Garzamartinsen1646

Objectives To evaluate a Kaiser Permanente Northern California physician-training-tool entitled "Effective Communication without Confrontation" (ECC) aimed at improving communication with vaccine-hesitant parents, building trust, and alleviating physician stress surrounding vaccination visits. Study design Trainings were held May - July 2015. Pre- and post-training surveys assessed physician comfort and perceived effectiveness in communicating with vaccine-hesitant parents. We measured vaccination coverage at two, four, and six-month well-child visits, and days under-vaccinated at nine months of age. We compared vaccination rates pre- and post- training. Results Of 415 physicians who received training, 249 completed post-training surveys. Physicians reported that the training helped them feel 'much more or more' comfortable talking with parents who are unsure (72.3%), want to delay (73.9%), or refuse (63.5%) vaccinations and 'much more or more' effective at persuading parents who are unsure (67.5%) or want to delay vaccinations (61.4%). They reported feeling 'the same or less' effective persuading parents who refuse vaccinations (66.3%). Vaccine coverage remained unchanged and high from pre- to post-training (95-96%), as did parent satisfaction with his/her child's provider (4.73/5.00). Conclusions The ECC training did not increase vaccine coverage but did improve physicians' comfort and perceived effectiveness communicating with most vaccine-hesitant parents and may help to ease potentially stressful vaccination visits.Background The c-MET oncoprotein drives cancer progression in a variety of tumors through its signaling transduction pathways. This oncoprotein is also degraded by multiple mechanisms involving the lysosome, proteasome and cleavage by proteases. Targeting c-MET degradation pathways may result in effective therapeutic strategies. Scope of review Since the discovery of oncogenic functions of c-MET, there has been a great deal of effort to develop anti-cancer drugs targeting this oncoprotein. Unexpectedly, novel di-2-pyridylketone thiosemicarbazones that demonstrate marked anti-tumor activity, down-regulate c-MET through their ability to bind intracellular iron and via mechanisms including, down-regulation of MET mRNA, enhanced lysosomal processing and increased metalloprotease-mediated cleavage. SGI-1776 Major conclusions The c-MET oncoprotein regulation and degradation pathways are complex. However, with increasing understanding of its degradation mechanisms, there is also greater opportunities to therapeutically target these pathways. General significance Understanding the mechanisms of degradation of c-MET protein and its regulation could lead to novel therapeutics.Background Implantable cardioverter defibrillators (ICDs) have been proven to prevent sudden cardiac death (SCD) in adult congenital heart disease (ACHD) patients. Although the left side is chosen by default, implantation from the right side is often required. However, little is known about the efficacy and safety of right-sided ICDs in ACHD patients. Methods A total of 191 ACHD patients undergoing ICDs/CRT-Ds (cardioverter resynchronization therapy defibrillator) implantation in our hospital between 2001 and 2019 (male n=134, age 41.5±14.8 years) were reviewed. Results Twenty-seven patients (14.1%) had right-sided devices. The most common causes of right-sided implantation were persistent left superior vena cava and vein occlusion (37.0%). Although,procedure time (202.8±60.5 vs 143.8±69.1 min, P=0.008) was longer and the procedural success was lower (92.6% vs 99.4%, P=0.008) for right-sided devices, no difference in R wave and pacing threshold were noted. Among 47 patients (24.6%) who underwent defibrillation threshold testing (DFT), no difference in DFT was observed (25.2±5.3J vs 23.8±4.1J, P=0.460). During the median follow-up of 42.4 months, appropriate ICD therapy was observed in 5 (18.5%) and 30 (18.3%) patients in right and left-sided ICDs/CRTDs, respectively (P=0.978). No significant difference was seen in complications between them. Conclusion Implantation of ICDs on the right side is technically challenging, however, it is feasible as an alternative approach for ACHD patients with contraindication to left-sided device implantation.A 64 year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic SARS-CoV2 infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval.Environmental cadmium (Cd) pollution can ultimately lead to chronic toxicity via food consumption. Previous studies have demonstrated that long-term low-dose Cd exposure decreases bone mineral density and bone mineralization. Cd may increase receptor activator of nuclear factor-κ B ligand (RANKL) expression by osteoclasts, and inhibit the expression of osteoprotegerin. However, the molecular mechanism underlying Cd toxicity toward osteoclasts is unclear. In this study, bone marrow monocytes were isolated from C57BL/6 mice and treated with macrophage colony-stimulating factor and RANKL to induce the formation of osteoclasts. The results show that low-dose Cd exposure induced osteoclast differentiation. Cd also increased the intracellular calcium concentration of osteoclasts by triggering release of calcium ions from the endoplasmic reticulum into the cytoplasm. Furthermore, the elevation of intracellular calcium levels was shown to activate the calmodulin (CaM)/calmodulin-dependent protein kinase (CaMK) pathway. NFATc1 is a downstream protein of CaM/CaMK signaling, as well as a key player in osteoclast differentiation. Overall, we conclude that Cd activates the CaM/CaMK/NFATc1 pathway and regulates osteoclast differentiation by increasing intracellular calcium concentration. Our data provide new insights into the mechanisms underlying osteoclast differentiation following Cd exposure. This study provides a theoretical basis for future investigations into the therapeutic application of CaMK inhibitors in osteoporosis induced by Cd exposure.