Endogenous endophthalmitis caused by Pseudomonas aeruginosa in a preterm infant: a case report

Endophthalmitis is an infection of the vitreous or aqueous humor of the eye. Although it rarely occurs in the neonatal period it has been previously diagnosed in preterm infants

Amplified B Lymphocyte CD40 Signaling Drives Regulatory B10 Cell Expansion in Mice

Aberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role in disease pathogenesis. Transgenic mice expressing CD154 by their B cells (CD154(TG)) have an expanded spleen B cell pool and produce autoantibodies (autoAbs). CD22 deficient (CD22(-/-)) mice also produce autoAbs, and importantly, their B cells are hyper-proliferative following CD40 stimulation ex vivo. Combining these 2 genetic alterations in CD154(TG)CD22(-/-) mice was thereby predicted to intensify CD40 signaling and autoimmune disease due to autoreactive B cell expansion and/or activation.CD154(TG)CD22(-/-) mice were assessed for their humoral immune responses and for changes in their endogenous lymphocyte subsets. Remarkably, CD154(TG)CD22(-/-) mice were not autoimmune, but instead generated minimal IgG responses against both self and foreign antigens. This paucity in IgG isotype switching occurred despite an expanded spleen B cell pool, higher serum IgM levels, and augmented ex vivo B cell proliferation. Impaired IgG responses in CD154(TG)CD22(-/-) mice were explained by a 16-fold expansion of functional, mature IL-10-competent regulatory spleen B cells (B10 cells: 26.7×10(6)±6 in CD154(TG)CD22(-/-) mice; 1.7×10(6)±0.4 in wild type mice, p<0.01), and an 11-fold expansion of B10 cells combined with their ex vivo-matured progenitors (B10+B10pro cells: 66×10(6)±3 in CD154(TG)CD22(-/-) mice; 6.1×10(6)±2 in wild type mice, p<0.01) that represented 39% of all spleen B cells.These results demonstrate for the first time that the IL-10-producing B10 B cell subset has the capacity to suppress IgG humoral immune responses against both foreign and self antigens. Thereby, therapeutic agents that drive regulatory B10 cell expansion in vivo may inhibit pathogenic IgG autoAb production in humans

Siglecg Limits the Size of B1a B Cell Lineage by Down-Regulating NFκB Activation

BACKGROUND: B1 B cells are believed to be a unique lineage with a distinct developmental pathway, function and activation requirement. How this lineage is genetically determined remained largely obscure. METHODS AND PRINCIPAL FINDINGS: Using the Siglecg-deficient mice with a knockin of green-fluorescent protein encoding sequence, we show here that, although the Siglecg gene is broadly expressed at high levels in all stages and/or lineages of B cells tested and at lower levels in other lineages, its deletion selectively expanded the B1a B cell lineages, including the frequency of the B1 cell progenitor in the bone marrow and the number of B1a cells in the peritoneal cavity, by postnatal expansion. The expansion of B1a B cells in the peritoneal correlated with enhanced activation of NFkappaB and was ablated by an IKK inhibitor. CONCLUSION AND SIGNIFICANCE: Our data revealed a critical role for Siglec G-NFkappaB pathway in regulating B1a B cell lineage. These data lead to a novel model of B1a lineage development that explains a large array of genetic data in this field

Prevalence and Correlates of At-Risk Drinking Among Older Adults: The Project SHARE Study

At-risk drinking, excessive or potentially harmful alcohol use in combination with select comorbidities or medication use, affects about 10% of elderly adults and is associated with higher mortality. Yet, our knowledge is incomplete regarding the prevalence of different categories of at-risk drinking and their associations with patient demographics. To examine the prevalence and correlates of different categories of at-risk drinking among older adults. Cross-sectional analysis of survey data. Current drinkers ages 60 and older accessing primary care clinics around Santa Barbara, California (n = 3,308). At-risk drinkers were identified using the Comorbidity Alcohol Risk Evaluation Tool (CARET). At-risk alcohol use was categorized as alcohol use in the setting of 1) high-risk comorbidities or 2) high-risk medication use, and 3) excessive alcohol use alone. Adjusted associations of participant characteristics with at-risk drinking in each of the three at-risk categories and with at-risk drinking of any kind were estimated using logistic regression. Over one-third of our sample (34.7%) was at risk. Among at-risk individuals, 61.9% had alcohol use in the context of high-risk comorbidities, 61.0% had high-risk medication use, and 64.3% had high-risk alcohol behaviors. The adjusted odds of at-risk drinking of any kind were decreased and significant for women (odds ratio, OR = 0.41; 95% confidence interval: 0.35-0.48; p-value &lt; 0.001), adults over age 80 (OR = 0.55; CI: 0.43-0.72; p &lt; 0.001 vs. ages 60-64), Asians (OR = 0.40; CI: 0.20-0.80; p = 0.01 vs. Caucasians) and individuals with higher education levels. Similar associations were observed in all three categories of at-risk drinking. High-risk alcohol use was common among older adults in this large sample of primary care patients, and male Caucasians, those ages 60-64, and those with lower levels of education were most likely to have high-risk alcohol use of any type. Our findings could help physicians identify older patients at increased risk for problems from alcohol consumption

Group B <em>Streptococcus </em>engages an inhibitory siglec through sialic acid mimicry to blunt innate immune and inflammatory responses <em>in vivo</em>

Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-κB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection

Representing 3D Space in Working Memory: Spatial Images from Vision, Hearing, Touch, and Language

The chapter deals with a form of transient spatial representation referred to as a spatial image. Like a percept, it is externalized, scaled to the environment, and can appear in any direction about the observer. It transcends the concept of modality, as it can be based on inputs from the three spatial senses, from language, and from long-term memory. Evidence is presented that supports each of the claimed properties of the spatial image, showing that it is quite different from a visual image. Much of the evidence presented is based on spatial updating. A major concern is whether spatial images from different input modalities are functionally equivalent— that once instantiated in working memory, the spatial images from different modalities have the same functional characteristics with respect to subsequent processing, such as that involved in spatial updating. Going further, the research provides some evidence that spatial images are amodal (i.e., do not retain modality-specific features)

Psychological responses to the proximity of climate change

A frequent suggestion to increase individuals’ willingness to take action on climate change and to support relevant policies is to highlight its proximal consequences. However, previous studies that have tested this proximising approach have not revealed the expected positive effects on individual action and support for addressing climate change. We present three lines of psychological reasoning that provide compelling arguments as to why highlighting proximal impacts of climate change might not be as effective a way to increase individual mitigation and adaptation efforts as is often assumed. Our contextualisation of the proximising approach within established psychological research suggests that, depending on the particular theoretical perspective one takes to this issue, and on specific individual characteristics suggested by these perspectives, proximising can bring about the intended positive effects, can have no (visible) effect, or can even backfire. Thus, the effects of proximising are much more complex than is commonly assumed. Revealing this complexity contributes to a refined theoretical understanding of the role psychological distance plays in the context of climate change and opens up further avenues for future research and for interventions

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects