Intracardiac echocardiography to diagnose pannus formation after aortic valve replacement

A 66-year-old female, under regular follow-up for 20 years after aortic valve replacement (19-mm Carbomedics), presented dyspnea on effort and hypotension during hemodialysis. A transthoracic echocardiogram showed elevation of transvalvular velocity up to 4 m/s, but the structure around the aortic prosthesis was difficult to observe due to artifacts. Fluoroscopy revealed normal motion of the leaflets of the mechanical valve. Intracardiac echocardiography (ICE) revealed a pannus-like structure in the left ventricular outflow tract. Transesophageal echocardiogram also revealed this structure. ICE can visualize structural abnormalities around a prosthetic valve after cardiac surgery even in patients in whom conventional imaging modalities failed.     

Migration and nucleogenesis of mouse precerebellar neurons visualized by in utero electroporation of a green fluorescent protein gene

Neural migration is a critical step for accurate CNS development, but the molecular mechanisms that regulate migration, settlement and nucleogenesis remain largely unknown. The precerebellar neurons (PCNs), generated in the lower rhombic lip (LRL), migrate towards their destinations: some neurons form the pontine gray nucleus (PGN) and reticulotegmental nucleus (RTN) in the ipsilateral pons, while others form the lateral reticular and external cuneate nuclei in the contralateral medulla after crossing the midline. Here, by introducing an EGFP gene into a unilateral LRL of mouse embryos by in utero electroporation, we specifically labeled and tracked the PCNs in vivo. We found that a substantial number of the labeled neurons crossed the midline and formed PGN/RTN on the contralateral side. In addition, we found that a subpopulation of the interpolar subnucleus of the spinal trigeminal nucleus, which projects the axons to the cerebellum, was one of the PCNs derived from the LRL. Furthermore, because the electroporated mice were born and grew up healthy, we could visualize the PCNs and their mossy fibers in the adult brain. Therefore, the EGFP labeling of PCNs can be applied to studying the physiology of the mossy fiber system as well as PCN development in embryos.     

Synaptic vesicle dynamics in the mossy fiber-CA3 presynaptic terminals of mouse hippocampus

The mossy fiber (MF)-CA3 synapse in the hippocampus is unique in the CNS because of its wide dynamic range of transmitter release during short- and long-term plasticity. The presynaptic mechanisms underlying the fidelity of transmission were investigated for the MF-CA3 synapses. The relative size of readily releasable pool (RRP) of vesicles was estimated by counting the number of docked vesicles at an active zone (AZ) on the transmission electron microscopy (TEM) image. The size of the releasable pool and the exo-endocytosis kinetics were directly measured from individual large MF boutons in hippocampal slices of transgenic mice that selectively express synaptopHluorin (SpH), a pH-sensitive GFP fused to the lumenal aspect of one of the vesicular membrane proteins, VAMP-2, in these boutons. Here we found (1) there are distinct two vesicle pools, the resting pool which is resistant to exocytosis, and the releasable pool, (2) the initially docked vesicles are easily depleted and the RRP is maintained by refilling from the reserve subpopulation of releasable pool ("reserve" releasable pool), and (3) the contribution of rapid reuse of recycled vesicles is relatively small. Therefore, the fidelity of transmission is suggested to be ensured by the rapid refilling rate of RRP.     

Fc alpha receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcR gamma adaptor

Myeloid cells bear Fc receptors (FcR) that mediate inflammatory signaling through the ITAM-containing FcRgamma adaptor. They express FcRgamma-associated FcalphaRI, which modulate either activating or inhibitory signaling depending on the type of ligand interaction. The role of FcalphaRIgamma in disease progression remains unknown, notably in IgA nephropathy (IgAN), one of major causes of end-stage renal disease, in which large amounts of circulating IgA-immune complexes (IC) may mediate receptor activation. To analyze the involvement of FcalphaRI activation in glomerulonephritis (GN), we generated Tg mice expressing a mutated, signaling-incompetent, human FcalphaRI(R209L) that cannot associate with FcRgamma. Like FcalphaRI(wt)-Tg mice, they developed mesangial IgA deposits but not macrophage infiltration. FcalphaRI activation in FcalphaRI(wt), but not in FcalphaRI(R209L), Tg mice resulted in marked inflammation with severe proteinuria and leukocyte infiltration in spontaneous IgAN or anti-glomerular basement membrane Ab-induced GN models. Receptor triggering of syngenically transferred FcalphaRI(wt) Tg macrophages into non-Tg animals induced their recruitment into injured kidneys during GN development. FcalphaRI(wt) cross-linking on macrophages activated MAP kinases and production of TNF-alpha and MCP-1. Moreover, IgA-IC from IgAN patients activated FcalphaRI and induced TNF-alpha production. Thus, FcalphaRI activation mediates GN progression by initiating a cytokine/chemokine cascade that promotes leukocyte recruitment and kidney damage.     

An analysis of qualitative and mixed methods abstracts from Japanese,UK and US primary care conferences

Background

As research in family medicine covers varied topics, multiple methodologies such as qualitative research (QR) and mixed methods research (MMR) are crucial. However, we do not know about the difference in the proportion of QR or MMR between Japan, the UK and the US. This knowledge is needed to shape future research within countries with developing primary care such as Japan and other Asian countries. This study aims to describe the use of QR and MMR in Japanese primary care and compare this to the UK and US; then to make informed recommendations for primary care research.

Methods

A repeated cross-sectional study (2012–2016) based on the abstracts submitted to the annual conferences of the Japanese Primary Care Association in Japan, the Royal College of General Practitioners in the UK, and the North American Primary Care Research Group in the US and other North American countries. The proportions of QR/MMR among all the posters and paper presentations for each of these three conferences were assessed. Also examined were trends and types of qualitative techniques for all three countries and participants/settings for Japan.

Results

There were 1080 abstracts for Japan, 575 for UK and 3614 for US conferences. QR/MMR proportions were 7.5%, 15.1% and 28.1%, respectively. Japan’s proportion was lower than that of UK and US (p?<?0.001). The proportion was increasing over time for the UK (p?=?0.02). Steps for coding and analyses was most popular for Japan, thematic analysis for the UK and grounded theory for the US. Primary care doctors and hospitals were the commonest contexts for Japan.

Conclusions

QR and MMR were not as popular in primary care in Japan compared to the UK and the US, whereas their use was increasing in the UK. Approaches, participants and settings may differ among these countries. Education and promotion of QR/MMR and multi-disciplinary collaborations need to be recommended in Japan with developing primary care.

     

Treatment effect estimators for count data models

In this paper, we consider a switching regression model with count data outcomes, where the possible outcome differs across two alternate states and individuals endogenously select one of the states. We assume lognormal latent heterogeneity. Building on the switching regression model, we derive estimators of various treatment effects: the average treatment effect, the average treatment effect on the treated, the local average treatment effect, and the marginal treatment effect. We illustrate an application that examines the effects of public insurance on the number of doctor visits using the data employed by previous studies.