Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Assessing the performance and satisfaction of medical residents utilizing standardized patient versus mannequin-simulated training

Ali A Alsaad,1 Swetha Davuluri,2 Vandana Y Bhide,3 Amy M Lannen,4 Michael J Maniaci3 1Department of Internal Medicine, Mayo Clinic, 2University of Miami, Coral Gables, 3Division of Hospital Internal Medicine, 4J. Wayne and Delores Barr Weaver Simulation Center, Mayo Clinic, Jacksonville, FL, USA Background: Conducting simulations of rapidly decompensating patients are a key part of internal medicine (IM) residency training. Traditionally, mannequins have been the simulation tool used in these scenarios. Objective: To compare IM residents’ performance and assess realism in specific-simulated decompensating patient scenarios using standardized patients (SPs) as compared to mannequin. Methods: Nineteen IM residents were randomized to undergo simulations using either a mannequin or an SP. Each resident in the two groups underwent four different simulation scenarios (calcium channel blocker overdose, severe sepsis, severe asthma exacerbation, and acute bacterial meningitis). Residents completed pretest and post-test evaluations as well as a questionnaire to assess the reality perception (realism score). Results: Nine residents completed mannequin-based scenarios, whereas 10 completed SP-based scenarios. Improvement in the post-test scores was seen in both groups. However, there were significantly higher post-test scores achieved with SP simulations in three out of the four scenarios (P=0.01). When compared with the mannequin group, the SP simulation group showed a significantly higher average realism score (P=0.002). Conclusions: Applying SP-based specific-simulation scenarios in IM residency training may result in better performance and a higher sense of a realistic experience by medical residents. Keywords: simulation, standardized patient, satisfaction, mannequin, assessment, resident educatio

Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells from Decidua Basalis of Human Term Placenta

Mesenchymal stem cell (MSC) therapies for the treatment of diseases associated with inflammation and oxidative stress employ primarily bone marrow MSCs (BMMSCs) and other MSC types such as MSC from the chorionic villi of human term placentae (pMSCs). These MSCs are not derived from microenvironments associated with inflammation and oxidative stress, unlike MSCs from the decidua basalis of the human term placenta (DBMSCs). DBMSCs were isolated and then extensively characterized. Differentiation of DBMSCs into three mesenchymal lineages (adipocytes, osteocytes, and chondrocytes) was performed. Real-time polymerase chain reaction (PCR) and flow cytometry techniques were also used to characterize the gene and protein expression profiles of DBMSCs, respectively. In addition, sandwich enzyme-linked immunosorbent assay (ELISA) was performed to detect proteins secreted by DBMSCs. Finally, the migration and proliferation abilities of DBMSCs were also determined. DBMSCs were positive for MSC markers and HLA-ABC. DBMSCs were negative for hematopoietic and endothelial markers, costimulatory molecules, and HLA-DR. Functionally, DBMSCs differentiated into three mesenchymal lineages, proliferated, and migrated in response to a number of stimuli. Most importantly, these cells express and secrete a distinct combination of cytokines, growth factors, and immune molecules that reflect their unique microenvironment. Therefore, DBMSCs could be attractive, alternative candidates for MSC-based therapies that treat diseases associated with inflammation and oxidative stress

Quality of Life in Family Members of Vitiligo Patients: A Questionnaire Study in Saudi Arabia

Many dermatologic disorders are known to adversely affect quality of life (QoL) in close relatives or partners of patients; however, it is unknown whether vitiligo impacts the QoL of family members.The aim of this study was to identify the level and domains in which the QoL of partners/relatives of patients with vitiligo are affected by the disease.A total of 141 patients with vitiligo, along with their family members, were recruited to complete validated QoL questionnaires, including the Dermatology Life Quality Index (DLQI) and the Family Dermatology Life Quality Index (FDLQI).Family member QoL was affected in 129 (91.5 %) of subjects. Mean FDLQI score was 10.3 ± 6.4 standard deviation. Higher FDLQI score (greater impairment in QoL) was significantly associated with male patients, a shorter duration of disease, and higher educational levels in family members. The most affected FDLQI items in order of decreasing incidence were emotional impact, burden of care, impact on the physical well-being of the family member, problems due to the reaction of others in response to the patient’s skin appearance and effect on social life. Overall FDLQI score and the number of items affected correlated with overall patient DLQI score (p < 0.001, r = 0.56 and p < 0.001, r = 0.53, respectively).Vitiligo has a major impact on the QoL of family members of patients and often significantly impairs many aspects of their lives. Educational and supportive programs are recommended for family members of vitiligo patients who are at an increased risk for QoL impairments