Induction of Central Host Signaling Kinases during Pneumococcal Infection of Human THP-1 Cells

Streptococcus pneumoniae is a widespread colonizer of the mucosal epithelia of the upper respiratory tract of human. However, pneumococci are also responsible for numerous local as well as severe systemic infections, especially in children under the age of five and the elderly. Under certain conditions, pneumococci are able to conquer the epithelial barrier, which can lead to a dissemination of the bacteria into underlying tissues and the bloodstream. Here, specialized macrophages represent an essential part of the innate immune system against bacterial intruders. Recognition of the bacteria through different receptors on the surface of macrophages leads thereby to an uptake and elimination of bacteria. Accompanied cytokine release triggers the migration of leukocytes from peripheral blood to the site of infection, where monocytes differentiate into mature macrophages. The rearrangement of the actin cytoskeleton during phagocytosis, resulting in the engulfment of bacteria, is thereby tightly regulated by receptor-mediated phosphorylation cascades of different protein kinases. The molecular cellular processes including the modulation of central protein kinases are only partially solved. In this study, the human monocytic THP-1 cell line was used as a model system to examine the activation of Fcγ and complement receptor-independent signal cascades during infection with S. pneumoniae. Pneumococci cultured either in chemically defined or complex medium showed no significant differences in pneumococcal phagocytosis by phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 cells. Double immuno-fluorescence microscopy and antibiotic protection assays demonstrated a time-dependent uptake and killing of S. pneumoniae 35A inside of macrophages. Infections of THP-1 cells in the presence of specific pharmacological inhibitors revealed a crucial role of actin polymerization and importance of the phosphoinositide 3-kinase (PI3K) and Protein kinase B (Akt) as well during bacterial uptake. The participation of essential host cell signaling kinases in pneumococcal phagocytosis was deciphered for the kinase Akt, ERK1/2, and p38 and phosphoimmunoblots showed an increased phosphorylation and thus activation upon infection with pneumococci. Taken together, this study deciphers host cell kinases in innate immune cells that are induced upon infection with pneumococci and interfere with bacterial clearance after phagocytosis

Depression and comorbid PTSD in veterans: evaluation of collaborative care programs and impact on utilization and costs

Thesis (Ph. D.)--University of Washington, 2007.Depressed patients with comorbid posttraumatic stress disorder (PTSD) are often more functionally impaired and more severely mentally ill than patients with depression alone. However, few studies have examined depression and comorbid PTSD in primary care settings. This dissertation describes three studies of depressed Veterans in primary cam clinics across the U.S. Data were drawn from two group-randomized trials of collaborative care depression treatment: a multi-site trial in nine Veterans Affairs (VA) primary care clinics, and a second trial based in the Seattle VA General Internal Medicine clinic. The first, cross-sectional study, found that PTSD screen positive (PTSD+) depressed patients had more frequent mental health, primary care depression, and outpatient visits, and a higher proportion were prescribed antidepressants than PTSD screen negative (PTSD-) patients. PTSD+ patients had correspondingly higher mental health, primary care depression, outpatient, and antidepressant costs. The second study evaluated the effectiveness and cost-effectiveness of collaborative care depression treatment compared to usual care over 9 months. Under collaborative care, a mental health team developed an individualized treatment plan for primary care providers, a social worker telephoned patients to enhance adherence, and suggested treatment modifications. In PTSD+ depressed veterans, there was a trend toward collaborative care improving depression symptoms and functioning but findings were not statistically significant. Collaborative care was associated with more depression-free days and moderately increased treatment costs. The third, pre-post comparison study, assessed whether depression care manager assessment, a crucial component of collaborative care, changed patients' knowledge and attitudes regarding mental health treatment among PTSD+ depressed veterans. The depression care manager assessment was a 45-minute phone intervention monitoring patient symptoms and problem-solving around treatment barriers. We found that this one-time assessment did not lead to greater knowledge, more positive attitudes towards depression treatment or less stigma in PTSD+ depressed veterans. As service members return from war, providers will see more patients with PTSD and depression and can expect increased outpatient and mental health services use and costs. There were some indications from these studies that collaborative care may be an effective treatment approach for depressed patients with PTSD, but more research is needed to confirm these trends

Liquids Confined in Nanopores; Novel Ice Structures - Pressure Enhancement Effects

Phenomena that occur only at very high pressures in the bulk phase are often observed to occur in the confined phase at normal pressures (the pressure of the bulk phase in equilibrium with the confined phase). Abundant experimental evidence suggests that adsorbates confined in nanoporous materials exhibit high pressures, such as high pressure crystal structures, high pressure chemical reactions, and the deformation of pore walls due to the adsorbate. Also molecular simulation studies of the pressure tensor for simple adsorbates in carbon nanopores of slit, cylindrical and spherical geometries show that for modest bulk phase pressures, the pressure normal to the wall is of the order of hundreds of MPa, and can be positive or negative depending on the pore size [1]. The ice structures experimentally observed in nanopores are typical for high pressures ice. We report X–ray diffraction studies of water and carbon tetrachloride adsorbed in nanoporous activated carbon fibres (ACFs) and CMK-3 carbon mesopores of different pore sizes. The fibres are built of turbostratic nanoparticles separated by quasi twodimensional voids, forming narrow slit-shaped pores; CMK-3 are the reverse carbon replica of silica SBA-15 porous matrices. In order to determine the structure of water within the pores and its influence on the fibres’ structure, mean interatomic and intermolecular distances have been estimated from the positions of the maxima of the normalized angular distribution functions obtained by X-ray diffraction [1]. We observe significant changes in the interlayer distance of the carbon nanoparticles; the results suggest that very high pressures arise within the pores, about a few hundred MPa, as has been observed in molecular simulations [1,2]. Such a results are confirmed by observation of high pressure forms of ice in cylindrical nanocarbons , using neutron and X–ray diffraction methods [3]. For water in multiwalled carbon nanotubes (MWCN), below the pore melting point the existence of cubic ice was observed. This kind of ice structure can be obtained during re-crystallisation from high pressure phases at low temperatures for bulk water. For CMK-3 mesopores we observe the existence of a stacking-disordered ice [4,5], Isd. This metastable ice is neither cubic nor hexagonal, and is not a simple mixture of the two, but a combination of cubic sequences intertwined with hexagonal sequences. Moreover, the stacking disorder may vary in complexity depending on the way the ice is formed and on the prevailing thermal conditions during this process. The analysis of the kind of Isd formed in CMK-3 of different pore size will be presented. These crystal forms, which occur in bulk water only at temperatures below 180 K in the case of cubic ice, and at pressures of hundreds or thousands MPa are stabilized by the confinement. References [1] M.Sliwinska-Bartkowiak, M.Drozdowski, M.Jazdzewska, Y.Long, J.Palmer, K.E.Gubbins, Phys. Chem. Chem. Phys., 14, 7145, (2012) [2] Y. Long, J.Palmer, B.Coasne, M.Sliwinska-Bartkowiak, K.E.Gubbins, Phys. Chem. Chem. Phys, 13, 17163 (2011) 17163; Y. Long at al, Microporous and Mesoporous Materials 154, 19-23 (2013). [3] M.Jazdzewska , M. Sliwinska-Bartkowiak, A.I. Beskrovnyy, S.G. Vasilovskiy, S.W. Ting, K.Y. Chan, L.L. Huang, K.E. Gubbins, Phys. Chem. Chem. Phys., 13, 9008 (2011). [4] Malkin, T. L., Murray, B. J., Salzmann, C., Molinero, V., Pickering, S. J., & Whale, T. F. Phys. Chem. Chem. Phys., 17, 60-76 (2014). [5] K. Domin, M.Sliwinska – Bartkowiak, K. Y. Chan, Hoi Yung, K.E.Gubbins, M. Jarek,, in press

Prevalence of Psychiatric Illnesses in Older Ethnic Minority Adults

OBJECTIVES: To compare lifetime and 12-month prevalence of DSM-IV psychiatric disorders among a national representative sample of older Latinos, Asians, African-Americans, and Afro-Caribbean to non-Latino Whites. DESIGN: Cross-sectional study conducted in 2001 through 2004. SETTING: Urban and rural households in the contiguous United States. PARTICIPANTS: A total of 4,245 community-dwelling residents aged 50 and older living in non-institutional settings. Data are from the NIMH Collaborative Psychiatric Epidemiology Surveys. METHODS: The World Health Organization Composite International Diagnostic Interview assessed lifetime and 12-month psychiatric disorders. Interviewers matched the cultural background and language preference of participants. Bayesian estimates compared psychiatric disorder prevalence rates among ethnic/racial groups. RESULTS: After gender adjustments, older non-Latino Whites had higher lifetime rates of any depressive disorder than African-Americans but were no different than older Latinos. Older Asians and Afro-Caribbean had significantly lower lifetime rates of any depressive, anxiety, and substance use disorders than non-Latino Whites. Immigrant Asians had higher lifetime rates of GAD than the U.S.-born Asians and immigrant Latinos had higher lifetime rates of dysthymia and GAD than U. S.-born Latinos. U.S. born Latinos had higher lifetime rates of substance abuse, especially alcohol abuse, than immigrant Latinos. There were no significant differences in the rates of 12-month psychiatric disorders between non-Latino whites and ethnic/racial minorities, except that older African-Americans had higher 12-month rates of any substance use disorder compared to non-Latino Whites. CONCLUSION: Prevalence rates vary considerably by ethnicity and race as well as by nativity for older minorities, suggesting different patterns of illness and risk

Dual use of VA and non-VA services among primary care patients with depression

Depression treatment requires close monitoring to achieve optimal, long-term control. Use of multiple sources of health care can affect coordination and continuity of treatment for depression. To assess levels of non-Veterans Health Administration (VA) use among depressed primary care patients by service type and examine patient factors associated with non-VA use. Cross-sectional comparison of dual and VA-only users among depressed primary care patients. Depression was defined as PHQ-9 >or=10. Five hundred fifty depressed patients from the baseline sample of a group-randomized trial of collaborative care for depression in ten VA primary care practices. VA and non-VA outpatient utilization for physical and emotional health problems in the prior 6 months, patient demographics, and co-morbid conditions. All measures were self-reported and obtained at the baseline interview. Overall, 46.8% of VA depressed primary care patients utilized non-VA care. Dual users were more likely to use acute care services (emergency room or inpatient), especially for physical health problems. Dual users of physical health services had more total visits, but fewer VA visits than VA-only users, while dual users of emotional health services had fewer total and VA visits. Factors associated with dual use were urban clinic location, having other insurance coverage, and dissatisfaction with physical health care in general. Almost half of depressed primary care patients used non-VA care, with most of their non-VA use for physical rather than emotional health problems. Care management strategies for depressed patients should include communication and coordination with non-VA providers

Research Article: Antidepressant use among Asians in the United States

Objectives : We examined the prevalence and predictors of past-year antidepressant use in a nationally representative sample of Asian Americans and non-Latino Whites. Methods : Analyses of 12-month antidepressant medication use were based on data from the Collaborative Psychiatric Epidemiology Surveys that surveyed Asian (Chinese, Filipino, Vietnamese, and others; N=2,284) and non-Latino White (N=6,696) household residents ages 18 years and older in the 48 contiguous United States and Hawaii. Results : Prevalence rates for 12-month antidepressant use for Asians with major depression ranged from 8.7% among Vietnamese to 17% among Chinese respondents. Compared to non-Latino Whites (32.4%), all Asians (10.9%) meeting criteria for 12-month depressive and anxiety disorders, but especially Filipinos (8.8%) were less likely to report past-year antidepressant use. Conclusions : We found disparities in past-year antidepressant use among all the examined major Asian groups meeting criteria for 12-month depressive and anxiety disorders. These disparities were not explained by mental health need or socioeconomic factors that enable access to care. Depression and Anxiety, 2010. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64896/1/20636_ftp.pd