Tissue Cytokine Responses in Canine Visceral Leishmaniasis

To elucidate the local tissue cytokine response of dogs infected with Leishmania chagasi, cytokine mRNA levels were measured in bone marrow aspirates from 27 naturally infected dogs from Brazil and were compared with those from 5 uninfected control animals. Interferon-γ mRNA accumulation was enhanced in infected dogs and was positively correlated with humoral (IgG1) but not with lymphoproliferative responses to Leishmania antigen in infected dogs. Increased accumulation of mRNA for interleukin (IL)4, IL-10, and IL-18 was not observed in infected dogs, and mRNA for these cytokines did not correlate with antibody or proliferative responses. However, infected dogs with detectable IL-4 mRNA had significantly more severe symptoms. IL-13 mRNA was not detectable in either control or infected dogs. These data suggest that clinical symptoms are not due to a deficiency in interferon-γ production. However, in contrast to its role in human visceral leishmaniasis, IL-10 may not play a key immunosuppressive role in dogs

The Importance of Learning for Changing Sexual Practices in Response to the HIV/AIDS Crisis in Ghana

This study examined how adults in Ghana learned to make changes in their sexual practices in response to HIV/AIDS crisis. Findings include changes made in sexual practices and a learning process that included four components: initial awareness, catalysts for further learning, engagement in learning activities, and other influential factors

Detection of Leishmania infantum by PCR, serology and cellular immune response in a cohort study of Brazilian dogs

The sensitivity and specificity of PCR, serology (ELISA) and lymphoproliferative response to Leishmania antigen for the detection of Leishmania infantum infection were evaluated in a cohort of 126 dogs exposed to natural infection in Brazil. For PCR, Leishmania DNA from bone-marrow was amplified with both minicircle and ribosomal primers. The infection status and time of infection of each dog were estimated from longitudinal data. The sensitivity of PCR in parasite-positive samples was 98%. However, the overall sensitivity of PCR in post-infection samples, from dogs with confirmed infection, was only 68%. The sensitivity of PCR varied during the course of infection, being highest (78–88%) 0–135 days post-infection and declining to around 50% after 300 days. The sensitivity of PCR also varied between dogs, and was highest in sick dogs. The sensitivity of serology was similar in parasite-positive (84%), PCR-positive (86%) and post-infection (88%) samples. The sensitivity of serology varied during the course of infection, being lowest at the time of infection and high (93–100%) thereafter. Problems in determining the specificity of serology are discussed. The sensitivity and specificity of cellular responsiveness were low. These data suggest that PCR is most useful in detecting active or symptomatic infection, and that serology can be a more sensitive technique for the detection of all infected dogs

Environmental monitoring of Mycobacterium bovis in badger feces and badger sett soil by real-time PCR, as confirmed by immunofluorescence, immunocapture, and cultivation

Real-time PCR was used to detect and quantify Mycobacterium bovis cells in naturally infected soil and badger faeces. Immunomagnetic capture, immunofluorescence and selective culture confirmed species identification and cell viability. These techniques will prove useful for monitoring M. bovis in the environment and for elucidating transmission routes between wildlife and cattle

PHARMACOGENOMICS AND PRESCRIBING RATES IN NORTHERN IRELAND

Background: Pharmacogenomic-considerate practice represents the next phase of quality healthcare provision.However, identification of drug-gene interactions that exist among currently prescribed medicines is the first critical steptowards fully understanding prescribing behaviour and ultimate integration of pharmacogenomic-considerate practice intoNorthern Ireland.Aim: The aim of this research is to identify the most commonly prescribed medicines that are deemed to bepharmacogenomically relevant with actionable drug-gene interactions, and to determine the prescribing rates of thesemedicines in Northern Ireland across a 24 month period between January 2021 to December 2022.Method: Medicines with actionable drug-gene interactions were identified by interrogation of pharmacogenomicdatabases including Pharmacogenomics Knowledge Base and the Clinical Pharmacogenetics ImplementationConsortium. Following compilation of the actionable medicines list, quantitative retrospective analysis of Northern Irelandprescribing data from January 2021 to December 2022 was undertaken. This enabled prescribing rates of medicines inNorthern Ireland with actionable drug-gene interactions to be determined. This data was analysed using Microsoft® Excel®(Version 2309) and statistical analysis conducted using IBM SPSS® Statistics (Version 29.0.1.0).Results: Of the 38,847,653 medicinal items prescribed in Northern Ireland from January 2021 to December 2021,20.71% (n = 8,046,666) were medicines that are known to have actionable drug-gene interactions, with 1,170 differentmedicines prescribed in Northern Ireland during this period. Interrogation of pharmacogenomic databases identified 108medicines classified as having actionable drug-gene interactions. An average of 75.46% (n = 82) were medicinesprescribed in Northern Ireland from January 2021 to December 2022. Of all medicinal items prescribed in NorthernIreland during this two-year period, 20.53% (n = 8,096,189) were medicines with actionable pharmacogenomic status.Analysis showed that the largest category of medicines included Central Nervous System medicine (43.21%; n = 35). Theremaining 56.79% of actionable pharmacogenomic medicines prescribed in this period are distributed among 11 othertherapeutic areas including Obstetrics & Gynaecology, Cardiovascular disease and immunosuppression, andMusculoskeletal disorders and joint disease.Conclusion: This study highlights that medicines with actionable drug-gene interactions are being prescribed in NorthernIreland without consideration of interpatient genetic variation. One-fifth of all medicinal items prescribed in NorthernIreland had actionable drug-gene interactions, validating the necessity for pharmacogenomic services in Northern Ireland.This work supports the need for widespread pharmacogenomic analysis to become a staple of prescribingconsiderations, given such vast prescirbing practice is already in place.References/Acknowledgments: Bowel Cancer UK. (2021) Bowel cancer patients in Northern Ireland join England andWales in receiving DPYD test to screen for serious reactions to chemotherapy. London: Bowel Cancer UK. Available at:https://www.bowelcanceruk.org.uk/news-and-blogs/research-blog/bowel-cancer-patients-in-england-to-receive-test-to-screen-for-serious-reactions-to-chemotherapy/#:~:text=Testing%20people%20with%20bowel%20cancer,chose%20a%20different

Witches Ways of Knowing: The Adult Learning Process in Joining Social Groups

This study explored what motivates adults to engage in learning that leads to membership in a marginalized social group and the nature of their learning process. By interviewing a sample of Wiccans, we discovered an intense internal motivation that endures over years and an integrated, holistic learning process

A prime/boost DNA/Modified vaccinia virus Ankara vaccine expressing recombinant Leishmania DNA encoding TRYP is safe and immunogenic in outbred dogs, the reservoir of zoonotic visceral leishmaniasis

Previous studies demonstrated safety, immunogenicity and efficacy of DNA/modified vaccinia virus Ankara (MVA) prime/boost vaccines expressing tryparedoxin peroxidase (TRYP) and Leishmania homologue of the mammalian receptor for activated C kinase (LACK) against Leishmania major challenge in mice, which was consistent with results from TRYP protein/adjuvant combinations in non-human primates. This study aimed to conduct safety and immunogenicity trials of these DNA/MVA vaccines in dogs, the natural reservoir host of Leishmania infantum, followed-up for 4 months post-vaccination. In a cohort of 22 uninfected outbred dogs, blinded randomised administration of 1000 μg (high dose) or 100 μg (low dose) DNA prime (day 0) and 1 × 108 pfu MVA boost (day 28) was shown to be safe and showed no clinical side effects. High dose DNA/MVA vaccinated TRYP dogs produced statistically higher mean levels of the type-1 pro-inflammatory cytokine IFN-γ than controls in whole blood assays (WBA) stimulated with the recombinant vaccine antigen TRYP, up to the final sampling at day 126, and in the absence of challenge with Leishmania. TRYP vaccinated dogs also demonstrated significantly higher TRYP-specific total IgG and IgG2 subtype titres than in controls, and positive in vivo intradermal reactions at day 156 in the absence of natural infection, observed in 6/8 TRYP vaccinated dogs. No significant increases in IFN-γ in LACK-stimulated WBA, or in LACK-specific IgG levels, were detected in LACK vaccinated dogs compared to controls, and only 2/9 LACK vaccinated dogs demonstrated DTH responses at day 156. In all groups, IgG1 subclass responses and antigen-specific stimulation of IL-10 were similar to controls demonstrating an absence of Th2/Treg response, as expected in the absence of in vivo restimulation or natural/experimental challenge with Leishmania. These collective results indicate significant antigen-specific type-1 responses and in vivo memory phase cellular immune responses, consistent with superior potential for protective vaccine immunogenicity of DNA/MVA TRYP over LACK

Perspective Transformation Over Time: A Two-year Follow-up Study of HIV-Positive Adults

This study investigated the stability of a perspective transformation over time. The findings confirmed that perspective transformations, at least in our sample, are irreversible; we also discovered that meaning schemes continue to change

Sources of variation in developmental language disorders: evidence from eye-tracking studies of sentence production

Skilled sentence production involves distinct stages of message conceptualization (deciding what to talk about) and message formulation (deciding how to talk about it). Eye-movement paradigms provide a mechanism for observing how speakers accomplish these aspects of production in real time. These methods have recently been applied to children with autism spectrum disorder (ASD) and specific language impairment (LI) in an effort to reveal qualitative differences between groups in sentence production processes. Findings support a multiple-deficit account in which language production is influenced not only by lexical and syntactic constraints, but also by variation in attention control, inhibition and social competence. Thus, children with ASD are especially vulnerable to atypical patterns of visual inspection and verbal utterance. The potential to influence attentional focus and prime appropriate language structures are considered as a mechanism for facilitating language adaptation and learning