Background: Cerebral infarction is an important neurological complication of childhood bacterial meningitis, but little is known about its epidemiology and outcomes. Aim: To determine the predictive ...factors, clinical features, causative pathogens, and outcomes of cerebral infarction secondary to perinatal and childhood bacterial meningitis. Design: Retrospective analysis Methods: Over the period 1986–2001, 166 perinatal and childhood patients were identified as having culture-proven bacterial meningitis, of whom 14 had cerebral infarction at admission. The clinical and CSF data of patients with and without cerebral infarctions on admission were compared. Results: Cerebral infarction patients accounted for 10% (14/166) of bacterial meningitis cases, mostly in the first year of life (11/14, 79%). Salmonella species (n = 4) and Streptococcus pneumoniae (n = 4) were the most frequent causative pathogens, accounting for 57% (8/14) of episodes. Single infarctions were found in four patients and multiple infarctions in 10. At 1 year follow-up, outcome was good in three, but poor in 11. Significant differences between the two patient groups at admission included age bands, presence of seizures, hydrocephalus, disturbed consciousness on admission, and CSF lactate concentration. Discussion: There was a high prevalence of cerebral infarctions when the disease was caused by S. pneumoniae and Salmonella species. Occurrence was highest in the first year of life, and the prognosis in this patient group is poor. Risk factors associated with cerebral infarction in our patients included age 28–365 days, seizures, hydrocephalus, disturbed consciousness on admission, and high CSF lactate concentrations.
In the 2021 residency application cycle, the average otolaryngology applicant applied to more than half of programs. Increasing application numbers make it difficult for applicants to stand out to ...programs of interest and for programs to identify applicants with sincere interest.
As part of the 2021 Match, otolaryngology applicants could participate in a preference signaling process, signaling up to 5 programs of particular interest at the time of application submission. Programs received a list of applicants who submitted signals to consider during interview offer deliberations. Applicants and program directors completed surveys to evaluate the signaling process and assess the impact of signals on interview offers.
All otolaryngology residency programs participated in the signaling process. In total, 611 students submitted applications for otolaryngology residency programs, 559 applicants submitted a Match list including an otolaryngology program, and 558 applicants participated in the signaling process. The survey response rate was 42% for applicants (n = 233) and 52% for program directors (n = 62). The rate of receiving an interview offer was significantly higher from signaled programs (58%) than from both nonsignaled programs (14%; P < .001) and the comparative nonsignal program (23%; P < .001) (i.e., the program an applicant would have signaled given a sixth signal). This impact was consistent across the spectrum of applicant competitiveness. Applicants (178, 77%) and program directors (53, 91%) strongly favored continuing the program.
Many specialties face high residency application numbers. Programs have difficulty identifying applicants with sincere interest, and applicants face limited opportunities to identify programs of particular interest. Applicants to these specialties may benefit from a preference signaling process like that in otolaryngology. Additional evaluation is needed to determine the impact of signals across racial and demographic lines and to validate these early outcomes.
Current methods of chemical vapour deposition (CVD) of graphene on copper are complicated by multiple processing steps and by high temperatures required in both preparing the copper and inducing ...subsequent film growth. Here we demonstrate a plasma-enhanced CVD chemistry that enables the entire process to take place in a single step, at reduced temperatures (<420 °C), and in a matter of minutes. Growth on copper foils is found to nucleate from arrays of well-aligned domains, and the ensuing films possess sub-nanometre smoothness, excellent crystalline quality, low strain, few defects and room-temperature electrical mobility up to (6.0±1.0) × 10(4) cm(2) V(-1) s(-1), better than that of large, single-crystalline graphene derived from thermal CVD growth. These results indicate that elevated temperatures and crystalline substrates are not necessary for synthesizing high-quality graphene.
Type I and type III interferons (IFNs) are the frontline of antiviral defense mechanisms that trigger hundreds of downstream antiviral genes. In this study, we observed that MERS-CoV nucleocapsid (N) ...protein suppresses type I and type III IFN gene expression. The N protein suppresses Sendai virus-induced IFN-β and IFN-λ1 by reducing their promoter activity and mRNA levels, as well as downstream IFN-stimulated genes (ISGs). Retinoic acid-inducible gene I (RIG-I) is known to recognize viral RNA and induce IFN expression through tripartite motif-containing protein 25 (TRIM25)-mediated ubiquitination of RIG-I caspase activation and recruitment domains (CARDs). We discovered that MERS-CoV N protein suppresses RIG-I-CARD-induced, but not MDA5-CARD-induced, IFN-β and IFN-λ1 promoter activity. By interacting with TRIM25, N protein impedes RIG-I ubiquitination and activation and inhibits the phosphorylation of transcription factors IFN-regulatory factor 3 (IRF3) and NF-κB that are known to be important for IFN gene activation. By employing a recombinant Sindbis virus-EGFP replication system, we showed that viral N protein downregulated the production of not only IFN mRNA but also bioactive IFN proteins. Taken together, MERS-CoV N protein functions as an IFN antagonist. It suppresses RIG-I-induced type I and type III IFN production by interfering with TRIM25-mediated RIG-I ubiquitination. Our study sheds light on the pathogenic mechanism of how MERS-CoV causes disease.
MERS-CoV causes death of about 35% of patients. Published studies showed that some coronaviruses are capable of suppressing interferon (IFN) expression in the early phase of infection and MERS-CoV proteins can modulate host immune response. In this study, we demonstrated that MERS-CoV nucleocapsid (N) protein suppresses the production of both type I and type III IFNs via sequestering TRIM25, an E3 ubiquitin ligase that is essential for activating the RIG-I signaling pathway. Ectopic expression of TRIM25 rescues the suppressive effect of the N protein. In addition, the C-terminal domain of the viral N protein plays a pivotal role in the suppression of IFN-β promoter activity. Our findings reveal how MERS-CoV evades innate immunity and provide insights into the interplay between host immune response and viral pathogenicity.
Summary Background Outbreaks of urinary tract infections (UTIs) due to contaminated ureteroscopes have been rarely reported. Aim To report such an outbreak at a regional teaching hospital in southern ...Taiwan. Methods From October to December 2010, ertapenem-resistant Enterobacter cloacae were identified from urine cultures of 15 patients who had undergone ureteroscopy prior to the infection. Three batches of surveillance cultures were obtained from the environmental objects and healthcare workers related to the procedures. Pulsed-field gel electrophoresis (PFGE) was used for bacterial typing. Antimicrobial susceptibility was assessed by disc diffusion and E-test methods. Polymerase chain reaction and sequencing were used to analyse β-lactamase genes. Findings A total of 70 specimens were obtained during the first surveillance operation. One ertapenem-resistant E. cloacae was isolated from a ureteroscope. Although the disinfection protocols for ureteroscopes were revised and implemented, seven additional UTI cases were identified thereafter. The pathogen was identified from two subsequent surveillance cultures and was not eliminated until ethylene oxide sterilization was added to the disinfection protocol. PFGE revealed that all 15 isolates from the patients and the three isolates from the ureteroscope shared a common pattern with minor variance. Most isolates were resistant to gentamicin, levofloxacin, ceftriaxone, ceftazidime, and ertapenem. All isolates were susceptible to amikacin, imipenem, and meropenem. SHV-12 and IMP-8 genes were simultaneously identified in 16 of the 18 isolates. Conclusion The outbreak of ertapenem-resistant E. cloacae was caused by a contaminated ureteroscope and was terminated by the implementation of a revised disinfection protocol for ureteroscopes.
Aim
To compare the cardiovascular risks associated with second‐line oral antidiabetic agents added to initial metformin therapy in a large nationwide observational study.
Methods
We conducted a ...nationwide retrospective cohort study using the Taiwan National Health Insurance database. A total of 36 118 users of different add‐on oral antidiabetic agents (sulphonylureas, glinides, pioglitazone, α‐glucosidase inhibitors and dipeptidyl peptidase‐4 inhibitors) after initial metformin therapy were included in the analysis. The reference group was sulphonylureas added to metformin, the most commonly used combination regimen. The main outcomes of interest were hospitalizations for any cardiovascular event including acute myocardial infarction, congestive heart failure and ischaemic stroke. In the main analysis, all patients were followed within their initiation groups until the study end, disregarding any changes in treatment status over time.
Results
In intention‐to‐treat analyses, there was no difference in the risk of any cardiovascular event among the add‐on combination treatment groups, but significantly lower risks of acute myocardial infarction were found for the glinides plus metformin treatment group (crude hazard ratio 0.52, adjusted hazard ratio 0.39; 95% CI 0.20–0.75) and for the α‐glucosidase inhibitors plus metformin treatment group (crude hazard ratio 0.63, adjusted hazard ratio 0.54; 95% CI 0.31–0.95). No difference in risk of congestive heart failure or ischaemic stroke risk was found among the combination treatment groups. In secondary as‐treated analyses, similar but less significant associations were found as compared with the primary intention‐to‐treat analyses for all treatment groups.
Conclusion
There were no differences in overall cardiovascular risks among several add‐on second‐line oral antidiabetic agents; however, glinide plus metformin and α‐glucosidase inhibitors plus metformin combination therapies might be associated with lower risks of acute myocardial infarction.
What's new?
No differences were found in overall cardiovascular risks among several second‐line oral antidiabetic agents as add‐ons to initial metformin therapy, with the exception of a possible lower risk of myocardial infarction associated with add‐on glinide or α‐glucosidase inhibitors.
OBJECTIVES: To compare the different correlations of body mass index (BMI) and percent body fat (BF%) with other ethnic groups and to evaluate the appropriateness of Asia-Pacific redefining obesity ...criteria in the Taiwanese population. The corresponding BF% to BMI cutoffs of overweight and obesity will also be studied. DESIGN: A cross-sectional epidemiological survey. SUBJECTS: A total of 509 male and 570 female Taiwanese subjects aged 20 y sampled by the systematic stratified clustering sampling method were analyzed. MEASUREMENTS: BMI was obtained by body weight (kg) divided by squared body height (m2). The estimated BMI (BMIe) was deduced from the Caucasian-based four-compartment equation (4C). BF% measured by the methods of dual-energy X-ray absorptiometry (DXA) or Caucasian-based 4C were used and abbreviated as DXA-BF and 4C-BF, respectively. RESULTS: The curvilinear relationship between age and BMI or DXA-BF was established. When compared by age-stratified groups, Taiwanese subjects had a higher BF% (4C-BF) in any given BMI than Caucasians. That is, the level of 4C-BF for BMI25 kg/m2 in Taiwanese subjects was similar to BMI30 kg/m2 in Caucasians. The BMIe values of 25 and 30 kg/m2 were nearly equal to the BMIs of 23.6 and 25.3 kg/m2 in males, and 22.7 and 24.8 kg/m2 in females, respectively. The 4C-BF of 25% was nearly equal to a BMI of 26.2 kg/m2 in males, and 35% was equal to a BMI of 24.4 kg/m2 in females. Consequently, the DXA-BF cutoffs for BMIs of 23 and 25 kg/m2 were compatible to 23 and 25% in males, and 35 and 38% in females, respectively. CONCLUSION: It was demonstrated that Taiwanese subjects had a relatively lower BMI but a higher BF% than Caucasians. In general, the newly proposed Asia-Pacific BMI cutoffs for overweight (23 kg/m2) and obesity (25 kg/m2) may be acceptable to both male and female Taiwanese subjects. The corresponding BF% (DXA-BF) cutoffs for obesity would be 25% in male and 38% in female Taiwanese subjects, respectively.
Connective tissue growth factor (CTGF) is a multi-functional secreted protein, and it has been shown either to promote or suppress tumor progression among different kinds of cancers. Here, we ...investigated the role of CTGF in oral squamous cell carcinoma (OSCC) invasion and metastasis. In five OSCC cell lines, endogenous CTGF negatively correlated with invasiveness. Exogenous CTGF protein or forced expression of CTGF gene in the oral cancer cell line SAS significantly decreased their invasive and migratory abilities. MicroRNA (miRNA) microarray analysis was performed in CTGF-overexpressed SAS cells (SAS/CTGF-M3) versus control cells to investigate the mechanism of CTGF-mediated inhibition of OSCC invasion. Among the miRNAs regulated by CTGF, miR-504 and miR-346 were the top two miRNAs downregulated in CTGF transfectants, and the result was confirmed by quantitative reverse transcriptase-PCR. Ectopic miR-504 increased migration and invasion in SAS/CTGF-M3, however, miR-346 did not have such impact on migration/invasion. Furthermore, we identified FOXP1, a member of forkhead transcription factors, as a target gene that takes part in the miR-504-induced cellular invasion. Knockdown of FOXP1 increased invasiveness in SAS/CTGF-M3, confirming the signal axis of CTGF/miR-504/FOXP1 in OSCC. Animal experiments showed that SAS/CTGF-M3-formed orthotopic tumors were associated with a lesser invasive phenotype than control cells. Expression of miR-504 in SAS/CTGF-M3 increased lymph node metastasis, and co-expression of FOXP1 in miR-504-transfected SAS/CTGF-M3 alleviated miR-504-induced metastasis. In OSCC samples, high CTGF was associated with a lower clinical stage and a better outcome. A reverse correlation between CTGF and miR-504, miR-504 and FOXP1, and a positive correlation between CTGF and FOXP1 were shown. Our study discovers a novel signal pathway involving the regulation of miRNA machinery by a secreted cytokine, which will be beneficial for developing therapeutic strategy against advanced OSCC.
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