OBJECTIVE To estimate whether racial/ethnic behavioral health service disparities are likely to be reduced through insurance expansion coverage expected through the Affordable Health Care Act. DATA SOURCES Pooled data from the nationally representative NIMH Collaborative Psychiatric Epidemiological Studies (2001-2003). STUDY DESIGN We employ a novel reweighting method to estimate service disparities in the presence and absence of insurance coverage. DATA COLLECTION Access to care was assessed by whether any behavioral health treatment was received in the past year. Need was determined by presence of prior year psychiatric disorder, psychiatric diagnoses, physical comorbidities, gender, and age. PRINCIPAL FINDINGS Improving patient education and availability of community clinics, combined with insurance coverage reduces service disparities across racial/ethnic groups.However, even with expanded insurance coverage, approximately 10 percent fewer African Americans with need for behavioral health services are likely to receive services compared to non-Latino whites while Latinos show no measurable disparity. CONCLUSIONS Expansion of insurance coverage might have different effects for racial/ethnic groups, requiring additional interventions to reduce disparities for all groups.

OBJECTIVE: Physical symptoms are common and a leading reason for primary care visits; however, data are lacking on their prevalence among racial/ethnic minorities in the United States. This study aimed to compare the prevalence of physical symptoms among White, Latino and Asian Americans, and examine the association of symptoms and acculturation. METHODS: We analyzed data from the National Latino and Asian American Study, a nationally representative survey of 4864 White, Latino and Asian American adults. We compared the age- and gender-adjusted prevalence of 14 physical symptoms among the racial/ethnic groups and estimated the association between indicators of acculturation (English proficiency, nativity, generational status and proportion of lifetime in the United States) and symptoms among Latino and Asian Americans. RESULTS: After adjusting for age and gender, the mean number of symptoms was similar for Whites (1.00) and Latinos (0.95) but significantly lower among Asian Americans (0.60, P<.01 versus Whites). Similar percentages of Whites (15.4%) and Latinos (13.0%) reported three or more symptoms, whereas significantly fewer Asian Americans (7.7%, P<.05 versus Whites) did. In models adjusted for sociodemographic variables and clinical status (psychological distress, medical conditions and disability), acculturation was significantly associated with physical symptoms among both Latino and Asian Americans, such that the most acculturated individuals had the most physical symptoms. CONCLUSIONS: The prevalence of physical symptoms differs across racial/ethnic groups, with Asian Americans reporting fewer symptoms than Whites. Consistent with a "healthy immigrant" effect, increased acculturation was strongly associated with greater symptom burden among both Latino and Asian Americans.

Pulmonary arterial hypertension (PAH) is a cardiovascular disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Heterozygous mutations in the type II receptor for bone morphogenetic protein (BMPR2) underlie the majority of the inherited and familial forms of PAH. The transforming growth factor β (TGFβ) pathway is activated in both human and experimental models of PAH. However, how these factors exert pro-proliferative and anti-apoptotic responses in PAH remains unclear. Using mouse primary PASMCs derived from knock-in (KI) mice, we demonstrated that BMPR-II dysfunction promotes the activation of SMAD-independent MAPK pathways via TGFβ-associated kinase 1 (TAK1), resulting in a pro-proliferative and anti-apoptotic response. Inhibition of the TAK1-MAPK axis rescues abnormal proliferation and apoptosis in these cells. In both hypoxia and monocrotaline-induced PAH rat models, which display reduced levels of bmpr2 transcripts, this study further indicates that the TGFβ-MAPK axis is activated in lungs following elevation of both expression and phosphorylation of TAK1 protein. In ex-vivo cell based assays, TAK1 inhibits BMP-responsive reporter activity and interacts with BMPR-II receptor. In the presence of pathogenic BMPR2 mutations observed in PAH patients, this interaction is greatly reduced. Taken together, these data suggest dysfunctional BMPR-II responsiveness intensifies TGFβ-TAK1-MAPK signaling and thus alters the ratio of apoptosis to proliferation. This axis may be a potential therapeutic target in PAH.

PURPOSE: There are no current psychiatric epidemiological studies examining prevalence estimates of neurasthenia across different racial and ethnic groups in the US. This study compares prevalence rates of International Classification of Diseases (ICD-10) lifetime and 12-month neurasthenia across racial/ethnic groups in the US (Asians, African Americans, Latinos, and non-Latino Whites) and by levels of acculturation. We examine comorbidity of neurasthenia with DSM-IV psychiatric disorders and the association between neurasthenia and impairment. METHODS: We used a pooled sample (N = 10, 118) from two nationally representative household surveys of adults ages 18 years and older: the National Comorbidity Survey-Replication (NCS-R) and the National Latino and Asian American Study (NLAAS). RESULTS: Among the total sample, the adjusted prevalence rates of lifetime and 12-month neurasthenia with exclusionary criteria were 2.22 and 1.19%. The adjusted prevalence rates for lifetime and 12-month neurasthenia without exclusionary criteria were 4.89 and 2.80%. There were significant racial/ethnic group differences in prevalence for both lifetime and past-year neurasthenia, with Asians reporting significantly lower prevalence of neurasthenia than their non-Latino White counterparts. Less acculturated individuals were at a decreased risk for lifetime and past-year neurasthenia. Lifetime neurasthenia was associated with increased odds of meeting lifetime criteria for any depressive, any anxiety, and any substance use disorder. Respondents with lifetime or past-year neurasthenia had significantly greater levels of impairment compared to those without neurasthenia. CONCLUSION: Neurasthenia is a prevalent condition deserving further research attention given its comorbidity with other psychiatric disorders and its association with functional impairment.

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC(50) ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21((Waf1/Cip1)), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1-4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21((Waf1/Cip1)) gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo.

A family of Mn(III)/Ni(II) heterometallic clusters,[Mn(III)(4)Ni(II)(5)(OH)(4)(hmcH)(4)(pao)(8)Cl(2)]·5DMF (1·5DMF),[Mn(III)(3)Ni(II)(6)(N(3))(2)(pao)(10)(hmcH)(2)(OH)(4)]Br·2MeOH·9H(2)O (2·2MeOH·9H(2)O),[Mn(III)Ni(II)(5)(N(3))(4)(pao)(6)(paoH)(2)(OH)(2)](ClO(4))·MeOH·3H(2)O (3·MeOH·3H(2)O), and [Mn(III)(2)Ni(II)(2)(hmcH)(2)(pao)(4)(OMe)(2)(MeOH)(2)]·2H(2)O·6MeOH (4·2H(2)O·6MeOH)[paoH = pyridine-2-aldoxime, hmcH(3)= 2, 6-Bis(hydroxymethyl)-p-cresol], has been prepared by reactions of Mn(II) salts with [Ni(paoH)(2)Cl(2)], hmcH(3), and NEt(3) in the presence or absence of NaN(3) and characterized. Complex 1 has a Mn(III)(4)Ni(II)(5) topology which can be described as two corner-sharing [Mn(2)Ni(2)O(2)] butterfly units bridged to an outer Mn atom and a Ni atom through alkoxide groups. Complex 2 has a Mn(III)(3)Ni(II)(6) topology that is similar to that of 1 but with two corner-sharing [Mn(2)Ni(2)O(2)] units of 1 replaced with [Mn(3)NiO(2)] and [MnNi(3)O(2)] units as well as the outer Mn atom of 1 substituted by a Ni atom. 1 and 2 represent the largest 3d heterometal/oxime clusters and the biggest Mn(III)Ni(II) clusters discovered to date. Complex 3 possesses a [MnNi(5)(μ-N(3))(2)(μ-OH)(2)](9+) core, whose topology is observed for the first time in a discrete molecule. Careful examination of the structures of 1-3 indicates that the Mn/Ni ratios of the complexes are likely associated with the presence of the different coligands hmcH(2-) and/or N(3)(-). Complex 4 has a Mn(III)(2)Ni(II)(2) defective double-cubane topology. Variable-temperature, solid-state dc and ac magnetization studies were carried out on complexes 1-4. Fitting of the obtained M/(Nμ(B)) vs H/T data gave S = 5, g = 1.94, and D =-0.38 cm(-1) for 1 and S = 3, g = 2.05, and D =-0.86 cm(-1) for 3. The ground state for 2 was determined from ac data, which indicated an S = 5 ground state. For 4, the pairwise exchange interactions were determined by fitting the susceptibility data vs T based on a 3-J model. Complex 1 exhibits out-of-phase ac susceptibility signals, indicating it may be a SMM.

OBJECTIVE Social anxiety disorder (SAD) is increasingly being recognized as a prevalent, unremitting, and highly comorbid disorder, yet studies focusing on this disorder among US Latinos and immigrant populations are not available. This article evaluates ethnic differences in the prevalence and comorbidity of SAD as well as the clinical and demographic characteristics associated with SAD. Cultural and contextual factors associated with risk of SAD are also examined within the Latino population more specifically. METHOD Data are analyzed from the National Latino and Asian American Study and the National Comorbidity Survey-Replication. Both studies utilized the World Health Organization-Composite International Diagnostic Interview, which estimates the prevalence of lifetime and 12-month psychiatric disorders according to DSM-IV criteria. RESULTS Latinos reported a lower lifetime and 12-month SAD prevalence and a later age at onset than US-born non-Latino whites. On the other hand, Latinos diagnosed with 12-month SAD reported higher impairment across home, work, and relationship domains than their non-Latino white counterparts. Relative to non-Latino whites, Latinos who entered the United States after the age of 21 years were less likely to have lifetime SAD comorbidity with drug abuse and dependence and more likely to report lifetime SAD comorbidity with agoraphobia. CONCLUSIONS The pattern of risk and associated characteristics of SAD varies for Latinos as compared to non-Latino whites. This is reflected by differences between these 2 groups across SAD prevalence, onset, impairment, and comorbidity. The particularly high comorbidity found with agoraphobia among Latinos who arrive in the United States as adults suggests that cultural factors and timing of immigration play a role in the manifestation and course of anxiety disorders. Interventions designed to decrease the levels of impairment associated with SAD are needed as well as efforts to target Latinos suffering from this disorder, specifically.

It has been shown that drug resistance is extremely common in hepatocellular carcinoma (HCC) and is one of the major problems in HCC chemotherapy. However, the detailed mechanisms remain largely unknown. We have previously shown that endoplasmic reticulum (ER) stress is involved in the tumorigenesis of HCC. Here, we demonstrated that the unfolded protein response (UPR) inhibits cisplatin-induced HCC cell apoptosis. In HCC cells, cisplatin treatment triggers the UPR, which subsequently inhibits cisplatin-induced apoptosis. Importantly, mild ER stress precondition suppresses the sensitivity of HCC cells to cisplatin-induced apoptosis through autophagy regulation. Furthermore, heat-shock protein 27 (Hsp27) is involved in the cytoprotective role of the UPR in cisplatin-induced apoptosis. We also demonstrated that Hsp27 inhibits cisplatin- induced HCC cell death through autophagy activation. Taken together, our results indicate that the UPR inhibits cisplatin-induced apoptosis in HCC cells, at least in part, by Hsp27-mediated autophagy activation.

The type 1 fimbriae of uropathogenic Escherichia coli (UPEC) have been described as important for the establishment of bladder infections and urinary tract infections (UTI). Urinary prostaglandin (PG) levels and cyclooxygenase (COX)-2 expression in urine particulates may increase with infectious and inflammatory processes, including UTIs. We investigated the mechanisms underlying the modulation of COX-2 expression through the invasion of type 1 fimbriated UPEC strain J96 (J96-1) in human bladder 5637 cells. Bladder 5637 cells infected with J96-1 induced increases in the expression of COX-2 and secretion of PGE(2). By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of extracellular signal-related kinase (ERK), c-Jun-NH(2)-terminal kinase (JNK) and p38 MAPK pathways is critical for J96-1-induced COX-2 expression. Luciferase reporters and chromatin immunoprecipitation assays suggest that J96-1 invasion increases NF-κB- and AP-1-DNA-binding activities in 5637 cells. Inhibition of NF-κB and AP-1 activations blocked the J96-1-induced COX-2 promoter activity and expression. The effect of J96-1 on 5637 cell signalling and COX-2 expression is mediated by Toll-like receptor (TLR)-4. In summary, our findings provide the molecular pathways underlying type 1 fimbriated J96-dependent COX-2 expression in 5637 cells, providing insight into the function of UPEC invasion in bladder epithelial cells.

Our previous studies demonstrated that eight prenylated flavanones (1-8), isolated from Taiwanese propolis, were capable of a broad spectrum of biological activities. Among them, nymphaeol A (3), nymphaeol B (4) and nymphaeol C (7), abundant in Taiwanese propolis, exhibited cytotoxicity against cancer cell lines. It therefore seemed interesting to improve their activity via a semi-synthetic strategy. In this study, 12 novel prenylated flavanones were synthesised in our laboratory and their activities were assessed for two human prostate cancer cell lines, PC-3 and DU-145, and a human hepatoma cell line, Hep-3B. Of these compounds, 10c, 11 and 12 showed more potent cytotoxicity against the PC-3 cell line than 5-Fu. Using cytometric analysis followed by double staining with annexin V-FITC and propidium iodide, it was observed that these compounds induced apoptosis as well. This suggests that prenylated flavanones 10c, 11 and 12 may have anticancer potential for further development.