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This case study focused on reclassifying infusion therapy space at the University of Arizona Medical Center to a physician-based treatment setting. The study followed the managerial decision-making process as it described how the space reclassification was recommended, adopted, and implemented. A successful reclassification required close attention to organizational structure, administrative policies and responsibilities, and related work-flow processes. [ABSTRACT FROM AUTHOR]

This case study concerns relocating rheumatology patients at Duke University Medical Center to a new infusion center located in a physician based treatment setting. The case study follows the managerial decision-making process as it describes how the infusion center treatment site was chosen, how it was set up, how it functions, and what benefits to patient care it provides. A successful site-of-car relocation requires strong managers who are able to weigh objectively alternative courses of action. Moreover, the project champion must be able to distinguish key factors inside and outside the organization and chart the project's course accordingly. [ABSTRACT FROM AUTHOR]

Repurposing an organelle for specialized metabolism provides an avenue for fermentable, unicellular organisms such as Saccharomyces cerevisiae to mimic compartmentalization of metabolic pathways within different plant tissues. Peroxisomes are attractive organelles for repurposing as they are not required for yeast viability when grown on glucose and can efficiently compartmentalize heterologous enzymes to enable physical separation of cytosolic native metabolism and peroxisomal engineered metabolism. However, when not required, peroxisomes are repressed, leading to low functional capacities for heterologous proteins. Here we engineer peroxisomes with enhanced functional capacities, with the goal of compartmentalizing up to eight metabolic enzymes to enhance titers. We implement a machine learning pipeline that allows the identification of factors to overexpress, culminating in a 137% increase in peroxisome functional capacity compared to a wild-type strain. Improved pathway compartmentalization enables an 80% increase in the biosynthesis titers of the monoterpene geraniol, up to 9.5 g L -1 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Propionic acidemia is a metabolic condition with multiple serious acute and chronic presentations that require strict monitoring. Literature on liver function abnormalities in propionic acidemia is scarce, and the mechanism of liver impairment in this condition remains unclear. Currently, there is no indication for liver-function tests during follow-up and their clinical or prognostic utility is unknown. This study aimed to determine aminotransferase trends in individuals with propionic acidemia at a single institution. We retrospectively evaluated and classified the aminotransferases of 12 patients with propionic acidemia during hospital admissions and routine office visits. The present findings suggest that aminotransferase elevations are very common in this population and can persist beyond acute illness. During hospitalization events, aminotransferases were not a predictor of severity, duration of stay, and readmission within 1 month. Understanding aminotransferase trends in these patients will help clinicians make decisions in the acute setting and potentially in the follow-up of new therapies., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Ventral hernias of umbilical, epigastric, and incisional types pose varied surgical challenges. Recent debates and research suggest that treatment strategies and outcomes may vary significantly based on hernia type and width. This study investigated whether differences in the risk of surgical outcomes among primary and incisional hernias are solely due to the hernia type. The primary outcome was reoperation for recurrence, and the secondary outcome was 90-day postoperative readmission., Methods: This study was based on prospectively collected data from the Danish Ventral Hernia Database linked with the Danish Civil Registration system and the National Patient Register. Data spanned from 2007 to 2022 and included patients with umbilical, epigastric, or incisional hernias. The 3 hernia types were analyzed for the risk of reoperation for recurrence, adjusted for sex, age, emergency repair, width, use of mesh, and Charlson comorbidity index., Results: We included 57,312 hernias: 34,147 umbilical, 9,433 epigastric, and 13,722 incisional hernias. Compared with patients with umbilical hernias, patients with epigastric hernias had a lower risk of reoperation (hazard ratio: 0.88, 95% confidence interval: 0.79-0.99) and those with incisional hernias had an increased risk (hazard ratio: 2.93, 95% confidence interval: 2.57-3.33). Postoperative 90-day readmission rates were also higher for patients with incisional hernias than for patients with umbilical and epigastric hernias., Conclusion: Incisional hernias exhibited a higher risk of reoperation for recurrence and 90-day postoperative readmission, underscoring their unique nature in terms of both origin and clinical behavior. The findings suggest that primary and incisional hernias should be separate entities in medical practice and research., Competing Interests: Conflict of Interest/Disclosure The authors report no potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Hernia meshes are used to reduce recurrence and pain rates, but the rates are still high. This could be improved with coatings of the mesh. This scoping review aimed to provide an overview of mesh coatings used to promote healing in abdominal hernia repair and to report beneficial and unbeneficial effects., Methods: We included human and animal studies with abdominal hernias that were repaired with non-commercially coated meshes. We searched Pubmed, Embase, Cochrane Central, LILACS, and CNKI without language constraints., Results: Of 2933 identified studies, 58 were included: six studies had a total of 408 humans and 52 studies had 2679 animals. The median follow-up was 12 months (range 1-156), and 95% of the hernias were incisional. There were 44 different coatings which included platelet-rich plasma, mesenchymal stem cells, growth factors, vitamin E, collagen-derived products, various polysaccharides, silk proteins, chitosan, gentamycin, doxycycline, nitrofurantoin, titanium, and diamond-like carbon. Mesenchymal stem cells and platelet-rich plasma were the most researched. Mesenchymal stem cells notably reduced inflammation and foreign body reactions but did not impact other healing metrics. In contrast, platelet-rich plasma positively influenced tissue ingrowth, collagen deposition, and neovascularization and had varying effects on inflammation and foreign body reactions., Conclusion: We identified 44 different mesh coatings and they showed varying results. Mesenchymal stem cells and platelet-rich plasma were the most studied, with the latter showing considerable promise in improving biomechanical properties in hernia repair. Further investigations are needed to ascertain their definitive use in humans., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chronic pain remains prevalent after open inguinal hernia repair and nerve-handling strategies are debated. Some guidelines suggest sparing nerves that are encountered; however, the nerve identification rates are unclear. This study aimed to investigate the nerve identification rates in a register-based nationwide cohort., Methods: This study was reported according to the RECORD guideline and used prospective, routinely collected data from the Danish Hernia Database, which was linked with the National Patient Registry. We included patients ≥ 18 years old, undergoing Lichtenstein hernia repair with information on nerve handling of the iliohypogastric and ilioinguinal nerves., Results: We included 30,911 open hernia repairs performed between 2012 and 2022. The ilioinguinal nerve was identified in 73% of the repairs and the iliohypogastric nerve in 66% of repairs. Both nerves were spared in more than 94% of cases where they were identified. Female patient sex, emergency and recurrence surgery, general anesthesia, medial and saddle hernias, and large defect size all result in lower nerve identification rates for both nerves., Conclusion: The Ilioinguinal nerve was recognized in 73% of cases, while the iliohypogastric nerve was recognized in 66% with almost all identified nerves being spared during surgery. Several pre- and intraoperative factors influenced identification rates of the ilioinguinal and iliohypogastric nerve., (© 2024. The Author(s).)

Background: Congenital Central Hypoventilation Syndrome (CCHS) has devastating consequences if not diagnosed promptly. Despite identification of the disease-defining gene PHOX2B and a facial phenotype, CCHS remains underdiagnosed. This study aimed to incorporate automated techniques on facial photos to screen for CCHS in a diverse pediatric cohort to improve early case identification and assess a facial phenotype-PHOX2B genotype relationship., Methods: Facial photos of children and young adults with CCHS were control-matched by age, sex, race/ethnicity. After validating landmarks, principal component analysis (PCA) was applied with logistic regression (LR) for feature attribution and machine learning models for subject classification and assessment by PHOX2B pathovariant., Results: Gradient-based feature attribution confirmed a subtle facial phenotype and models were successful in classifying CCHS: neural network performed best (median sensitivity 90% (IQR 84%, 95%)) on 179 clinical photos (versus LR and XGBoost, both 85% (IQR 75-76%, 90%)). Outcomes were comparable stratified by PHOX2B genotype and with the addition of publicly available CCHS photos (n = 104) using PCA and LR (sensitivity 83-89% (IQR 67-76%, 92-100%)., Conclusions: Utilizing facial features, findings suggest an automated, accessible classifier may be used to screen for CCHS in children with the phenotype and support providers to seek PHOX2B testing to improve the diagnostics., Impact: Facial landmarking and principal component analysis on a diverse pediatric and young adult cohort with PHOX2B pathovariants delineated a distinct, subtle CCHS facial phenotype. Automated, low-cost machine learning models can detect a CCHS facial phenotype with a high sensitivity in screening to ultimately refer for disease-defining PHOX2B testing, potentially addressing gaps in disease underdiagnosis and allow for critical, timely intervention., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Glucosylsphingosine (lyso-GL1) is a biomarker used to monitor disease and treatment response in Gaucher disease. Data from adults show that higher values of lyso-GL1 are associated with increased disease progression, however similar data in the pediatric population is lacking. In a cohort of pediatric patients, we present a relationship between lyso-GL1 value and Gaucher type, age, and treatment response. Data from this study may serve as a reference for providers monitoring children with Gaucher disease., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: We aimed describe the patient characteristics, surgical details, postoperative outcomes, and prevalence and incidence of obturator hernias. Obturator hernias are rare with high mortality and no consensus on the best surgical approach. Given their rarity, substantial data is lacking, especially related to postoperative outcomes., Methods: The study was based on data from the nationwide Danish Hernia Database. All adults who underwent obturator hernia surgery in Denmark during 1998-2023 were included. The primary outcomes were demographic characteristics, surgical details, postoperative outcomes, and the prevalence and incidence of obturator hernias., Results: We included 184 obturator hernias in 167 patients (88% females) with a median age of 77 years. Emergency surgeries constituted 42% of repairs, and 72% were laparoscopic. Mesh was used in 77% of the repairs, with sutures exclusively used in emergency repairs. Concurrent groin hernias were found in 57% of cases. Emergency surgeries had a 30-day mortality of 14%, readmission rate of 21%, and median length of stay of 6 days. Elective surgeries had a 30-day mortality of 0%, readmission rate of 10%, and median length of stay of 0 days. The prevalence of obturator hernias in hernia surgery was 0.084% (95% CI: 0.071%-0.098%), with an incidence of one per 400,000 inhabitants annually., Conclusions: This was the largest cohort study to date on obturator hernias. They were rare, affected primarily elderly women. The method of repair depends on whether the presentation is acute, and emergency repair is associated with higher mortality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Introduction: Artificial intelligence has started to become a part of scientific studies and may help researchers with a wide range of tasks. However, no scientific studies have been published on its ussefulness in writing cover letters for scientific articles. This study aimed to determine whether Generative Pre-Trained Transformer (GPT)-4 is as good as humans in writing cover letters for scientific papers., Methods: In this randomised non-inferiority study, we included two parallel arms consisting of cover letters written by humans and by GPT-4. Each arm had 18 cover letters, which were assessed by three different blinded assessors. The assessors completed a questionnaire in which they had to assess the cover letters with respect to impression, readability, criteria satisfaction, and degree of detail. Subsequently, we performed readability tests with Lix score and Flesch Kincaid grade level., Results: No significant or relevant difference was found on any parameter. A total of 61% of the blinded assessors guessed correctly as to whether the cover letter was written by GPT-4 or a human. GPT-4 had a higher score according to our objective readability tests. Nevertheless, it performed better than human writing on readability in the subjective assessments., Conclusion: We found that GPT-4 was non-inferior at writing cover letters compared to humans. This may be used to streamline cover letters for researchers, providing an equal chance to all researchers for advancement to peer-review., Funding: This study received no financial support from external sources., Trial Registration: This study was not registered before the study commenced., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background Natural language processing models are increasingly used in scientific research, and their ability to perform various tasks in the research process is rapidly advancing. This study aims to investigate whether Generative Pre-trained Transformer 4 (GPT-4) is equal to humans in writing introduction sections for scientific articles. Methods This randomized non-inferiority study was reported according to the Consolidated Standards of Reporting Trials for non-inferiority trials and artificial intelligence (AI) guidelines. GPT-4 was instructed to synthesize 18 introduction sections based on the aim of previously published studies, and these sections were compared to the human-written introductions already published in a medical journal. Eight blinded assessors randomly evaluated the introduction sections using 1-10 Likert scales. Results There was no significant difference between GPT-4 and human introductions regarding publishability and content quality. GPT-4 had one point significantly better scores in readability, which was considered a non-relevant difference. The majority of assessors (59%) preferred GPT-4, while 33% preferred human-written introductions. Based on Lix and Flesch-Kincaid scores, GPT-4 introductions were 10 and two points higher, respectively, indicating that the sentences were longer and had longer words. Conclusion GPT-4 was found to be equal to humans in writing introductions regarding publishability, readability, and content quality. The majority of assessors preferred GPT-4 introductions and less than half could determine which were written by GPT-4 or humans. These findings suggest that GPT-4 can be a useful tool for writing introduction sections, and further studies should evaluate its ability to write other parts of scientific articles., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sikander et al.)

Mycobacteria can colonize environments where the availability of metal ions is limited. Biological or inorganic chelators play an important role in limiting metal availability, and we developed a model to examine Mycobacterium smegmatis survival in the presence of the chelator sodium citrate. We observed that instead of restricting M. smegmatis growth, concentrated sodium citrate killed M. smegmatis . RNAseq analysis during sodium citrate treatment revealed transcriptional signatures of metal starvation and hyperosmotic stress. Notably, metal starvation and hyperosmotic stress, individually, do not kill M. smegmatis under these conditions. A forward genetic transposon selection was conducted to examine why sodium citrate was lethal, and several sodium-citrate-tolerant mutants were isolated. Based on the identity of three tolerant mutants, mgtE , treZ , and fadD6, we propose a dual stress model of killing by sodium citrate, where sodium citrate chelate metals from the cell envelope and then osmotic stress in combination with a weakened cell envelope causes cell lysis. This sodium citrate tolerance screen identified mutants in several other genes with no known function, with most conserved in the pathogen M. tuberculosis . Therefore, this model will serve as a basis to define their functions, potentially in maintaining cell wall integrity, cation homeostasis, or osmotolerance. IMPORTANCE Bacteria require mechanisms to adapt to environments with differing metal availability. When Mycobacterium smegmatis is treated with high concentrations of the metal chelator sodium citrate, the bacteria are killed. To define the mechanisms underlying killing by sodium citrate, we conducted a genetic selection and observed tolerance to killing in mutants of the mgtE magnesium transporter. Further characterization studies support a model where killing by sodium citrate is driven by a weakened cell wall and osmotic stress, that in combination cause cell lysis., Competing Interests: R.B.A. is the founder and owner of Tarn Biosciences, Inc., a company that is working to develop new antimycobacterial drugs.

Purpose: Inguinal hernia repair is one of the most common operations worldwide and despite this, the incidence of chronic pain remains high after inguinal hernia repair. The optimal nerve handling strategy is controversial and the rate at which nerves are identified remains uncertain. This study aimed to determine the identification rates of the ilioinguinal, iliohypogastric, and genitofemoral nerves as well as nerve handling strategies., Methods: This review was registered on PROSPERO (CRD 42023416576). PubMed, Embase, and Cochrane Central were systematically searched. Studies with more than 10 patients were included if they reported an identification rate for at least one of the nerves during elective open inguinal hernia repair in adults. Studies requiring nerve identification in their study design were excluded. Bias was assessed with the JBI critical appraisal tool and Cochrane's RoB-2 tool. The overall estimate of the prevalence was analysed with prevalence meta-analyses., Results: A total of 23 studies were included. The meta-analyses included 18 studies, which resulted in an identification rate of 82% (95% CI: 76-87%) for the ilioinguinal nerve, 62% (95% CI: 54-71%) for the iliohypogastric nerve, and 41% (95% CI: 27-55%) for the genitofemoral nerve. Nerves were spared in 82% of all repairs., Conclusion: The ilioinguinal, iliohypogastric, and genitofemoral nerves were identified in 82%, 62%, and 41% of surgeries, respectively. Most studies used a nerve-preserving strategy. The role of nerve identification in the development of chronic pain remains uncertain, as well as the optimal nerve handling strategy., (© 2023. The Author(s).)

Latent tuberculosis infection (LTBI) constitutes an important public health problem because of risk of progression to TB disease. Effective treatment of multi-drug resistant (MDR) LTBI would prevent progression to MDR TB disease, which would improve patient and public health outcomes. The majority of MDR LTBI treatment studies have focused on the use of fluoroquinolone-based antibiotic regimens. Options for and experience in the treatment of fluoroquinolone-resistant MDR LTBI are limited in the published literature and not comprehensively addressed in current guidelines. In this review, we share our experience with the treatment of fluoroquinolone-resistant MDR LTBI with linezolid. We discuss treatment options for MDR TB that provide context for predicting effective MDR LTBI treatment, with a focus on the microbiologic and pharmacokinetic properties of linezolid that support its use. We then summarize the evidence for treatment of MDR LTBI. Finally, we present our experiences treating fluoroquinolone-resistant MDR LTBI with linezolid with an emphasis on dosing considerations to optimize efficacy and minimize potential toxicities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Up to 40% of young medical doctors feel that the internships prepared them insufficiently for the clinical work. This study investigated whether a Clinical Task Force (CTF) could improve internship quality., Methods: The CTF visited internship departments with a triple-targeted approach: first, departments pre-filled a self-evaluating questionnaire; secondly, CTF visited departments to discuss the self-evaluation and previous student evaluations; and thirdly, CTF and departments agreed on several quality-improving focus points to work on after the meeting. Focus points were followed-up after three and 12 months. The impact on internship quality was assessed with departments' student evaluation scores, number of completed focus points, and the effect of completed focus points on a range of learning parameters. The CTF learned several things along the way, that potentially could affect the quality of internships. A shortlist of these was provided to illustrate unmeasurable benefits., Results: The CTF met with 53 out of 60 eligible departments. The CTF and departments agreed upon 197 focus points of which 64% were completed. The three most frequent categories of focus points were Introduction of the students, The departments' evaluation percentage, and The departments' function as an educational site. The mean student evaluation scores did not change significantly, but the individual evaluation parameters changed significantly in two categories. It decreased in the category regarding the students' satisfaction with the clinical lecturers and the scheduled teaching and increased in the category regarding the percentage of students evaluating the department., Conclusion: The CTF's triple-targeted approach did not increase the mean student evaluation score significantly. For departments that completed the agreed focus points, one category increased and another decreased. However, the unmeasurable benefits illustrated that CTF was a good viable linking element between the faculty, departments, and students with the potential of improving other aspects of the quality of internships., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Aim: We aimed to investigate how celestial phenomena like zodiac signs, lunar phases, and Friday the 13th impacted the risk of reoperation after groin hernia repair., Methods: We conducted a nationwide register-based study based on the Danish Hernia Database and Danish Patient Safety Authority's Online Register between 2000-2019. We included patients ≥18 years undergoing open Lichtenstein or laparoscopic groin hernia repair. The main outcomes were risk of reoperation after groin hernia repair in relation to patient and surgeon zodiac sign, lunar phase at the time of the repair, and Friday the 13th vs other Fridays., Results: 151,901 groin hernias were included in the analysis of patient zodiac sign, and 25,075 groin hernias were included in the analysis of surgeon zodiac sign. Compared with the Sagittarius, there was a significantly higher risk of reoperation (HR [95% CI]) if the performing surgeon was born under the Capricorn (1.93 [1.16-3.12]); Pisces (1.68 [1.09-2.57]); Aries (1.61 [1.07-2.38]); Taurus (1.62 [1.04-2.54]); Cancer (2.21 [1.48-3.28]); or Virgo (1.71 [1.13-2.59]). Repairs performed under the waxing (1.23 [1.03-1.46]) and the new moon (1.54 [1.11-2.13]) had significantly higher risk of reoperation (HR [95% CI]) compared with the waning moon. Neither patient zodiac sign nor Friday the 13th affected risk of reoperation after groin hernia repair., Conclusions: Surgeons' zodiac sign and lunar phase significantly affected the risk of reoperation after groin hernia repair. Neither patients' zodiac sign nor Friday the 13th influenced on the risk of reoperation after groin hernia repair. This indicates why significant findings should be considered carefully to distinguish between random statistical association and cause-and-effect relations., Competing Interests: Nil, (© PMA.)

Objective: To compare the reoperation rate for recurrence between different mesh types in laparoscopic ventral hernia repair., Summary of Background Data: Ventral hernia repair has improved over the last decades. Nevertheless, recurrence rates are still high, and one type of mesh was recently found to increase it even more., Methods: A nationwide cohort study based on prospectively collected data from the Danish Ventral Hernia Database. We included adult patients that had undergone a laparoscopic ventral hernia repair for either an incisional or a primary hernia. The primary and incisional hernias were analyzed in separate cohorts. The mesh-group with the lowest reoperation for recurrence curve was used as the reference. The outcome was reoperation for recurrence., Results: Study population comprised 2874 patients with primary hernias and 2726 with incisional hernias. For primary hernias, Physiomesh [HR = 3.45 (2.16-5.51)] and Proceed Surgical Mesh [HR = 2.53 (1.35-4.75)] had a significantly higher risk of reoperation for recurrence than DynaMesh-IPOM. For incisional hernias, Physiomesh [HR = 3.90 (1.80-8.46), Ventralex Hernia Patch (HR = 2.99 (1.13-7.93), Parietex Composite (incl. Optimized) (HR = 2.55 (1.17-5.55), and Proceed Surgical Mesh (HR = 2.63 (1.11-6.20)] all had a significantly higher risk of reoperation for recurrence than Ventralight ST Mesh., Conclusion: For primary hernias, Physiomesh and Proceed Surgical Mesh had a significantly higher risk of reoperation for recurrence compared with DynaMesh-IPOM. For incisional hernias, the risk was significantly higher for Physiomesh, Parietex Composite, Ventralex Hernia Patch, and Proceed Surgical Mesh compared with Ventralight ST Mesh. This indicates that type of mesh may be associated with outcomes, and mesh choice could therefore depend on hernia type., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

In defined media supplemented with single carbon sources, Mycobacterium tuberculosis (Mtb) exhibits carbon source specific growth restriction. When supplied with glycerol as the sole carbon source at pH 5.7, Mtb establishes a metabolically active state of nonreplicating persistence known as acid growth arrest. We hypothesized that acid growth arrest on glycerol is not a metabolic restriction, but rather an adaptive response. To test this hypothesis, we selected for and identified several Mtb mutants that could grow under these restrictive conditions. All mutations were mapped to the ppe51 gene and resulted in variants with 3 different amino acid substitutions- S211R, E215K, and A228D. Expression of the ppe51 variants in Mtb promoted growth at acidic pH showing that the mutant alleles are sufficient to cause the dominant gain-of-function, Enhanced Acid Growth (EAG) phenotype. Testing growth on other single carbon sources showed the PPE51 variants specifically enhanced growth on glycerol, suggesting PPE51 plays a role in glycerol uptake. Using radiolabeled glycerol, enhanced glycerol uptake was observed in Mtb expressing the PPE51 (S211R) variant, with glycerol overaccumulation in triacylglycerol. Notably, the EAG phenotype is deleterious for growth in macrophages, where the mutants have selectively faster replication and reduced survival in activated macrophages compared to resting macrophages. Recombinant PPE51 protein exhibited differential thermostability in the wild type (WT) or S211R variants in the presence of glycerol, supporting the model that EAG substitutions alter PPE51-glycerol interactions. Together, these findings support that PPE51 variants selectively promote glycerol uptake and that slowed growth at acidic pH is an important adaptive mechanism required for macrophage pathogenesis. IMPORTANCE It is puzzling why Mycobacterium tuberculosis (Mtb) cannot grow on glycerol at acidic pH, as it has a carbon source and oxygen, everything it needs to grow. In this study, we found that Mtb limits uptake of glycerol at acidic pH to restrict its growth and that mutations in ppe51 promote uptake of glycerol at acidic pH and enable growth. That is, Mtb can grow well at acidic pH on glycerol, but has adapted instead to stop growth. Notably, ppe51 variants exhibit enhanced replication and reduced survival in activated macrophages, supporting a role for pH-dependent slowed growth during macrophage pathogenesis.