were significantly higher; LVEDD ((4.13±0.40) mm vs.(4.44±0.46)mm, P<0.05), LVESD((3.07±0.39) mm vs. (3.46±0.52)mm, P<0.05), the heart weight/body weight ratio((0.59±0.06)% vs. (0.68±0.10)%, P<0.05)was significantly lower and infarct size ((23.4±2.36)% vs. (39.4±2.06)%, P<0.05) was significantly reduced in MI+ Sch B group than those in MI+ vehicle group. In MI+ vehicle group, HE staining showed a large number of inflammatory cells in the peri-infarctl region, and the permutation structure was very disorganized, while above changes were significantly reduced in the MI+ Sch B group. Masson staining results showed that the degree of myocardial fibrosis in MI+ Sch B group was significantly less than that of MI+ vehicle group.Moreover, Sch B could down-regulate some inflammatory cytokines, like NF-κB、TGF-ß、TNF-α and IL-1ß, activate Akt-eNOS pathway, upgrade Bcl-2 and downgrade Bax and reduce cell apoptosis as compared with MI+ vehicle group (all P<0.05). Conclusions: Our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and attenuate cardiac remodeling and improve cardiac function in this mice MI model.Sch B might serve as a potential novel therapeutic agent for ischemic heart disease.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics.

Early statin therapy in patients with acute intracerebral hemorrhage without prior statin use.

BACKGROUND AND PURPOSE: Statin therapy is beneficial for primary and secondary prevention of ischaemic stroke, but its influence in patients with intracerebral hemorrhage (ICH) is unclear. An assessment was made of the effect of early statin therapy on patients with acute ICH. METHODS: Taiwan's National Health Insurance Research Database was screened for patients without prior statin therapy admitted from January to December 2008 for newly diagnosed ICH. Patients taking statins during hospitalization or within 3 months post-discharge were the early statin group (n = 749); patients who were not were the control group (n = 7583). The study end-points were recurrent ICH and all-cause mortality during follow-up. RESULTS: All eligible patients were followed up until 31 December 2010. During the follow-up, 69 (9.2%) patients in the early statin group and 677 (8.9%) control group patients had recurrent ICH. Cox proportional hazards analyses showed that early statin use did not increase the risk of recurrent ICH (adjusted hazard ratio 1.044; 95% confidence interval 0.812-1.341). During the same period, 90 (12.0%) of the early statin group and 1519 (20.0%) control group patients died. All-cause mortality was lower in the early statin group (adjusted hazard ratio 0.742; 95% confidence interval 0.598-0.919) than in the control group. Matched propensity score analyses were consistent with findings in Cox proportional hazards analyses. CONCLUSIONS: Early statin group patients with acute ICH did not have a higher recurrent risk of ICH and might have lower all-cause mortality during follow-up. It is concluded that statin therapy might be beneficial for patients with ICH.

Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in drug-naïve patients with bipolar II disorder after a twelve-week pharmacological intervention.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma BDNF with mood symptoms and metabolic indices in patients with BD-II over a 12-week pharmacological intervention. METHOD: Drug-naïve patients with BD-II (n=117) were recruited. Metabolic profiles [cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI)] and plasma BDNF wtrun "tblautotrun "tblsctrun "tbl_contere measured at baseline and 2, 8, and 12 weeks after beginning medication. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. RESULTS: Seventy-six (65.0%) patients completed the intervention. Plasma BDNF levels were significantly associated with BMI (P=9.6E-5), low-density lipoprotein (P=0.034) and total (P=0.001) cholesterol, but not with the Hamilton Depression Rating Scale-17 and Young Mania Rating Scale scores over the 12-week treatment. CONCLUSION: We found initial evidence of a positive correlation between plasma BDNF levels and BMI, low-density lipoprotein and total cholesterol in drug-naïve patients with BD-II. The specific function of BDNF in regulating and maintaining peripheral metabolic health requires additional investigation.

Quantifying midbrain serotonin transporter in depression: a preliminary study of diagnosis and naturalistic treatment outcome.

INTRODUCTION: Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain. METHODS: In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment. RESULTS: A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT. DISCUSSION: The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.

P300 waveform and dopamine transporter availability: a controlled EEG and SPECT study in medication-naive patients with schizophrenia and a meta-analysis.

BACKGROUND: Reduced P300 event-related potential (ERP) amplitude and latency prolongation have been reported in patients with schizophrenia compared to healthy controls. However, the influence of antipsychotics (and dopamine) on ERP measures are poorly understood and medication confounding remains a possibility. METHOD: We explored ERP differences between 36 drug-naive patients with schizophrenia and 138 healthy controls and examined whether P300 performance was related to dopamine transporter (DAT) availability, both without the confounding effects of medication. We also conducted a random effects meta-analysis of the available literature, synthesizing the results of three comparable published articles and our local study. RESULTS: No overall significant difference was found in mean P300 ERP between patients and controls in latency or in amplitude. There was a significant gender effect, with females showing greater P300 amplitude than males. A difference between patients and controls in P300 latency was evident with ageing, with latency increasing faster in patients. No effect of DAT availability on P300 latency or amplitude was detected. The meta-analysis computed the latency pooled standardized effect size (PSES; Cohen's d) of -0.13 and the amplitude PSES (Cohen's d) of 0.48, with patients showing a significant reduction in amplitude. CONCLUSIONS: Our findings suggest the P300 ERP is not altered in the early stages of schizophrenia before medication is introduced, and the DAT availability does not influence the P300 ERP amplitude or latency. P300 ERP amplitude reduction could be an indicator of the progression of illness and chronicity.

The occurrence of melioidosis is related to different climatic conditions in distinct topographical areas of Taiwan.

This study assessed the correlations between the incidence of melioidosis and rainfall, wind strength and wind direction in both the flat and hilly regions of Taiwan. Data from the melioidosis and climate databases from 2005 to 2011 were combined and analysed. With the inclusion of a lag time accounting for a possible incubation period for melioidosis, the daily rainfall and wind-speed data were correlated with the number of confirmed melioidosis cases. The incidence of melioidosis in the flat region was related to the wind speed (>19 m/s) and the specific angle (150°, 220°, 280°) of the wind direction. Rainfall is a common environmental factor that contributes to an increase in the incidence of melioidosis in both areas; however, the contribution of wind strength or wind direction to the spread of melioidosis was restricted to areas with specific topographical characteristics, such as hills.

Impact of early statin therapy in patients with ischemic stroke or transient ischemic attack.

BACKGROUND: Statin therapy has demonstrated benefits in ischemic stroke patients. However, little is known about whether the timing of statin initiation affects clinical outcomes. The possible association of statin use and cerebral hemorrhage is also a concern for early statin therapy after stroke. The objective of this study was to evaluate the efficacy and safety of the initiation timing of statins in acute ischemic stroke. METHODS: A cohort study was performed using 5-year National Health Insurance Research Database in Taiwan. Patients without prior statin therapy admitted for their new ischemic stroke or transient ischemic attack (TIA) were enrolled. Patients were recognized as inhospital use group (2019 patients, statin initiation during hospitalization), intermediate use group (2266 patients, statin initiation within 1 year after discharge) or late use group (2958 patients, statin initiation 1 year later after discharge). The study endpoint was the composite outcome of ischemic stroke, TIA, hemorrhagic stroke, or acute coronary event. RESULTS: As compared with inhospital use, patients with late use had a 49% increased risk (adjusted HR: 1.49, 95% CI: 1.26-1.76) of composite endpoint. In contrast, patients with intermediate use had similar risk of endpoint as those with inhospital use. The risk of cerebral hemorrhage was similar in patients receiving inhospital, intermediate, or late statin treatment. CONCLUSIONS: In acute ischemic stroke, patients receiving late statin treatment carried a poorer clinical outcome than those with earlier statin initiation. Inhospital statin use after an acute ischemic stroke did not increase the risk of cerebral hemorrhage.

Effect of statin treatment on three-month outcomes in patients with stroke-associated infection: a prospective cohort study.

BACKGROUND AND PURPOSE: Infection is a major medical problem in patients with acute stroke. Recent evidences suggest that statins reduce infection-associated complications. The purpose of this study was to examine the influence of statin treatment on mortality and functional outcomes in patients with stroke-associated infection. METHODS: In this prospective observational cohort study, 514 patients with acute ischaemic stroke or transient ischaemic attack (mean age, 74 ± 11 years; men, 48%) with infection occurring in the first 7 days after admission were included. We examined the effect of in-hospital statin treatment on mortality and favorable functional outcome (modified Rankin Scale score ≤2) at 3 months follow-up. RESULTS: Infection occurred at 0.93 ± 1.49 days after admission. All patients had not received statin treatment prior to admission, and 121 patients (24%) received statin at 1.71 ± 1.28 days after admission. Follow-up at 3 months was completed for 511 patients (99%). National Institutes of Health Stroke Scale score and Charlson index were the most important independent predictors of mortality and functional outcome. Univariate [hazard ratio (HR), 0.82; 95% confidence intervals (CI), 0.47-1.42] and multivariate (HR, 1.68; 95% CI, 0.79-3.56) Cox regression analysis showed that statin did not significantly decrease the morality. In propensity analysis, statin treatment still had no significant association with mortality (HR, 1.54; 95% CI, 0.68-3.47) in the multivariate analyses after adjusting for age, sex, and propensity score. CONCLUSIONS: Statin use was not associated with a better functional outcome or survival in patients with stroke-associated infection.

Ectopic expression of sex peptide alters reproductive behavior of female D. melanogaster.

Sex peptide, a secreted component of the male accessory glands, has been shown to induce behavioral and physiological changes in mated Drosophila. We transformed flies with a hybrid gene containing an hsp70 promoter fused to a cDNA encoding sex peptide. Heat-induced ectopic expression of the peptide in transgenic virgin females altered their reproductive behavior, in the presence of courting males, to that observed in mated females. This demonstrates that the peptide is functional as expected. Time course studies revealed that the behavioral change appeared earlier than the stimulated ovulation. We have also introduced a modified sex peptide gene that is driven by the yp1 enhancer, conferring expression in adult females, and shown that these flies refuse mating constitutively in the presence of courting males and lay unfertilized eggs at the rate of mated females.

Homocysteine induced oxidative stress in human umbilical vein endothelial cells via regulating methylation of SORBS1.

OBJECTIVE: The aim of the present study was to investigate the mechanism of homocysteine (Hcy) induced oxidative stress in the human umbilical vein endothelial cells (HUVECs). PATIENTS AND METHODS: The HUVECs were isolated from umbilical vein vascular wall of 12 patients and treated with Hcy. The malondialdehyde (MDA) level was measured using the thiobarbituric acid (TBA) method. The expressions of superoxide dismutase 2 (SOD2), endothelial nitric oxide synthase (eNOS), and intercellular adhesion molecule 1 (ICAM-1) were detected by Western blot and RT-PCR. The genome-wide DNA methylation assay was performed using the Infinium Human Methylation 450 BeadChip. The specific DNA methylation was determined using bisulfite sequencing analysis. To evaluate the role of sorbin and SH3 domain-containing protein 1 (SORBS1), the HUVECs were transfected with small interfere RNA (siRNA) targeting SORBS1 (SORBS1-siRNA). RESULTS: Hcy induced MDA level in HUVECs, and increased ICAM-1 expression both in protein and mRNA levels. The protein and mRNA levels of SOD2 and eNOS were inhibited by Hcy induction. However, the effects of Hcy on MDA level and expressions of SOD2, eNOS, and ICAM-1 were attenuated by folic acid (Fc) and vitamin B12 (B12) treatment. DNA total methylation level in Hcy treated cells was significantly decreased compared to the control group, while the DNA total methylation levels were increased after treatment with Fc and B12. The methylation level of SORBS1 in Hcy treatment group was higher than that of control group. And the methylation level of SORBS1 induced by Hcy was attenuated by Fc and B12 treatment. SORBS1-siRNA transfection induced the MDA levels and reduced the expressions of SOD2 in HUVECs. CONCLUSIONS: We indicated that Hcy induced oxidative stress in HUVECs via regulating methylation of SORBS1. We also found that Fc and B12 treatment attenuated the oxidative stress and inflammation induced by Hcy in HUVECs. The findings indicated that Fc and B12 might be effective agents for the treatment of Hcy induced AS.

The relation between atrial fibrillation wavefront characteristics and accessory pathway conduction.

Although the source-sink relationship for impulse propagation in cardiac tissues has been demonstrated in vitro, there has been no verification of this hypothesis in humans. Accordingly, eight patients undergoing surgical division of their accessory pathways were studied. A 56-channel (7 x 8) bipolar plaque electrode array was placed over the atrioventricular groove on the accessory pathway and atrial fibrillation electrically induced. 10 episodes of QRS transition from consecutively preexcited to nonpreexcited complexes were analyzed. This showed that consecutively preexcited QRS complexes were always associated with uniform large atrial wavefronts. Immediately prior to QRS transition, four general types of changes were observed: (a) premature invasion by secondary wavefronts creating local conduction block (n = 5); (b) wavefront collision leading to wavefront curvature (n = 2); (c) transition from a uniform large atrial wavefront to multiple fractionated small wavefronts (n = 1); and (d) uniform atrial wavefronts "marching" into the accessory pathway refractory period (n = 2). We conclude that local atrial wavefront characteristics are important factors influencing impulse propagation through the accessory pathway. The findings that local wavefront collision, curvature, or fractionation often precede loss of accessory pathway conduction support the notion that source-sink relationship is an important determinant of the safety factor for impulse propagation in the human heart.

Activation during ventricular defibrillation in open-chest dogs. Evidence of complete cessation and regeneration of ventricular fibrillation after unsuccessful shocks.

To test the hypothesis that a defibrillation shock is unsuccessful because it fails to annihilate activation fronts within a critical mass of myocardium, we recorded epicardial and transmural activation in 11 open-chest dogs during electrically induced ventricular fibrillation (VF). Shocks of 1-30 J were delivered through defibrillation electrodes on the left ventricular apex and right atrium. Simultaneous recordings were made from septal, intramural, and epicardial electrodes in various combinations. Immediately after all 104 unsuccessful and 116 successful defibrillation shocks, an isoelectric interval much longer than that observed during preshock VF occurred. During this time no epicardial, septal, or intramural activations were observed. This isoelectric window averaged 64 +/- 22 ms after unsuccessful defibrillation and 339 +/- 292 ms after successful defibrillation (P less than 0.02). After the isoelectric window of unsuccessful shocks, earliest activation was recorded from the base of the ventricles, which was the area farthest from the apical defibrillation electrode. Activation was synchronized for one or two cycles following unsuccessful shocks, after which VF regenerated. Thus, after both successful and unsuccessful defibrillation with epicardial shocks of greater than or equal to 1 J, an isoelectric window occurs during which no activation fronts are present; the postshock isoelectric window is shorter for unsuccessful than for successful defibrillation; unsuccessful shocks transiently synchronize activation before fibrillation regenerates; activation leading to the regeneration of VF after the isoelectric window for unsuccessful shocks originates in areas away from the defibrillation electrodes. The isoelectric window does not support the hypothesis that defibrillation fails solely because activation fronts are not halted within a critical mass of myocardium. Rather, unsuccessful epicardial shocks of greater than or equal to 1 J halt all activation fronts after which VF regenerates.

Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.

We have presented evidence that ventricular fibrillation is deterministic chaos arising from quasiperiodicity. The purpose of this study was to determine whether the transition from chaos (ventricular fibrillation, VF) to periodicity (ventricular tachycardia) through quasiperiodicity could be produced by the progressive reduction of tissue mass. In isolated and perfused swine right ventricular free wall, recording of single cell transmembrane potentials and simultaneous mapping (477 bipolar electrodes, 1.6 mm resolution) were performed. The tissue mass was then progressively reduced by sequential cutting. All isolated tissues fibrillated spontaneously. The critical mass to sustain VF was 19.9 +/- 4.2 g. As tissue mass was decreased, the number of wave fronts decreased, the life-span of reentrant wave fronts increased, and the cycle length, the diastolic interval, and the duration of action potential lengthened. There was a parallel decrease in the dynamical complexity of VF as measured by Kolmogorov entropy and Poincaré plots. A period of quasiperiodicity became more evident before the conversion from VF (chaos) to a more regular arrhythmia (periodicity). In conclusion, a decrease in the number of wave fronts in ventricular fibrillation by tissue mass reduction causes a transition from chaotic to periodic dynamics via the quasiperiodic route.

Quasiperiodicity and chaos in cardiac fibrillation.

In cardiac fibrillation, disorganized waves of electrical activity meander through the heart, and coherent contractile function is lost. We studied fibrillation in three stationary forms: in human chronic atrial fibrillation, in a stabilized form of canine ventricular fibrillation, and in fibrillation-like activity in thin sheets of canine and human ventricular tissue in vitro. We also created a computer model of fibrillation. In all four studies, evidence indicated that fibrillation arose through a quasiperiodic stage of period and amplitude modulation, thus exemplifying the "quasiperiodic transition to chaos" first suggested by Ruelle and Takens. This suggests that fibrillation is a form of spatio-temporal chaos, a finding that implies new therapeutic approaches.

Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity.

Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, has been shown to be an inhibitor of histone deacetylase (HDAC). Our previous study has demonstrated that VPA pretreatment reduces lipopolysaccharide (LPS)-induced dopaminergic (DA) neurotoxicity through the inhibition of microglia over-activation. The aim of this study was to determine the mechanism underlying VPA-induced attenuation of microglia over-activation using rodent primary neuron/glia or enriched glia cultures. Other histone deacetylase inhibitors (HDACIs) were compared with VPA for their effects on microglial activity. We found that VPA induced apoptosis of microglia cells in a time- and concentration-dependent manner. VPA-treated microglial cells showed typical apoptotic hallmarks including phosphatidylserine externalization, chromatin condensation and DNA fragmentation. Further studies revealed that trichostatin A (TSA) and sodium butyrate (SB), two structurally dissimilar HDACIs, also induced microglial apoptosis. The apoptosis of microglia was accompanied by the disruption of mitochondrial membrane potential and the enhancement of acetylation levels of the histone H3 protein. Moreover, pretreatment with SB or TSA caused a robust decrease in LPS-induced pro-inflammatory responses and protected DA neurons from damage in mesencephalic neuron-glia cultures. Taken together, our results shed light on a novel mechanism whereby HDACIs induce neuroprotection and underscore the potential utility of HDACIs in preventing inflammation-related neurodegenerative disorders such as Parkinson's disease.

Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation.

Blood, buccal swab and hair follicles are among the most commonly used sources for forensic science, parentage testing and personal identification. A total of 29 patients who have had a sustained engraftment from 15 months to 21.5 years after allogeneic hematopoietic stem cell transplantation (HSCT) without rejection, relapse or chronic GVHD involving oral mucosa were enrolled for a chimerism study. PCR-amplified short tandem repeat analyses were conducted per patient every 3 months for at least three consecutive times. The results for blood were all donor type except one who had a mixed chimerism, 14.5 years after receiving a transplant for lymphoma. As for buccal swab, mixed chimerism ranging from 10 to 96% donor origin was noted for 28 recipients except the one who had mixed chimerism of blood and retained total recipient type. In contrast, hair follicles were 100% recipient type for the entire group. It is concluded that the hair follicle is devoid of adult stem cell plasticity and may serve as a reliable source of recipient's origin when pre-transplant DNA fingerprinting or reference DNA is not available for people who have successfully received allogeneic HSCT while in need of a personal identification.