BACKGROUNDGemifloxacin is a fluoroquinolone antibiotic with broad spectrum of antibacterial activity. The aim of the study was to evaluate the comparative effectiveness and safety of gemifloxacin for the treatment of patients with community-acquired pneumonia (CAP) or acute exacerbation of chronic bronchitis (AECB).

METHODSWe performed a meta-analysis of randomized controlled trials (RCTs) comparing gemifloxacin with other approved antibiotics. The PubMed, EMBASE, Chinese Biomedical Literature Database and the Cochrane Central Register of Controlled Trials were searched, with no language restrictions.

RESULTSTen RCTs, comparing gemifloxacin with other quinolones (in 5 RCTs) and β-lactams and/or macrolides (in 5 RCTs), involving 3940 patients, were included in this meta-analysis. Overall, the treatment success was higher for gemifloxacin when compared with other antibiotics (odds ratio 1.39, 95% confidence interval 1.15 - 1.68 in intention-to-treat patients, and 1.33, 1.02 - 1.73 in clinically evaluable patients). There was no significant difference between the compared antibiotics regarding microbiological success (1.19, 0.84 - 1.68) or all-cause mortality (0.82, 0.41 - 1.63). The total drug related adverse events were similar for gemifloxacin when compared with other quinolones (0.89, 0.56 - 1.41), while lower when compared with β-lactams and/or macrolides (0.71, 0.57 - 0.89). In subgroup analyses, administration of gemifloxacin was associated with fewer cases of diarrhoea and more rashes compared with other antibiotics (0.66, 0.48 - 0.91, and 2.36, 1.18 - 4.74, respectively).

CONCLUSIONSThe available evidence suggests that gemifloxacin 320 mg oral daily is equivalent or superior to other approved antibiotics in effectiveness and safety for CAP and AECB. The development of rash represents potential limitation of gemifloxacin.

Anti-Bacterial Agents ; therapeutic use ; Bronchitis, Chronic ; drug therapy ; Community-Acquired Infections ; drug therapy ; Fluoroquinolones ; therapeutic use ; Humans ; Naphthyridines ; therapeutic use ; Pneumonia ; drug therapy ; Quinolones ; therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

Background/Aims: The pathophysiology of jackhammer esophagus (JE) remains unknown but may be related to gastroesophageal reflux disease or medication use. We aim to determine if pathologic acid exposure or the use of specific classes of medications (based on the mechanism of action) is associated with JE. Methods: High-resolution manometry (HRM) studies from November 2013 to March 2019 with a diagnosis of JE were identified and compared to symptomatic control patients with normal HRM. Esophageal acid exposure and medication use were compared between groups. Multivariate regression analysis was performed to look for predictors of mean distal contractile integral. Results: Forty-two JE and 127 control patients were included in the study. Twenty-two (52%) JE and 82 (65%) control patients underwent both HRM and ambulatory pH monitoring. Two (9%) JE patients and 14 (17%) of controls had evidence of abnormal acid exposure (DeMeester score > 14.7); this difference was not significant (P = 0.290). Thirty-six (86%) JE and 127 (100%) control patients had complete medication lists. Significantly more JE patients were on long-acting beta agonists (LABA) (JE = 5, control = 4; P = 0.026) and calcium channel blockers (CCB) (JE = 5, control = 3; P = 0.014). Regular opioids (β = 0.298, P = 0.042), CCB (β = 0.308, P = 0.035), and inhaled anticholinergics (β = 0.361, P = 0.049) predicted mean distal contractile integral (R2 = 0.082, F = 4.8; P = 0.003). Conclusions Pathologic acid exposure does not appear to be associated with JE. JE patients had increased CCB and LABA use. The unexpected finding of increased LABA use warrants more investigation and may provide support for a cholinergic etiology of JE.

Background: Cardiothoracic anesthesiology training presents learners with unique challenges, procedural skills, and the management of high-intensity critical scenarios. An effective relationship between educator and learner can serve as the backbone for effective learning, which is crucial for the development of budding anesthesiologists. Strengthening this educational alliance between teachers and trainees involves understanding the educational values educators and learners find most important to their learning experiences. This study aimed to identify the key educational values related to cardiothoracic anesthesia for both learners and educators. By identifying these values in separate cohorts (learners and educators), the importance of various educational values can be examined and compared between the trainees and teachers. Methods: Two separate surveys (one for learners and one for teachers) were adapted from the Pratt and Collins Teaching Perspectives Inventory to establish the importance of various educational values related to cardiothoracic anesthesia. Surveys were sent to 165 Accreditation Council for Graduate Medical Education-accredited anesthesiology residency training programs in the United States to trainees (residents and cardiothoracic anesthesiology fellows) and educators (board-certified cardiothoracic anesthesiologists). Results: Analysis of survey results from 19 educators and 57 learners revealed no statistical differences across the two groups, except Q15: “Let trainee perform critical technical steps” (P value = 0.02). Conclusions While learners and educators in cardiothoracic anesthesia hold similar values regarding cardiac anesthesia education, they differ in the degree to which critical technical steps should be performed by learners.

Background: Cardiothoracic anesthesiology training presents learners with unique challenges, procedural skills, and the management of high-intensity critical scenarios. An effective relationship between educator and learner can serve as the backbone for effective learning, which is crucial for the development of budding anesthesiologists. Strengthening this educational alliance between teachers and trainees involves understanding the educational values educators and learners find most important to their learning experiences. This study aimed to identify the key educational values related to cardiothoracic anesthesia for both learners and educators. By identifying these values in separate cohorts (learners and educators), the importance of various educational values can be examined and compared between the trainees and teachers. Methods: Two separate surveys (one for learners and one for teachers) were adapted from the Pratt and Collins Teaching Perspectives Inventory to establish the importance of various educational values related to cardiothoracic anesthesia. Surveys were sent to 165 Accreditation Council for Graduate Medical Education-accredited anesthesiology residency training programs in the United States to trainees (residents and cardiothoracic anesthesiology fellows) and educators (board-certified cardiothoracic anesthesiologists). Results: Analysis of survey results from 19 educators and 57 learners revealed no statistical differences across the two groups, except Q15: “Let trainee perform critical technical steps” (P value = 0.02). Conclusions While learners and educators in cardiothoracic anesthesia hold similar values regarding cardiac anesthesia education, they differ in the degree to which critical technical steps should be performed by learners.

Background: Cardiothoracic anesthesiology training presents learners with unique challenges, procedural skills, and the management of high-intensity critical scenarios. An effective relationship between educator and learner can serve as the backbone for effective learning, which is crucial for the development of budding anesthesiologists. Strengthening this educational alliance between teachers and trainees involves understanding the educational values educators and learners find most important to their learning experiences. This study aimed to identify the key educational values related to cardiothoracic anesthesia for both learners and educators. By identifying these values in separate cohorts (learners and educators), the importance of various educational values can be examined and compared between the trainees and teachers. Methods: Two separate surveys (one for learners and one for teachers) were adapted from the Pratt and Collins Teaching Perspectives Inventory to establish the importance of various educational values related to cardiothoracic anesthesia. Surveys were sent to 165 Accreditation Council for Graduate Medical Education-accredited anesthesiology residency training programs in the United States to trainees (residents and cardiothoracic anesthesiology fellows) and educators (board-certified cardiothoracic anesthesiologists). Results: Analysis of survey results from 19 educators and 57 learners revealed no statistical differences across the two groups, except Q15: “Let trainee perform critical technical steps” (P value = 0.02). Conclusions While learners and educators in cardiothoracic anesthesia hold similar values regarding cardiac anesthesia education, they differ in the degree to which critical technical steps should be performed by learners.

Background: Cardiothoracic anesthesiology training presents learners with unique challenges, procedural skills, and the management of high-intensity critical scenarios. An effective relationship between educator and learner can serve as the backbone for effective learning, which is crucial for the development of budding anesthesiologists. Strengthening this educational alliance between teachers and trainees involves understanding the educational values educators and learners find most important to their learning experiences. This study aimed to identify the key educational values related to cardiothoracic anesthesia for both learners and educators. By identifying these values in separate cohorts (learners and educators), the importance of various educational values can be examined and compared between the trainees and teachers. Methods: Two separate surveys (one for learners and one for teachers) were adapted from the Pratt and Collins Teaching Perspectives Inventory to establish the importance of various educational values related to cardiothoracic anesthesia. Surveys were sent to 165 Accreditation Council for Graduate Medical Education-accredited anesthesiology residency training programs in the United States to trainees (residents and cardiothoracic anesthesiology fellows) and educators (board-certified cardiothoracic anesthesiologists). Results: Analysis of survey results from 19 educators and 57 learners revealed no statistical differences across the two groups, except Q15: “Let trainee perform critical technical steps” (P value = 0.02). Conclusions While learners and educators in cardiothoracic anesthesia hold similar values regarding cardiac anesthesia education, they differ in the degree to which critical technical steps should be performed by learners.

Background: Cardiothoracic anesthesiology training presents learners with unique challenges, procedural skills, and the management of high-intensity critical scenarios. An effective relationship between educator and learner can serve as the backbone for effective learning, which is crucial for the development of budding anesthesiologists. Strengthening this educational alliance between teachers and trainees involves understanding the educational values educators and learners find most important to their learning experiences. This study aimed to identify the key educational values related to cardiothoracic anesthesia for both learners and educators. By identifying these values in separate cohorts (learners and educators), the importance of various educational values can be examined and compared between the trainees and teachers. Methods: Two separate surveys (one for learners and one for teachers) were adapted from the Pratt and Collins Teaching Perspectives Inventory to establish the importance of various educational values related to cardiothoracic anesthesia. Surveys were sent to 165 Accreditation Council for Graduate Medical Education-accredited anesthesiology residency training programs in the United States to trainees (residents and cardiothoracic anesthesiology fellows) and educators (board-certified cardiothoracic anesthesiologists). Results: Analysis of survey results from 19 educators and 57 learners revealed no statistical differences across the two groups, except Q15: “Let trainee perform critical technical steps” (P value = 0.02). Conclusions While learners and educators in cardiothoracic anesthesia hold similar values regarding cardiac anesthesia education, they differ in the degree to which critical technical steps should be performed by learners.

Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.
Astrocytoma ; genetics ; metabolism ; pathology ; Cell Adhesion Molecules ; genetics ; metabolism ; Cell Line, Tumor ; Central Nervous System Neoplasms ; genetics ; metabolism ; pathology ; CpG Islands ; genetics ; DNA Methylation ; Down-Regulation ; Gene Deletion ; Glioblastoma ; genetics ; metabolism ; pathology ; Humans ; Oligodendroglioma ; genetics ; metabolism ; pathology ; Promoter Regions, Genetic ; genetics ; Survival Rate

A systematic phylogenetic footprinting approach was performed to identify conserved transcription factor binding sites (TFBSs) in mammalian promoter regions using human, mouse and rat sequence alignments. We found that the score distributions of most binding site models did not follow the Gaussian distribution required by many statistical methods. Therefore, we performed an empirical test to establish the optimal threshold for each model. We gauged our computational predictions by comparing with previously known TFBSs in the PCK1 gene promoter of the cytosolic isoform of phosphoenolpyruvate carboxykinase, and achieved a sensitivity of 75% and a specificity of approximately 32%. Almost all known sites overlapped with predicted sites, and several new putative TFBSs were also identified. We validated a predicted SP1 binding site in the control of PCK1 transcription using gel shift and reporter assays. Finally, we applied our computational approach to the prediction of putative TFBSs within the promoter regions of all available RefSeq genes. Our full set of TFBS predictions is freely available at http://bfgl.anri.barc.usda.gov/tfbsConsSites.

A systematic phylogenetic footprinting approach was performed to identify conserved transcription factor binding sites (TFBSs) in mammalian promoter regions using human, mouse and rat sequence alignments. We found that the score distributions of most binding site models did not follow the Gaussian distribution required by many statistical methods. Therefore, we performed an empirical test to establish the optimal threshold for each model. We gauged our computational predictions by comparing with previously known TFBSs in the PCK1 gene promoter of the cytosolic isoform of phosphoenolpyruvate carboxykinase, and achieved a sensitivity of 75% and a specificity of approximately 32%. Almost all known sites overlapped with predicted sites, and several new putative TFBSs were also identified. We validated a predicted SP1 binding site in the control of PCK1 transcription using gel shift and reporter assays. Finally, we applied our computational approach to the prediction of putative TFBSs within the promoter regions of all available RefSeq genes. Our full set of TFBS predictions is freely available at http://bfgl.anri.barc.usda.gov/tfbsConsSites.
Algorithms ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; genetics ; Cell Line, Tumor ; Computational Biology ; methods ; Conserved Sequence ; Electrophoretic Mobility Shift Assay ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Luciferases ; genetics ; metabolism ; Mice ; Normal Distribution ; Oligonucleotides ; genetics ; metabolism ; Phosphoenolpyruvate Carboxykinase (GTP) ; genetics ; Promoter Regions, Genetic ; genetics ; Protein Binding ; Rats ; Recombinant Fusion Proteins ; genetics ; metabolism ; Regulatory Sequences, Nucleic Acid ; genetics ; Reproducibility of Results ; Sp1 Transcription Factor ; genetics ; metabolism ; Transcription Factors ; metabolism ; Transfection