The role of the Secondary lymphoid organs in West Nile virus encephalitis: Immune-modifying microparticle treatment

West Nile virus (WNV) is a neuroinvasive flavivirus initiating an immunopathological response that causes lethal encephalitis. Recently, in a mouse model of intranasal WNV infection we showed intravenous immune-modifying microparticles (IMP) reduce CNS infiltration of Ly6Chi inflammatory monocytes by 50%, resulting in >60% survival in this lethal model. IMP+ inflammatory monocytes are sequestered by the spleen in the red pulp, with many IMP in marginal zone macrophages (MZM). Depletion of MZM with clodronate during WNV infection did not impair IMP efficacy. However, splenectomy abrogated the survival effect of IMP treatment. Importantly, splenectomised survivors showed long-term WNV immunity. Thus, by a yet undefined mechanism, the spleen, but not MZM, mediates the efficacy of IMP treatment in WNV encephalitis, but is not crucial for immunity, suggesting a role for secondary lymphoid organs in generating the adaptive immune response and contributing to immunopathology. Investigating leukocyte population dynamics in this model, we showed significant clonal expansion in the cervical lymph node, while the mesenteric and inguinal nodes had reduced T cell numbers. Our data suggest that T cells migrate to the cervical lymph nodes to contribute to the T cell effector populations generated in the adaptive immune response to CNS infection

Is the majority always right? Young children's normative interpretations of majority and dissenting peer behavior

The present study investigates the social-cognitive underpinnings of young children's bias to follow the majority. More specifically, we focus on the question of whether children not only copy the behavior of a majority of peers, but whether they also understand this majority behavior as a social norm that everyone needs to follow. Additionally, we investigated whether seeing a unanimous majority or a majority and dissenting peer makes a difference for children's normative understanding. Participants included 180 preschool-age children (4-to-5 years old) who engaged in a conformity paradigm, where they either saw the behavior of a unanimous majority of peers, or additionally the behavior of a single dissenting peer, or only the behavior of two individual peers behaving differently (Control). Afterward, children mostly copied the unanimous majority and protested against others, when they deviated from this majority, thus indeed interpreting the behavior of a unanimous majority as a norm that others need to follow. However, when they had seen a majority as well as a dissenter, children's protest and copying in favor of the majority dropped. Overall, our findings show that preschool children interpret the behavior of a unanimous majority as normative. However, when children additionally see a dissenter's behavior, this normative interpretation is weakened

Peritoneal tuberculosis in two young immigrants with fever of unknown origin

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Expressionscharakterisierung und Identifizierung tumorrelevanter Gene beim humanen hepatozellulären Karzinom

Das hepatozelluläre Karzinom (HCC) zählt zu den häufigsten Tumorerkrankungen weltweit. In etwa 80% der Fälle liegt der Hepatokarzinogenese eine chronische Lebererkrankung mit einer definierten Ätiologie, wie z.B. chronische Infektionen mit den Hepatitis-Viren B und C (HBV, HCV), zu Grunde. Die molekularen Mechanismen, die zur Entstehung von HCCs vor dem Hintergrund einer meist zirrhotisch veränderten Leber führen, sind nur unzureichend verstanden. Eine molekulare Subtypisierung des HCC von potentiell mechanistischer und therapeutischer Bedeutung konnte bisher nicht erzielt werden. In der vorliegenden Arbeit wurden 43 verschiedene humane HCC-Proben und drei HCC-Zelllinien im Vergleich mit gesunder, adulter Leber mit Hilfe von cDNA-Microarrays untersucht. Dreiundfünfzig Gene konnten identifiziert werden, die HCCs mit starker Differenzierung (Differenzierungsgrad G1) von solchen mit geringer Differenzierung (G3) unterscheiden, z.B. Histon-deacetylase 2 (HDAC2), Nucleolin (NCL), oder seven in absentia homologue-1 (Siah-1). Die Gruppierungs-(cluster-) analyse der Microarray-Daten der HCCs und der Zelllinien nach Genen mit den stärksten Expressionsunterschieden innerhalb der Tumoren ergab eine Unterteilung in zwei Hauptgruppen (benannt Gruppe A (65%) und Gruppe B (35%)). Die HCCs der Gruppe A waren durch die Induktion einer Reihe Interferon-regulierter Gene charakterisiert, während die Gruppe B hauptsächlich durch die Reduktion der Expression einiger apoptoserelevanter und Interferon-regulierter Gene charakterisiert war. Auf zellulärer Ebene konnte mit Hilfe von immunhistochemischen Färbungen gezeigt werden, dass die Zahl der apoptotischen Zellen und die Zahl Tumor-infiltrierender Lymphozyten in den Tumoren der Gruppe A im Vergleich zu denen der Gruppe B signifikant höher war. Die Gruppe B konnte aufgrund ihres Expressionsmusters in zwei weitere Untergruppen (bezeichnet als Subgruppe B1 (sechs von 43 Tumoren, 14%) und Subgruppe B2 (neun von 43 Tumoren, 21%)) unterteilt werden. Ein Hauptcharakteristikum der Subgruppe B1 war die hohe Überexpression von Insulin-like growth factor II (IGF-II). Alle getesteten HCC-Zelllinien exprimierten vergleichbar hohe Konzentrationen des dem fötalen Expressionsmuster von IGF-II entsprechenden Transkripts und gruppierten in der cluster-Analyse zusammen mit den Tumoren der Subgruppe B1. Die IGF-II-Überexpression schloss auch dann noch die Induktion Interferon-regulierter Gene aus, als die Untersuchungen auf Analysen der Expressionsprofile anderer Tumor-Entitäten ausgedehnt wurden. Zudem wurde die IGF-II-Expression in HCC-Zelllinien durch deren Behandlung mit Interferon  signifikant reduziert. Insgesamt zeigen die Ergebnisse der cDNA-Microarray-Analyse eine Subtypisierung des HCC auf, die mit der intratumorösen Inflammation und der Tumorzellapoptose assoziiert ist. Diese Expressionsanalyse könnte sowohl für die Entstehung als auch für die Therapie von HCC von Bedeutung sein, da die Überexpression von IGF-II bereits mit einer reduzierten Apoptose und einer erhöhten Proliferation in Verbindung gebracht wurde und einen möglichen Ansatzpunkt für einen therapeutischen Eingriff darstellt. Der zweite Schwerpunkt dieser Arbeit war die Untersuchung der Rolle von Stathmin in der Hepatokarzinogenese. Stathmin, ein zytoplasmatisches Phosphoprotein, das u.a. über die Kontrolle der Stabilität von Mikrotubuli mit dem Zellzyklus assoziiert ist, wurde in der cDNA-Microarray-Analyse in allen HCCs überexprimiert. Die Untersuchung der Transkriptmenge mit Hilfe der real-time-PCR ergab, das Stathmin in 38% der HCCs (13 von 34 Tumoren) im Vergleich zur normalen Leber um mindestens den Faktor zwei hochreguliert war. Auf Proteinebene konnte mit Hilfe von multi tissue microarrays eine hochsignifikante Korrelation der Zunahme und Häufigkeit der Expression von Stathmin mit der Entdifferenzierung der HCCs nachgewiesen werden. Eine solche Korrelation konnte ebenfalls für die Expression des Proliferationsmarkers Ki-67 sowie für p53 gezeigt werden. Die Analyse der Proteinexpression von Stathmin in einer Reihe von Zelllinien zeigte eine Verbindung zum Expressionsstatus von p53 auf. Zelllinien, die die Wildtyp-Form des p53 exprimieren, zeigten keine Expression des Stathmins. Eine deutliche Steigerung der Expression von Stathmin in Zelllinien konnte jedoch beobachtet werden, wenn das p53-Gen hingegen mutiert oder deletiert vorlag. Dies ist ein deutlicher Hinweis darauf, dass p53 die Expression von Stathmin beeinflusst. Stathmin scheint, wie bereits für andere Tumorentitäten gezeigt werde konnte, auch im HCC ein wichtiger Faktor bei der Entdifferenzierung und Proliferation zu sein. Durch seine wichtige Rolle in der Mitose stellt es eine interessante Zielstruktur für einen therapeutischen Ansatz dar

Music-inspired free play to foster scientific exploration in early childhood

Background: The importance of music and play in early childhood development is widely acknowledged. However, no recent studies have investigated the potential of music-inspired free play to foster scientific exploration.   Aim: The purpose of this qualitative case study is to explain the rationale in utilising musical skills, knowledge and experiences during free play to foster scientific exploration, applying a constructivist approach with the learner placed at the centre of the educational process, while the teacher acts as observer and facilitator.   Setting: Data were primarily collected through documents to create a concept map that informed observations of preschoolers during free play at two day-care centres in Mohadin in the North-West Province of South Africa.   Methods: An explanatory case study provided the context for this study and a document analysis informed the findings.   Results: Through data analysis, key themes were identified from the literature and observations to generate a conceptual model that illustrates the influence of music-inspired free play to foster scientific exploration by stimulating creativity and emphasising the necessity of free play in preschool settings.   Conclusion: The conclusion of this investigation was a better understanding of the capacity of young learners to apply scientific exploration, utilising a transdisciplinary approach for teaching and learning the sciences in the early years to develop a better understanding of their world through music-inspired free play

History of malaria research and its contribution to the malaria control success in Suriname: a review

Suriname has cleared malaria from its capital city and coastal areas mainly through the successful use of chloroquine and DDT (dichloro-diphenyl-trichloroethane) during the Global Malaria Eradication programme that started in 1955. Nonetheless, malaria transmission rates remained high in the interior of the country for a long time. An impressive decline in malaria cases was achieved in the past few years, from 14,403 registered cases in 2003 to 1,371 in 2009. The introduction of artemisinin-based combination therapy (ACT) in 2004 has further fuelled the decrease in the number of infections with Plasmodium falciparum. The only population group still heavily burdened with malaria is gold mining industry workers. Interestingly, an important part of malaria cases diagnosed and treated in Suriname originate from border regions. Therefore, practical initiatives of combined efforts between neighbouring countries must be scaled up in order to effectively attack these specific areas. Furthermore, it is of vital importance to keep investing into the malaria control programme and public awareness campaigns. Especially the correct use of ACT must be promoted in order to prevent the emergence of resistance. However, effective preventive measures and adequate therapeutic options are on their own not enough to control, let alone eliminate malaria. Changing personal and social behaviour of people is particularly difficult, but crucial in making the current success sustainable. With this in mind, research on successfully implemented interventions, focusing on behavioural modifications and methods of measuring their effectiveness, must be expanded

The induction, leadership and support to the newly appointed teacher via an effective mentor system in Mpumalanga schools

Text in AfrikaansDie studie poog om die doeltreffendheid van beginneronderwysers se aanpassing en ervaring van werksbevrediging in werksomstandighede te hersien. Enige organisasie kan nuwe mense aanstel maar kan nie verwag dat hierdie "aanstelling" hul beste werk lewer en doelwitte bereik voordat die persoon aangepas is in sy werk, omgewing en by sy kollegas nie (Steyn & Van Niekerk 2008:205, Steyn 2004:82, Whitaker 2001:7, Arends & Phurutse 2009:7). Beginneronderwysers moet leiding en ondersteuning ontvang om so gou as moontlik effektief by die skool in te skakel sodat hulle 'n produktiewe bydrae kan lewer ten opsigte van opvoeding en onderrig vir leerders en die onderwys in Suid-Afrika. Met hierdie navorsing wil die navorser dus ondersoek in stel om te bepaal of beginneronderwysers goed genoeg toegerus word om aan te pas en in te skakel by werksomstandighede en of hulle werksbevrediging ervaar. Die navorsingstudie is gedoen deur agt beginneronderwysers in vier laerskole in die Gert Sibande-streek van Mpumalanga te betrek. In hierdie studie maak die navorser gebruik van die kwalitatiewe navorsingsbenadering. Die kwalitatiewe navorsingsmetode is die geskikste metode om die ervarings van beginneronderwysers te beskryf. Individuele onderhoudvoering is dat data insamelingstegnieke gebruik om vas te stel wat die aard, omvang en moontlike oplossings is vir die navorsingsprobleem. Die navorsingstudie het bevind dat die beginneronderwyser begeleiding en ondersteuning benodig tydens inskakeling. Positiewe strategieë sluit in inskakelingsprogramme, handleidings asook ervare toegewysde mentors. Uit die bevindinge van die navorsing is daar ongetwyfel 'n sterk behoefte aan leiding en ondersteuning vir beginneronderwysers om effektief in te skakel by die skool. Beginneronderwysers moet bemagtig word om optimaal te kan ontwikkel, hulself te bevorder en te kan handhaaf in die onderwys in Suid-Afrika.The study aims to review the effectiveness of novice teachers' adaptation and experience of job satisfaction in working conditions. Any organisation can appoint new people but cannot expect that this "appointment" to do their best work and reach goals before the person has been adapted in his work environment and to his colleagues (Steyn & Van Niekerk 2008: 205, Steyn 2004: 82, Whitaker 2001: 7 Arends & Phurutse 2009: 7). Beginner teachers should receive guidance and support quickly and effectively as soon as possible at school so they have a productive contribution to education and training for students and education in South Africa. This research would therefore examine to determine whether novice teachers are well equipped enough to adapt and to participate in working conditions and whether they experience job satisfaction. The research study was conducted by involving eight novice teachers in four primary schools in the Gert Sibande region of Mpumalanga. In this study, the researcher used a qualitative approach. The qualitative research method is the most appropriate way to describe the experiences of novice teachers. The data collection techniques that were used included individual interviews to determine the nature, extent and possible solutions to the research problem. The research study found that the new teacher needed guidance and support during integration. Positive strategies for guidance include induction programs, manuals and experienced dedicated mentors. From the findings of the research, there is a strong need for guidance and support for beginning teachers to be involved in the school. Beginner teachers should be empowered to develop their potential, to promote themselves and to maintain in education in South Africa.Educational Leadership and ManagementM. Ed. (Education Management

Effecten van waterrecirculatie op voeropname en voerbenutting van paling

Recirculatie van water in visteeltsystemen veroorzaakt sterke en complexe veranderingen in waterkwaliteit. Visteelt in recirculatiesystemen vereist daarom grondige kennis van de behoeften die vissen aan de waterkwaliteit stellen. Voor een relatief klein aantal parameters, zoals zuurstof, pH, ammonium, nitriet en nitraat kunnen deze veranderingen goed , beschreven worden. Voor die parameters zijn bij paling redelijk goed onderbouwde grenswaarden ontwikkeld. Met behulp van dergelijke grenswaarden kunnen systemen ontworpen worden en kan met het dagelijkse management de waterkwaliteit bijgestuurd worde

Ethnic disparities in tuberculosis incidence and related factors among indigenous and other communities in ethnically diverse Suriname

Background: In Suriname, a country home to many ethnic groups, a high incidence of tuberculosis (TB) has been found among Indigenous Trio Amerindians. However, whether wider ethnic disparities in TB incidence and its associated risk factors (e.g., diabetes mellitus and HIV) exist in Suriname, is not known. We sought to investigate disparities in TB incidence and its risk factors on ethnicity in Suriname, as this could give way to targeted TB intervention programs. Methods: Anonymized patient data from 2011 to 2015 was extracted from the National TB Registry and analyzed. Differences in the five-year incidence rates of TB for the six largest ethnic groups-Creole, Hindustani, Indigenous, Javanese, Maroon, and Mixed-were assessed using a chi-square goodness-of-fit test, and TB patient differences regarding ethnicity were evaluated for selected factors using a multinomial logistic regression with Creole patients as reference. Results: 662 Patients were eligible for analyses with the following ethnic makeup: Creole (36.4%), Hindustani (15.6%), Indigenous (8.6%), Javanese (10.6%), Maroon (15.1%), and Mixed ethnicity (13.7%). Differences in five-year incidence rates for TB were significant, chi(2)(5, N = 662) = 244.42, p Conclusions: Our study has demonstrated that ethnic disparities in tuberculosis incidence exist in Suriname and that they are associated with specific, known risk factors such as HIV (especially for Creole people). For Indigenous people, risk factors may include diminished access to health care facilities and low socioeconomic status. However, direct data on these factors was unavailable. These findings call for targeted national intervention programs-with special attention given to the vulnerabilities of susceptible ethnic groups-and improved data collection