UNRAVELING CRP/cAMP-MEDIATED METABOLIC REGULATION IN ESCHERICHIA COLI PERSISTER CELLS.

A substantial gap persists in our comprehension of how bacterial metabolism undergoes rewiring during the transition to a persistent state. Also, it remains unclear which metabolic mechanisms become indispensable for persister cell survival. To address these questions, we directed our efforts towards persister cells in Escherichia coli that emerge during the late stationary phase. These cells have been recognized for their exceptional resilience and are commonly believed to be in a dormant state. Our results demonstrate that the global metabolic regulator Crp/cAMP redirects the metabolism of these antibiotic-tolerant cells from anabolism to oxidative phosphorylation. Although our data indicates that persisters exhibit a reduced metabolic rate compared to rapidly growing exponential-phase cells, their survival still relies on energy metabolism. Extensive genomic-level analyses of metabolomics, proteomics, and single-gene deletions consistently emphasize the critical role of energy metabolism, specifically the tricarboxylic acid (TCA) cycle, electron transport chain (ETC), and ATP synthase, in sustaining the viability of persisters. Altogether, this study provides much-needed clarification regarding the role of energy metabolism in antibiotic tolerance and highlights the importance of using a multipronged approach at the genomic level to obtain a broader picture of the metabolic state of persister cells.

Impact of a structured reporting template on the quality of HRCT radiology reports for interstitial lung disease.

PURPOSE: This QI study compared the completeness of HRCT radiology reports before and after the implementation of a disease-specific structured reporting template for suspected cases of interstitial lung disease (ILD). MATERIALS AND METHODS: A pre-post study of radiology reports for HRCT of the thorax at a multicenter health system was performed. Data was collected in 6-month period intervals before (June 2019-November 2019) and after (January 2021-June 2021) the implementation of a disease-specific template. The use of the template was voluntary. The primary outcome measure was the completeness of HRCT reports graded based on the documentation of ten descriptors. The secondary outcome measure assessed which descriptor(s) improved after the intervention. RESULTS: 521 HRCT reports before and 557 HRCT reports after the intervention were reviewed. Of the 557 reports, 118 reports (21%) were created using the structured reporting template. The mean completeness score of the pre-intervention group was 9.20 (SD = 1.08) and the post-intervention group was 9.36 (SD = 1.03) with a difference of -0.155, 95% CI [-0.2822, -0.0285, p < 0.0001]. Within the post-intervention group, the mean completeness score of the unstructured reports was 9.25 (SD = 1.07) and the template reports was 9.93 (SD = 0.25) with a difference of -0.677, 95% CI [-0.7871, -0.5671, p < 0.0001]. After the intervention, the use of two descriptors improved significantly: presence of honeycombing from 78.3% to 85.1% (p < 0.0039) and technique from 90% to 96.6% (p < 0.0001). DISCUSSION: Shifting to disease-specific structured reporting for HRCT exams of suspected ILD is beneficial, as it improves the completeness of radiology reports. Further research on how to improve the voluntary uptake of a disease-specific template is needed to help increase the acceptance of structured reporting among radiologists.

Six logical steps that connect the introduction of the Nernst equation to its clinical application.

The Nernst equation is key to understanding the electrophysiology of the cell membrane and the pathophysiology of K+ imbalances (i.e., hyperkalemia and hypokalemia). However, in our experience teaching medical students over the years, many students struggle to make connections between a brief introduction of the Nernst equation and its clinical application to K+ imbalances. This article aims to connect the introduction of the equation to its clinical application to understand K+ imbalances using six logical steps with detailed visual illustrations that make the connection explicit and cohesive. In addition, we highlight a few common areas related to the six steps that are often overlooked by both teachers and students. Students who are able to thoroughly demonstrate an understanding of all the six steps highlighted in this article will achieve mastery of this topic.NEW & NOTEWORTHY This article fills the gaps in teaching about the Nernst equation, which is important in medical physiology. Six logical steps are presented that connect the introduction of the equation to its clinical applications to hyperkalemia and hypokalemia, two conditions that can be life-threatening if left untreated. Only when students know how to apply the equation will their learning transition from surface to mastery.

Persistent Orthostatic Hypotension in a Patient With Acromegaly: Resolution With Transsphenoidal Hypophysectomy.

Acromegaly is a rare condition characterized by excessive secretion of growth hormone from a pituitary tumor. It can affect multiple systems and can be fatal with cardiac dysfunction being the most common cause of death in these patients. Autonomic dysfunction is a less studied subject in patients with acromegaly, and the exact pathophysiology is still unclear. Here we present a case of a patient with persistent orthostatic hypotension, who was found to have acromegaly and pituitary adenoma upon further evaluation. Her orthostatic symptoms failed to improve with conservative measures and medical management, but unexpectedly resolved after transsphenoidal hypophysectomy was performed.

Cellular Self-Digestion and Persistence in Bacteria.

Cellular self-digestion is an evolutionarily conserved process occurring in prokaryotic cells that enables survival under stressful conditions by recycling essential energy molecules. Self-digestion, which is triggered by extracellular stress conditions, such as nutrient depletion and overpopulation, induces degradation of intracellular components. This self-inflicted damage renders the bacterium less fit to produce building blocks and resume growth upon exposure to fresh nutrients. However, self-digestion may also provide temporary protection from antibiotics until the self-digestion-mediated damage is repaired. In fact, many persistence mechanisms identified to date may be directly or indirectly related to self-digestion, as these processes are also mediated by many degradative enzymes, including proteases and ribonucleases (RNases). In this review article, we will discuss the potential roles of self-digestion in bacterial persistence.