IPNV with high and low virulence: host immune responses and viral mutations during infection

<p>Abstract</p> <p>Background</p> <p>Infectious pancreatic necrosis virus (IPNV) is an aquatic member of the <it>Birnaviridae </it>family that causes widespread disease in salmonids. IPNV is represented by multiple strains with markedly different virulence. Comparison of isolates reveals hyper variable regions (HVR), which are presumably associated with pathogenicity. However little is known about the rates and modes of sequence divergence and molecular mechanisms that determine virulence. Also how the host response may influence IPNV virulence is poorly described.</p> <p>Methods</p> <p>In this study we compared two field isolates of IPNV (NFH-Ar and NFH-El). The sequence changes, replication and mortality were assessed following experimental challenge of Atlantic salmon. Gene expression analyses with qPCR and microarray were applied to examine the immune responses in head kidney.</p> <p>Results</p> <p>Significant differences in mortality were observed between the two isolates, and viral load in the pancreas at 13 days post infection (d p.i.) was more than 4 orders of magnitude greater for NFH-Ar in comparison with NFH-El. Sequence comparison of five viral genes from the IPNV isolates revealed different mutation rates and Ka/Ks ratios. A strong tendency towards non-synonymous mutations was found in the HRV of VP2 and in VP3. All mutations in VP5 produced precocious stop codons. Prior to the challenge, NFH-Ar and NFH-El possessed high and low virulence motifs in VP2, respectively. Nucleotide substitutions were noticed already during passage of viruses in CHSE-214 cells and their accumulation continued in the challenged fish. The sequence changes were notably directed towards low virulence. Co-ordinated activation of anti-viral genes with diverse functions (IFN-a1 and c, sensors - Rig-I, MDA-5, TLR8 and 9, signal transducers - Srk2, MyD88, effectors - Mx, galectin 9, galectin binding protein, antigen presentation - b2-microglobulin) was observed at 13 d p.i. (NFH-Ar) and 29 d p.i. (both isolates).</p> <p>Conclusions</p> <p>Mortality and expression levels of the immune genes were directly related to the rate of viral replication, which was in turn associated with sequences of viral genes. Rapid changes in the viral genome that dramatically reduced virus proliferation might indicate a higher susceptibility to protective mechanism employed by the host. Disease outbreak and mortality depend on a delicate balance between host defence, regulation of signalling cascades and virus genomic properties.</p

Are dementia services and support organisations meeting the needs of Lesbian, Gay, Bisexual and Transgender (LGBT) caregivers of LGBT people living with dementia? A scoping review of the literature

Objectives More than 60% of people with dementia live at home, where assistance is usually provided by informal caregivers. Research on the experiences of the Lesbian, Gay, Bisexual and Transgender (LGBT) caregivers is limited. This scoping review of the literature synthesizes international evidence on support provision for the population of LGBT caregivers. Methods Eight electronic databases and Google Scholar were searched using terms including ‘Dementia’, ‘LGBT’ and ‘Caregiver’ for all types of articles, including empirical studies, grey literature and sources from charity/third sector/lobbying organisations. Article selection was performed by two raters. Data were analysed through deductive thematic analysis, and three themes were established a priori: Distinct experiences of LGBT caregivers; current barriers to support; strategies to overcome the current challenges. Results Twenty articles were included. Distinct experiences of LGBT caregivers included a loss of LGBT identity, the impact of historical events, families of choice, and disclosing LGBT identities. Current barriers to support included poor representation of LGBT caregivers in support services, negative attitudes of staff and reluctance of caregivers to seek support. Strategies to overcome the current challenges included staff awareness training and kite-marking inclusion. Conclusion Limited cultural competency of staff and a subsequent reluctance to seek help have an impact on use of support services among LGBT caregivers. Implications for practice include the development of cost-effective, feasible, and acceptable inclusiveness training for services. Implications for policy include implementation in organisations of top-down agendas supporting staff to understand sexuality and non-heteronormative relationships in older age

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

&lt;p&gt;Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.&lt;/p&gt; &lt;p&gt;Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.&lt;/p&gt

Multilab Direct Replication of Flavell, Beach, and Chinsky (1966): Spontaneous Verbal Rehearsal in a Memory Task as a Function of Age

Work by Flavell, Beach, and Chinsky indicated a change in the spontaneous production of overt verbalization behaviors when comparing young children (age 5) with older children (age 10). Despite the critical role that this evidence of a change in verbalization behaviors plays in modern theories of cognitive development and working memory, there has been only one other published near replication of this work. In this Registered Replication Report, we relied on researchers from 17 labs who contributed their results to a larger and more comprehensive sample of children. We assessed memory performance and the presence or absence of verbalization behaviors of young children at different ages and determined that the original pattern of findings was largely upheld: Older children were more likely to verbalize, and their memory spans improved. We confirmed that 5- and 6-year-old children who verbalized recalled more than children who did not verbalize. However, unlike Flavell et al., substantial proportions of our 5- and 6-year-old samples overtly verbalized at least sometimes during the picture memory task. In addition, continuous increase in overt verbalization from 7 to 10 years old was not consistently evident in our samples. These robust findings should be weighed when considering theories of cognitive development, particularly theories concerning when verbal rehearsal emerges and relations between speech and memory

The views and experiences of bisexual people regarding their psychosocial support needs: a qualitative evidence synthesis

Introduction Despite consistent evidence of poor mental health among what is a relatively large population group, research examining bisexual mental health remains sparse. Aim To identify the psychosocial needs of people who are bisexual and establish factors that may support or inhibit access to appropriate psychosocial interventions and supports. Method A qualitative evidence syntheses of the empirical evidence. Results A total of 15 papers were included in the review. The PRISMA process was used. Following data analysis, four main themes emerged that were (a) experiences of being bisexual, (b) mental health experiences and concerns, (c) service access and responses and (iv) communities and supports. Discussion Bisexual people have unique and specific psychosocial support needs that relate to, but are also different from, the needs of the broader LGBTIQ+ community. This study provides valuable insights into how future policy, practice, education and training and research can better address the needs of this highly vulnerable group. Implications for Practice This study highlights the psychosocial complexities associated with bisexuality and provides evidence for the need for improvement in current support services to ensure inclusivity and culturally competent care

BVDV and BHV-1 Infections in Dairy Herds in Northern and Northeastern Thailand

Bulk milk samples from 220 dairy herds were collected at 9 public milk collection centres in the northeastern and northern Thailand, and a subset of 11 herds was selected for individual testing. The samples were tested for presence of antibodies to BVDV and BHV-1 using an indirect ELISA. The results from the bulk milk testing demonstrated a moderate level of exposure to BVDV and BHV-1 (73% and 67%, respectively). However, the low proportion of herds with high BVDV antibody-levels (13%) and the low within-herd seroprevalence of BVDV and BHV-1 in the 11 herds (24% and 5%, respectively), particularly among the young stock (15% and 0%, respectively), demonstrated a low prevalence of active BVDV infection and a low rate of reactivation of latent BHV-1. The presence of a self-clearance process was also indicated by the results from the individual testing. Moreover, a surprisingly low prevalence of BVDV and BHV-1 antibody-positive herds at one of the milk centres was found. This centre was established 5–10 years before the others. Our impression is that this reflects the self-clearance process, where consecutive replacement of imported infected animals without further spread has resulted in a nearly total elimination of the infections. Based on our experiences and on these results we are convinced that this process can continue if there is awareness of herd biosecurity. This is especially important in the context of a future intensification of the dairy production

Children’s Initiatives in the Finnish Early Childhood Education Context

Pedagogical practices in early childhood education, which embrace children’s initiatives and agency, have been found to have an effect on children’s learning and competence skills. These initiatives can be seen crucial for children’s well-being and self-motivation. However, children’s initiatives are sometimes considered only as wants and that children are incapable to express meaningful initiatives in educational settings. In this chapter, we introduce children’s initiatives in their educational settings and examine the gap between children’s experiences and teachers’ observations. Children’s initiatives exist in a myriad of ways through the daily practices and processes that nourish motivation to ultimately create meanings through actions. It is essential to focus on children’s participation as it encourages and promotes agency and motivation within early childhood development.Peer reviewe

Estimating loss of Brucella abortus antibodies from age-specific serological data in elk

Serological data are one of the primary sources of information for disease monitoring in wildlife. However, the duration of the seropositive status of exposed individuals is almost always unknown for many free-ranging host species. Directly estimating rates of antibody loss typically requires difficult longitudinal sampling of individuals following seroconversion. Instead, we propose a Bayesian statistical approach linking age and serological data to a mechanistic epidemiological model to infer brucellosis infection, the probability of antibody loss, and recovery rates of elk (Cervus canadensis) in the Greater Yellowstone Ecosystem. We found that seroprevalence declined above the age of ten, with no evidence of disease-induced mortality. The probability of antibody loss was estimated to be 0.70 per year after a five-year period of seropositivity and the basic reproduction number for brucellosis to 2.13. Our results suggest that individuals are unlikely to become re-infected because models with this mechanism were unable to reproduce a significant decline in seroprevalence in older individuals. This study highlights the possible implications of antibody loss, which could bias our estimation of critical epidemiological parameters for wildlife disease management based on serological data