Non-invasive biomarkers for detecting progression toward hypovolemic cardiovascular instability in a lower body negative pressure model.

Occult hemorrhages after trauma can be present insidiously, and if not detected early enough can result in patient death. This study evaluated a hemorrhage model on 18 human subjects, comparing the performance of traditional vital signs to multiple off-the-shelf non-invasive biomarkers. A validated lower body negative pressure (LBNP) model was used to induce progression towards hypovolemic cardiovascular instability. Traditional vital signs included mean arterial pressure (MAP), electrocardiography (ECG), plethysmography (Pleth), and the test systems utilized electrical impedance via commercial electrical impedance tomography (EIT) and multifrequency electrical impedance spectroscopy (EIS) devices. Absolute and relative metrics were used to evaluate the performance in addition to machine learning-based modeling. Relative EIT-based metrics measured on the thorax outperformed vital sign metrics (MAP, ECG, and Pleth) achieving an area-under-the-curve (AUC) of 0.99 (CI 0.95-1.00, 100% sensitivity, 87.5% specificity) at the smallest LBNP change (0-15 mmHg). The best vital sign metric (MAP) at this LBNP change yielded an AUC of 0.6 (CI 0.38-0.79, 100% sensitivity, 25% specificity). Out-of-sample predictive performance from machine learning models were strong, especially when combining signals from multiple technologies simultaneously. EIT, alone or in machine learning-based combination, appears promising as a technology for early detection of progression toward hemodynamic instability.

Is Laser Better than Cold Steel (Dissection and Snare) for Tonsillectomy?

OBJECTIVE: To analyse the surgical outcome of CO2 laser assisted tonsillectomy with the cold steel (conventional dissection and snare) tonsillectomy. MATERIALS AND METHODS: This prospective, non-randomised, single blind study was conducted in 25 cases suffering with recurrent tonsillitis. The left tonsillectomy was performed with CO2 laser while the right tonsil was excised using cold steel method (conventional dissection and snare method). The surgical time, blood loss and post-operative pain for each method was recorded and analysed. RESULTS: CO2 laser tonsillectomy had highly significant less intra-operative blood loss (41.8ml vs. 78.8ml with p = 0.001) and postoperative pain levels on postoperative day 1,3, and 5 ( p value of 0.013, 0.006 and 0.000 respectively) as compared to cold steel method. However; there was no statistically significant difference in operative time between the two techniques (p > 0.05). CONCLUSION: CO2 laser tonsillectomy appeared to be better technique than cold steel in terms of intra-operative haemorrhage and pain.

An Epidemiological Study of Addictive Behavior Pattern Among Adolescent Tobacco Users.

Background: The risk of developing tobacco-related cancer and chronic heart and lung disease is greater if addiction starts in adolescence. Even experimental use of tobacco in adolescents significantly increases the risk of addiction in adulthood. This study intends to collect valuable data regarding sociodemographic characteristic of tobacco use, pattern of dependence among adolescent tobacco users, which will be essential for formulating recommendations, and their possible intervention aimed at reducing the problem of tobacco use. Methods: A community-based cross-sectional study was done where 400 subjects were enrolled. Nonprobability Snowball sampling technique was used to locate adolescents aged 12-18 years, who were practicing tobacco use. Face-to-face interviews were taken for data collection. Fragerstorm dependency test for tobacco was used to classify dependency of tobacco product into high and low dependency. Data was analyzed using Chi-square test and proportions using SPSS software version 21. Results: Majority of the subjects were in the age group of 16-18 years; mean age for initiation of tobacco was 15.6 years. Gutkha was the predominant form of tobacco product being used. Peer pressure 192 (48.0%) was the major reason for initiation of tobacco use. A significant association was found between dependency on tobacco and age, literacy, and socioeconomic status. Conclusions: Tobacco use starting from early age has many health implications. There is a need for stringent laws against the selling of tobacco to adolescents and targeted health awareness program against tobacco.

Prevalence and Risk Factors of Hypertension among Police Personnel of District Gwalior- A Cross Sectional Study.

Context: Hypertension is an emerging public health problem due to its high prevalence and association with cardiovascular and overall morbidity and mortality. Police personnel constitute a special occupational group with exposure to violence and stress at work, which affects their health directly and indirectly. Methodology: A cross-sectional study was conducted to find out the prevalence of hypertension and its relation with respect to police duty profile along with other risk factors among the police personnel of the Gwalior district stationed at various police stations. Results: In total, 402 police personnel were included in the study. Forty (14.7%) participants reported that they had h/o hypertension, while 26 (9.5%) reported that they were diagnosed as hypertensive in recent 1-2 months. As per the findings of our study, 273 (67.91%) participants come out to be hypertensive; among them, 207 (75.8%) were diagnosed in the current study. With increase in hierarchy, more police personnel suffered with hypertension. Conclusions: Long duty hours, higher rank, prolonged service duration, and inappropriate eating habits are the significant factors for the high prevalence of hypertension in police personnel.

Spatial and temporal patterns in dynamic-contrast enhanced intraoperative fluorescence imaging enable classification of bone perfusion in patients undergoing leg amputation.

Dynamic contrast-enhanced fluorescence imaging (DCE-FI) classification of tissue viability in twelve adult patients undergoing below knee leg amputation is presented. During amputation and with the distal bone exposed, indocyanine green contrast-enhanced images were acquired sequentially during baseline, following transverse osteotomy and following periosteal stripping, offering a uniquely well-controlled fluorescence dataset. An unsupervised classification machine leveraging 21 different spatiotemporal features was trained and evaluated by cross-validation in 3.5 million regions-of-interest obtained from 9 patients, demonstrating accurate stratification into normal, suspicious, and compromised regions. The machine learning (ML) approach also outperformed the standard method of using fluorescence intensity only to evaluate tissue perfusion by a two-fold increase in accuracy. The generalizability of the machine was evaluated in image series acquired in an additional three patients, confirming the stability of the model and ability to sort future patient image-sets into viability categories.

Detection of subclinical hemorrhage using electrical impedance: a porcine study.

Objective.Analyze the performance of electrical impedance tomography (EIT) in an innovative porcine model of subclinical hemorrhage and investigate associations between EIT and hemodynamic trends.Approach. Twenty-five swine were bled at slow rates to create an extended period of subclinical hemorrhage during which the animal's heart rate (HR) and blood pressure (BP) remained stable from before hemodynamic deterioration, where stable was defined as <15% decrease in BP and <20% increase in HR-i.e.hemorrhages were hidden from standard vital signs of HR and BP. Continuous vital signs, photo-plethysmography, and continuous non-invasive EIT data were recorded and analyzed with the objective of developing an improved means of detecting subclinical hemorrhage-ideally as early as possible.Main results. Best area-under-the-curve (AUC) values from comparing bleed to no-bleed epochs were 0.96 at a 80 ml bleed (∼15.4 min) using an EIT-data-based metric and 0.79 at a 120 ml bleed (∼23.1 min) from invasively measured BP-i.e.the EIT-data-based metric achieved higher AUCs at earlier points compared to standard clinical metrics without requiring image reconstructions.Significance.In this clinically relevant porcine model of subclinical hemorrhage, EIT appears to be superior to standard clinical metrics in early detection of hemorrhage.

Case report: paradoxically reversible perfusion defects on vasodilator stress imaging in a case of metastatic coronary compression.

Background: Patients with malignancy who experience metastasis to cardiac structures may exhibit ST-segment elevations and acute coronary syndrome (ACS) through poorly understood pathophysiologic mechanisms. We present a case in which vasodilator stress cardiovascular magnetic resonance provides unique insight into one such patient who suffered from recurrent episodes resembling ACS. Case summary: A 58-year-old male with metastatic lung adenocarcinoma presented with refractory angina and dynamic inferior electrocardiogram changes. The patient was referred for adenosine stress cardiovascular magnetic resonance, revealing multiple territories of abnormal perfusion during rest with improvement during adenosine infusion. Subsequent computed tomography displayed tumour encasement of the right coronary artery. Taken together, vasodilator-responsive extrinsic compression of multiple epicardial coronary arteries was suspected. Outpatient oncology follow-up for chemoimmunotherapy initiation was arranged with the hope that reducing tumour burden might alleviate coronary compression. However, in the ensuing months, the patient's disease advanced beyond the point of which his symptoms could be controlled medically, and he was ultimately enrolled in hospice care. Discussion: Encasement of coronary arteries can result in anginal symptoms if their position impairs coronary arterial flow. The presented case highlights the unique manner in which these lesions might behave on stress cardiac magnetic resonance imaging. Clinicians who encounter such unusual findings on vasodilator stress imaging should consider metastatic lesions to the cardiac structures on the differential diagnosis.

Combined Coronary Orbital Atherectomy and Intravascular Lithotripsy for the Treatment of Severely Calcified Coronary Stenoses: The First Case Series.

OBJECTIVE: Severely calcified coronary stenoses remain a significant challenge during contemporary percutaneous coronary intervention (PCI), often requiring advanced therapies to circumvent suboptimal lesion preparation and major adverse cardiac events (MACEs). Recent reports suggest combined coronary atherectomy and intravascular lithotripsy (IVL) may achieve superior preparation of severely calcified coronary stenoses during PCI. We sought to evaluate the safety and utility of combined orbital atherectomy (OA) and IVL for the modification of coronary artery calcification (CAC) prior to drug-eluting stent (DES) implantation in PCI. METHODS: We performed a retrospective review of all patients who underwent coronary OA and IVL within a single PCI procedure at our institution. The primary outcome was procedural success, defined as successful DES implantation with a residual percent diameter stenosis of <30% and Thrombolysis in Myocardial Infarction (TIMI) 3 flow following PCI without occurrence of in-hospital MACE (cardiac death, myocardial infarction, or target-vessel revascularization). MACE was additionally assessed at 30 days post intervention. RESULTS: Eight patients underwent combined coronary OA and IVL within a single PCI procedure. The mean percent diameter stenosis prior to intervention was 80.5 ± 8.3%, with a mean calcific arc of 338 ± 42°. Procedural success was achieved in 7 of 8 cases (87.5%). Both in-hospital and 30-day MACE rates were 0%. CONCLUSION: We report the safe and effective use of combined coronary OA and IVL for the preparation of severely calcified coronary stenoses during PCI. Through their distinct yet complementary mechanisms of action, the combined use of these therapies may achieve superior preparation of severely calcified coronary stenoses during PCI.

An Unusual Case of Pancytopenia: The Lessons Learnt.

Pancytopenia is a common hematological abnormality encountered in clinical practice. We here report a 36-year-old male who presented to emergency department with complaints of weakness of bilateral lower limbs, burning sensation in all four limbs with history of loose stools, and vomiting 5 days back. The complete blood count of patient showed pancytopenia with no circulating atypical cells. Bone marrow examination performed showed nonspecific but characteristic findings. After excluding the possibility of infective etiology, a possibility of heavy metal toxicity was suspected in multidisciplinary meeting. The urine and blood levels of arsenic done came out very high, and a diagnosis of arsenic poisoning was made. Patient had multisystemic involvement with features characteristic of arsenic poisoning. The present case was a diagnostic challenge in face of nonforthcoming history. This case beautifully highlighted the importance of multidepartmental approach in such cases to arrive at unerring diagnosis and the unique bone marrow findings, although nonspecific were sufficient enough to indicate the possibility of acute insult to the hematopoiesis. How to cite this article: Nair RR, Singh PK, Sharma J, Gambhir I, Khanna S, Jain AK, et al. An Unusual Case of Pancytopenia: The Lessons Learnt. Indian J Crit Care Med 2022;26(1):141-144.

Epidemiological study of adverse events following immunization in under 5 year children.

BACKGROUND: The present study was conducted to study the socioeconomic and the demographic profile of children reporting with adverse events following immunization (AEFI) along with the determinants associated with AEFIs, based on investigation of each case and to assess the proportion of programmatic errors linked with AEFI cases. MATERIALS AND METHODS: Record-based cross-sectional study conducted among sample of 118 cases of AEFI were reported. The case reports of all AEFI cases were procured and analyzed to identify factors associated with reported AEFI. The questionnaires related with preliminary investigation reports (PIRs) including forensic evidence of death cases were analyzed. Percentage analysis of data was done by proportions, measures of central tendencies, and Chi-square test. RESULTS: Most of the cases reported were between 0 and 3 months of age constituting 39%. AEFI was seen more in male child than female. more than half of cases of AEFI were recorded following immunization with OPV/DPT/HBV together (66.94%). Most common AEFI reported were convulsion (68.64 %) and fever (58.47%) followed by local swelling at site of injection (11.86%). More than half of the cases of AEFI occurred within 12 hours of immunization (61.88%). Birth weight of most cases of AEFI were in the range between 2 and 2.4 kg (44.06%), followed by range between 2.5 and 2.9 kg (32.20%), the mean of birth weight was 2.51 kg. CONCLUSION: Convulsion was the most commonly reported AEFI, majority of AEFI occur within 12 h of immunization. Most of the AEFI were recorded following immunization with OPV/DPT/HBV together.

The Utility of Peripheral Intravascular Lithotripsy in Calcific Coronary Artery Disease: A Case Series.

BACKGROUND: Coronary intravascular lithotripsy (IVL) is an emerging therapy for the modification of coronary artery calcification (CAC). Data on its use in several clinical and lesion subsets are limited due to their exclusion from preapproval trials. METHODS: We performed a retrospective review of patients who were excluded from preapproval trials of coronary IVL and underwent CAC modification with the off-label use of a peripheral IVL system. The primary outcome was a composite of procedural success, defined as residual stenosis <10%, and no major adverse cardiac event (MACE), ie, cardiac death, myocardial infarction, or target- vessel revascularization, in hospital and at 30 days. RESULTS: Between June 2019 and April 2020, a total of 9 patients who underwent off-label coronary IVL were identified. Exclusion criteria from preapproval trials included a target lesion within an unprotected left main coronary artery (ULMCA; n = 3) and/or ostial location (n = 5), a target lesion involving in-stent restenosis (n = 3), a second target-vessel lesion with >50% stenosis (n = 1), and/or New York Heart Association class III/IV heart failure (n = 5). The primary outcome was achieved in 8 patients. MACE rate was 0% in hospital and at 30 days. For ULMCA lesions (n = 3), residual stenosis was 0% in 2 patients and 10% in 1 patient. For right coronary artery lesions (n = 3), residual stenosis was 0% in 2 patients and 40% in 1 patient. For left anterior descending coronary artery lesions (n = 3), residual stenosis was 0% in all patients. CONCLUSION: Coronary IVL with a peripheral IVL system may be an effective therapy for CAC modification within ULMCA disease, ostial disease, in-stent restenosis, and New York Heart Association class III/IV heart failure.

Catheter-based embolectomy prior to right ventricular mechanical circulatory support placement after heart transplantation.

Severe acute isolated right ventricular failure has limited dedicated percutaneous temporary mechanical circulatory support options, especially after orthotopic heart transplantation. The advent of the Impella RP device provides a newer option, though an absolute contraindication to device placement is thrombus within the right heart. We present a novel case where catheter-based embolectomy was used to evacuate right heart thrombus before Impella RP placement in a patient with severe acute right ventricular failure due to primary graft dysfunction after orthotopic heart transplantation.

Early growth response gene mediates in VEGF and FGF signaling as dissected by CRISPR in corpus luteum of water buffalo.

The EGR family comprises of EGR 1, EGR 2, EGR 3 and EGR 4 which are involved in the transactivation of several genes. A broad range of extracellular stimuli by growth factors is capable of activating EGR mediated transactivation of genes involved in angiogenesis and cell proliferation. However, their role in controlling VEGF A and FGF 2 signaling in the CL of water buffalo is not known. The present study was conducted to understand the role of EGR mediated regulation of VEGF A and FGF 2 signaling in buffalo luteal cells. Towards this goal, luteal cells were cultured and treated with VEGF A and FGF 2 and the mRNA expression pattern of EGR family members were documented. The EGR 1 message was found to be up-regulated in luteal cells of buffalo at 72 hours of culture. The functional validation of EGR 1 gene was accomplished by knocking out (KO) of EGR 1 in cultured luteal cells by CRISPR/Cas9 mediated gene editing technology. The EGR 1 KO cells were then cultured and stimulated with VEGF A and FGF 2. It was observed that VEGF A and FGF 2 induced angiogenesis, cell proliferation and steroidogenesis in wild type luteal cells, whereas the response of the growth factors was attenuated in the EGR 1 KO cells. Taken together our study provides evidence convincingly that both VEGF and FGF mediate their biological action through a common intermediate, EGR 1, to regulate corpus luteum function of buffalo.

Transcriptional Regulation of Thrombospondins and Its Functional Validation through CRISPR/Cas9 Mediated Gene Editing in Corpus Luteum of Water Buffalo (Bubalus Bubalis).

BACKGROUND/AIMS: Thrombospondins (TSPs) are large multi-modular proteins, identified as natural angiogenesis inhibitors that exert their activity by binding to CD36 and CD47 receptors. The anti-angiogenic effect of TSPs in luteal regression of water buffalo has not been addressed. The present study characterized the expression pattern and localization of TSPs and their receptors in ovarian corpus luteum during different stages of development in buffalo. This study also elucidated the effect of exogenous Thrombospondin1 (TSP1) or the knocking out of the endogenous protein on luteal cell viability and function. Further, the in vitro transcriptional interaction of TSP1 with hormones, LH, PGF2α and angiogenic growth factors, VEGF and FGF2 were also evaluated. METHODS: First, the CLs were classified into four groups based on macroscopic observation and progesterone concentration. mRNA expression of examined factors was measured by qPCR, localization by immunoblotting and immunohistochemistry. TSP1 was knocked out (KO) in cultured luteal cells isolated from late luteal stage CLs (day 1116) by CRISPR/Cas9 mediated gene editing technology in order to functionally validate the TSP1 gene. Isolated cells from late stage CLs were also stimulated with different doses of TSP1, LH, PGF2α, VEGF and FGF2 for various time intervals to determine transcriptional regulation of thrombospondins. RESULTS: mRNA expression of TSPs and their receptors were found to be significantly higher in late and regressed stage of CL as compared to other groups which was consistent with the findings of immunoblotting and immunolocalization experiments. It was observed that TSP1 induced apoptosis, down regulated angiogenic growth factors, VEGF and FGF2 and attenuated progesterone production in cultured luteal cells. However, knocking out of endogenous TSP1 with CRISPR/Cas9 system improved the viability of luteal cells, progesterone synthesis and upregulated the expression of VEGF and FGF2 in the KO luteal cells. PGF2α induced the upregulation of TSPs and Caspase 3 transcripts, whereas treatment with LH and angiogenic growth factors (VEGF and FGF2) down regulated the TSP system in luteal cells. CONCLUSION: Collectively, these data provide evidence that thrombospondins along with their receptors are expressed at varying levels in different stages of CL progression with maximum expression during the late and regressing stages. These results are consistent with the hypothesis that thrombospondins stimulated by PGF2α plays an essential modulatory role in bringing about structural and functional luteolysis in buffalo.

Regulation of steroidogenic function of luteal cells by thrombospondin and insulin in water buffalo (Bubalus bubalis).

The present study examined the effect of exogenous thrombospondin 1 (TSP1) on the steroidogenic function of luteal cells cultured invitro. Furthermore, the transcriptional interaction of insulin with TSP1 and its receptor, cluster of differentiation 36 (CD36) were also investigated. At the highest dose (500ngmL-1) TSP1 significantly downregulated the expression of the angiogenic marker von Willebrand factor (vWF) and progesterone production in cultured luteal cells. Moreover, the simultaneous upregulation in the expression of caspase 3 by exogenous TSP1 was consistent with a reduction in the number of viable luteal cells as determined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltertrazolium bromide (MTT) assay after 72h of culture. However, the expression of critical enzymes in the progesterone synthetic pathway was not significantly modulated by treatment with TSP1 in cultured luteal cells. Knocking out of endogenous TSP1 with the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPRassociated protein9 (Cas9) system improved the viability of luteal cells as well as increasing progesterone production and decreasing caspase 3 activation. Insulin treatment suppressed the expression of TSP1 and CD36 in cultured luteal cells in a dose- and time-dependent manner. To conclude, TSP1 acts as a negative endogenous regulator of angiogenesis that attenuates progesterone production, possibly by reducing the number of luteal cells via apoptosis during luteal regression, whereas insulin as a luteinising signal may have inhibited the thrombospondin system for the efficient development of luteal function.

Unsatisfactory rate in liquid-based cervical samples as compared to conventional smears: A study from tertiary care hospital.

BACKGROUND: Developed countries adopted liquid-based cytology (LBC) cervical cytology, partly because of its lower proportions of unsatisfactory (U/S)/inadequate samples. This study was carried out to evaluate effect on the rate of U/S samples after introduction of LBC in our laboratory. MATERIALS AND METHODS: An audit of U/S cervical samples was performed, which included split samples (n = 1000), only conventional Pap smear (CPS) smears (n = 1000), and only LBC samples (n = 1000). The smears were reviewed by two observers independently, and adequacy for the samples was assessed as per The Bethesda System 2001. The reasons for U/S rate in split samples were categorized into various cytologic and/or technical reasons. RESULTS: U/S rate was far less in only LBC samples (1.2%) as compared to only CPS (10.5%) cases. Cases in the satisfactory but limited category were also less in only LBC (0.4%) as compared to only CPS (3.2%) samples. The main reasons for U/S smears in split samples were low cell count (37.2% in CPS; 58.8% in LBC). The second main reason was low cellularity with excess blood and only excess blood in CPS samples. CONCLUSION: There was a significant reduction of U/S rate in LBC samples as compared to CPS samples, and the difference was statistically significant. The main cause of U/S samples in LBC was low cellularity indicating a technical fault in sample collection. The main cause of U/S rate in CPS was low cellularity followed by low cellularity with excess blood. Adequate training of sample takers and cytologists for the precise cell count to determine adequacy in smears can be of great help in reducing U/S rate.

Screening of antitubercular compound library identifies novel shikimate kinase inhibitors of Mycobacterium tuberculosis.

Shikimate kinase of Mycobacterium tuberculosis is involved in the biosynthesis of aromatic amino acids through shikimate pathway. The enzyme is essential for the survival of M. tuberculosis and is absent from mammals, thus providing an excellent opportunity for identifying new chemical entities to combat tuberculosis with a novel mechanism of action. In this study, an antitubercular library of 1000 compounds was screened against M. tuberculosis shikimate kinase (MtSK). This effort led to the identification of 20 inhibitors, among which five promising leads exhibited half maximal inhibitory concentration (IC50) values below 10 µM. The most potent inhibitor ("5631296") showed an IC50 value of 5.10 µM ± 0.6. The leads were further evaluated for the activity against multidrug-resistant (MDR)-TB, Gram-positive and Gram-negative bacterial strains, mode of action, docking simulations, and combinatorial study with three frontline anti-TB drugs. Compound "5491210" displayed a nearly synergistic activity with rifampicin, isoniazid, and ethambutol while compound "5631296" was synergistic with rifampicin. In vitro cytotoxicity against HepG2 cell line was evaluated and barring one compound; all were found to be non-toxic (SI > 10). In order to rule out mitochondrial toxicity, the promising inhibitors were also evaluated for cell cytotoxicity using galactose medium where compounds "5631296" and "5122752" appeared non-toxic. Upon comprehensive analysis, compound "5631296" was found to be the most promising MtSK inhibitor that was safe, synergistic with rifampicin, and bactericidal against M. tuberculosis.

Identification and characterization of novel small molecule inhibitors of the acetyltransferase activity of Escherichia coli N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU).

This study aims at identifying novel chemical scaffolds as inhibitors specific to the acetyltransferase domain of a bifunctional enzyme, Escherichia coli GlmU, involved in the cell wall biosynthesis of Gram-negative organisms. A two-pronged approach was used to screen a 50,000 small-molecule library. Using the first approach, the library was in silico screened by docking the library against acetyltransferase domain of E. coli GlmU studies. In the second approach, complete library was screened against Escherichia coli ATCC 25922 to identify the whole cell active compounds. Active compounds from both the screens were screened in a colorimetric absorbance-based assay to identify inhibitors of acetyltransferase domain of E. coli GlmU which resulted in the identification of 1 inhibitor out of 56 hits identified by in silico screening and 4 inhibitors out of 35 whole cell active compounds on Gram-negative bacteria with the most potent inhibitor showing IC50 of 1.40 ± 0.69 µM. Mode of inhibition studies revealed these inhibitors to be competitive with AcCoA and uncompetitive with GlcN-1-P. These selected inhibitors were also tested for their antibacterial and cytotoxic activities. Compounds 5175178 and 5215319 exhibited antibacterial activity that co-related with GlmU inhibition. These compounds, therefore, represent novel chemical scaffolds targeting acetyltransferase activity of E. coli GlmU.