Gain-of-Function Mutations in Acid Stress Response (evgS) Protect Escherichia coli from Killing by Gallium Nitrate, an Antimicrobial Candidate.

Widespread antimicrobial resistance encourages repurposing/refining of nonantimicrobial drugs for antimicrobial indications. Gallium nitrate (GaNt), an FDA-approved medication for cancer-related hypercalcemia, recently showed good activity against several clinically significant bacteria. However, the mechanism of GaNt antibacterial action is still poorly understood. In the present work, resistant and tolerant mutants of Escherichia coli were sought via multiple rounds of killing by GaNt. Multiround-enrichment yielded no resistant mutant; whole-genome sequencing of one representative GaNt-tolerant mutant uncovered mutations in three genes (evgS, arpA, and kdpD) potentially linked to protection from GaNt-mediated killing. Subsequent genetic analysis ruled out a role for arpA and kdpD, but two gain-of-function mutations in evgS conferred tolerance. The evgS mutation-mediated GaNt tolerance depended on EvgS-to-EvgA phosphotransfer; EvgA-mediated upregulation of GadE. YdeO, and SarfA also contributed to tolerance, the latter two likely through their regulation of GadE. GaNt-mediated killing of wild-type cells correlated with increased intracellular reactive oxygen species (ROS) accumulation that was abolished by the evgS-tolerant mutation. Moreover, GaNt-mediated killing was mitigated by dimethyl sulfoxide, and the evgS-tolerant mutation upregulated genes encoding enzymes involved in ROS detoxification and in the glyoxylate shunt of the tricarboxylic acid (TCA) cycle. Collectively, these findings indicate that GaNt kills bacteria through elevation of ROS; gain-of-function mutations in evgS confer tolerance by constitutively activating the EvgA-YdeO/GadE cascade of acid resistance pathways and by preventing GaNt-stimulated ROS accumulation by upregulating ROS detoxification and shifting TCA cycle carbon flux. The striking lethal activity of GaNt suggests that clinical use of the agent may not quickly lead to resistance.

Life Experience of Chinese Pediatric Medulloblastoma Survivors: A Qualitative Study.

ABSTRACT: BACKGROUND: With the improvement of technology and the advancement of medical treatment in recent decades, more and more pediatric medulloblastoma survivors reintegrate to the community. This study aimed to examine the experiences of pediatric medulloblastoma survivors. METHODS: A qualitative research was conducted. Twenty Chinese pediatric medulloblastoma survivors were interviewed. Interviews were recorded and transcribed. Colaizzi's analysis method was used to analyze data. RESULTS: There were 4 themes in this study: physical health issues, community reintegration challenges, overcoming psychological pressure, and multiple unmet needs. CONCLUSION: Pediatric medulloblastoma survivors face challenges in the physical, psychological, and social aspects of their health, along with multiple unmet healthcare needs. Nurses should comprehensively assess the survivor's needs from admission, plan for discharge, and provide regular follow-up care after discharge. Furthermore, nurses should collaborate with caregivers, clinicians, and schoolteachers to develop programs aimed at enhancing the quality of life for survivors. It is also important to explore the survival experiences of individuals in different regions.

Analysis of Risk Factors of Neurobiological Pipeline Care and Investigation of Preventive Measures.

During clinical care, most neurosurgical patients are critically ill. They have sudden onset of illness that should be treated on time with proper care. The patients require continuous hospitalization for proper treatment. The recovery of patients may be relatively slow and takes some time. Patients and Methods. To explore where the risks of pipeline care lie and the preventive measures. (1) In this paper, 100 neurosurgical patients were treated in our hospital from September 2018 to March 2020. They were firstly selected and divided into two groups. Group A was implemented with routine pipeline care and group B was implemented with the intervention developed by the pipeline team. (2) The design and SMOTE assume that, during the generation of a new synthetic sample of minority classes, the immediate neighbors of the minority class instances were also all minority classes, regardless of their true distribution characteristics, to analyze risk factors during care and summarize preventive measures. Results. The experimental results showed that the total efficiency of nursing care was higher in group B as compared to group A, P < 0.05; also, the number of pipeline accidents was lower in group B. Conclusion It is important to be meticulous and thoughtful in pipeline care and to comprehensively analyze the possible risk events and then propose preventive measures so that risk events can be reduced.

Infants Learn to Follow Gaze in Stages: Evidence Confirming a Robotic Prediction.

Gaze following is an early-emerging skill in infancy argued to be fundamental to joint attention and later language development. However, how gaze following emerges is a topic of great debate. Representational theories assume that in order to follow adults' gaze, infants must have a rich sensitivity to adults' communicative intention from birth. In contrast, learning-based theories hold that infants may learn to gaze follow based on low-level social reinforcement, without the need to understand others' mental states. Nagai et al. (2006) successfully taught a robot to gaze follow through social reinforcement and found that the robot learned in stages: first in the horizontal plane, and later in the vertical plane-a prediction that does not follow from representational theories. In the current study, we tested this prediction in an eye-tracking paradigm. Six-month-olds did not follow gaze in either the horizontal or vertical plane, whereas 12-month-olds and 18-month-olds only followed gaze in the horizontal plane. These results confirm the core prediction of the robot model, suggesting that children may also learn to gaze follow through social reinforcement coupled with a structured learning environment.

[Histopathological changes post cryoablation in canine myocardium].

OBJECTIVE: The purpose of this study was to observe histopathological changes post cryoablation in canine myocardium, to characterize the specific ablation lesion post cryoablation. METHODS: Cryothermal ablation was applied on myocardium (both epicardium and endocardium) of 14 mongrel dogs with different ablation parameters (-25 degrees C x 4 min, -50 degrees C x 4 min, -75 degrees C x 4 min, -75 degrees C x 2 min, -75 degrees C x 6 min, -75 degrees C x 8 min). Lesion dimensions and histopathologic changes were observed. RESULTS: The discrete, sharply delimited lesions were detected in cryoablated myocardium. Histologically, cryoablation in all temperatures studied induced heterogeneous necrosis of the myocardium. Lesion dimensions are related to freezing time and temperature. CONCLUSION: Cryoablation is a feasible and preferably choice for clinical application due to its controllable myocardium lesions.