Implant selection for successful reverse total shoulder arthroplasty

Reverse total shoulder arthroplasty (RTSA) emerged as a new concept of arthroplasty that does not restore normal anatomy but does restore function. It enables the function of the torn rotator cuff to be performed by the deltoid and shows encouraging clinical outcomes. Since its introduction, various modifications have been designed to improve the outcome of the RTSA. From the original cemented baseplate with peg or keel, a cementless baseplate was designed that could be fixed with central and peripheral screws. In addition, a modular-type glenoid component enabled easier revision options. For the humeral component, the initial design was an inlay type of long stem with cemented fixation. However, loss of bone stock from the cemented stem hindered revision surgery. Therefore, a cementless design was introduced with a firm metaphyseal fixation. Furthermore, to prevent complications such as scapular notching, the concept of lateralization emerged. Lateralization helped to maintain normal shoulder contour and better rotator cuff function for improved external/internal rotation power, but excessive lateralization yielded problems such as subacromial notching. Therefore, for patients with pseudoparalysis or with risk of subacromial notching, a medial eccentric tray option can be used for distalization and reduced lateralization of the center of rotation. In summary, it is important that surgeons understand the characteristics of each implant in the various options for RTSA. Furthermore, through preoperative evaluation of patients, surgeons can choose the implant option that will lead to the best outcomes after RTSA.Level of evidence: IV

5′-Triphosphate-RNA-independent activation of RIG-I via RNA aptamer with enhanced antiviral activity

RIG-I is a cytosolic receptor for non-self RNA that mediates immune responses against viral infections through IFNα/β production. In an attempt to identify novel tools that modulate IFNα/β production, we used SELEX technology to screen RNA aptamers that specifically target RIG-I protein. Most of the selected RIG-I aptamers contained polyU motifs in the second half regions that played critical roles in the activation of RIG-I-mediated IFNβ production. Unlike other known ligands, RIG-I aptamer bound and activated RIG-I in a 5′-triphosphate-independent manner. The helicase and RD domain of RIG-I were used for aptamer binding, but intact RIG-I protein was required to exert aptamer-mediated signaling activation. Furthermore, replication of NDV, VSV and influenza virus in infected host cells was efficiently blocked by pre- or post-treatment with RIG-I aptamer. Based on these data, we propose that RIG-I aptamer has strong potential to be an antiviral agent that specifically boosts the RIG-I-dependent signaling cascade

Selective Inhibition of Bakuchicin Isolated from Psoralea corylifolia on CYP1A in Human Liver Microsomes

Bakuchicin is a furanocoumarin isolated from Psoralea corylifolia and shows several biological activities. Although there have been studies on the biological effects of bakuchicin, its modulation potency of CYP activities has not been previously investigated. Here, we investigated the inhibitory effects of bakuchicin on the activities of CYP isoforms by using a cocktail of probe substrates in pooled human liver microsomes (HLMs) and human recombinant cDNA-expressed CYP. Bakuchicin strongly inhibited CYP1A-mediated phenacetin O-deethylation with an IC 50 value of 0.43 M in HLMs. It was confirmed by human recombinant cDNA-expressed CYP1A1 and CYP1A2 with a value of 0.11 M and 0.32 M, respectively. A Lineweaver-Burk plot indicated that the inhibition mechanism of bakuchicin was competitive inhibition. Overall, this is the first study to investigate the potential CYP1A1 and CYP1A2 inhibition associated with bakuchicin and to report its competitive inhibitory effects on HLMs

Patterns of inflammatory immune responses in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine: clustering analysis in Korea

Background Sepsis is characterized by heterogeneous immune responses that may evolve during the course of illness. This study identified inflammatory immune responses in septic patients receiving vitamin C, hydrocortisone, and thiamine. Methods This was a single-center, post-hoc analysis of 95 patients with septic shock who received the vitamin C protocol. Blood samples were drawn on days 1–2, 3–4, and 6–8 after shock onset. Group-based multi-trajectory modeling was used to identify immune trajectory groups. Results The median age was 78 years (interquartile range, 70–84 years), and 56% were male. Clustering analysis identified group 1 (n=41), which was characterized by lower interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels, and these levels remained stationary or mildly increased until day 7. Conversely, group 2 (n=54) expressed initially higher IL-6, TNF-α, and IL-10 levels that decreased rapidly by day 4. There was a nonsignificant increase in lymphocyte count and a decrease in C-reactive protein level until day 7 in group 2. The intensive care unit mortality rate was significantly lower in group 2 (39.0% vs. 18.5%, P=0.03). Group 2 also had a significantly higher decrease in the mean (standard deviation) vasopressor dose (norepinephrine equivalent: –0.09±0.16 μg/kg/min vs. –0.23±0.31 μg/kg/min, P<0.001) and Sequential Organ Failure Assessment score (0±5 vs. –4±3, P=0.002) between days 1 and 4. Conclusions There may be different subphenotypes in septic patients receiving the vitamin C protocol

Hepatic Metastasis from Choriocarcinoma: Angiographic Findings in Two Cases

We report two cases of hepatic metastases from choriocarcinoma in women of childbearing age in whom imaging studies performed at presentation revealed the presence of liver masses, and who had clinically progressive anemia or intraabdominal hemorrhage. CT demonstrated heterogeneously enhanced liver masses. Characteristic angiographic findings included hypervascular hepatic masses with aneurysmal dilatations of the peripheral hepatic arteries at the arterial phase and persistent vascular lakes at the venous phase

A Cdo–Bnip-2–Cdc42 signaling pathway regulates p38α/β MAPK activity and myogenic differentiation

The p38α/β mitogen-activated protein kinase (MAPK) pathway promotes skeletal myogenesis, but the mechanisms by which it is activated during this process are unclear. During myoblast differentiation, the promyogenic cell surface receptor Cdo binds to the p38α/β pathway scaffold protein JLP and, via JLP, p38α/β itself. We report that Cdo also interacts with Bnip-2, a protein that binds the small guanosine triphosphatase (GTPase) Cdc42 and a negative regulator of Cdc42, Cdc42 GTPase-activating protein (GAP). Moreover, Bnip-2 and JLP are brought together through mutual interaction with Cdo. Gain- and loss-of-function experiments with myoblasts indicate that the Cdo–Bnip-2 interaction stimulates Cdc42 activity, which in turn promotes p38α/β activity and cell differentiation. These results reveal a previously unknown linkage between a cell surface receptor and downstream modulation of Cdc42 activity. Furthermore, interaction with multiple scaffold-type proteins is a distinctive mode of cell surface receptor signaling and provides one mechanism for specificity of p38α/β activation during cell differentiation

Clinical outcomes of chemoradiotherapy for locally recurrent rectal cancer

<p>Abstract</p> <p>Background</p> <p>To assess the clinical outcome of chemoradiotherapy with or without surgery for locally recurrent rectal cancer (LRRC) and to find useful and significant prognostic factors for a clinical situation.</p> <p>Methods</p> <p>Between January 2001 and February 2009, 67 LRRC patients, who entered into concurrent chemoradiotherapy with or without surgery, were reviewed retrospectively. Of the 67 patients, 45 were treated with chemoradiotherapy plus surgery, and the remaining 22 were treated with chemoradiotherapy alone. The mean radiation doses (biologically equivalent dose in 2-Gy fractions) were 54.6 Gy and 66.5 Gy for the chemoradiotherapy with and without surgery groups, respectively.</p> <p>Results</p> <p>The median survival duration of all patients was 59 months. Five-year overall (OS), relapse-free (RFS), locoregional relapse-free (LRFS), and distant metastasis-free survival (DMFS) were 48.9%, 31.6%, 66.4%, and 40.6%, respectively. A multivariate analysis demonstrated that the presence of symptoms was an independent prognostic factor influencing OS, RFS, LRFS, and DMFS. No statistically significant difference was found in OS (p = 0.181), RFS (p = 0.113), LRFS (p = 0.379), or DMFS (p = 0.335) when comparing clinical outcomes between the chemoradiotherapy with and without surgery groups.</p> <p>Conclusions</p> <p>Chemoradiotherapy with or without surgery could be a potential option for an LRRC cure, and the symptoms related to LRRC were a significant prognostic factor predicting poor clinical outcome. The chemoradiotherapy scheme for LRRC patients should be adjusted to the possibility of resectability and risk of local failure to focus on local control.</p

Zanthoxylum ailanthoides

Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF-α, suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells