Effects Of An Educational Program On Breast Health Promotion In Elderly Women

Breast cancer risk increases with age, and disease mortality has a direct correlation to the stage of detection. Mammography remains the gold standard for early detection of the disease, yet females aged 65 and over have demonstrated a lack of compliance with recommended screening frequency. The purpose of this study was to determine the effects of an educational program on the variables of perceived susceptibility to breast cancer, benefits of and barriers to mammography, and intention to obtain mammography. The variables are constructs of the Health Belief Model which served as the theoretical framework for the study. The variables were assessed through use of Champion\u27s Susceptibility, Benefits, and Barriers Scale for Mammography Screening. The quasiexperimental, pretest-posttest, one-group study was conducted in small group settings in five senior housing facilities located in the metropolitan area of a large southeastern city in the United States. The educational program intervention was offered to a convenience sample of females aged 65 years and older. The sample (N = 13) was drawn from this population and included those women with no history of breast cancer and no mammogram in the i i i past 2 years. Statistical data included demographic analysis and paired t tests. There was no statistically significant difference in the perceived susceptibility to breast cancer, benefits and barriers of mammography, or intention to obtain a mammogram after the educational program. Women who were in compliance with mammography screening guidelines had higher perceptions of the benefits of mammography than those who were not current on their mammograms. The majority of women who chose to attend the educational program were current with the mammography screening recommendations and met the goal of 60% compliance set by the Healthy People 2 00 0 initiative. Recommendations for further research include replication of this study with a larger and more diverse sample. A similar study could be conducted specifically targeting women who are not in compliance with guidelines. Qualitative research studies could be implemented to explore the reasons why those women who are in compliance with mammography screening are compliant. The role the health care provider plays in the recommendation to obtain mammography should be ascertained through additional study

2D spin-orbit-coupled frustrated magnets

The dissertation presents the complete way from the synthesis over the structural characterization to the thermodynamic properties of two compounds based on Ru, Na2RuO3 and Na3RuO4, and of two compounds based on Co, Na2BaCo(PO4)2 and Na2SrCo(PO4)2. The individual interplay of Hund’s coupling, spin-orbit coupling, and crystal field effects governs the magnetism in these compounds. In Na2RuO3 the Ru ions form a honeycomb lattice. Temperature dependent heat capacity and magnetization measurements point towards a spin-orbit entangled J=0 ground state. Excitations from the non-magnetic ground state to higher lying J levels were spectroscopically detected. In Na3RuO4 triangular features are found on two different length scales. The edge-shared RuO6 octahedra form tetramers which are composed of two triangles and the tetramers form a secondary triangular lattice. With neutron diffraction it was shown that the tetramers are antiferromagnetic units and competing exchange interactions on the secondary triangular lattice lead to an incommensurately modulated magnetic structure. The Co ions with effective spin 1/2 in Na2BaCo(PO4)2 form a direct triangular lattice. The compound was presented as quantum spin liquid candidate in the literature. However, the data shown in this work reveal a phase transition at around 150 mK and heat capacity and direction dependent magnetization data are accurately described with the nearest neighbor XXZ model. Based on the analysis of the temperature dependent synchrotron powder diffraction data the space group was revised to P-3 and structural dynamics were shown to be present. This was confirmed by NMR measurements. The compound was further compared to Na2SrCo(PO4)2 with a monoclinic symmetry and the structural differences were directly related to the differences of the thermodynamic properties.Die Doktorarbeit präsentiert den Weg von der Synthese über die strukturelle Charakterisierung zu den thermodynamischen Eigenschaften zweier Verbindungen basierend auf Ru, Na2RuO3 und Na3RuO4, und zweier Verbindungen basierend auf Co, Na2BaCo(PO4)2 und Na2SrCo(PO4)2. Das individuelle Zusammenspiel von Hundscher Kopplung, Spin-Bahn-Kopplung und Kristallfeldeffekten bestimmt den Magnetismus in diesen Verbindungen. In Na2RuO3 formen die Ru Ionen ein Honigwabengitter. Temperaturabhängige Wärmekapazitäts- und Magnetisierungsmessungen deuten einen Spin-Bahn gekoppelten J=0 Grundzustand an. Anregungen vom nicht magnetischen Grundzustand zu energetisch höher gelegenen J Niveaus wurden spektroskopisch nachgewiesen. In Na3RuO4 ist das Motiv des Dreiecks auf zwei Längenskalen zu finden. Die über die Kanten verknüpften RuO6 Oktaeder formen Tetramere, die aus zwei Dreiecken zusammengesetzt sind. Die Tetramere bilden ein sekundäres Dreiecksgitter. Mit Hilfe von Neutronendiffraktometrie wurde gezeigt, dass die Tetramere antiferromagnetische Einheiten sind und dass konkurrierende Wechselwirkungen auf dem sekundären Dreiecksgitter zu einer inkommensurablen magnetischen Struktur führen. In Na2BaCo(PO4)2 formen die Co Ionen mit effektivem Spin 1/2 ein direktes Dreiecksgitter. Die Verbindung wurde als Quantenspinflüssigkeit in der Literatur vorgestellt. Allerdings zeigen die Daten, die in dieser Arbeit präsentiert werden, einen Phasenübergang bei einer Temperatur von circa 150 mK. Die Daten aus Wärmekapazitäts- und richtungsabhängigen Magnetisierungsmessungen können mit dem XXZ Model für nächste Nachbarn beschrieben werden. Die Analyse der Daten aus Pulver-Synchrotron Messungen ergab, dass die Raumgruppe zu P-3 revidiert werden muss und es wurde gezeigt, dass strukturelle Dynamiken vorliegen. Dies wurde durch NMR Messungen bestätigt. Die Verbindung wurde außerdem mit Na2SrCo(PO4)2 verglichen. Na2SrCo(PO4)2 hat eine monokline Symmetrie und die strukturellen Unterschiede wurden direkt mit den Unterschieden der thermodynamischen Eigenschaften in Verbindung gebracht

Cannabis use in early adolescence: evidence of amygdala hypersensitivity to signals of threat

Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70) of 14-year olds with a history of cannabis use to a group (n = 70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood

Urinary renin in patients and mice with diabetic kidney disease

In patients with diabetic kidney disease (DKD), plasma renin activity is usually decreased, but there is limited information on urinary renin and its origin. Urinary renin was evaluated in samples from patients with longstanding type I diabetes mellitus and mice with streptozotocin-induced diabetes mellitus. Renin-reporter mouse model (Ren1d-Cre;mT/ mG) was made diabetic with streptozotocin to examine whether the distribution of cells of the renin lineage was altered in a chronic diabetic environment. Active renin was increased in urine samples from patients with DKD (n=36), compared with those without DKD (n=38; 3.2 versus 1.3 pg/mg creatinine; P<0.001). In mice with streptozotocin-induced diabetes mellitus, urine renin was also increased compared with nondiabetic controls. By immunohistochemistry, in mice with streptozotocin-induced diabetes mellitus, juxtaglomerular apparatus and proximal tubular renin staining were reduced, whereas collecting tubule staining, by contrast, was increased. To examine the role of filtration and tubular reabsorption on urinary renin, mice were either infused with either mouse or human recombinant renin and lysine (a blocker of proximal tubular protein reabsorption). Infusion of either form of renin together with lysine markedly increased urinary renin such that it was no longer different between nondiabetic and diabetic mice. Megalin mRNA was reduced in the kidney cortex of streptozotocin-treated mice (0.70±0.09 versus 1.01±0.04 in controls, P=0.01) consistent with impaired tubular reabsorption. In Ren1d-Cre;mT/mG with streptozotocin-induced diabetes mellitus, the distribution of renin lineage cells within the kidney was similar to nondiabetic renin-reporter mice. No evidence for migration of cells of renin linage to the collecting duct in diabetic mice could be found. Renin mRNA in microdissected collecting ducts from streptozotocin-treated mice, moreover, was not significantly different than in controls, whereas in kidney cortex, largely reflecting juxtaglomerular apparatus renin, it was significantly reduced. In conclusion, in urine from patients with type 1 diabetes mellitus and DKD and from mice with streptozotocin-induced diabetes mellitus, renin is elevated. This cannot be attributed to production from cells of the renin lineage migrating to the collecting duct in a chronic hyperglycemic environment. Rather, the elevated levels of urinary renin found in DKD are best attributed to altered glomerular filteration and impaired proximal tubular reabsorption.Fil: Tang, Jeannette. Northwestern University; Estados UnidosFil: Wysocki, Jan. Northwestern University; Estados UnidosFil: Ye, Minghao. Northwestern University; Estados UnidosFil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Rein, Johannes. Northwestern University; Estados UnidosFil: Shirazi, Mina. Northwestern University; Estados UnidosFil: Bader, Michael. Charité Universitätsmedizin; AlemaniaFil: Gomez, Roberto Ariel. University of Virginia; Estados UnidosFil: Sequeira Lopez, Maria Luisa S.. University of Virginia; Estados UnidosFil: Afkarian, Maryam. University of California at Davis; Estados UnidosFil: Batlle, Daniel. Northwestern University; Estados Unido

The 1.2 A resolution crystal structure of TcpG, the Vibrio cholerae DsbA disulfide-forming protein required for pilus and cholera-toxin production

The enzyme TcpG is a periplasmic protein produced by the Gram-negative pathogen Vibrio cholerae. TcpG is essential for the production of ToxR-regulated proteins, including virulence-factor pilus proteins and cholera toxin, and is therefore a target for the development of a new class of anti-virulence drugs. Here, the 1.2 Å resolution crystal structure of TcpG is reported using a cryocooled crystal. This structure is compared with a previous crystal structure determined at 2.1 Å resolution from data measured at room temperature. The new crystal structure is the first DsbA crystal structure to be solved at a sufficiently high resolution to allow the inclusion of refined H atoms in the model. The redox properties of TcpG are also reported, allowing comparison of its oxidoreductase activity with those of other DSB proteins. One of the defining features of the Escherichia coli DsbA enzyme is its destabilizing disulfide, and this is also present in TcpG. The data presented here provide new insights into the structure and redox properties of this enzyme, showing that the binding mode identified between E. coli DsbB and DsbA is likely to be conserved in TcpG and that the [beta]5-[alpha]7 loop near the proposed DsbB binding site is flexible, and suggesting that the tense oxidized conformation of TcpG may be the consequence of a short contact at the active site that is induced by disulfide formation and is relieved by reduction

Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis

Cytoplasmic dynein functions at several sites during mitosis; however, the basis of targeting to each site remains unclear. Tandem mass spectrometry analysis of mitotic dynein revealed a phosphorylation site in the dynein intermediate chains (ICs) that mediates binding to kinetochores. IC phosphorylation directs binding to zw10 rather than dynactin, and this interaction is needed for kinetochore dynein localization. Phosphodynein associates with kinetochores from nuclear envelope breakdown to metaphase, but bioriented microtubule (MT) attachment and chromosome alignment induce IC dephosphorylation. IC dephosphorylation stimulates binding to dynactin and poleward streaming. MT depolymerization, release of kinetochore tension, and a PP1-γ mutant each inhibited IC dephosphorylation, leading to the retention of phosphodynein at kinetochores and reduced poleward streaming. The depletion of kinetochore dynactin by moderate levels of p50(dynamitin) expression disrupted the ability of dynein to remove checkpoint proteins by streaming at metaphase but not other aspects of kinetochore dynein activity. Together, these results suggest a new model for localization of kinetochore dynein and the contribution of kinetochore dynactin

HIV-1 Tat protein inhibits neurosecretion by binding to phosphatidylinositol 4,5-bisphosphate.

HIV-1 transcriptional activator (Tat) enables viral transcription and is also actively released by infected cells. Extracellular Tat can enter uninfected cells and affect some cellular functions. Here, we examine the effects of Tat protein on the secretory activity of neuroendocrine cells. When added to the culture medium of chromaffin and PC12 cells, Tat was actively internalized and strongly impaired exocytosis as measured by carbon fiber amperometry and growth hormone release assay. Expression of Tat mutants that do not bind to phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] did not affect secretion, and overexpression of phosphatidylinositol 4-phosphate 5-kinase (PIP5K), the major PtdIns(4,5)P2 synthesizing enzyme, significantly rescued the Tat-induced inhibition of neurosecretion. This suggests that the inhibition of exocytosis may be the consequence of PtdIns(4,5)P2 sequestration. Accordingly, expression of Tat in PC12 cells interfered with the secretagogue-dependent recruitment of annexin A2 to the plasma membrane, a PtdIns(4,5)P2-binding protein that promotes the formation of lipid microdomains that are required for exocytosis. In addition Tat significantly prevented the reorganization of the actin cytoskeleton necessary for the movement of secretory vesicles towards plasma membrane fusion sites. Thus, the capacity of extracellular Tat to enter neuroendocrine cells and sequester plasma membrane PtdIns(4,5)P2 perturbs several PtdIns(4,5)P2-dependent players of the exocytotic machinery, thereby affecting neurosecretion. We propose that Tat-induced inhibition of exocytosis is involved in the neuronal disorders associated with HIV-1 infection.journal articleresearch support, non-u.s. gov't2013 Jan 152012 11 23importe

Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary infection in rabbits

Background: Pulmonary infection of humans by Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), results in active disease in 5-10% of individuals, while asymptomatic latent Mtb infection (LTBI) is established in the remainder. The host immune responses that determine this differential outcome following Mtb infection are not fully understood. Using a rabbit model of pulmonary TB, we have shown that infection with the Mtb clinical isolate HN878 (a hyper-virulent W-Beijing lineage strain) leads to progressive cavitary disease similar to what is seen in humans with active TB. In contrast, infection with Mtb CDC1551 (a hyper-immunogenic clinical isolate) is efficiently controlled in rabbit lungs, with establishment of LTBI, which can be reactivated upon treatment with immune-suppressive drugs. We hypothesize that the initial interaction of Mtb with the cells of the host response in the lungs determine later outcome of infection. Results: To test this hypothesis, we used our rabbit model of pulmonary TB and infected the animals with Mtb HN878 or CDC1551. At 3 hours, with similar lung bacillary loads, HN878 infection caused greater accumulation of mononuclear and polymorphonuclear leukocytes (PMN) in the lungs, compared to animals infected with CDC1551. Using whole-genome microarray gene expression analysis, we delineated the early transcriptional changes in the lungs of HN878- or CDC1551-infected rabbits at this time and compared them to the differential response at 4 weeks of Mtb-infection. Our gene network and pathway analysis showed that the most significantly differentially expressed genes involved in the host response to HN878, compared to CDC1551, at 3 hours of infection, were components of the inflammatory response and STAT1 activation, recruitment and activation of macrophages, PMN, and fMLP (N-formyl-Methionyl-Leucyl-Phenylalanine)-stimulation. At 4 weeks, the CDC1551 bacillary load was significantly lower and the granulomatous response reduced compared to HN878 infection. Moreover, although inflammation was dampened in both Mtb infections at 4 weeks, the majority of the differentially expressed gene networks were similar to those seen at 3 hours. Conclusions: We propose that differential regulation of the inflammation-associated innate immune response and related gene expression changes seen at 3 hours determine the long term outcome of Mtb infection in rabbit lungs

Kex2 protease converts the endoplasmic reticulum α1,2-mannosidase of Candida albicans into a soluble cytosolic form

Cytosolic α-mannosidases are glycosyl hydrolases that participate in the catabolism of cytosolic free N-oligosaccharides. Two soluble α-mannosidases (E-I and E-II) belonging to glycosyl hydrolases family 47 have been described in Candida albicans. We demonstrate that addition of pepstatin A during the preparation of cell homogenates enriched α-mannosidase E-I at the expense of E-II, indicating that the latter is generated by proteolysis during cell disruption. E-I corresponded to a polypeptide of 52 kDa that was associated with mannosidase activity and was recognized by an anti-α1,2-mannosidase antibody. The N-mannan core trimming properties of the purified enzyme E-I were consistent with its classification as a family 47 α1,2-mannosidase. Differential density-gradient centrifugation of homogenates revealed that α1,2-mannosidase E-I was localized to the cytosolic fraction and Golgi-derived vesicles, and that a 65 kDa membrane-bound α1,2-mannosidase was present in endoplasmic reticulum and Golgi-derived vesicles. Distribution of α-mannosidase activity in a kex2Δ null mutant or in wild-type protoplasts treated with monensin demonstrated that the membrane-bound α1,2-mannosidase is processed by Kex2 protease into E-I, recognizing an atypical cleavage site of the precursor. Analysis of cytosolic free N-oligosaccharides revealed that cytosolic α1,2-mannosidase E-I trims free Man8GlcNAc2 isomer B into Man7GlcNAc2 isomer B. This is believed to be the first report demonstrating the presence of soluble α1,2-mannosidase from the glycosyl hydrolases family 47 in a cytosolic compartment of the cell

Comparison of TNFα to Lipopolysaccharide as an Inflammagen to Characterize the Idiosyncratic Hepatotoxicity Potential of Drugs: Trovafloxacin as an Example

Idiosyncratic drug reactions (IDRs) are poorly understood, unpredictable, and not detected in preclinical studies. Although the cause of these reactions is likely multi-factorial, one hypothesis is that an underlying inflammatory state lowers the tolerance to a xenobiotic. Previously used in an inflammation IDR model, bacterial lipopolysaccharide (LPS) is heterogeneous in nature, making development of standardized testing protocols difficult. Here, the use of rat tumor necrosis factor-α (TNFα) to replace LPS as an inflammatory stimulus was investigated. Sprague-Dawley rats were treated with separate preparations of LPS or TNFα, and hepatic transcriptomic effects were compared. TNFα showed enhanced consistency at the transcriptomic level compared to LPS. TNFα and LPS regulated similar biochemical pathways, although LPS was associated with more robust inflammatory signaling than TNFα. Rats were then codosed with TNFα and trovafloxacin (TVX), an IDR-associated drug, and evaluated by liver histopathology, clinical chemistry, and gene expression analysis. TNFα/TVX induced unique gene expression changes that clustered separately from TNFα/levofloxacin, a drug not associated with IDRs. TNFα/TVX cotreatment led to autoinduction of TNFα resulting in potentiation of underlying gene expression stress signals. Comparison of TNFα/TVX and LPS/TVX gene expression profiles revealed similarities in the regulation of biochemical pathways. In conclusion, TNFα could be used in lieu of LPS as an inflammatory stimulus in this model of IDRs