Route of Infection in Melioidosis

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Prevalence of Imipenemase and Verona Integron-Encoded Metallo-β-Lactamase in Imipenem-Resistant Pseudomonas aeruginosa

Objective: To determine the prevalence of metallo-β-lactamase (MBL) including imipenemase (IMP) and Verona integronencoded metallo-β-lactamase (VIM) in imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates and investigate the in vitro activities of 9 antimicrobial agents against MBL-positive isolates. Material and Methods: Seventy-eight IRPA isolates were obtained from Songklanagarind Hospital. MBL production was detected by the combined-disk test, and the blaIMP and blaVIM genes were determined via Polymerase Chain Reaction (PCR). The in vitro activities of amikacin, gentamicin, aztreonam, ceftazidime, meropenem, ciprofloxacin, colistin, piperacillin/ tazobactam, and ticarcillin/clavulanate were determined using the E-test method. Results: Of the 78 IRPA isolates, 20 (25.6%, 95% CI 17.2-36.4%) were MBL phenotype-positive, and 30 (38.5%, 95% CI 28.5-49.6%) were MBL genotype-positive (29 Imipenemase (IMP)-type and 1 Verona integron-encoded metallo-βlactamase (VIM)-type). Ninety percent of the MBL genotype-positive isolates were MDR. Most MBL genotype- positive isolates were susceptible to colistin (susceptibility rate of 96.7% and MIC50 value of 1.5 µg/mL). Conclusion: Our results showed a high prevalence of MBL-positive isolates (38.5%) in IRPAs, and the IMP-type isolates were dominant among the metallo-β-lactamase-producing imipenem-resistant P. aeruginosa tested. Most MBL-positive isolates were susceptible to colistin and had low MIC50 values

The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 engages the glucagon-like peptide-1 incretin hormone axis to lower levels of blood glucose in db/db mice

Aim: To establish if alpha-7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 exerts a blood glucose-lowering action in db/db mice, and to test if this action requires coordinate α7nAChR and GLP-1 receptor (GLP-1R) stimulation by GTS-21 and endogenous GLP-1, respectively. Materials and Methods: Blood glucose levels were measured during an oral glucose tolerance test (OGTT) using db/db mice administered intraperitoneal GTS-21. Plasma GLP-1, peptide tyrosine tyrosine 1-36 (PYY1-36), glucose-dependent insulinotropic peptide (GIP), glucagon, and insulin levels were measured by ELISA. A GLP-1R–mediated action of GTS-21 that is secondary to α7nAChR stimulation was evaluated using α7nAChR and GLP-1R knockout (KO) mice, or by co-administration of GTS-21 with the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the GLP-1R antagonist, exendin (9-39). Insulin sensitivity was assessed in an insulin tolerance test. Results: Single or multiple dose GTS-21 (0.5-8.0 mg/kg) acted in a dose-dependent manner to lower levels of blood glucose in the OGTT using 10-14 week-old male and female db/db mice. This action of GTS-21 was reproduced by the α7nAChR agonist, PNU-282987, was enhanced by sitagliptin, was counteracted by exendin (9-39), and was absent in α7nAChR and GLP-1R KO mice. Plasma GLP-1, PYY1-36, GIP, glucagon, and insulin levels increased in response to GTS-21, but insulin sensitivity, body weight, and food intake were unchanged. Conclusions: α7nAChR agonists improve oral glucose tolerance in db/db mice. This action is contingent to coordinate α7nAChR and GLP-1R stimulation. Thus α7nAChR agonists administered in combination with sitagliptin might serve as a new treatment for type 2 diabetes

Structured Multidisciplinary Approach to Ruptured Abdominal Aortic Aneurysm: Impact on Mortality and Complications in a 13-Year Cohort

Objective: To evaluate the impact of a comprehensive multidisciplinary protocol on 30-day survival in ruptured abdominal aortic aneurysm (rAAA) patients and to identify factors influencing outcomes. Materials and Methods: We conducted a retrospective study comparing outcomes before and after implementation a multidisciplinary protocol for rAAA management at Siriraj Hospital. The study included 182 patients (pre-protocol: n=99, Jan 2010-Dec 2017; post-protocol: n=83, Jan 2018-Mar 2023). Primary outcome was 30-day overall survival, with secondary outcomes including factors influencing survival, need for aortic balloon occlusion, operative parameters, length of stay, and complications. Results: The 30-day mortality rate significantly decreased from 16.2% pre-protocol to 6.0% post-protocol (p=0.037). Kaplan-Meier analysis showed improved 30-day survival in the post-protocol group (94.0% vs 83.8%, p=0.034). However, while protocol implementation was associated with a non-significant reduction in mortality hazard (adjusted HR 0.509, 95% CI 0.175-1.478, p=0.213), multivariable analysis identified cardiac arrest (aHR 8.180, p<0.001) and unfit patient status (aHR 6.420, p=0.003) as independent predictors of mortality. The post-protocol group had significantly reduced myocardial ischemia (7.2% vs 21.2%, p=0.015) and septicemia (1.2% vs 20.2%, p<0.001), with no significant differences in operative parameters or length of stay. Conclusion: Implementation of a multidisciplinary protocol for rAAA management was associated with improved 30-day survival and reduced postoperative complications, supporting the use of structured protocols in rAAA management