Thesis (M.Ed.)--Regis University, Denver, Colo., 2006. / Title from PDF title page (viewed on Feb. 14, 2007). Includes bibliographical references.

Type IV secretion systems have been identified in several human pathogens including Bordetella pertussis, Helicobacter pylori, and Legionella pneumophila. These systems are responsible for the translocation of virulence proteins and/or DNA, thereby playing an important role in the pathogenesis of infection and plasticity of genomes. Burkholderia cenocepacia is an important opportunistic human pathogen, particularly in persons with cystic fibrosis (CF). Respiratory tract infection by B. cenocepacia in CF patients is often associated with a decline in respiratory function, and can result in acute systemic infection. Burkholderia cenocepacia strain K56-2 is part of the epidemic and clinically problematic ET12 lineage. Two type IV secretion systems have been identified in this strain; one system is plasmid encoded (designated the Ptw type IV secretion system) whereas the other is chromosomally encoded (designated the VirB/D type IV secretion system) and shows homology to the Agrobacterium tumefaciens VirB/D4 type IV secretion system. It was determined that the plasmid encoded Ptw system is a chimeric type IV secretion system composed of VirB/D4-like elements and F-specific subunits. More recently, it was found that this system translocates a protein effector (PtwE1) that is cytotoxic to plant cells. It was also determined that the positively charged C-terminal region of PtwE1 is important for translocation via the Ptw type IV secretion system. Strains of the epidemic B. cenocepacia PHDC lineage contain only a chromosomal VirB/D4-like type IV secretion system (designated BcVirB/D); and a putative effector protein associated with this system has been identified that has C-terminal transport signal and sequences different from the effectors of the Ptw type IV secretion system. It has also been shown that a competing plasmid substrate and a plasmid fertility inhibition factor act to render B. cenocepacia of the PHDC lineage incapable of expressing a plant phenotype. Thus, three type IV secretion systems have been identified in epidemic B. cenocepacia lineages. From two of these, an effector has been identified that has cytotoxic effects on eukaryotic cells, and at least one of these type IV secretion systems is able to translocate DNA substrates.

Giacconi et al. (1962) discovered a diffuse cosmic X-ray background with rocket experiments when they searched for lunar X-ray emission. Later satellite missions found a spectral peak in the cosmic X-ray background at ~30 keV. Imaging X-ray satellites such as ROSAT (1990-1999) were able to resolve up to 80% of the background below 2 keV into single point sources, mainly active galaxies. The cosmic X-ray background is the integration of all accreting super-massive (several million solar masses) black holes in the centre of active galaxies over cosmic time. Synthesis models need further populations of X-ray absorbed active galaxy nuclei (AGN) in order to explain the cosmic X-ray background peak at ~30 keV. Current X-ray missions such as XMM-Newton and Chandra offer the possibility of studying these additional populations. This Ph.D. thesis studies the populations that dominate the X-ray sky. For this purpose the 120 ksec XMM-Newton Marano field survey, named for an earlier optical quasar survey in the southern hemisphere, is analysed. Based on the optical follow-up observations the X-ray sources are spectroscopically classified. Optical and X-ray properties of the different X-ray source populations are studied and differences are derived. The amount of absorption in the X-ray spectra of type II AGN, which are considered as a main contributor to the X-ray background at ~30 keV, is determined. In order to extend the sample size of the rare type II AGN, this study also includes objects from another survey, the XMM-Newton Serendipitous Medium Sample. In addition, the dependence of the absorption in type II AGN with redshift and X-ray luminosity is analysed. We detected 328 X-ray sources in the Marano field. 140 sources were spectroscopically classified. We found 89 type I AGN, 36 type II AGN, 6 galaxies, and 9 stars. AGN, galaxies, and stars are clearly distinguishable by their optical and X-ray properties. Type I and II AGN do not separate clearly. They have a significant overlap in all studied properties. In a few cases the X-ray properties are in contradiction to the observed optical properties for type I and type II AGN. For example we find type II AGN that show evidence for optical absorption but are not absorbed in X-rays. Based on the additional use of near infra-red imaging (K-band), we were able to identify several of the rare type II AGN. The X-ray spectra of type II AGN from the XMM-Newton Marano field survey and the XMM-Newton Serendipitous Medium Sample were analysed. Since most of the sources have only ~40 X-ray counts in the XMM-Newton PN-detector, I carefully studied the fit results of simulated X-ray spectra as a function of fit statistic and binning method. The objects revealed only moderate absorption. In particular, I do not find any Compton-thick sources (absorbed by column densities of NH > 1.5 x 10^24 cm^−2). This gives evidence that type II AGN are not the main contributor of the X-ray background around 30 keV. Although bias effects may occur, type II AGN show no noticeable trend of the amount of absorption with redshift or X-ray luminosity. / Giacconi et al. (1962) entdeckten mit Hilfe von Raketenexperimenten auf der Suche nach Röntgenstrahlung vom Mond eine scheinbar diffuse extragalaktische Röntgenhintergrundstrahlung. Spätere Satellitenmissionen detektierten ein Maximum dieser Strahlung bei ~30 keV. Abbildenden Röntgensatelliten wie ROSAT (1990-1999) gelang es, bis zu 80% des diffusen Hintergrundes unter 2 keV in einzelne Punktquellen aufzulösen, von denen die überwiegende Mehrheit aktive Galaxienkerne waren. Der Röntgenhintergrund ist somit wahrscheinlich als die Emission der Gesamtheit aller akkretierenden superschweren (mehrere Millionen Sonnenmassen) schwarzen Löcher in den Zentren von Galaxien in der kosmischen Geschichte zu verstehen. Zur Erklärung des Maximums der spektralen Energieverteilung der Röntgenhintergrundstrahlung bei ~30 keV benötigen theoretische Modelle jedoch zusätzliche Populationen von röntgenabsorbierenden aktiven Galaxienkernen (AGN). Derzeitige Röntgenmissionen wie XMM-Newton und Chandra ermöglichen die Untersuchung dieser Quellklassen. Die vorliegende Arbeit untersucht die Quellpopulationen, die den Röntgenhimmel dominieren. Dazu wird die 120 ksec XMM-Newton Beobachtung im Marano Feld, Ziel einer früheren optischen AGN-Durchmusterung am Südhimmel, ausgewertet. Die optischen und Röntgeneigenschaften der unterschiedlichen Quellpopulationen werden untersucht und Unterschiede erarbeitet. Für die röntgenabsorbierende Objektklasse der Typ II AGN, die man als möglichen Erzeuger der Röntgenstrahlung um 30 keV betrachtet, wird aus den Röntgenspektren das Ausmaß der Absorption ermittelt. Um die Anzahl dieser selten gefundenen Objekte zu erhöhen, werden in dieser Arbeit zusätzliche Objekte aus der Röntgendurchmusterung des “XMM-Newton Serendipitous Medium Sample” einbezogen. Die Abhängigkeit der Absorption von der Rotverschiebung und der Röntgenleuchtkraft wird untersucht. Von 328 Röntgenquellen im Marano Feld konnten 140 spektroskopisch klassifiziert werden. Es wurden 89 Typ I AGN, 36 Typ II AGN, 6 Galaxien und 9 Sterne gefunden. Nur basierend auf den optischen und Röntgeneigenschaften können AGN, Galaxien und Sterne unterschieden werden. Typ I und II AGN lassen sich nicht klar trennen und zeigen große Gemeinsamkeiten in den untersuchten Eigenschaften. Mit Hilfe von zusätzlichen Aufnahmen im nahen Infraroten (K-Band) konnten erfolgreich mehrere seltene Typ II AGN identifiziert werden. Die Röntgenspektren von Typ II AGN aus dem XMM-Newton Marano Feld und dem “XMM-Newton Serendipitous Medium Sample” wurden ausgewertet. Die Objekte weisen nur eine mäßige Absorption auf und scheinen somit nicht einen Hauptbestandteil des Röntgenstrahlungshintergrundes um 30 keV zu erzeugen. Obwohl Selektionseffekte nicht vollständig verstanden sind, zeigen Typ II AGN keine erkennbare Abhängigkeit der Absorption von der Rotverschiebung oder der Röntgenleuchtkraft.

Type 1 Diabetes (T1D) is a serious chronic disease that results from an autoimmune destruction of the insulin-producing beta cells. Sweden has the second highest incidence of T1D in the world, and it affects more and more children each year. Genes controlling key functions of the immune system regulation of autoimmunity has been associated to T1D. Polymorphism in the Human Leukocyte Antigen (HLA) Class II is a major risk determinant for T1D but also Cytotoxic T lymphocyte Antigen 4 (CTLA-4) polymorphism can affect predisposition. Immune responses towards Glutamic Acid Decarboxylase 65 (GAD65), Insulin, insulinoma-associated antigen 2 (IA-2) and Heat Shock protein 60 have all been implicated in T1D pathogenesis. We aimed to study the effect and role of CTLA-4 and HLA Class II in the T1D immunity. By focusing on the immune responses associated to T1D in healthy children with risk genotypes we aimed to study immunological effects of T1D risk. We found that HSP60-peptide induced a higher IFN- response in subjects with risk associated CTLA-4 +49GG allele while GAD65 induced IL-4 secretion was lower in risk subjects. Individuals with T1D neutral HLA showed higher IFN- responses to GAD65 than DR3-DQ2 and DR4-DQ8 positive children. We did also detect that T1D patients have reduced IFN- responses to GAD65 compared to healthy children. Interestingly, HLA and CTLA-4 risk genotype seem to reduce those responses to become similar to responses of T1D patients. We also found that CTLA-4 and HLA risk is associated to reduced percentages of lymphocytes expressing intracellular CTLA-4 in healthy children. In another study we recorded maintained levels of CTLA-4 and TGF- mRNA responsiveness to GAD65 in recent onset T1D patients receiving ECP treatment although clinical outcome was certainly limited. In conclusion, HLA Class II risk genes but also CTLA-4 +49A/G to some extent, influence CTLA-4 capacity and T1D protective antigen-specific responses in a manner that might explain the genes’ predisposing and pathogenic capability. / Varför har Sverige näst efter Finland världens högsta incidens av barndiabetes? Typ 1 diabetes (T1D) är vanligare i norra Europa och särskilt i de nordiska länderna. Genetisk profil, infektioner och andra miljöfaktorer påverkar en individs mottaglighet för T1D. Hittills är det dock okänt vad som till slut utlöser den process som leder till att aktiverade immunförsvarsceller ”byter sida” och förstör kroppens egna insulinproducerande celler i bukspottskörteln. Ett grundläggande problem utifrån immunförsvarets perspektiv är att kunna skilja mellan vän och fiende, dvs skilja skadliga bakterie- eller virusfragment från fragment som tillhör kroppen själv. För att lära sig vad som är vad, utbildas immunförsvarets dirigenter, T-cellerna (en sorts vita blodkroppar) i thymus-körteln. Där sorteras överreagerande celler bort och de som blir kvar skickas ut i kroppen för att hjälpa oss att hålla oss friska. En förutsättning för att cellerna ska kunna göra den här åtskillnaden är att de nedbrutna bakterie- och virusfragment i form av äggviteämnen, visas upp för andra vita blodkroppar. HLA klass II molekylen fungerar som en serveringsbricka och håller upp det som ätarceller hittat och brutit ned. Variationer i konstruktionskoden för HLA gör att risken för att utveckla T1D ökar eller minskar. Möjligen sker detta genom att de HLA-varianter som finns i 95 % av T1D patienter serverar äggviteämnen på ett sätt som immunförsvaret missförstår som farligt. Vissa virus har identiska sektioner med äggviteämnen i de insulinproducerande cellerna vilket gör att immunförsvaret skulle kunna missta betacellerna för virusinfekterade celler och attackera dem. Det har på senare år visat sig att utbildningssystemet i thymus inte fungerar perfekt, utan faktiskt släpper igenom en del överreagerande celler, som skulle kunna starta reaktioner mot kroppens egna celler. För att hindra detta utnyttjar immunförsvaret ett kontrollsystem bestående av regulatoriska signaler och T-celler (T-reg celler). Treg celler har till uppgift att hålla eventuella självreaktiva immunprocesser i schack och undervisa immunförsvaret att tolerera ofarliga äggviteämnen. Ett viktigt äggviteämne i detta kontrollsystem är CTLA-4. Det är en ytmarkör som finns i och på T-celler, och framförallt T-reg celler. CTLA-4 fungerar som en sorts tröskel, så det krävs en tillräckligt stark (=säker) hotsignal för att komma över denna tröskel så att immunförsvaret sen kan gå till attack. CTLA-4 aktivitet tros vara väldigt viktigt i de mekanismer som kan bromsa eller hejda utvecklingen av T1D. Dessa skyddande mekanismer är målet för en del av forskningen kring framtida behandlingar av T1D. Konstruktionskoden för CTLA-4 varierar något mellan olika personer. Några varianter har visat sig vara sammankopplade med ökad risk för T1D och andra sjukdomar där immunförsvaret överreagerar och angriper kroppens egna vävnader (så kallade autoimmuna sjukdomar). Tidigare studier har visat att immunförsvarets signalmolekyler, cytokiner, driver in systemet mot i huvudsak två olika profiler, Typ1 och Typ2. De här profilerna är en viktig del i den normala kampen mot virus och bakterier, men i vissa sjukdomar visas en övervikt av den ena eller den andra profilen. Typ1 är vanligare bland personer som utvecklar typ 1 diabetes, medan Typ2 verkar skydda. Både immunprofil och Treg celler går att spåra med hjälp av signaler som är karakteristiska för celltyperna. Populärt förfarande vid utredning av T1D-immunologi och genetik är att man antingen studerar signalerna inom immunförsvaret och dess inbördes förhållanden, eller att man studerar hur stor andel av individerna med en viss genvariant som utvecklar sjukdomen. Detta är förstås värdefull information, men det lämnar en kunskapslucka i relationen mellan gen och immunförsvar. Det som är unikt med vår forskning är att vi studerat just vad för effekt de genetiska förändringarna får på immunförsvaret och särskilt det immunreglerande proteinet CTLA-4. Vår hypotes är att genom att gruppera friska och sjuka individer för olika kända riskgener - och sedan studera deras immunreaktioner – så kan vi identifiera delar av den process som riskgenerna verkar genom. Vi har fokuserat vår forskning på att försöka ta reda på hur de olika varianterna i HLA och CTLA-4 påverkar immunförsvaret så att de insulinproducerande cellerna angrips. Vi har observerat att immunsvaret i individer med den sjukdomsassocierade varianten av CTLA-4 har en större övervikt mot typ 1 när det retas med ett särskilt äggviteämne som är intressant inom diabetesforskning. Vi kunde även observera att friska barn med HLA klass II risk att utveckla T1D reagerade med svagare Typ1 svar än barn med neutrala gener när deras celler retades med ett äggviteämne som verkar vara aktivt i sjukdomsmekanismen av T1D. Intressant nog verkar barn med HLA risk ha en responsprofil som liknar de barn som redan utvecklat T1D. Observationer från ett annat projekt visar tecken på att barn med både CTLA-4 och HLA risk har försämrad förmåga till att uppreglera tolerans. Cellernas depåer av äggviteämnet CTLA-4 som är en viktig aktör i den toleransprocessen, är lägre i friska barn med genetisk risk. Inom avhandlingen har vi dessutom studerat effekter på toleranssystemen efter behandling med en tidigare föreslagen terapikandidat vid T1D, fotoferes. Behandlingen som i princip gick ut på att en andel av de vita blodkropparna bestrålades med UV-ljus, hade begränsade kliniska resultat men vi kunde se att behandlingen verkade stödja toleranssystemen. Genom att studera centrala immunologiska mekanismer och gener starkt förknippade med T1D har vi kunnat observera interaktioner mellan dessa system. Om vi drar oss till minnes att 95% av individerna som utvecklar T1D har HLA risk, kan vi nära nog säga att HLA risk är nästintill en förutsättning för att senare utveckla sjukdom. Vi visar att friska barn med HLA risk har en försämrad kapacitet att motverka ett självreaktivt immunförsvar. Kan det alltså vara så att T1D föregås av en försämring av kontrollsystemen? Det är viktigt att fortsätta undersöka hur CTLA-4 och framförallt HLA påverkar immunförsvaret och vad det betyder för personer med riskvarianter av dessa gener. I framtiden kanske vår forskning leder till att vi blir bättre på att se vem som riskerar att bli sjuk och hur detta går till. Det är också av yttersta vikt att vi får en tydligare bild av hur dessa centrala toleransmekanismer verkar när vi utvärderar den möjliga effekten av det nu aktuella T1D-”vaccinet” Diamyd och andra kliniska terapiförsök.

Introduction: Diabetes type 1 is a common chronic disease in children and adolescents. The disease affect, not only the child, but also the parents in their everyday life. The specialist diabetic nurse has a huge responsibility in supporting the parents to feel confident in managing the child’s diabetes. Aims of the study: To investigate how parents of children with diabetes type 1 perceive the care given from the specialist diabetic nurse and what wishes they have concerning the care they receive. Design and methods: Searches for studies in electronic databases were conducted between January 2013 and march 2013. A literature review containing 16 studies was compiled. Both qualitative and quantitative studies were used and analyzed according to Friberg (2006). Findings: Several parents had a positive view of the diabetic care they had received from the specialist diabetic nurse. Great knowledge, expertise in diabetic care and ability to inform the family in a proficient way were considered as important by the parents. To receive knowledge regarding diabetic care the parents preferred to be given practical education from the nurse, but also appreciated to get written information. The parents would have liked to get more emotional support during the time of the diagnosis, especially in forms of counseling and encouragement. They also whished that caregivers would have been more eager to prepare them in managing the disease outside the hospital.  Conclusions: The majority of the parents had an optimistic experience of the care they had received from the specialist nurse in diabetic care. To prepare the family for a life with diabetes it’s necessary with adequate education, encouragement and emotional support from the specialist diabetic nurse.

The purpose of this study was two fold: 1) To examine possible differences in menstrual reporting between two different age groups, and 2) To examine possible differences in menstrual reporting between two dichotomized action emotion typography groups-- Type A and Type B.The population consisted of 50 women in the age group of 15 to 20 and 50 women in the age group of 30 to 40 years. Data was collected simultaneously and the interrelationships were considered statistically. The Jenkins Activity Survey appropriate for age, and three factors on the Moos Menstrual Distress Questionnaire-- pain, negative concentration, and affective changes during the premenstrual phase and menstrual phase of the cycle were the variables being studied.The design of the study was a 2 x 2 factorial design. In the multivariate sense, the main effects were tested and then univariate statistics were used to interpret significant main effects.No significant differences were found in the vectors of Type A and Type B on any of the three factors, either when premenstrual scores were totaled with menstrual scores or when those two scores were considered separately. No significant differences were found in premenstrual or menstrual pain reporting in the different age groups. No significant differences were found in premenstrual or menstrual reporting of negative concentration factors. A significant difference was found in greater affective change reporting in the older age group. This difference was found to be in premenstrual reporting, but not in menstrual reporting.1. Women in the 30 to 40 age group report significantly more premenstrual affective changes than women in the 15 to 20 age group. 2. Action emotion typography did not prove to be a predictor of differential menstrual reporting.The implications of these findings as related to feminine development were discussed and recommendations for replication and further research were presented.This dissertation contains an extensive bibliography of the most recent research related to the menstrual cycle, Type A and Type B research, stress, and stress as related to the menstrual cycle.

The purpose of this correlational study was to determine if specific personality characteristics existed between groups of psychologists who identified themselves as operating within behavioral (N = 14) or psychoanalytic (N = 13) theoretical principles.Previous studies of this nature have resulted in mixed findings regarding Personality-theory relationships. Major weaknesses in these studies were found to include the use of theoretically immature psychologist-subjects, poor deliniation of subject theoretical orientation and one-sided (i.e. continuous or categorical) treatment of Myers-Briggs type Indicator data. The present study attempted to improve on these three weaknesses in order to provide stronger evidence for theory-Personality relationships.The subjects in the present study were randomly selected from two theoretically oriented professional directories. All of the subjects held doctorates in psychology for at least two years. The settings from which the subjects were drawn varied widely while the study itself was conducted from a midwestern university of approximately 19,000 students.Subject personality variables were measured using the Myers-Briggs Type Indicator - MBTI (Form G). A Theoretical Orientation Form was developed to assess the psychological theory from which subjects operated. This form required subjects to 1) endorse theoretically-bound techniques in response to case vignettes, and 2) endorse one of two labels of theoretical orientation. Only those subjects who endorsed all the vignettes and the respective label were included in the experimental group.Four null hypotheses were posed for those subjects meeting criteria: 1) no statisticallysignificant (p. <.05) differences would be found between groups (beavioral versus psycholanalytic) on the MBTI measure of extraversion - introversion, 2) no statistically significant differences would be found between these groups on the MBTI measure of sensing-intuition, 3) no statistically different differences would be found between these two groups on the MBTI measure of thinking-feeling, and 4). no statistically different differences would be found between these two groups on the MBTI measure of judgement-perception.Continuous scores of those subjects meeting criteria were examined via desriptive and inferential statistical procedures. Beyond the more common descriptive findings (i.e., means and standard deviations) the use of multidimensional scaling allowed for appreciation of both the categorical and continuous properties of the MBTI data.The data was also subjected to a MANOVA which yielded both multivariate and univariate F tests. The multivariate F (2,27) = p. < .10 allowed for further analysis with univariate F tests. A significant difference was found on only the third test of group comparisons on the thinking feeling dimension where F (2,27) = p..025.The analysis desribed above allowed for rejection of only the third null hypothesis which questioned group differences on the thinking-feeling dimension. In this group of psychologists, behaviorists were much more likely to prefer the thinking mode of judgement while psychoanalytic psychologists showed definite preference for the feeling dimension. This finding is supported by previous research as well.A secondary finding of the present study was that the perceptive process of intuition did not prove do be as important to this sample of psychologists as previous writers would contend. Although the presence of the intuitive preference was found in the majority of the subjects, its level of importance was of an auxiliary nature to most of these individuals.

Compared to other Canadians, Aboriginal people suffer disproportionately from Type 2 diabetes and its complications. In an attempt to fill gaps in services for Aboriginal people to support better management of diabetes and to prevent further complications, the West Side Community Clinic launched a monthly outreach diabetes education program using an informal hands-on approach to learning about meal planning and other forms of diabetes management. The purpose of this qualitative study was to determine the impact that the program has had on the participants' health and well-being through the stories they shared in a group or individual interview. Out of the core group of 30 women, most of them Aboriginal, eleven participated in the group interview and five women participated in individual interviews.<p>Findings reveal that the program's impact on participants' health and well-being is embedded within the context of their lives. Diabetes is managed within multiple life realities in an individual, a familial and a community context. The women report learning management skills and sharing support among participants and staff of Diabetes Morning; and altered health status such as regulated blood glucose levels and weight loss. Opportunities for change include more programming like Diabetes Morning, more often, more information, access to low-cost diabetes-friendly foods, communication with health care practitioners, and integrating knowledge on a day-to-day basis. Domains for outcome indicators and contextual indicators are suggested for the program.

<i>Salmonella enterica</i> serovar Enteritidis (<i>S.</i> Enteritidis) is a major cause of gastrointestinal disease in humans worldwide that is mainly associated with the consumption of contaminated poultry meat and eggs. During the course of infection, <i>S.</i> Enteritidis uses two Type 3 Secretion Systems (T3SS), one of which is encoded by <i>Salmonella</i> Pathogenicity Island-1 (SPI-1). SPI-1 plays a major role in the invasion process.<p> In order to study the role of SPI-1 in the colonization of chickens, we constructed deletion mutants affecting either the complete SPI-1 region (40 kb) or <i>invG</i>, a single gene located on this pathogenicity island. The mutants were impaired in the secretion of effector proteins and were less invasive compared to the wild type strain in polarized Caco-2 cells. Similarly, when chicken cecal and small intestinal explants were co-infected with the wild type and ÄSPI-1 mutant strains we found that the ÄSPI-1 mutant strain was less invasive relative to the wild type strain. Oral challenge of 1-week-old chickens with the wild type or ÄSPI-1 strains demonstrated that there was no difference in chicken cecal colonization. However, systemic infection, measured as levels of <i>Salmonella</i> in the liver and spleen, was delayed in birds that were challenged with the ÄSPI-1 strain. This demonstrates that SPI-1 facilitates systemic infection but is not essential for invasion and systemic spread of S. Enteritidis in chickens.<p> Based on the above results, we examined the effect of sera against SPI-1 T3SS components to <i>S.</i> Enteritidis invasion. Anti-SipD serum protected Caco-2 cells against entry of wild type <i>S.</i>Enteritidis, but not against invasion of a mutant strain lacking sipD. On the other hand, sera against InvG, PrgI, SipA, SipC, SopB, SopE and SopE2 did not affect S. Enteritidis entry. To illustrate the specificity of anti-SipD mediated inhibition, SipD specific antibodies were depleted from the serum. Depleted serum restored the invasion of S. Enteritidis, demonstrating that the SipD protein may be an important target in blocking SPI-1 mediated virulence.<p> To determine if SPI-1 T3SS proteins were protective against <i>S.</i> Enteritidis oral challenge, chickens were vaccinated subcutaneously twice at 14 and 28 days of age with PrgI and SipD. The results indicate that these proteins induce strong IgG antibody responses and confer significant protection against infection of the livers in vaccinated birds. In another study, we vaccinated hens with selected SPI-1 T3SS proteins to determine if their progeny could be protected from <i>S.</i> Enteritidis oral challenge. The proteins induced strong antibody responses but did not affect the levels of the challenge strain in the ceca or internal organs of the vaccinates. Taken together, our results establish that <i>S.</i> Enteritidis SPI-1 is an important virulence factor in chickens and that the proteins associated with this T3SS may form components of a subunit vaccine used for protection against colonization by <i>S.</i> Enteritidis in poultry.

HSV-2 may have adverse consequences in HIV. I evaluated the impact of HSV-2 co-infection on (highly active antiretroviral therapy)-untreated HIV infection in a systematic review of observational studies (study 1) and a retrospective cohort (study 2). I further evaluated whether HSV reactivation rates in co-infected persons differ by use of suppressive cART (study 3). Study 1 found modest evidence that HSV-2 seropositivity may be associated with accelerated progression to opportunistic infection or clinical AIDS, but not with increased HIV viral load. Some evidence suggests that HSV-2 disease activity is associated with increased HIV viral load and decreased CD4 counts. Study 2 compared rates of CD4 count change by HSV-2 status (Focus HerpeSelect ELISA) among 218 patients with a past period of ART-untreated follow-up using mixed linear regression models. No significant difference in the rate of CD4 count change was observed in HSV-2 seropositives at +13.6 cells/mm3/year (p=0.12) in univariate analysis, and -4.5 cells/mm3/year (p=0.68) in analysis adjusted for sex, HSV-1, oral and genital HSV symptoms, immigrant status, and immigrant*time interaction. These findings support the need for carefully designed and executed studies of HSV-2 suppression as an adjunctive management strategy for HIV disease, but raise questions regarding the exact mechanism of negative synergy between these viruses and the relative importance of HSV-2 latency and replication in driving these effects. In Study 3, 44 cART-naïve and 41 treated (HIV RNA<50 copies/mL) HIV+ adults with HSV-1 and/or 2 co-infection collected oral, genital and anal swabs daily for 28 days. Negative binomial models were used to quantify the relationship between cART and HSV shedding (Roche LightCycler HSV1/2). Overall HSV shedding was low, at a median (IQR) of 3.6% (0, 14.3%) of days. No relationship was seen between cART and HSV-1 or 2 shedding in univariate (RR=1.55, 95%CI=0.83,2.87) or multivariate analysis adjusted for sex, baseline CD4, recent immigrant status, and time since HIV diagnosis (aRR=1.05, 95%CI=0.43,2.58). Null results were also observed for HSV-1 and HSV-2 considered separately. That HSV shedding persists despite cART suggests that trials of anti-HSV drugs for improving HIV outcomes may be warranted in such patients.