Impact of pneumococcal conjugate vaccination on otitis media: A systematic review

Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0-9 in randomized trials and 17-23 in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3-5 years before 7vCRM introduction (mean change,-15; range, +14 to-24) and continued to decline afterward (mean,-19; range, +7 to-48). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM. © 2012 The Author.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation

In many cell types, nuclear A-type lamins regulate multiple cellular functions, including higher-order genome organization, DNA replication and repair, gene transcription, and signal transduction; however, their role in specialized immune cells remains largely unexplored. We showed that the abundance of A-type lamins was almost negligible in resting naïve T lymphocytes, but was increased upon activation of the T cell receptor (TCR). The increase in lamin-A was an early event that accelerated formation of the immunological synapse between T cells and antigen-presenting cells. Polymerization of F-actin in T cells is a critical step for immunological synapse formation, and lamin-A interacted with the linker of nucleoskeleton and cytoskeleton (LINC) complex to promote F-actin polymerization. We also showed that lamin-A expression accelerated TCR clustering and led to enhanced downstream signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, as well as increased target gene expression. Pharmacological inhibition of the ERK pathway reduced lamin-A-dependent T cell activation. Moreover, mice lacking lamin-A in immune cells exhibited impaired T cell responses in vivo. These findings underscore the importance of A-type lamins for TCR activation and identify lamin-A as a previously unappreciated regulator of the immune response.Spanish Ministerio de Economia y Competitividad (MINECO) [SAF2011-25834, SAF2010-16044]; Comunidad de Madrid [INDISNET-S2011/BMD-2332]; Instituto de Salud Carlos III (ISCIII) [RD12/0042/0028, RD12/0042/0056, CP11/00145]; Progeria Research Foundation [PRF 2012-42]; European Commission [ERC-2011AdG 294340-GENTRIS, 317916-Liphos]; Sara Borrell ISCIII program [CP11/00145]; Miguel Servet ISCIII program [CP11/00145]; Fundacion Mario Losantos del Campo; Fundacion Ferrer para la Investigacion; Obra Social Cajastur; Spanish MINECO; Pro-CNIC FoundationS