Nitric oxide (NO), synthesized from L-arginine by a family of constitutive and inducible NO synthases (iNOS), is a small, diffusible, diatomic, highly reactive molecule with a variety of cellular functions in all mammalian cells. 1) Recently, it was shown that NO plays an important role in stem cell proliferation and differentiation. It has been reported that, at physiological concentrations, NO functions as a negative regulator of stem/progenitor cell proliferation and is critical to the initiation of cell differentiation.2,3) NO also promotes bone and chondrocyte terminal differentiation ; stimulates preadipocyte differentiation in rat 6) ; and mediates osteoblastic differentiation.7) In addition, NO synthase inhibitors have been shown to arrest differentiation toward a cardiac phenotype in mouse embryonic stem cells; differentiation is rescued by NO donors. 8) In contrast, NO donor sodium nitroprusside (SNP) inhibits mineralization in the mouse chondrocyte-like ATDC5 cell line. 9) However, whether NO can affect the differentiation of periodontal ligament (PDL) cells is unknown.The PDL is a non-mineralized connective tissue which surrounds the tooth and exhibits osteoblast-like features, such as high alkaline phosphatase (ALP) activity and expression of osteonectin (ON), bone sialoprotein (BSP), osteocalcin (OC), and osteopontin (OPN). The cells that compose the PDL are capable of differentiating into osteoblasts or cementoblasts.10) Moreover, PDL cells have demonstrated stem cell properties such as self-renewal, clonogenicity, and multitissue differentiation potential.11) In addition, PDL cells can differentiate in response to a variety of extracellular stimuli, serving either to maintain homeostasis or to remodel, repair, and regenerate the surrounding hard tissue.12) Recently, increased NO production during osteogenic differentiation has been reported in human PDL cells, 13) but the role of NO in osteoblastic differentiation of these cells requires further investigation.Heme oxygenase (HO) is the rate-limiting enzyme involved in the catabolism of heme, yielding equimolar quantities of carbon monoxide (CO), free iron, and biliverdin; the latter two compounds are converted to ferritin and bilirubin, respectively. 14) One of three mammalian HO isoforms, HO-1 (also called heat shock protein 32), is a stress-responsive protein induced by various agents and is involved in a variety of regulatory and protective mechanisms in cells. 15,16) We previously reported that HO-1 is induced by pro-inflammatory cytokines, NO, substance P, hydrogen peroxide, and mechanical stress, [17][18][19][20][21][22][23] and that it may play a cytoprotective role in human pulp and PDL cells. However, HO-1-mediated NOinductive effects of osteoblastic differentiation in PDL cells has not yet been reported.Understanding the mechanisms that regulate osteogenic differentiation in human PDL cells will have important implications for the development of new therapeutic strategies in periodontal defects. This study aimed to investigate whether h...

The purpose of this study was to report a case of a previously healthy 20-year-old woman diagnosed with splenic infarction following infectious mononucleosis (IM) by Epstein-Barr virus (EBV) infection and to perform the first systematic review of the clinical characteristics of splenic infarction associated with IM. A systematic review was conducted using English, French, and Japanese literatures of splenic infarction associated with IM due to EBV infection published between 1961 and 2015 in PubMed Medline. A total of 19 cases were extracted from the collected articles. Left upper quadrant (LUQ) pain was observed in 15 (79%) patients. Splenectomy was performed in five (26%) cases, among which four patients presented with stable vital signs. Splenic rupture was accompanied in two (10%) patients. The median time from the onset of IM symptoms to the diagnosis of splenic infarction was 5 days (range, 1-25 days). Fourteen (74%) of 19 patients experienced improvement through medical treatment, and there were no deaths. Splenic infarction associated with IM due to EBV infection can show a favorable clinical outcome after medical treatment. Clinicians should consider the possibility of splenic infarction when patients with IM experience LUQ pain. J. Med. Virol. 89:332-336, 2017. © 2016 Wiley Periodicals, Inc.

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BackgroundA substantial portion of Clostridium difficile infection (CDI) cases occur in communities, and community-onset CDI (CO-CDI) can lead to serious complications including mortality. This study aimed to identify the risk factors for a poor outcome in CO-CDI.MethodsWe performed a retrospective review of all inpatients with CDI, in a 1300-bed tertiary-care hospital in Korea, from 2008 through 2015. CO-CDI was defined as CDI occurring within 48 h of admission. Poor outcome was defined as follows: 1) all-cause 30-day mortality, 2) in-hospital mortality, or 3) surgery due to CDI.ResultsOf a total 1256 CDIs occurring over 8 years, 152 (12.1%) cases were classified as CO-CDI and 23 (15.1%) had a poor outcome, including 22 (14.5%) cases of mortality and 2 (1.3%) cases of surgery. Patients with a poor outcome had a higher mean age than those without a poor outcome (75.8 vs. 69.6 years, p = 0.03). The proportion of men and prior proton pump inhibitor (PPI) use were significantly higher in the poor outcome group (65.2% vs. 41.9%, p = 0.04; 39.1% vs. 17.6%, p = 0.02, respectively). Multivariate binary logistic model showed that PPI use and anemia (hemoglobin < 10 g/dL) at presentation were significantly associated with a poor outcome (adjusted odds ratio [aOR], 3.76; 95% confidence interval [95CI], 1.26–11.21, aOR, 4.67; 95CI, 1.52–14.34, respectively).ConclusionsClinicians should not only be aware of the possibility of CDI in the community setting but also pay more attention to PPI-using elderly patients with anemia in consideration of a poor outcome.Electronic supplementary materialThe online version of this article (10.1186/s13756-018-0365-6) contains supplementary material, which is available to authorized users.

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BackgroundDespite vancomycin use is a major risk factor for the emergence of vancomycin resistance, it is frequently inappropriately prescribed, especially as empirical treatment. We evaluated the effect of an antimicrobial stewardship intervention targeting for inappropriate continued empirical vancomycin use.MethodsThis was a quasi-experimental study comparing vancomycin use in a 6-month pre-intervention and 6-month intervention period. If empirical vancomycin was continued for more than 96 h without documentation of beta-lactam-resistant gram-positive microorganisms, it was considered inappropriate continued empirical vancomycin use. The intervention consisted of the monitoring of appropriateness by a pharmacist and direct discussion with the prescribing physicians by infectious disease specialists when empirical vancomycin was continued inappropriately. An interrupted time series analysis was used to compare vancomycin use before and during the intervention.ResultsFollowing implementation of the intervention, overall vancomycin consumption decreased by 14.6%, from 37.6 defined daily doses (DDDs)/1000 patient-days in the pre-intervention period to 32.1 DDDs/1000 patient-days in the intervention period (P <  0.001). The inappropriate consumption of vancomycin also declined from 8.0 DDDs/1000 patient-days to 5.8 DDDs/1000 patient-days (P = 0.009).ConclusionInterventions such as direct communication with prescribing physicians and infectious disease clinicians can help reduce the inappropriate continued use of vancomycin.

Background Reports on metastatic or invasive infections by hypervirulent Klebsiella pneumoniae (hvKP) have increased recently. However, the effects of its virulence on clinical course and outcomes in pneumonia patients have rarely been addressed. We assessed and compared the clinical features of hvKp and classic K. pneumoniae (cKP) strains isolated from patients with pneumonia caused by K. pneumoniae . We also investigated the effects of virulence factors and the K. pneumoniae capsular serotypes K1 and K2 on mortality. Methods In this retrospective study, we enrolled 91 patients diagnosed as having pneumonia caused by K. pneumoniae and obtained their demographic and clinical data from medical records. We evaluated genes for K1 and K2, antimicrobial susceptibility, and the virulence genes rmpA, iutA, entB, ybtS, kfu, mrkD , and allS . Strains that possessed rmpA and iutA were defined as hvKP (N=39), while the remaining were classified as cKP (N=52). Odds ratio (OR) for the risk factors associated with 30-day mortality was calculated using the binary logistic regression model. Results The 30-day mortality in all patients was 23.1%; it was 17.9% (7/39) in the hvKP group and 26.9% (14/52) in the cKP group ( P =0.315). Bacteremia (OR=38.1; 95% confidence interval [CI], 2.5–570.2), altered mental status (OR=8.8; 95% CI, 1.7–45.0), and respiratory rate >30 breaths/min (OR=4.8; 95% CI, 1.2–20.0) were independent risk factors for 30-day mortality in all patients. Conclusions Our results suggest that hypervirulence determinants do not have a significant effect on 30-day mortality in patients with pneumonia caused by K. pneumoniae .

BackgroundSurveillance and interventions of central line-associated bloodstream infections (CLABSIs) had mainly been targeted in intensive care units (ICUs). Central lines are increasingly used outside ICUs. Therefore, we performed a hospital-wide survey of CLABSIs to evaluate the current status and develop strategies to reduce CLBASI rates.MethodsAll hospitalized patients with central venous catheters (CVCs) were screened for CLABSIs from January 2014 through December 2015 at a 1,328 bed tertiary care teaching hospital in Korea using an electronic data-collecting system. Clinical information including type of CVC was collected. CLABSI rates were calculated using the definitions of the National Health and Safety Network after excluding mucosal barrier injury laboratory-confirmed bloodstream infection (BSI).ResultsA total of 154 CLABSIs were identified, of which 72 (46.8%) occurred in general wards and 82 (53.2%) in ICUs (0.81 and 2.71 per 1,000 catheter days), respectively. Non-tunneled CVCs were most common (68.6%) among 70 CLABSI events diagnosed within one week of their maintenance. On the other hand, tunneled CVCs and peripherally inserted central catheters (PICCs) were more common (60.5%) among 114 CLABSI events diagnosed more than a week after maintenance. Whereas the majority (72.2%) of CLABSIs in ICUs were associated with non-tunneled CVCs, tunneled CVCs (38.9%) and PICCs (36.8%) were more common in general wards.ConclusionCLABSIs are less common in general wards than in ICUs, but they are more often associated with long-term indwelling catheters. Therefore, interventions to prevent CLABSIs should be tailored according to the type of ward and type of catheter.