Inhibition of S. aureus biofilm formation by linezolid alleviates sepsis-induced lung injury caused by S. aureus infection through direct inhibition of icaA activity.

Antibiotic-resistant S. aureus infections can be life-threatening. Linezolid is known to hinder S. aureus biofilm formation, but the underlying molecular mechanism remains unclear. Molecular docking revealed that linezolid can bind to icaA, and this was confirmed by thermal drift assays. Linezolid demonstrated a dose-dependent inhibition of icaA enzyme activity. Mutating Trp267, a key residue identified through molecular docking, significantly decreased linezolid binding and inhibitory effects on mutant icaA activity. However, the mutant icaA Trp267Ala showed only slight activity reduction compared to icaA. Linezolid had minimal impact on icaB's thermal stability and activity. The 50S ribosomal L3ΔSer145 mutant S. aureus exhibited similar growth and biofilm formation to the wild-type strain. Linezolid effectively suppressed the growth and biofilm formation of wildtype S. aureus. Although linezolid lost its ability to inhibit the growth of the mutant strain, it still effectively hindered its biofilm formation. Linezolid exhibited weaker attenuation of sepsis-induced lung injury caused by 50S ribosomal L3ΔSer145 mutant S. aureus compared to wild-type S. aureus. These findings indicate that linezolid hampers S. aureus biofilm formation by directly inhibiting icaA activity, independently of its impact on bacterial growth.

The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae.

IMPORTANCE: The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.

Clinical characteristics and outcomes of patients with multidrug-resistant Gram-negative bacterial infections treated with ceftazidime/avibactam.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics and outcomes of patients with infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) treated with ceftazidime/avibactam (CAZ/AVI) during the period September 2019 to June 2020 since CAZ/AVI had been marketed in China. METHODS: A total of 20 MDR-GNB-infected patients were retrospectively identified using the electronic medical record system in West China Hospital. RESULTS: The mean age of the 20 patients was 54.5 ± 17.37 years and 14 (70%) were male. Pneumonia (n = 12; 60%), complicated intra-abdominal infection (n = 10; 50%), and bloodstream infection (n = 7; 35%) were the most common infection sources. Klebsiella pneumoniae (55% 18/33) was the predominant pathogen. The 14-day clinical cure rate was 45%. The 14-day and 30-day mortality rates were 25% and 55%, respectively. No significant difference was found in 30-day mortality between treatment with CAZ/AVI monotherapy and combination regimens (P > 0.05). Three patients suffered from adverse drug reactions such as diarrhoea. CONCLUSION: No significant difference was found between the effectiveness of CAZ/AVI in the clinical failure and cure groups as salvage treatment of MDR-GNB infection.

Replication of a Dog-Origin H6N1 Influenza Virus in Cell Culture and Mice.

The world's first natural avian-origin H6N1 influenza A virus infection case in dogs was confirmed in Taiwan in 2014. The H6N1 virus in chickens has been endemic in Taiwan since 1972. Whether the dog H6N1 virus has interspecies transmission potential is the key issue we aim to understand. Following one virus passage in embryonated eggs and two further passages in MDCK cells, we obtained two virus derivatives, E01EE (PB1 739E and PB2 627E) and E01GK (PB1 739G and PB2 627K), respectively. The pathogenicity of E01EE and E01GK was investigated using plaque assay, growth dynamic analysis and cell viability quantification in cells from different animal species. The impact of amino acid mutation on PB1 739 and PB2 627 on viral ribonucleoprotein (RNP) activity was also analyzed. Further mouse infection experiments were performed. The results showed that both E01EE and E01GK decreased cell relative viability of canine MDCK cells, human A549 cells and chicken DF1 cells. E01Gk caused greater cellular harm in MDCK and A549 cells and had significantly higher virus titers in all of the cells compared to E01EE. The PB2 627K but not PB1 739G was the critical mutation that influenced the viral RNP activity. Both E01EE and E01GK caused mice pneumonia and considerable virus shedding, especially E01GK. This report verifies PB2 E627K mutation in virulence and spotlights the potential for the dog H6N1 virus to extend interspecies transmission.

Assessing Mentor Academy Program Effectiveness using Mixed Methods.

The purpose of our study was to assess how an academic health center (AHC) mentor academy program affected mentor competence and optimized mentor-mentee relationship. Mixed methods were used to assess the effectiveness of an AHC mentor program at a clinical translational science institute (CTSI). Twenty biomedical research faculty mentors took a validated survey and submitted reflective writings to discover if they corroborated or refuted statistically significant survey results. There was significant improvement in participants' confidence of mentor skills, integral mentoring quality and the extent to which they fulfill mentees' expectations. Males provided constructive feedback and helped mentees develop goal strategies more often compared to females. Reflective writings supported these findings yet refuted two survey findings. The use of a mixed methods approach offers novel insight into how mentoring programs benefit translational research mentoring capacity building and raises questions about the sole use of surveys as evidence of program effectiveness.

A Multi-Institutional Study of Dental Student Readiness to Address Adolescent Risk Behaviors.

The aim of this replication study was to determine if prior findings at one U.S. dental school about dental students' comfort discussing and perceptions of the relevance of 15 risk behaviors to adolescent patient oral health care would be observed at other institutions. All first- and fourth-year dental students (n=414) at three U.S. dental schools in fall 2017 were invited to participate, and 218 completed the survey (52.7% response rate). These students reported feeling comfortable to uncomfortable discussing risk behaviors with adolescent patients, yet perceived those risk behaviors as relevant to their oral health. There were significant differences in student comfort discussing risk behaviors with adolescents and their perceptions of relevance by gender, age, class status, and school location. Males were more comfortable than females discussing oral health risk behaviors. There were no significant differences by race/ethnicity. Fourth-year students had higher levels of comfort discussing risk behaviors than first-year students. Compared to students in the South and Midwest schools, students at the West school were more comfortable discussing selected topics and had higher perceptions of their relevance to adolescent oral health care. These results suggest there is room for improvement in this area of dental education. Dental schools should aim to strengthen students' knowledge of and comfort in discussing oral health risk behaviors with adolescent patients with the use of educational activities and clinical experiences.

Clinical research coordinators' instructional preferences for competency content delivery.

INTRODUCTION: A lack of standardized clinical research coordinator (CRC) training programs requires determining appropriate approaches for content delivery. The purpose of this study was to assess CRCs preferred training delivery methods related to the 8 designated Joint Task Force Clinical Trial Competency domains. METHODS: Repeated measures analysis of variance and split-plot analysis of variance were adopted to compare the group means among 5 training delivery methods by 8 competency content domains and to examine whether demographic variables caused different preference patterns on the training delivery methods. RESULTS: Participants reported a preference for online video; mentoring/coaching was the least preferred. Significant training delivery method preferences were reported for 3 content domains: participant safety considerations, medicines development and regulation, and clinical trials operations. DISCUSSION: Observed statistical differences in the training delivery methods by the content domains provides guidance for program development. Ensuring that standardized educational training is aligned with the needs of adult learners may help ensure that CRCs are appropriately prepared for the workforce.

Rapid creation of a temporary isolation ward for patients with severe acute respiratory syndrome in Taiwan.

OBJECTIVES: To rapidly establish a temporary isolation ward to handle an unexpected sudden outbreak of severe acute respiratory syndrome (SARS) and to evaluate the implementation of exposure control measures by healthcare workers (HCWs) for SARS patients. DESIGN: Rapid creation of 60 relatively negative pressure isolation rooms for 196 suspected SARS patients transferred from 19 hospitals and daily temperature recordings of 180 volunteer HCWs from 6 medical centers. SETTING: A military hospital. RESULTS: Of the 196 patients, 34 (17.3%) met the World Health Organization criteria for probable SARS with positive results of serologic testing for SARS-associated coronavirus (SARS-CoV), reverse transcriptase polymerase chain reaction (RT-PCR) from nasopharyngeal or throat swabs for SARS-CoV, or both. Seventy-four patients had suspected SARS based on unprotected exposure to SARS patients; three of them had positive results on RT-PCR but negative serologic results. The remaining 88 patients did not meet the criteria for a probable or suspected SARS diagnosis. Of the 34 patients with probable SARS, 13 were transferred to medical centers to receive mechanical ventilation due to rapid deterioration of chest x-ray results, and three patients died of SARS despite intensive therapy in medical centers. During the study period, one nurse developed probable SARS due to violation of infection control measures, but there was no evidence of cross-transmission to other HCWs. CONCLUSIONS: Despite the use of full personal protection equipment, the facility failed to totally prevent exposures of HCWs to SARS but minimized the risk of nosocomial transmission. Better training and improvements in infection control infrastructure may limit the impact of SARS.

Pericecal hernia of the inferior ileocecal recess: CT findings.

Internal abdominal herniations are rare. A 34-year-old healthy man was seen in the emergency room because of severe lower abdominal pain and episodic vomiting. Pericecal internal herniation of the inferior ileocecal recess was suspected by abdominal CT study and confirmed by exploratory laparotomy. Finally, the herniated ileal loops were reduced, and the redundant peritoneum was resected. In the present case, CT demonstrates the precise anatomic diagnosis and shows acute complications that should be recommended preoperatively. Urgent surgical intervention is necessary to prevent strangulation, which is responsible for high mortality. Early diagnosis and treatment had a good outcome.