Parents' vaccination information seeking, satisfaction with and trust in medical providers in Switzerland: a mixed-methods study.

OBJECTIVES: The aim of this study was to better understand parental trust in and satisfaction with information sources and medical providers regarding decision making about childhood vaccines. SETTING: The study was part of a Swiss national research programme investigating vaccine hesitancy and underimmunisation. PARTICIPANTS: We conducted qualitative interviews with 37 providers and 30 parents, observed 34 vaccination consultations, and then conducted quantitative surveys with 130 providers (both complementary and alternative medicine (CAM) oriented and biomedically oriented) and 1390 parents. MAIN OUTCOME MEASURES: Participants' vaccination information sources used in their decision-making process, parents' trust in and satisfaction with these sources and providers. RESULTS: Based on the Parent Attitudes about Childhood Vaccines scale, we considered 501 parents as vaccine-hesitant (VH) and 889 parents as non-VH. Whereas both groups mentioned providers as the most trusted source of information, VH-parents were less likely to mention paediatricians (N=358 (71%) vs N=755 (85%)) and public health authorities (N=101 (20%) vs N=333 (37%)) than non-VH-parents. VH-parents were more likely to have consulted another provider (N=196 (39%) vs N=173 (19%)) than non-VH-parents, to express less satisfaction with both their primary (N=342 (82%) vs N=586 (91%)) and other providers (N=82 (42%) vs N=142 (82%)) and less trust in their primary (N=368 (88%) vs N=632 (98%)) and other providers (N=108 (55%) vs N=146 (84%)). VH-parents were less likely to be satisfied with their biomedical primary provider than non-VH-parents (100 (69%) vs 467 (91%)). However, when the primary provider was CAM-oriented, there were similar levels of satisfaction among both groups (237 (89%) VH-parents vs 118 (89%) non-VH-parents). All differences were significant (p<0.05). CONCLUSIONS: While the provider remains the main information source, VH parents turn to additional sources and providers, which is likely related to VH parents being rather dissatisfied with and distrusting in obtained information and their provider. ETHICS: The local ethics committee (Ethikkommission Nordwest- und Zentralschweiz, EKNZ; project ID number 2017-00725) approved the study.

Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade.

Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on IκB kinase epsilon (IKKε) which has not been investigated in this context before. Therefore, we applied the pan-HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) as well as HDAC-specific siRNA. Administration of HDACi reduced HDAC activity and decreased expression of IKKε although its acetylation was increased. Other pro-inflammatory genes (IL-1ß, iNOS, TNFα) also decreased while COX-2 expression increased. HDAC 2, 3 and 4, respectively, might be involved in IKKε and iNOS downregulation with potential participation of NF-κB transcription factor inhibition. Suppression of HDAC 1-3, activation of NF-κB and RNA stabilization mechanisms might contribute to increased COX-2 expression. In conclusion, our results indicate that TSA and SAHA exert a number of histone- and HDAC-independent functions. Furthermore, the data show that different HDAC enzymes fulfill different functions in macrophages and might lead to both pro- and anti-inflammatory effects which have to be considered in therapeutic approaches.

PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate.

PAM (Protein Associated with Myc) is an almost ubiquitously expressed protein that is one of the most potent inhibitors of adenylyl cyclase activity known so far. Here we show that PAM is localized at the endoplasmic reticulum in HeLa cells and that upon serum treatment PAM is recruited to the plasma membrane, causing an inhibition of adenylyl cyclase activity. We purified the serum factor that induced PAM translocation and identified it as sphingosine-1-phosphate (S1P). Within 15 min after incubation with S1P, PAM appeared at the plasma membrane and was detectable for up to 120 min. Sphingosine-1-phosphate induced adenylyl cyclase inhibition in two phases: an initial (1-10 min) and a late (20-240 min) phase. The initial adenylyl cyclase inhibition was Gi-mediated and PAM independent. In the late phase, adenylyl cyclase inhibition was PAM dependent and attenuated cyclic AMP (cAMP) signaling by various cAMP-elevating signals. This makes PAM the longest lasting nontranscriptional regulator of adenylyl cyclase activity known to date and presents a novel mechanism for the temporal regulation of cAMP signaling.