Cooperative Stimulation of Dendritic Cells by Cryptococcus neoformans Mannoproteins and CpG Oligodeoxynucleotides

While mannosylation targets antigens to mannose receptors on dendritic cells (DC), the resultant immune response is suboptimal. We hypothesized that the addition of toll-like receptor (TLR) ligands would enhance the DC response to mannosylated antigens. Cryptococcus neoformans mannoproteins (MP) synergized with CpG-containing oligodeoxynucleotides to stimulate enhanced production of proinflammatory cytokines and chemokines from murine conventional and plasmacytoid DC. Synergistic stimulation required the interaction of mannose residues on MP with the macrophage mannose receptor (MR), CD206. Moreover, synergy with MP was observed with other TLR ligands, including tripalmitoylated lipopeptide (Pam3CSK4), polyinosine-polycytidylic acid (pI:C), and imiquimod. Finally, CpG enhanced MP-specific MHC II-restricted CD4+ T-cell responses by a mechanism dependent upon DC expression of CD206 and TLR9. These data suggest a rationale for vaccination strategies that combine mannosylated antigens with TLR ligands and imply that immune responses to naturally mannosylated antigens on pathogens may be greatly augmented if TLR and MR are cooperatively stimulated.National Institutes of Health (RO1 AI25780, RO1 AI37532, K08 AI 53542

Adoption and Foster Care by Gay and Lesbian Parents in the United States

Discussion and debate about adoption and foster care by gay, lesbian, and bisexual (GLB) parents occurs frequently among child welfare policymakers, social service agencies, and social workers. They all need better information about GLB adoptive and foster parents and their children as they make individual and policy-level decisions about placement of children with GLB parents. This report provides new information on GLB adoption and foster care from the U.S. Census 2000, the National Survey of Family Growth (2002), and the Adoption and Foster Care Analysis and Reporting System (2004)

Gender differences in the pathways from childhood disadvantage to metabolic syndrome in adulthood: An examination of health lifestyles.

We investigate whether socioeconomic status (SES) in childhood shapes adult health lifestyles in domains of physical activity (leisure, work, chores) and diet (servings of healthy [i.e., nutrient-dense] vs. unhealthy [energy-dense] foods). Physical activity and food choices vary by gender and are key factors in the development of metabolic syndrome (MetS). Thus, we examined gender differences in the intervening role of these behaviors in linking early-life SES and MetS in adulthood. We used survey data (n = 1054) from two waves of the Midlife in the U.S. Study (MIDUS 1 and 2) and biomarker data collected at MIDUS 2. Results show that individuals who were disadvantaged in early life are more likely to participate in physical activity related to work or chores, but less likely to participate in leisure-time physical activity, the domain most consistently linked with health benefits. Women from low SES families were exceedingly less likely to complete recommended amounts of physical activity through leisure. Men from low SES consumed more servings of unhealthy foods and fewer servings of healthy foods. The observed associations between childhood SES and health lifestyles in adulthood persist even after controlling for adult SES. For men, lack of leisure-time physical activity and unhealthy food consumption largely explained the association between early-life disadvantage and MetS. For women, leisure-time physical activity partially accounted for the association, with the direct effect of childhood SES remaining significant. Evidence that material deprivation in early life compromises metabolic health in adulthood calls for policy attention to improve economic conditions for disadvantaged families with young children where behavioral pathways (including gender differences therein) may be shaped. The findings also underscore the need to develop gender-specific interventions in adulthood

Physiology engages with functional genomics - at last

A report on the XXXV International Congress of Physiological Sciences, held together with Experimental Biology 2005, San Diego, USA, 31 March - 6 April 2005

Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P<0.05) and eosinophils (1.09 ± 0.28 × 10(5) (n = 18) vs. 2.94 ± 0.6 × 10(5) (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11) vs. 8.56 ± 2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1 ± 3.6 (n = 8) vs. 28.8 ± 8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma

Determining Annoyance Thresholds of Tones in Noise

Building services equipment often produces noise signatures with significant tones in them that can lead to complaints in the built environment. Previous studies have investigated prominence levels of assorted tonal frequencies, but it is still unclear what prominence of the tones across varying tonal frequencies can lead to human annoyance. This project seeks to apply two different methods towards defining annoyance thresholds of tones in noise at two tonal frequencies: 125 Hz and 500 Hz. In the first, subjects are asked to perform a task, while exposed to ten minutes of a broadband noise spectrum with a specific level of tonal prominence. They are subsequently asked to rate their annoyance to that noise condition. Five prominence levels of each of the two tones are tested above two different background noise levels, for a total of 20 test trials. In the second methodology, subjects listen to each of the two tonal frequencies at a predetermined level above each of the two background noise levels, and then adjust the level of the tone up or down until it becomes just annoying. The strengths, weaknesses, and results obtained for the annoyance thresholds of tones in noise from each of these methods are compared

A Time-Motion Study of Emergency and Hospitalist Physicians in a Community Hospital Setting

Introduction: Research has shown that low physician work satisfaction correlates with burnout. Having sufficient time at the patient’s bedside is one element that contributes to work satisfaction. Interruptions, on the other hand, have been implicated as a potential cause of both worker dissatisfaction and clinical error. Better understanding how direct patient care and interruptions affect physician satisfaction may aid in developing future interventions to reduce burnout and improve patient safety. Methods: We conducted an observational, time-motion study to assess how physicians spend their time and correlated these findings to physician satisfaction. This study was conducted in July 2020 (7/1/20 - 7/15/20) at a 591-bed community hospital. A total of 114 emergency medicine (EM) physicians and hospitalists were eligible for participation. Participants were recruited by email. Two trained medical students categorized and recorded the activities of 13 EM and 8 hospitalist physicians and documented the number of interruptions they experienced. An anonymous survey was also employed to investigate participants’ perceptions about interruptions and how they spend their time. We compared the responses from the subjective survey to the objective data to identify activities that may positively or negatively impact participant satisfaction. Results: 18.4% of all eligible physicians participated in the study. In summary, our study showed that EM and hospitalist physicians dedicate roughly double the amount of time to indirect patient care (56.3%) compared to direct patient care (25.8%). EM physicians had more than twice the number of interruptions as hospitalists (every 4.4 minutes vs. every 11.3 minutes). From our survey results, we found no statistically significant difference between the perceived and observed proportion of time spent on direct and indirect patient care for EM physicians (p = 0.62 direct; 0.21 indirect) or hospitalists (p = 0.82 direct; 0.69 indirect). However, there was a statistically significant difference between perceived (overestimated) and observed number of interruptions reported by EM physicians (p = 0.02). Conclusion: The observational data along with the survey results indicate a desire to reduce indirect patient care and increase time at the bedside — suggesting that interventions that target this discrepancy may increase physician work satisfaction and therefore decrease burnout. Additionally, we found that EM physicians far overestimate the actual number of interruptions they experience —however, EM does still engender more than double the interruptions as hospitalists encounter, despite experiencing similar percentages of direct and indirect patient care

Glycomic analysis of high density lipoprotein shows a highly sialylated particle.

Many of the functional proteins and lipids in high density lipoprotein (HDL) particles are potentially glycosylated, yet very little is known about the glycoconjugates of HDL. In this study, HDL was isolated from plasma by sequential micro-ultracentrifugation, followed by glycoprotein and glycolipid analysis. N-Glycans, glycopeptides, and gangliosides were extracted and purified followed by analysis with nano-HPLC Chip quadrupole time of flight mass spectrometry and MS/MS. HDL particles were found to be highly sialylated. Most of the N-glycans (∼90%) from HDL glycoproteins were sialylated with one or two neuraminic acids (Neu5Ac). The most abundant N-glycan was a biantennary complex type glycan with two sialic acids (Hexose5HexNAc4Neu5Ac2) and was found in multiple glycoproteins using site-specific glycosylation analysis. The observed O-glycans were all sialylated, and most contained a core 1 structure with two Neu5Acs, including those that were associated with apolipoprotein CIII (ApoC-III) and fetuin A. GM3 (monosialoganglioside, NeuAc2-3Gal1-4Glc-Cer) and GD3 (disialoganglioside, NeuAc2-8NeuAc2-3Gal1-4Glc-Cer) were the major gangliosides in HDL. A 60% GM3 and 40% GD3 distribution was observed. Both GM3 and GD3 were composed of heterogeneous ceramide lipid tails, including d18:1/16:0 and d18:1/23:0. This report describes for the first time a glycomic approach for analyzing HDL, highlighting that HDL are highly sialylated particles