Larahickman9934

BACKGROUND Our objective was to obtain estimates of the impact of the Dutch vaccination programme on medication use, outpatient visits, hospitalization and mortality at age 65. METHODS We linked population-wide mortality, hospitalization and municipality registries to identify influenza-related deaths and hospitalizations, and used health interview surveys to identify medication use and outpatient visits during 1996-2008. We applied a regression discontinuity design to estimate the intention-to-treat effect of the personal invitation for a free influenza vaccination sent to every Dutch inhabitant at age 65 years on each of the outcomes, separately in influenza-epidemic and non-epidemic months. RESULTS Invitation receipt for free influenza vaccination at age 65 led to a 9.8 percentage points [95% confidence interval (CI) = 3.5 to16.1; P  less then  0.01] rise in influenza vaccination. During influenza-epidemic months, it was associated with 1.5 fewer influenza/pneumonia deaths per 100 000 individuals (95% CI = -3.1 to -0.0; P = 0.05), a 15 percentage point lower probability to use prescribed medicines (95% CI = -28 to -3; P = 0.02) and 0.13 fewer General Practitioner (GP) visits per month (95% CI = -0.28 to 0.02; P = 0.09), while the association with hospitalizations due to influenza/pneumonia was small and imprecisely estimated (seven more hospitalizations per 100 000 individuals, 95% CI = -20 to 33; P = 0.63). No associations were found with any outcomes during non-epidemic months. CONCLUSIONS Personal invitations for a free influenza vaccination sent to every Dutch inhabitant at age 65 took pressure off primary health care but had small effects on hospitalizations and mortality. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association.Aluminum precipitates have long been used as adjuvants for human vaccines, but there is a clear need for safer and more effective adjuvants. Here we report in a mouse model that the Psoriasis drug Oxarol ointment is a highly effective vaccine adjuvant. By applying Oxarol ointment onto skin, humoral responses and germinal center (GC) reactions were augmented, and the treated mice were protected from death caused by influenza virus infection. Keratinocyte-specific Vitamin D3 receptor (Vdr) gene expression was required for these responses through induction of the Thymic stromal lymphopoietin (Tslp) gene. Experiments involving administration of recombinant Tslp or, conversely, anti-Tslp antibody demonstrated that Tslp plays a key role in the GC reactions. Furthermore, cell type-specific Tslpr gene deletion or diphtheria toxin-mediated deletion of specific cell types, revealed that CD11c+ cells excluding Langerhans cells were responsible for the Oxarol-mediated GC reactions. These results indicate that active vitamin D3 is able to enhance the humoral response via Tslp induction in the skin and serves as a new vaccine adjuvant. © The Japanese Society for Immunology. 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.INTRODUCTION Advances in the portability of ultrasound have allowed it to be increasingly employed at the point of care in austere settings. Battlefield constraints often limit the availability of medical officers throughout the operational environment, leading to increased interest in whether highly portable ultrasound devices can be employed by military medics to enhance their provision of combat casualty care. Data evaluating optimal training for effective medic employment of ultrasound is limited however. This prospective observational cohort study's primary objective was to assess the impact of a 4-hour introductory training intervention on ultrasound-naïve military medic participants' knowledge/performance of the eFAST application. MATERIALS AND METHODS Conventional U.S. Army Medics, all naïve to ultrasound, were recruited from across JBLM. Volunteer participants underwent baseline eFAST knowledge assessment via a 50-question multiple-choice exam. Participants were then randomized to receive either convrmed. © Association of Military Surgeons of the United States 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.In this study, we explore the inhibitory effects of protriptyline, a tricyclic antidepressant drug, on voltage-dependent K+ (Kv) channels of rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Protriptyline inhibited the vascular Kv current in a concentration-dependent manner, with an IC50 value of 5.05 ± 0.97 μM and a Hill coefficient of 0.73 ± 0.04. Protriptyline did not affect the steady-state activation kinetics. However, the drug shifted the steady-state inactivation curve to the left, suggesting that protriptyline inhibited the Kv channels by changing their voltage sensitivity. Y-27632 Application of 20 repetitive train pulses (1 or 2 Hz) progressively increased the protriptyline-induced inhibition of the Kv current, suggesting that protriptyline inhibited Kv channels in a use (state)-dependent manner. The extent of Kv current inhibition by protriptyline was similar during the first, second, and third step pulses. These results suggest that protriptyline-induced inhibition of the Kv current mainly occurs principally in the closed state. The increase in the inactivation recovery time constant in the presence of protriptyline also supported use (state)-dependent inhibition of Kv channels by the drug. In the presence of the Kv1.5 inhibitor, protriptyline did not induce further inhibition of the Kv channels. However, pretreatment with a Kv2.1 or Kv7 inhibitor induced further inhibition of Kv current to a similar extent to that observed with protriptyline alone. Thus, we conclude that protriptyline inhibits the vascular Kv channels in a concentration- and use-dependent manner by changing their gating properties. Furthermore, protriptyline-induced inhibition of Kv channels mainly involves the Kv1.5. © The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please email journals.permissions@oup.com.