Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds

Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds

Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice

Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Spatiotemporal overlapping of dengue, chikungunya, and malaria infections in children in Kenya

Abstract Malaria, chikungunya virus (CHIKV), and dengue virus (DENV) are endemic causes of fever among children in Kenya. The risks of infection are multifactorial and may be influenced by built and social environments. The high resolution overlapping of these diseases and factors affecting their spatial heterogeneity has not been investigated in Kenya. From 2014-2018, we prospectively followed a cohort of children from four communities in both coastal and western Kenya. Overall, 9.8% were CHIKV seropositive, 5.5% were DENV seropositive, and 39.1% were malaria positive (3521 children tested). The spatial analysis identified hot-spots for all three diseases in each site and in multiple years. The results of the model showed that the risk of exposure was linked to demographics with common factors for the three diseases including the presence of litter, crowded households, and higher wealth in these communities. These insights are of high importance to improve surveillance and targeted control of mosquito-borne diseases in Kenya

Majority of pediatric dengue virus infections in Kenya do not meet 2009 WHO criteria for dengue diagnosis.

From 1975-2009, the WHO guidelines classified symptomatic dengue virus infections as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. In 2009 the case definition was changed to a clinical classification after concern the original criteria was challenging to apply in resource-limited settings and not inclusive of a substantial proportion of severe dengue cases. Our goal was to examine how well the current WHO definition identified new dengue cases at our febrile surveillance sites in Kenya. Between 2014 and 2019 as part of a child cohort study of febrile illness in our four clinical study sites (Ukunda, Kisumu, Msambweni, Chulaimbo) we identified 369 dengue PCR positive symptomatic cases and characterized whether they met the 2009 revised WHO diagnostic criteria for dengue with and without warning signs and severe dengue. We found 62% of our PCR-confirmed dengue cases did not meet criteria per the guidelines. Our findings also correlate with our experience that dengue disease in children in Kenya is less severe as reported in other parts of the world. Although the 2009 clinical classification has recently been criticized for being overly inclusive and non-specific, our findings suggest the 2009 WHO dengue case definition may miss more than 50% of symptomatic infections in Kenya and may require further modification to include the African experience

Effects of partial or total fish meal replacement by agricultural by-product diets on gonad maturation, sex steroids and vitellogenin dynamics of African catfish (Clarias gariepinus)

The establishment of the first sexual maturation was characterized in African catfish (Clarias gariepinus) in order to study the efficiency of replacement of fish meal (FM) by diets composed of local vegetable ingredients. Four diets were formulated containing decreasing levels of FM (50-0% for diet 1 to diet 4) and increasing proportions of vegetable ingredients (50-100%). Gonadosomatic index (GSI), diameter and percentages of developmental stages of oocytes, plasma sex steroids and vitellogenin dynamics were investigated from February to June using one-year-old fish. Fish were individually tagged, and 12 individuals from each diet were investigated monthly. Replacement of FM with plant ingredients did not affect the GSI neither in males, nor in females. All males were spermiating, and no abnormal gonads were found. In females, GSI and percentages of advanced stages of oocytes decreased during the dry season, indicating seasonal changes in gonad development. Moreover, oocytes were in late exogenous vitellogenesis, but no final maturation stages were observed, whatever the diet. Higher plasma levels of E2 in females and of androgens (T and 11-KT) in both sexes were observed in fish fed diet 4 than in those receiving diet 1 depending on the season. Levels of plasma E2 and ALP (indicator for vitellogenin) in males did not differ among treatments and seasons suggesting no phytoestrogenic activity. The results showed that total replacement of FM by vegetable diets composed of groundnut oilcakes, bean and sunflower meals has no deleterious effect on the onset of sexual maturation in African catfish but, may stimulate the sex steroid production and in turns may potentially exert some positive actions on reproductive success