Identification of hospitalized elderly patients at risk for adverse in-hospital outcomes in a university orthopedics and trauma surgery environment - Fig 1

<p><b>Prevalence of ISAR items (A) for the total cohort, (B) for ISAR+ and (C) for ISAR-.</b> Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187801#pone.0187801.t001" target="_blank">Table 1</a>.</p

Characteristics of the total study cohort also split by ISAR score and CGA results.

<p>Characteristics of the total study cohort also split by ISAR score and CGA results.</p

Predictors of nursing hours per day for patients with ISAR+ receiving CGA (n = 300).

<p>Predictors of nursing hours per day for patients with ISAR+ receiving CGA (n = 300).</p

Predictors of total length of hospital stay in days for patients with ISAR+ receiving CGA (n = 300).

<p>Predictors of total length of hospital stay in days for patients with ISAR+ receiving CGA (n = 300).</p

Medical main diagnosis of the total study cohort also split by ISAR score and CGA results.

<p>Medical main diagnosis of the total study cohort also split by ISAR score and CGA results.</p

Predictors of total hours of physiotherapy for patients with ISAR+ receiving CGA (n = 300).

<p>Predictors of total hours of physiotherapy for patients with ISAR+ receiving CGA (n = 300).</p

Association of ISAR and CGA results with type of discharge.

<p>*p<0.05 compared with ISAR-, †p<0.05 compared with ISAR+/CGA normal. Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187801#pone.0187801.t001" target="_blank">Table 1</a>.</p

Additional file 2: Figure S2. of Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients

CD56dim NK cells do not respond to CCR2 ligands. NK cells were incubated in the absence (–) or presence of 0.5 ng/ml of recombinant human CCL2, CCL8, CCL7, and CCL12, or with conditioned medium (CM) from MSCs for 12 h. Thereafter, the cells were stimulated with IL-12 (1 ng/ml) and IL-18 (5 ng/ml). Dot plots of intracellular staining of IFN-γ in gated CD3–CD56dim NK cells (gating strategy as shown in Fig. 1d). Data are representative for one out of five experiments. The threshold of positive staining for IFN-γ was set according to the isotype control (iso). Numbers indicate the percentage of IFN-γ-positive NK cells. MSC mesenchymal stromal/stem cell, CCL C-C ligand, IFN interferon. (PDF 36 kb

Characterising diflunisal as a transthyretin kinetic stabilizer at relevant concentrations in human plasma using subunit exchange

Transthyretin (TTR) dissociation is the rate limiting step for both aggregation and subunit exchange. Kinetic stabilisers, small molecules that bind to the native tetrameric structure of TTR, slow TTR dissociation and inhibit aggregation. One such stabiliser is the non-steroidal anti-inflammatory drug (NSAID), diflunisal, which has been repurposed to treat TTR polyneuropathy. Previously, we compared the efficacy of diflunisal, tafamidis, tolcapone, and AG10 as kinetic stabilisers for transthyretin. However, we could not meaningfully compare diflunisal because we were unsure of its plasma concentration after long-term oral dosing. Herein, we report the diflunisal plasma concentrations measured by extraction, reversed phase HPLC separation, and fluorescence detection after long-term 250 mg BID oral dosing in two groups: a placebo-controlled diflunisal clinical trial group and an open-label Japanese polyneuropathy treatment cohort. The measured mean diflunisal plasma concentration from both groups was 282.2 μM ± 143.7 μM (mean ± standard deviation). Thus, quantification of TTR kinetic stabilisation using subunit exchange was carried out at 100, 200, 300, and 400 μM diflunisal concentrations, all observed in patients after 250 mg BID oral dosing. A 250 μM diflunisal plasma concentration reduced the wild-type TTR dissociation rate in plasma by 95%, which is sufficient to stop transthyretin aggregation, consistent with the clinical efficacy of diflunisal for ameliorating transthyretin polyneuropathy.</p

<i>BCL2</i> -938C>A Genotype Distribution.

<p><i>BCL2</i> -938C>A Genotype Distribution.</p