Endodontic considerations of survival rate for autotransplanted third molars: a nationwide population-based study.

AIM: To investigate whether the timing of root canal treatment (primary aim) or other endodontic parameters (secondary aim) is associated with the survival probability of autotransplanted third molars, using a nationwide population-based database. METHODOLOGY: A total of 1811 third molars autotransplanted between 2000 and 2013 met the inclusion criteria and were followed until the end of 2016. The teeth were classified into three groups on the basis of timing between root canal treatment and the autotransplantation: preoperative, extraoral and postoperative treatment groups. Univariate and multivariate Cox proportional hazards models were used to estimate the association between the timing of root canal treatment and the risk of tooth extraction after autotransplantation. RESULTS: Of the 1811 autotransplanted third molars, 462 were extracted, yielding a 17-year survival probability of 0.578. The survival probability of autotransplanted teeth that received postoperative root fillings after 17 years was 0.583, which was significantly higher than the 0.434 and 0.566 for teeth that received preoperative and extraoral root fillings, respectively (P = 0.0013). After adjustment for potential confounding factors, teeth that received postoperative root fillings were associated with a significantly lower tooth extraction hazard ratio (HR) compared with those that received extraoral root fillings (adjusted HR, 1.43; 95% confidence interval [CI], 1.14-1.78) and those that received preoperative root fillings (adjusted HR, 2.13; 95% CI, 1.19-3.82). Furthermore, the use of a rubber dam during postoperative root filling was associated with a significantly lower extraction rate after autotransplantation (adjusted HR, 0.54; 95% CI, 0.43-0.69). CONCLUSIONS: Postoperative root canal treatment resulted in a significantly lower extraction rate than did preoperative or extraoral root canal treatment amongst autotransplanted third molars during a mean follow-up period of 8.33 years. Rubber dam use is recommended during postoperative root canal treatment to improve the outcomes of autotransplantation.

Use of independent component analysis to improve signal-to-noise ratio in multi-probe fluorescence microscopy.

In conventional multi-probe fluorescence microscopy, narrow bandwidth filters on detectors are used to avoid bleed-through artefacts between probes. The limited bandwidth reduces the signal-to-noise ratio of the detection, often severely compromising one or more channels. Herein, we describe a process of using independent component analysis to discriminate the position of different probes using only a dichroic mirror to differentiate the signals directed to the detectors. Independent component analysis was particularly effective in samples where the spatial overlap between the probes is minimal, a very common case in cellular microscopy. This imaging scheme collects nearly all of the emitted light, significantly improving the image signal-to-noise ratio. In this study, we focused on the detection of two fluorescence probes used in vivo, NAD(P)H and ANEPPS. The optimal dichroic mirror cutoff frequency was determined with simulations using the probes spectral emissions. A quality factor, defined as the cross-channel contrast-to-noise ratio, was optimized to maximize signals while maintaining spatial discrimination between the probes after independent component analysis post-processing. Simulations indicate that a ∼3 fold increase in signal-to-noise ratio using the independent component analysis approach can be achieved over the conventional narrow-band filtering approach without loss of spatial discrimination. We confirmed this predicted performance from experimental imaging of NAD(P)H and ANEPPS in mouse skeletal muscle, in vivo. For many multi-probe studies, the increased sensitivity of this 'full bandwidth' approach will lead to improved image quality and/or reduced excitation power requirements.

ST22 and ST239 MRSA duopoly in Singaporean hospitals: 2006-2010.

Surveillance is integral for the monitoring and control of infectious diseases. We conducted prospective laboratory surveillance of methicillin-resistant Staphylococcus aureus (MRSA) in five Singaporean public-sector hospitals from 2006 to 2010, using WHONET 5.6 for data compilation and analysis. Molecular profiling using multilocus variable-number tandem-repeat analysis, staphylococcal cassette chromosome mec classification and multilocus sequence typing was performed for a random selection of isolates. Our results showed overall stable rates of infection and bacteraemia, although there was significant variance among the individual hospitals, with MRSA rates increasing in two smaller hospitals and showing a trend towards decreasing in the two largest hospitals. The proportion of blood isolates that are EMRSA-15 (ST22-IV) continued to increase over time, slowly replacing the multi-resistant ST239-III. A new MRSA clone - ST45-IV - is now responsible for a small subset of hospital infections locally. More effort is required in Singaporean hospitals in order to reduce the rates of MRSA infection significantly.

Prospective audit and feedback on antibiotic prescription in an adult hematology-oncology unit in Singapore.

We evaluated the impact of a prospective audit and feedback antimicrobial stewardship program (ASP) on antibiotic prescription and resistance trends in a hematology-oncology unit in a university hospital (National University Cancer Institute, Singapore [NCIS]). A prospective interrupted time-series study comprising 11-month pre-intervention (PIP) and intervention evaluation phases (IEP) flanking a one-month implementation phase was carried out. Outcome measures included defined daily dose per 100 (DDD/100) inpatient-days of ASP-audited and all antibiotics (encompassing audited and non-audited antibiotics), and the incidence-density of antibiotic-resistant microorganisms at the NCIS. Internal and external controls were DDD/100 inpatient-days of paracetamol at the NCIS and DDD/100 inpatient-days of antibiotics prescribed in the rest of the hospital. There were 580 ASP recommendations from 1,276 audits, with a mean monthly compliance of 86.9%. Significant reversal of prescription trends towards reduced prescription of audited (coefficient = -2.621; 95% confidence interval [CI]: -4.923, -0.319; p = 0.026) and all evaluated antibiotics (coefficient = -4.069; 95% CI: -8.075, -0.063; p = 0.046) was observed. No changes were seen for both internal and external controls, except for the reversal of prescription trends for cephalosporins hospital-wide. Antimicrobial resistance did not change over the time period of the study. Adverse outcomes-the majority unavoidable-occurred following 5.5% of accepted ASP recommendations. Safe and effective ASPs can be implemented in the complex setting of hematology-oncology inpatients.

Acinetobacter calcoaceticus-Acinetobacter baumannii complex species in clinical specimens in Singapore.

This study was performed to determine the prevalence, distribution of specimen sources, and antimicrobial susceptibility of the Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) species complex in Singapore. One hundred and ninety-three non-replicate Acb species complex clinical isolates were collected from six hospitals over a 1-month period in 2006. Of these, 152 (78·7%) were identified as A. baumannii, 18 (9·3%) as 'Acinetobacter pittii' [genomic species (gen. sp.) 3], and 23 (11·9%) as 'Acinetobacter nosocomialis' (gen. sp. 13TU). Carbapenem resistance was highest in A. baumannii (72·4%), followed by A. pittii (38·9%), and A. nosocomialis (34·8%). Most carbapenem-resistant A. baumannii and A. nosocomialis possessed the bla(OXA-23-like) gene whereas carbapenem-resistant A. pittii possessed the bla(OXA-58-like) gene. Two imipenem-resistant strains (A. baumannii and A. pittii) had the bla(IMP-like) gene. Representatives of carbapenem-resistant A. baumannii were related to European clones I and II.

Use of procalcitonin (PCT) to guide discontinuation of antibiotic use in an unspecified sepsis is an antimicrobial stewardship program (ASP).

Clinicians have used procalcitonin (PCT) (biomarker to differentiate bacterial from non-bacterial sepsis) to guide use of antibiotics in patients. As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program (ASP) are lacking, we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP. An antimicrobial stewardship (AS) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis, source of sepsis unknown or negative bacteriological cultures, who had completed an adequate course of antibiotic therapy and had a PCT of <0.5 µg/L. Main outcomes evaluated were 14-day re-infection, 30-day mortality and readmission. Antibiotic therapy was discontinued in 42 patients in 1 year. Unknown source of sepsis was found in 38% of the patients (including possible malignant fever) and culture-negative pneumonia was found in 21%. Two patients died of advanced cancer. One patient decided for comfort care and died one week later. One patient died due to a second episode of pneumonia 37 days after first PCT test. Six patients were readmitted within 30 days due to non-infectious causes. Three patients were readmitted due to culture-negative pneumonia. None had a 14-day re-infection. PCT used to discontinue antibiotics under our ASP did not compromise patients' outcome.

KMUP-1 inhibits H441 lung epithelial cell growth, migration and proinflammation via increased NO/CGMP and inhibited RHO kinase/VEGF signaling pathways.

This study investigates whether KMUP-1 protects soluble guanylate cyclase (sGC) and inhibits vascular endothelial growth factor (VEGF) expression in lung epithelial cells in hypoxia, therapeutically targeting epithelial proinflammation. H441 cells were used as a representative epithelial cell line to examine the role of sGC and VEGF in hypoxia and the anti-proinflammatory activity of KMUP-1 in normoxia. Human H441 cells were grown in hypoxia for 24-72 h. KMUP-1 (1, 10, 100 microM) arrested cells at the G0/G1 phase of the cell cycle, reduced cell survival and migration, increased p21/p27, restored eNOS, increased soluble guanylate cyclase (sGC) and PKG and inhibited Rho kinase II (ROCK-II). KMUP-1 (0.001-0.1 microM) concentration dependently increased eNOS in normoxia and did not inhibit phosphodiesterase-5A (PDE-5A) in hypoxic cells. Hypoxia-induced factor-1alpha (HIF-1alpha) and VEGF were suppressed by KMUP-1 but not by L-NAME (100 microM). The PKG inhibitor Rp-8-CPT-cGMPS (10 microM) blunted the inhibition of ROCK-II by KMUP-1. KMUP-1 inhibited thromboxane A2-mimetic agonist U46619-induced PDE-5A, TNF-alpha (100 ng/ml)-induced iNOS, and ROCK-II and associated phospho-p38 MAPK, suggesting multiple anti-proinflammatory activities. In addition, increased p21/p27 by KMUP-1 at higher concentrations might contribute to an increased Bax/Bcl-2 and active caspase-3/procaspase-3 ratio, concomitantly causing apoptosis. KMUP-1 inhibited ROCK-II/VEGF in hypoxia, indicating its anti-neoplastic and anti-inflammatory properties. KMUP-1 inhibited TNF-alpha-induced iNOS and U46619-induced PDE-5A and phospho-p38 MAPK in normoxia, confirming its anti-proinflammatory action. KMUP-1 could be used as an anti-proinflammatory to reduce epithelial inflammation.

Association of depression and diabetes complications and mortality: a population-based cohort study.

AIMS: Several studies suggested that depression might worsen the clinical outcome of diabetes mellitus; however, such association was confounded by duration of illness and baseline complications. This study aimed to assess whether depression increases the risk of diabetes complications and mortality among incident patients with diabetes. METHODS: This was a population-based matched cohort study using Taiwan's National Health Insurance Research Database. A total of 38 537 incident patients with diabetes who had depressive disorders and 154 148 incident diabetes patients without depression who were matched by age, sex and cohort entry year were randomly selected. The study endpoint was the development of macrovascular and microvascular complications, all-cause mortality and cause-specific mortality. RESULTS: Among participants, the mean (±SD) age was 52.61 (±12.45) years, and 39.63% were male. The average duration of follow-up for mortality was 5.5 years, ranging from 0 to 14 years. The adjusted hazard ratios were 1.35 (95% confidence interval [CI], 1.32-1.37) for macrovascular complications and 1.08 (95% CI, 1.04-1.12) for all-cause mortality. However, there was no association of depression with microvascular complications, mortality due to cardiovascular diseases or mortality due to diabetes mellitus. The effect of depression on diabetes complications and mortality was more prominent among young adults than among middle-aged and older adults. CONCLUSIONS: Depression was associated with macrovascular complications and all-cause mortality in our patient cohort. However, the magnitude of association was less than that in previous studies. Further research should focus on the benefits and risks of treatment for depression on diabetes outcome.

Incorrect diagnoses in patients with neutralizing anti-interferon-gamma-autoantibodies.

OBJECTIVES: Early diagnosis of adult-onset immunodeficiency associated with neutralizing anti-interferon-gamma autoantibodies (anti-IFNγ Abs) remains difficult given the lack of a distinctive phenotype and a routine test. This study aimed to investigate the determinants of incorrect tentative diagnoses and useful clues for early disease recognition. METHODS: This study enrolled adult patients who had unexplained opportunistic infections diagnosed at six hospitals and identified those having neutralizing anti-IFNγ Abs (cases). Demographics, medical history, initial presentations and laboratory data, causative pathogens, tentative diagnoses, and treatment were analysed and compared among individuals having neutralizing anti-IFNγ Abs (cases) and those without (controls). RESULTS: Among the 154 patients enrolled, neutralizing anti-IFN-γ Abs were detected in 50 (71%) of 70 patients with disseminated non-tuberculous mycobacterial infection (dNTM) but not in 84 patients without dNTM. The median time from disease onset to the recognition of dNTM associated with neutralizing anti-IFNγ Abs was 1.6 years (range, 0.25-19 years). Incorrect tentative diagnoses resulted in the administration of anti-tuberculosis regimens (60%, 30/50), immunosuppressants (48%, 24/50), and systemic chemotherapy (2%, 10/50) to the 50 cases. Multivariate analysis revealed that case patients were more likely than controls to present with multiple bone lesions (adjusted odds ratio (OR), 27.16; 95% confidence interval (CI), 1.21-609.59) and leukocytosis (adjusted OR, 1.48; 95% CI, 1.12-1.95); however, the controls had a higher rate of mycobacterial bloodstream infection (adjusted OR, 0.05; 95% CI 0.00-0.66). CONCLUSIONS: The high rate of incorrect tentative diagnoses led to frequent inappropriate management in patients with neutralizing anti-IFNγ Abs, and highlighted the need for increased awareness among clinicians.

Prevalence and molecular characteristics of Staphylococcus aureus isolates colonizing patients with atopic dermatitis and their close contacts in Singapore.

BACKGROUND: Staphylococcus aureus colonization is an established pathogenic factor for disease flare in atopic dermatitis (AD). OBJECTIVES: We conducted a study to investigate the colonization of S. aureus in patients with AD and their close contacts in order to evaluate the possibility of intrafamilial transmission. We sought to determine the distribution of the bacterial virulence factors and their correlation with disease severity. METHODS: Nasal swabs and skin swabs (patients with AD only) were taken from patients with AD aged 2-21 years and their close contacts, seen at the National Skin Centre from January to March 2007. All S. aureus isolates were typed using multilocus variable-number tandem-repeat fingerprinting (MLVF) and screened for virulence factors via polymerase chain reaction (PCR) analysis. AD severity was determined by the SCORAD index. RESULTS: A total of 34 patients with AD and 55 close contacts were recruited. Thirty-one (91%) patients were colonized with S. aureus. Twenty-five (45%) of their close contacts were also colonized, and MLVF showed a high concordance of S. aureus isolates in index patients and their close contacts. On multivariate analysis, patients with a moderate SCORAD were more likely to be colonized by enterotoxin B-positive S. aureus (P = 0.027). No virulence factor was significantly associated with a severe SCORAD. CONCLUSIONS: The prevalence of S. aureus colonization was high among patients with AD and their close contacts. However, no predominant isolate of S. aureus was found to be associated with AD. The presence of superantigen B is possibly associated with moderate rather than severe disease in our population.

Phase transition and crystal structure of the 37 degrees C form of cholesterol.

Crystalline cholesterol undergoes a phase transition a few degrees below human body temperature. The high-temperature form has an unusually complex structure with 16 independent molecules. In the transition two molecules change side chain conformation, four reorient about their long axes, and ten remain unchanged. The transition mechanism implies relatively nonspecific intermolecular interactions, qualitatively consistent with the behavior of cholesterol in biomembranes. The transition preserves a remarkably closely obeyed pseudosymmetry present in the structure.

System for real-time monitoring of mutation-in-progress.

AIMS: There has been an increasing number of pathogens becoming resistant to multiple classes of antibiotics. The study on how mutation emerges is therefore crucial to promote further understanding in this area. Conventional methods for such studies involve the monitoring of growth by standard plate count and biomolecular sequencing. This is however tedious and not cost effective. The aim of this paper is thus to introduce a novel system that enables real-time monitoring of bacterial 'mutation-in-progress'. METHODS AND RESULTS: This system provides real-time data, thus enabling confirmatory and further work to be performed at the important points when mutation is initiated. The system integrates spectroscopic techniques as the detection system and various supporting systems, such as a nutrient replenishing system, a pH control system and a waste system to allow for extended monitoring. In this paper, the feasibility of monitoring the emergence of ciprofloxacin resistance in Staphylococcus aureus was demonstrated as an initial example. The integrated system was found to require significantly less material resource and manpower compared with conventional techniques. CONCLUSIONS: The novel system to monitor bacterial mutation-in-progress is presented. The work reported herein demonstrates such a system to be effective and efficient in performing real-time monitoring of mutation-in-progress, especially in extended time frames for mutation into the weeks and months. SIGNIFICANCE AND IMPACT OF THE STUDY: With the successful optimization of this system, researchers can learn about the dynamics of antibiotic resistance and further understand how the mutation of bacteria occurs.

Emergence of community-associated methicillin-resistant Staphylococcus aureus in Singapore: a further six cases.

INTRODUCTION: The clinical features and molecular epidemiology of further cases of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in Singapore are described. METHODS: Six cases of CA-MRSA infection that occurred between April and October 2004 are described. The bacterial isolates were tested for the presence of Panton-Valentine leukocidin (PVL) genes and typed via pulsedfield gel electrophoresis, staphylococcal chromosomal cassette mec (SCCmec) and multi-locus sequence typing. The results were compared with that of previously-reported local and international CA-MRSA isolates. RESULTS: There were four cases of cutaneous abscesses and one each of chronic osteomyelitis and endocarditis. CA-MRSA isolates from the last two cases tested negative for PVL genes. Three isolates were identical and related to the Oceanian clone, and one isolate to the predominant Taiwanese clone. The isolate causing osteomyelitis had a novel sequence type. CONCLUSION: CA-MRSA, though uncommon, is being isolated with increasing frequency in Singapore. A predominant clone (ST30- MRSA-IV) seems to be emerging locally.

Directly Placed Restorative Materials: Review and Network Meta-analysis.

For restoring cavitated dental lesions, whether carious or not, a large number of material combinations are available. We aimed to systematically review and synthesize data of comparative dental restorative trials. A systematic review was performed. Randomized controlled trials published between 2005 and 2015 were included that compared the survival of ≥2 restorative and/or adhesive materials (i.e., no need for restorative reintervention). Pairwise and Bayesian network meta-analyses were performed, with separate evaluations for cervical cavitated lesions and load-bearing posterior cavitated lesions in permanent and primary teeth. A total of 11,070 restorations (5,330 cervical, 5,740 load bearing) had been placed in 3,633 patients in the included trials. Thirty-six trials investigated restoration of cervical lesions (all in permanent teeth) and 36 of load-bearing lesions (8 in primary and 28 in permanent teeth). Resin-modified glass ionomer cements had the highest chance of survival in cervical cavitated lesions; composites or compomers placed via 2-step self-etch and 3-step etch-and-rinse adhesives were ranked next. Restorations placed with 2-step etch-and-rinse or 1-step self-etch adhesives performed worst. For load-bearing restorations, conventional composites had the highest probability of survival, while siloranes were found least suitable. Ambiguity remains regarding which adhesive strategy to use in load-bearing cavitated lesions. Most studies showed high risk of bias, and several comparisons were prone for publication bias. If prioritized for survival, resin-modified glass ionomer cements might be recommended to restore cervical lesions. For load-bearing ones, conventional or bulk fill composites seem most suitable. The available evidence is quantitatively and qualitatively insufficient for further recommendations, especially with regard to adhesive strategies in posterior load-bearing situations. Moreover, different material classifications might yield different findings on the same materials. Future trials should aim for sufficient power, longer follow-up times, and high internal validity to prove or refute differences between certain material combinations. An agreed material classification for future syntheses is desirable.

Rapidly growing mycobacteria in Singapore, 2006-2011.

Nontuberculous mycobacteria infection is a growing global concern, but data from Asia are limited. This study aimed to describe the distribution and antibiotic susceptibility profiles of rapidly growing mycobacterium (RGM) isolates in Singapore. Clinical RGM isolates with antibiotic susceptibility tests performed between 2006 and 2011 were identified using microbiology laboratory databases and minimum inhibitory concentrations of amikacin, cefoxitin, clarithromycin, ciprofloxacin, doxycycline, imipenem, linezolid, moxifloxacin, sulfamethoxazole or trimethoprim-sulfamethoxazole, tigecycline and tobramycin were recorded. Regression analysis was performed to detect changes in antibiotic susceptibility patterns over time. A total of 427 isolates were included. Of these, 277 (65%) were from respiratory specimens, 42 (10%) were related to skin and soft tissue infections and 36 (8%) were recovered from blood specimens. The two most common species identified were Mycobacterium abscessus (73%) and Mycobacterium fortuitum group (22%), with amikacin and clarithromycin being most active against the former, and quinolones and trimethoprim-sulfamethoxazole against the latter. Decreases in susceptibility of M. abscessus to linezolid by 8.8% per year (p 0.001), M. fortuitum group to imipenem by 9.5% per year (p 0.023) and clarithromycin by 4.7% per year (p 0.033) were observed. M. abscessus in respiratory specimens is the most common RGM identified in Singapore. Antibiotic options for treatment of RGM infections are increasingly limited.

Treating pit-and-fissure caries: a systematic review and network meta-analysis.

For shallow or moderately deep pit-and-fissure lesions, various treatment options are available: (1) noninvasive treatments (e.g., fluoride application, antibacterial treatments, oral hygiene advice) avoid any dental hard tissue removal; (2) microinvasive treatments (e.g., sealing) remove only a few micrometers of hard tissues by etching; and minimally invasive methods (e.g., "preventive" resin/sealant restoration) remove carious dentin but avoid sacrificing sound tissues. We aimed at systematically reviewing and comparing these strategies for treating pit-and-fissure lesions in permanent teeth using network meta-analysis. Randomized or nonrandomized clinical trials investigating shallow or moderately deep primary caries lesions in fissured or pitted surfaces were included. We compared the risk of requiring invasive treatments or any retreatments in noninvasive, microinvasive, and minimally invasive treated lesions; untreated lesions were used as controls. Five electronic databases were systematically screened up to September 2013 and cross-referencing performed. Pairwise and network meta-analyses were performed and odds ratios and 95% confidence intervals (CI) calculated. Certainty of estimates was evaluated via GRADE criteria. From a total of 2,214 identified records, 14 studies representing 1,440 patients with 3,551 treated lesions were included. Pairwise meta-analysis found microinvasive and minimally invasive treated lesions to require less invasive retreatments than control lesions (odds ratios [95% confidence intervals]: 0.13 [0.07 to 0.26], 0.13 [0.03 to 0.50], respectively), whereas the estimate for noninvasively treated lesions remained nonsignificant (0.64 [0.39 to 1.06]). These findings were reflected in the strategy ranking stemming from network meta-analysis (first, minimally invasive; second, microinvasive; third, noninvasive). However, microinvasive treatment required significantly more total retreatments (including resealing) than minimally or noninvasive treatments. Due to limited study quality, the evidence was graded as low or very low. Clinical treatment decisions should consider the long-term sequelae and costs stemming from different therapies as well as their subjective impact on the patient. Available treatment options seem suitable for treating shallow or moderately deep pit-and-fissure lesions in permanent teeth; further conclusions are not possible.