Repeated Low-Grade Infections Predict Antidepressant-Resistant Depression: A Nationwide Population-Based Cohort Study.

BACKGROUND: The relationship between severe inflammation and clinical depression in the context of major medical illnesses has been addressed, but the relationship between inflammation caused by mild infections and clinical depression is unclear. We aimed to examine whether a history of repeated low-grade infections (RLGI) in medically healthy subjects (MHS) could increase their vulnerability to major depressive disorder (MDD) (ICD-9-CM) and whether RLGI could be associated with higher resistance to antidepressants in those developing MDD. METHOD: A nationwide, population-based cohort study (January 1996 to December 2011) was conducted for MHS with and without a history of RLGI. The rates of MDD during an up to 8-year follow-up period were compared between the 2 groups in 2 independent cohorts. The stratified responses to adequate antidepressant trials, including easy-to-treat (ETT) and difficult-to-treat (DTT) responses, were also compared in the MDD patients. RESULTS: During the follow-up, the 2 cohorts consistently revealed that the RLGI(+) (ie, high-inflammation; n = 727) group had a significantly higher chance of developing MDD over time than the RLGI(-) (ie, low-inflammation; n = 443) group: Cox proportional hazards regression models showed that the hazard ratio associated with a history of RLGI was 1.369 to 1.911 (P < .001), after adjusting for confounding factors. The RLGI(+) group was consistently associated with a higher likelihood of DTT responses than was the RLGI(-) group (Cohort-2002: 11.5% vs 7.6%; Cohort-2004: 11.8% vs 4.3%; P < .05 by Wald χ² tests in both cohorts). CONCLUSIONS: This is the first large-scale retrospective cohort study to report a reliable temporal association between a history of RLGI and subsequent diagnosis of MDD and poor responses to antidepressants in 2 independent cohorts. Our data support the view that repeated mild infections play a role in the pathophysiology of MDD and antidepressant-resistant depression.

Mesenchymal stem cells and their conditioned medium can enhance the repair of uterine defects in a rat model.

BACKGROUND: Our aim was to examine the roles of mesenchymal stem cell (MSC) transplantation in the repair of large uterine defects. METHODS: Uterine defects were created in both uterine horns of female rats by a punch instrument, and bone marrow-derived MSCs, MSC-conditioned medium (MSC-CM) or vehicle were injected into the myometrium around the defect. The rate of uterine defect repair was monitored on day 2 and 4 after operation. Cytokine array of MSC-CM was performed, followed by neutralizing antibody experiments to clarify the exact cytokine participating in the MSC-CM-enhanced wound repair. RESULTS: Transplantation of MSCs, but not myometrial cells, significantly enhanced uterine defect repair. The transplanted MSCs were detected in the uterine horn with no signs of rejection on day 4 after transplantation, when the MSC-transplanted uterine wound was nearly healed. Moreover, uterine defect repair was also accelerated by injection of MSC-CM, indicating the paracrine effects of MSCs on uterine wound healing. Cytokine array analysis further revealed that MSC-CM contained abundant cytokines and chemokines, among which high levels of interleukin-6 (IL-6) were found. Additionally, antibodies against IL-6 were shown to block MSC-CM-enhanced uterine defect repair. CONCLUSION: This study demonstrated that transplantation of MSCs could enhance uterine defect repair by paracrine effects involving IL-6, which are findings that may be applied to facilitate uterine wound healing in the removal of huge intramural masses.

Interleukin-18 deteriorates Fabry cardiomyopathy and contributes to the development of left ventricular hypertrophy in Fabry patients with GLA IVS4+919 G>A mutation.

RATIONALE: A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry disease of the later-onset cardiac phenotype, has been reported in Taiwan. However, suitable biomarkers or potential therapeutic surrogates for Fabry cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT) remain unknown. OBJECTIVE: Using FC patients carrying IVS4+919 G>A mutation, we constructed an induced pluripotent stem cell (iPSC)-based disease model to investigate the pathogenetic biomarkers and potential therapeutic targets in ERT-treated FC. RESULTS AND METHODS: The iPSC-differentiated cardiomyocytes derived from FC-patients (FC-iPSC-CMs) carried IVS4+919 G>A mutation recapitulating FC characteristics, including low α-galactosidase A enzyme activity, cellular hypertrophy, and massive globotriaosylceramide accumulation. Microarray analysis revealed that interleukin-18 (IL-18), a pleiotropic cytokine involved in various myocardial diseases, was the most highly upregulated marker in FC-iPSC-CMs. Meanwhile, IL-18 levels were found to be significantly elevated in the culture media of FC-iPSC-CMs and patients' sera. Notably, the serum IL-18 levels were highly paralleled with the progression of left ventricular hypertrophy in Fabry patients receiving ERT. Finally, using FC-iPSC-CMs as in vitro FC model, neutralization of IL-18 with specific antibodies combined with ERT synergistically reduced the secretion of IL-18 and the progression of cardiomyocyte hypertrophy in FC-iPSC-CMs. CONCLUSION: Our data demonstrated that cardiac IL-18 and circulating IL-18 are involved in the pathogenesis of FC and LVH. IL-18 may be a novel marker for evaluating ERT efficacy, and targeting IL-18 might be a potential adjunctive therapy combined with ERT for the treatment of advanced cardiomyopathy in FC patients with IVS4+919 G>A mutation.

Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing.

Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn.

Poly(ADP-Ribose) Polymerase 1: Cellular Pluripotency, Reprogramming, and Tumorogenesis.

Poly(ADP-ribos)ylation (PARylation) is the catalytic function of the Poly(ADP-ribose) polymerases (Parps) family for post-translational modification in cellular process. Being a major member of Parps, Parp1 is a crucial nuclear factor with biological significance in modulating DNA repair, DNA replication, transcription, DNA methylation and chromatin remodeling through PARylation of downstream proteins. In addition, high expression level and activity of Parp1 are correlated with pluripotent status, reprogramming, and cancer. Furthermore, epigenetic modulation of Parp1 is explored for regulating wide variety of gene expression. Genetic and pharmaceutical disruption of Parp1 further confirmed the importance of Parp1 in cell growth, DNA repair, and reprogramming efficiency. Taken together, the proximity toward the understanding of the modulation of Parp1 including interaction and modification in different fields will provide new insight for future studies. In this review, the biological significance of Parp1 in transcription and the epigenetic modulation of Parp1 in pluripotent status, reprogramming process and cancer will be summarized.

CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming.

PARP1 and poly(ADP-ribosyl)ation (PARylation) have been shown to be essential for the initial steps of cellular reprogramming. However, the mechanism underlying PARP1/PARylation-regulated activation of pluripotency loci remains undetermined. Here, we demonstrate that CHD1L, a DNA helicase, possesses chromatin remodeling activity and interacts with PARP1/PARylation in regulating pluripotency during reprogramming. We found that this interaction is mediated through the interplay of the CHD1L macro-domain and the PAR moiety of PARylated-PARP1. Chromatin immunoprecipitation assays demonstrated the co-occupancy of CHD1L and PARP1 at Pou5f1, Nanog, and Esrrb pluripotency loci. Knockdown of CHD1L significantly blocked the binding activity of PARP1 at pluripotency loci and inhibited the efficiency of PARP1-driven reprogramming. Notably, we found that CHD1L-promoted reprogramming requires both a PARP1-interacting domain and DNA helicase activity, partly contributing to the chromatin-remodeling states of pluripotency loci. Taken together, these results identify CHD1L as a key chromatin remodeler involved in PARP1/PARylation-regulated early-stage reprogramming and pluripotency in stem cells.

The role of nitric oxide in the outgrowth of trophoblast cells on human umbilical vein endothelial cells.

OBJECTIVE: Embryo implantation is a complex process that requires coordinated trophoblast-endometrial interactions. Previous studies demonstrated that the identification of nitric oxide synthase (NOS) in trophoblast cells and the remodeling of the implantation process by nitric oxide (NO) support the important role of NO during implantation. However, the role of NO in trophoblast-endometrial interactions is unclear and is therefore examined in this study. MATERIALS AND METHODS: We cocultured BeWo trophoblast spheroids with human umbilical vein endothelial cell (HUVEC) monolayers to mimic the trophoblast-endometrial interaction. N(ω)-Nitro-l-arginine methyl ester hydrochloride (l-NAME), a competitive inhibitor of NOS, and sodium nitroprusside (SNP), an NO donor, were used to test the role of NO in the trophoblast-endometrial interaction. RESULTS: l-NAME diminished spheroid expansion on HUVEC monolayers in a concentration-dependent manner (p < 0.05). However, trophoblast spreading on HUVEC-free culture surfaces was unaffected by l-NAME treatment (p > 0.05). Significant suppression of spheroid expansion was found at the higher dose (1mM) of SNP (p < 0.05). CONCLUSION: NO may be needed in the process of implantation, and an adequate but not overly NO-containing environment might be an important factor for successful implantation. This finding is worthy of further investigation.

A longitudinal cohort study of incidence rates of inguinal hernia repair in 0- to 6-year-old children.

BACKGROUND/PURPOSE: This study provides epidemiologic data on the incidence of inguinal hernia repair in preschool children using the Taiwan National Health Insurance Research Database. We believe that the data on hernia repair in said database provide a close approximation of the true incidence of inguinal hernia in young children. METHOD: A cohort of 1,073,891 deidentified individuals was randomly selected from an insured population of 23 million. Subjects born during the period 1997-2004 were followed from birth to 6 years. The chi-square test and logistic regression modeling were used for statistical analyses. RESULT: A total of 92,308 individuals were born during the study period. Of these individuals, 3881 underwent hernia repairs. The cumulative incidence of hernia repair in children aged 0 to 6 years was 4.20%/7 years. The boy/girl ratio was 4.27:1 and the unilateral/bilateral ratio was 3.77:1. The incidence of hernia repair among boys was highest during the first year of life, but then decreased with age. In contrast, the incidence among girls remained stable during the first 6 years of life. Boys younger than 1 year had more bilateral repairs than boys in other age groups (p<0.0001) and girls had significantly more bilateral repairs than boys (p<0.0001). Subjects with a history of preterm birth also had a higher incidence of hernia repair than subjects who were born at full term (odds ratio=2.34, p<0.0001). CONCLUSION: Yearly incidence of hernia repair was obtained from a nationwide database. Some of the observations have not been reported elsewhere.

A tumor necrosis factor-α inhibitor reduces the embryotoxic effects of endometriotic peritoneal fluid.

OBJECTIVE: To determine whether a tumor necrosis factor-α (TNF-α) inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women with endometriosis. DESIGN: Experimental clinical study. SETTING: University hospital. PATIENT(S): Twelve women with chocolate cysts and 12 control women without endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We collected the PF from patients with chocolate cysts (CH-PF) and patients without endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies, development and apoptosis were evaluated in two-cell stage mouse embryos after incubation with CH-PF and N-PF, with or without a TNF-α inhibitor. RESULT(S): We found that CH-PF significantly decreased the rate of blastocyst development and increased the percentage of apoptotic cells in the embryos. Cytokine assays showed that the concentrations of several cytokines, including TNF-α, were higher in embryos incubated with CH-PF than in those incubated with N-PF. Furthermore, the treatment of embryos with TNF-α retarded development and induced apoptosis. Important, adalimumab, a TNF-α inhibitor, effectively abrogated the embryotoxicity that was induced by CH-PF. CONCLUSION(S): These data collectively highlight the crucial role of TNF-α in CH-PF-induced embryotoxicity and suggest that TNF-α inhibitors may be potential therapeutic agents for treating endometriosis-induced infertility.

Apical hypertrophic cardiomyopathy: correlations between echocardiographic parameters, angiographic left ventricular morphology, and clinical outcomes.

BACKGROUND: Echocardiographic parameters could be implicated in the development of apical asynergy (characterized by apical sequestration or apical aneurysm) and worse cardiovascular outcome in patients with apical hypertrophic cardiomyopathy (ApHCM). HYPOTHESIS: Echocardiographic parameters and morphological patterns of left ventriculograms are associated with cardiovascular morbidity and mortality in patients with ApHCM. METHODS: We followed 47 cases with echocardiographically documented ApHCM. Echocardiographic findings of the extent and degree of hypertrophy, sustained cavity obliteration, and paradoxical diastolic jet flow were measured. All patients underwent a cardiac catheterization except for the cases whose informed consent was not acquired. The clinical manifestations were assessed and recorded by the attending physicians during 35.4 ± 23.7 months follow-up. RESULTS: Among the 47 patients with ApHCM, 30 patients presented as the "pure" form and 17 patients present as the "mixed" form. Seventeen of 28 patients with sustained cavity obliteration showed paradoxical flow by echocardiography. Thirty-one underwent left ventriculograms and showed morphological abnormalities, including "ace-of-spades" configuration (15/31), apical sequestration (12/31), and apical aneurysm (4/31). The results demonstrated that cardiovascular morbidities occurred in 21 of 47 patients and were closely related to the presence of mixed form ApHCM, cavity obliteration, and paradoxical flow by univariate and multivariate Cox analysis. During the period of follow-up, 4 patients (9.5%) died, and among them 3 had concomitant apical aneurysm. CONCLUSIONS: We concluded that detection of cavity obliteration and paradoxical flow and discrimination of pure form from mixed form by echocardiography, as well apical sequestration from apical aneurysm in ApHCM patients, is warranted.

Collagen IV significantly enhances migration and transplantation of embryonic stem cells: involvement of α2ß1 integrin-mediated actin remodeling.

Embryonic stem (ES) cell transplantation represents a potential means for the treatment of degenerative diseases and injuries. As appropriate distribution of transplanted ES cells in the host tissue is critical for successful transplantation, the exploration of efficient strategies to enhance ES cell migration is warranted. In this study we investigated ES cell migration under the influence of various extracellular matrix (ECM) proteins, which have been shown to stimulate cell migration in various cell models with unclear effects on ES cells. Using two mouse ES (mES) cell lines, ESC 26GJ9012-8-2 and ES-D3 GL, to generate embryoid bodies (EBs), we examined the migration of differentiating cells from EBs that were delivered onto culture surfaces coated with or without collagen I, collagen IV, Matrigel, fibronectin, and laminin. Among these ECM proteins, collagen IV exhibited maximal migration enhancing effect. mES cells expressed α2 and ß1 integrin subunits and the migration enhancing effect of collagen IV was prevented by RGD peptides as well as antibodies against α2 and ß1 integrins, indicating that the enhancing effect of collagen IV on cell migration was mediated by α2ß1 integrin. Furthermore, staining of actin cytoskeleton that links to integrins revealed well-developed stress fibers and long filopodia in mES cells cultured on collagen IV, and the actin-disrupting cytochalasin D abolished the collagen IV-enhanced cell migration. In addition, pretreatment of undifferentiated or differentiated mES cells with collagen IV resulted in improved engraftment and growth after transplantation into the subcutaneous tissue of nude mice. Finally, collagen IV pretreatment of osteogenically differentiated mES cells increased osteogenic differentiation-like tissue and decreased undifferentiation-like tissue in the grafts grown after transplantation. Our results demonstrated that collagen IV significantly enhanced the migration of differentiating ES cells through α2ß1 integrin-mediated actin remodeling and could promote ES cell transplantation efficiency, which may be imperative to stem cell therapy.

Non-classical estrogen receptors action on human dermal fibroblasts.

OBJECTIVE: To study the possible non-genomic effect of selective estrogen receptor modulators on human dermal fibroblasts (HDF). MATERIALS AND METHODS: WS1 cells were used to test the effect of raloxifene. The mRNA expressions of estrogen receptor (ER) α and ß and G protein-coupled ER 1(GRP30) were examined by reverse transcription polymerase chain reaction. Apoptosis was identified by TUNEL assay and FACS analysis. MAPK and PI3 K/Akt pathways were determined by immunoblotting analysis. RESULTS: Neither ERα nor ERß, but GPR30 was detected in WS1 cells. Raloxifene increased apoptosis, which was blocked by pertussis toxin, an inhibitor of G protein, or by LY294002. Phosphorylated p38 MAPK and Akt were also increased after raloxifene treatment. CONCLUSION: SERMs could induce apoptosis of HDF through G protein and PI3 K/Akt signaling, which may help understand the role of SERMs on the skin.

TGF-beta1 blockade of microglial chemotaxis toward Abeta aggregates involves SMAD signaling and down-regulation of CCL5.

BACKGROUND: Overactivated microglia that cluster at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in Alzheimer's disease (AD). Therefore, attenuating microglial clustering can reduce focal neuroinflammation at neuritic plaques. Previously, we identified CCL5 and CCL2 as prominent chemokines that mediate the chemotaxis of microglia toward beta-amyloid (Abeta)aggregates. Although transforming growth factor-beta1 (TGF-beta1) has been shown to down-regulate the expression of chemokines in activated microglia, whether TGF-beta1 can reduce the chemotaxis of microglia toward neuritic plaques in AD remains unclear. METHODS: In the present study, we investigated the effects of TGF-beta1 on Abeta-induced chemotactic migration of BV-2 microglia using time-lapse recording, transwell assay, real-time PCR, ELISA, and western blotting. RESULTS: The cell tracing results suggest that the morphological characteristics and migratory patterns of BV-2 microglia resemble those of microglia in slice cultures. Using this model system, we discovered that TGF-beta1 reduces Abeta-induced BV-2 microglial clustering in a dose-dependent manner. Chemotactic migration of these microglial cells toward Abeta aggregates was significantly attenuated by TGF-beta1. However, these microglia remained actively moving without any reduction in migration speed. Pharmacological blockade of TGF-beta1 receptor I (ALK5) by SB431542 treatment reduced the inhibitory effects of TGF-beta1 on Abeta-induced BV-2 microglial clustering, while preventing TGF-beta1-mediated cellular events, including SMAD2 phosphorylation and CCL5 down-regulation. CONCLUSIONS: Our results suggest that TGF-beta1 reduces Abeta-induced microglial chemotaxis via the SMAD2 pathway. The down-regulation of CCL5 by TGF-beta1 at least partially contributes to the clustering of microglia at Abeta aggregates. The attenuating effects of SB431542 upon TGF-beta1-suppressed microglial clustering may be mediated by restoration of CCL5 to normal levels. TGF-beta1 may ameliorate microglia-mediated neuroinflammation in AD by preventing activated microglial clustering at neuritic plaques.

IL-13 downregulates PPAR-gamma/heme oxygenase-1 via ER stress-stimulated calpain activation: aggravation of activated microglia death.

Interleukin 13 (IL-13) has been shown to induce the death of activated microglia. We observed that IL-13, but not IL-4 or IL-10, significantly enhanced endoplasmic reticulum (ER) stress induction, apoptosis and death in microglia activated by lipopolysaccharide (LPS). IL-13 enhanced ER stress-regulated calpain activation and calpain-II expression in LPS-activated microglia. Calpain-II siRNA effectively reversed the IL-13 + LPS-activated caspase-12 activation. Expression of heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) was also increased in activated microglia, and this was effectively blocked by IL-13 and recombinant calpain. Both HO-1 inhibitor and PPAR-gamma antagonist augmented, but calpain inhibitor and PPAR-gamma agonists reversed, apoptosis induction in activated microglia. Transfection of PPAR-gamma siRNA effectively inhibited HO-1 protein expression in activated microglia. LPS stimulated transcriptional activation of HO-1 via an increase in PPAR-gamma DNA binding activity, which was reversed by IL-13. These results indicate that an ER stress-related calpain-down-regulated PPAR-gamma/HO-1 pathway is involved in the IL-13-enhanced activated death of microglia.

Assessing myocardial bridging and left ventricular configuration by 64-slice computed tomography in patients with apical hypertrophic cardiomyopathy presenting with chest pain.

OBJECTIVE: We aimed to assess the usefulness of multislice computed tomographic (CT) angiography to detect coronary artery disease (CAD), including myocardial bridging (MB) and left ventricular morphology (LVG), in patients with apical hypertrophic cardiomyopathy (AHCM) who presented with angina and apical asynergy. MATERIALS AND METHODS: Sixty-four-slice CT angiography was performed in 14 patients with echocardiographically diagnosed AHCM who presented with typical or atypical chest pain. Coronary angiography was performed in 7 patients because of either suspected CAD or echocardiographic apical hypokinesia. We assessed the correlations between coronary anatomy, apical thickness, and LV configuration that were determined by echocardiography, LVG, and 64-slice CT angiography. RESULTS: The multislice CT confirmed the diagnosis of AHCM in 14 patients. The LVGs were all compatible between the 64-slice CT angiography and the LVG in the 7 patients who had "ace-of-spades" configurations, apical sequestrations, and an apical aneurysm. Furthermore, 2 significant CADs and 7 MBs were detected by 64-slice CT angiography. CONCLUSIONS: Multislice CT can offer high accuracy for the noninvasive detection of apical wall thickness and left ventricular configuration in patients with AHCM. It also provides additional information about significant coronary stenosis and MB in patients with chest pain. This promising technology has a potential to complement invasive cardiac catheterization in clinical practice.

Development and implementation of a national telehealth project for long-term care: a preliminary study.

The aging population is a global phenomenon. The skyrocketing costs of healthcare and the shortage of healthcare providers will soon become a crucial issue all over the world. Taiwan's government executed the Taiwan's Telehealth Pilot Project (TTPP) from July 1, 2008 to December 31, 2008, using healthcare information technology to tackle these problems. The system has three different models, the home-care, the community-care, and the residential-care model to assist the elderly in the pursuit of better healthcare and improved quality of life. The results revealed both the home-care and community-care models facilitated timely medical responses if the enrolled patients had emergent conditions. In the home-care model, the hospital readmission rate was reduced from 8.19% to 3.17%, and the hospital visit rate was decreased from 2.95% to 2.90%. In community-care model, the medication nonadherence rate was reduced from 38.20% to 9.20%. In the residential-care model, reduced rates of readmission to the hospital, nosocomial infection and the adverse drug event were found. Telehealth enabled the aged with chronic illnesses to live independently and helped the institutionalized elderly get acute care more efficiently without increased manpower of healthcare organization.

Obstruction and sequestration: a case of apical hypertrophic cardiomyopathy concomitant with subaortic obstruction, apical sequestration, and valvular aortic stenosis.

We presented an unique case of apical hypertrophic cardiomyopathy concomitant with subaortic obstruction, apical sequestration, and valvular aortic stenosis. The echocardiographic findings were conflicting and characterized by quadruple pressure gradients within the left ventricle, which were compatible with the findings of 64-slice computed tomography imaging and cardiac catheterization.

Enlargement of Abeta aggregates through chemokine-dependent microglial clustering.

The number of microglia surrounding senile plaques is correlated with the size of plaques in Alzheimer's disease (AD). It is unclear whether more microglia are passively recruited toward larger senile plaques or, conversely, microglia recruited to senile plaques directly contribute to the growth of plaques. In this study, BV-2 microglia were used to delineate the role of microglia in the growth of plaques using time-lapse recording. Aggregated beta amyloid peptide (Abeta)-induced BV-2 microglia to form clusters. The recruitment of BV-2 microglia bearing membrane-adhered Abeta enlarged preexisting Abeta aggregates. The receptors involved in the microglial uptake of Abeta, including integrin, formyl peptide like receptor 1, and scavenger receptors, also mediated the microglial clustering. Neutralization antibodies against chemokines significantly attenuated Abeta-induced microglial clustering and the enlargement of Abeta aggregates. Our results reveal a novel role of microglia in directly increasing the size of Abeta aggregates and suggest the targeting of Abeta-mediated microglial chemotactic migration in developing therapeutic interventions for AD.

Roles of estrogen and progesterone in endometrial hemodynamics and vascular endothelial growth factor production.

BACKGROUND: The endometrium becomes receptive to the embryo after sequential actions of estrogen and progesterone. The purpose of this study was to examine the effects of estrogen and progesterone on endometrial hemodynamics and on secretion of vascular endothelial growth factor (VEGF) from endometrial epithelial cells (EEC). METHODS: Six early postmenopausal women taking sequential estrogen and progestin [days 1-11: estradiol valerate (estrogen) 2 mg daily; days 12-21: estradiol valerate 2 mg plus norethisterone acetate (progestin) 1 mg daily] were recruited. Three-dimensional power Doppler angiography (3D-PDA) was performed before hormone treatment (phase 0), on days 10-11 of hormone treatment (phase E), and on days 18-20 of hormone treatment (phase E + P). Ishikawa EEC were treated with or without 17-beta-estradiol and progesterone for 24 hours, followed by determination of VEGF concentrations in the supernatants. RESULTS: The endometrial volume was significantly increased in phase E and phase E + P as compared with that in phase 0. The vascularization index, flow index, and vascularization flow index in the subendometrial region, as measured by 3D-PDA, were significantly higher in phase E + P than in phase 0, but there were no significant differences in these indices between phase 0 and phase E. While treatment of EEC with 17-beta-estradiol had little enhancing effect on VEGF production, progesterone alone or in combination with 17-beta-estradiol significantly increased VEGF secretion from EEC. CONCLUSION: Our data suggested that progesterone could stimulate VEGF secretion from EEC and subsequently increase subendometrial vascularity and blood flow.

Epidemiology of Blastocystis hominis and other intestinal parasites among the immigrant population in northeastern Taiwan by routine physical examination for residence approval.

BACKGROUND AND PURPOSE: Blastocystis hominis has not been reported as an endemic disease in Taiwan, but high prevalence rates have been found among immigrants. Due to the increasing number of immigrants in Taiwan, B. hominis may become a public health problem in Taiwan. This study was performed to determine the prevalence of B. hominis among immigrant populations. METHODS: Stool examination data from the Immigrant Physical Examination for Residence Approval in 2006 were examined. RESULTS: Among the 932 immigrants from 4 countries, 188 individuals (20.2%) were infected with B. hominis. The prevalence was higher among immigrants from Southeast Asian countries (Indonesia, 26.4%; Vietnam, 20.6%; The Philippines, 19.3%) than among those from China (7.6%). Coinfection with intestinal parasites of fecal-oral transmission (Endolimax nana and Entamoeba hartmannii) was a risk factor for B. hominis infection (odds ratio, 16.9; 95% confidence interval, 6.84-43.55). No significant differences in prevalence for sex and age were observed. CONCLUSION: To prevent local transmission and endemic spread of B. hominis, obligatory routine health screening for immigrant populations and early eradication of the infection are important policies for this high-risk group.