Viral and mycoplasmal pneumonias

Many different agents are known to cause nonbacterial pneumonias, but the clinical findings may not vary. An understanding of the epidemiology and pathogenesis of these infections—as well as the possible etiologic agents—is important in diagnosis, prevention, and treatment. Although treatment is now mainly symptomatic, new antiviral agents will soon be available for specific therapy.     

Chemical screening identifies filastatin,a small molecule inhibitor of Candida albicans adhesion,morphogenesis, and pathogenesis

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.     

A proposed framework for addressing supervisee-supervisor value conflict

Value conflicts between supervisees and supervisors can adversely affect supervisee development, service provision, and the supervision relationship. However, the role of value conflicts in supervision has been minimally considered. Building on the Farnsworth and Callahan (2013) model for addressing client-clinician value conflict, we propose a supervision-specific framework to help supervisors and supervisees navigate value conflicts that emerge during supervision. The proposed framework consists of three steps: (a) detection of value conflict in supervision; (b) identification and articulation of value conflicts; and (c) determination of appropriate recommendations for supervisees. Neither punitive nor corrective in purpose, the model is eminently exploratory and educational in nature.     

Macrophages,fat, and the emergence of immunometabolism

Over the last century, our modern concepts and understanding of metabolism and immunology have evolved largely in parallel. Notably, during the last decade, there has been a sharpened focus on the convergence of metabolism and immune function. In part motivated by studies originally published in the JCI, we now recognize that the immune system monitors the metabolic state of tissues and organisms and responds in kind by modulating metabolic function. The complexity of these interactions, both adaptive and pathologic, continues to be studied and revealed, with the hope that harnessing the reins that control immune function may one day be used for metabolic benefit.     

Long-Term Occupational Exposure to DDT

The hepatic effects of long-term occupational exposure to high levels of DDT were investigated. Workers exposed to equivalent oral intakes of 3.6 to 18 mg daily for periods averaging 21 years were studied. Based on the findings of extensive medical inquiries, liver function tests, and DDT serum levels, no evidence of hepatic disease or liver function abnormalities was detected.     

Role of C825T Polymorphism of GNβ3 Gene in Preeclampsia

Objective: The main objective of the study was to understand the role of C825T polymorphism that generates a splice variant in the β3 subunit of heterotrimeric G-protein in preeclampsia. Results: We analyzed genomic DNA of 151 women with preeclampsia (72 Caucasians and 79 African-Americans) and 198 women with normal delivery (102 Caucasians and 96 African-Americans) for C825T polymorphism of GNβ3 gene. The T-allele frequency in Caucasian women with preeclampsia was 0.42 as compared to 0.25 in normal pregnant women (p = 0.0004) and in African-American women with preeclampsia was 0.82 as compared to 0.68 in normal pregnant women (p = 0.0028). Conclusions: Results of these experiments show that the allele frequency of C825T polymorphism is significantly different in women with preeclampsia compared with women with normal delivery in Caucasian as well as African-American population.     

Diffusion tensor imaging detects treatment effects of FTY720 in experimental autoimmune encephalomyelitis mice

Fingolimod (FTY720) is an orally available sphingosine‐1‐phosphate (S1P) receptor modulator reducing relapse frequency in patients with relapsing–remitting multiple sclerosis (RRMS). In addition to immunosuppression, neuronal protection by FTY720 has also been suggested, but remains controversial. Axial and radial diffusivities derived from in vivo diffusion tensor imaging (DTI) were employed as noninvasive biomarkers of axonal injury and demyelination to assess axonal protection by FTY720 in experimental autoimmune encephalomyelitis (EAE) mice. EAE was induced through active immunization of C57BL/6 mice using myelin oligodendrocyte glycoprotein peptide 35–55 (MOG_35–55). We evaluated both the prophylactic and therapeutic treatment effect of FTY720 at doses of 3 and 10 mg/kg on EAE mice by daily clinical scoring and end‐point in vivo DTI. Prophylactic administration of FTY720 suppressed the disease onset and prevented axon and myelin damage when compared with EAE mice without treatment. Therapeutic treatment by FTY720 did not prevent EAE onset, but reduced disease severity, improving axial and radial diffusivity towards the control values without statistical significance. Consistent with previous findings, in vivo DTI‐derived axial and radial diffusivity correlated with clinical scores in EAE mice. The results support the use of in vivo DTI as an effective outcome measure for preclinical drug development. Copyright © 2013 John Wiley & Sons, Ltd.