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BackgroundBecause most community hospitals in Japan do not maintain 24-h availability of in-house anesthesiologists, surgeons, and interventional radiologists, staffing dramatically declines during off hours. It is unclear whether, in such under-resourced hospitals, trauma patients presenting during off hours and requiring subspecialty intervention have worse outcomes than those who present during business hours.MethodsThis was a retrospective cohort study at a community hospital in Japan. Participants were all injured patients requiring emergency trauma surgery or transarterial embolization who presented from January 2002 to December 2013. We investigated whether outcomes of these patients differed between business hours (8:01 AM to 6:00 PM weekdays) and off hours (6:01 PM to 8:00 AM weekdays plus all weekend hours). The primary outcome measure was mortality rate, and the secondary outcome measures were duration of emergency room (ER) stay; unexpected death (death/probability of survival > 0.5); and adverse events occurring in the ER. We adjusted for potential confounders of age, sex, Injury Severity Score (ISS), Revised Trauma Score, presentation phase (2002–2005, 2006–2009, and 2010–2013), Charlson Comorbidity Index, and injury type (blunt or penetrating) using logistic regression models.ResultsOf the 805 patients included, 379 (47.1%) presented during business hours and 426 (52.9%) during off hours. Off-hours presentation was associated with longer ER stays for patients with systolic blood pressure < 90 mmHg on admission (p = 0.021), ISS >15 (p = 0.047), and pelvic fracture requiring transarterial embolization (p < 0.001). Off-hours presentation was also associated with increased risk of adverse events in the ER (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1–2.7, p = 0.020). After adjustment for confounders, an increased risk of adverse events (OR 1.6, 95% CI 1.1–2.7, p = 0.049) persisted, but no differences were detected in mortality (p = 0.80) and unexpected death (p = 0.44) between off hours and business hours.ConclusionsAt a community hospital in Japan, presentation during off hours was associated with a longer ER stay for severely injured patients and increased risk of adverse events in the ER. However, these disadvantages did not impact mortality or unexpected outcome.

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Nogo receptor type 1 (NgR1) is known to inhibit neuronal regeneration in the CNS. We have previously identified lateral olfactory tract usher substance (LOTUS) interacts with NgR1 and inhibits its function by blocking its ligand binding. Therefore, LOTUS is expected to have therapeutic potential for the promotion of neuronal regeneration. However, it remains unknown whether the soluble form of LOTUS (s-LOTUS) also has an inhibitory action on NgR1 function as a candidate for therapeutic agents. Here, we show that s-LOTUS inhibits NgR1-mediated signaling by inhibiting the molecular interaction between NgR1 and its co-receptor p75 neurotrophin receptor (p75). In contrast to the membrane-bound form of LOTUS, s-LOTUS did not block ligand binding to NgR1. However, we identified p75 as a novel LOTUS binding partner, and found that s-LOTUS suppressed the interaction between p75 and NgR1. s-LOTUS inhibited myelin-associated inhibitor (MAI)-induced RhoA activation in murine cortical neurons. Functional analyses revealed that s-LOTUS inhibited MAI-induced growth cone collapse and neurite outgrowth inhibition in chick DRG neurons. In addition, while olfactory bulb (OB) neurons of -KO mice are sensitive to MAI due to a lack of LOTUS expression, treatment with s-LOTUS inhibited MAI-induced growth cone collapse in these neurons. Finally, we observed that s-LOTUS promoted axonal regeneration in optic nerve crush injury of mice (either sex). These findings suggest that s-LOTUS inhibits NgR1-mediated signaling possibly by interfering with the interaction between NgR1 and p75 Thus, s-LOTUS may have potential as a therapeutic agent for neuronal regeneration in the damaged CNS.Nogo receptor type 1 (NgR1) is a well-known receptor to inhibit neuronal regeneration in the CNS. Because the membrane-bound form of LOTUS antagonizes NgR1 through a cis-type molecular interaction between LOTUS and NgR1, the soluble form of LOTUS (s-LOTUS) is expected to be a therapeutic agent for neuronal regeneration. In our present study, we show that s-LOTUS inhibits the interaction between NgR1 and p75, NgR1 ligand-induced RhoA activation, growth cone collapse and neurite outgrowth inhibition, and promotes axonal regeneration. Our results indicate that s-LOTUS inhibits NgR1-mediated signaling through a trans-type molecular interaction between LOTUS and NgR1, and therefore, s-LOTUS may have therapeutic potential for neuronal regeneration.

Summary Rats were fed diets with and without 0.5% L -cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C ϩ 0.65% methionine or 25C ϩ 0.4% guanidinoacetic acid. Hepatic S -adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine ␤ -synthase and betaine-homocysteine S -methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine. Key Words hypohomocysteinemic effect, cysteine, homocysteine, low protein diet, low methionine diet Homocysteine is an intermediate in the metabolism of methionine (Fig. 1) ( 1 ), but a number of studies have suggested that an elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease ( 2 -4 ). It is thought that elevated plasma homocysteine concentrations cause arterial damage by several mechanisms, e.g., endothelial cell injury, platelet activation, and increased oxidizability of low-density lipoproteins ( 4 ). In humans, the normal range of plasma homocysteine concentration is 5 to 15 M , and a 5-M increase in the concentration of this amino acid is associated with a 60-80% increased risk of coronary heart disease ( 3 ). The plasma homocysteine concentration is affected by various factors, such as nutritional, physiological, hormonal, pharmacological, lifestyle, disease, and genetic factors ( 2 -4 ). Of these factors, genetic and nutritional factors are thought to have a greater influence on plasma homocysteine concentration. Many studies have been conducted in humans to investigate the effect of dietary treatments on plasma homocysteine concentration. However, studie...