Disruption of trehalose periplasmic recycling dysregulates cAMP-CRP signaling in Escherichia coli during stationary phase.

IMPORTANCE: Survival during starvation hinges on the ability to manage intracellular energy reserves and to initiate appropriate metabolic responses to perturbations of such reserves. How Escherichia coli manage carbon storage systems under starvation stress, as well as transpose changes in intracellular metabolite levels into regulatory signals, is not well understood. Endogenous trehalose metabolism may be at the center of these processes, coupling carbon storage with carbon starvation responses. The coupled transport to the periplasm and subsequent hydrolysis of trehalose back to glucose for transport to the cytoplasm may function as a crucial metabolic signaling pathway. Although trehalose has been characterized as a stress protectant in E. coli, the disaccharide also functions as both an energy storage compound and a regulator of carbohydrate metabolism in fungi, plants, and other bacteria. Our research explores the metabolic regulatory properties of trehalose in E. coli and a potential mechanism by which the intracellular carbon pool is interconnected with regulatory circuits, enabling long-term survival.

Accuracy of liver metastasis detection and characterization: Dual-energy CT versus single-energy CT with deep learning reconstruction.

PURPOSE: To assess whether image quality differences between SECT (single-energy CT) and DECT (dual-energy CT 70 keV) with equivalent radiation doses result in altered detection and characterization accuracy of liver metastases when using deep learning image reconstruction (DLIR), and whether DECT spectral curve usage improves accuracy of indeterminate lesion characterization. METHODS: In this prospective Health Insurance Portability and Accountability Act-compliant study (March through August 2022), adult men and non-pregnant adult women with biopsy-proven colorectal cancer and liver metastases underwent SECT (120 kVp) and a DECT (70 keV) portovenous abdominal CT scan using DLIR in the same breath-hold (Revolution CT ES; GE Healthcare). Participants were excluded if consent could not be obtained, if there were nonequivalent radiation doses between the two scans, or if the examination was cancelled/rescheduled. Three radiologists independently performed lesion detection and characterization during two separate sessions (SECT DLIRmedium and DECT DLIRhigh) as well as reported lesion confidence and overall image quality. Hounsfield units were measured. Spectral HU curves were provided for any lesions rated as indeterminate. McNemar's test was used to test the marginal homogeneity in terms of diagnostic sensitivity, accuracy and lesion detection. A generalized estimating equation method was used for categorical outcomes. RESULTS: 30 participants (mean age, 58 years ± 11, 21 men) were evaluated. Mean CTDIvol was 34 mGy for both scans. 141 lesions (124 metastases, 17 benign) with a mean size of 0.8 cm ± 0.3 cm were identified. High scores for image quality (scores of 4 or 5) were not significantly different between DECT (N = 71 out of 90 total scores from the three readers) and SECT (N = 62) (OR, 2.01; 95% CI:0.89, 4.57; P = 0.093). Equivalent image noise to SECT DLIRmed (HU SD 10 ± 2) was obtained with DECT DLIRhigh (HU SD 10 ± 3) (P = 1). There was no significant difference in lesion detection between DECT and SECT (140/141 lesions) (99.3%; 95% CI:96.1%, 100%).The mean lesion confidence scores by each reader were 4.2 ± 1.3, 3.9 ± 1.0, and 4.8 ± 0.8 for SECT and 4.1 ± 1.4, 4.0 ± 1.0, and 4.7 ± 0.8 for DECT (odds ratio [OR], 0.83; 95% CI: 0.62, 1.11; P = 0.21). Small lesion (≤5mm) characterization accuracy on SECT and DECT was 89.1% (95% CI:76.4%, 96.4%; 41/46) and 84.8% (71.1%, 93.7%; 39/46), respectively (P = 0.41). Use of spectral HU lesion curves resulted in 34 correct changes in characterizations and no mischaracterizations. CONCLUSION: DECT required a higher strength of DLIR to obtain equivalent noise compared to SECT DLIR. At equivalent radiation doses and image noise, there was no significant difference in subjective image quality or observer lesion performance between DECT (70 keV) and SECT. However, DECT spectral HU curves of indeterminate lesions improved characterization.

Clinical importance of second-opinion interpretations of abdominal imaging studies in a cancer hospital and its impact on patient management.

PURPOSE: The purpose of this retrospective study was to evaluate the quality of outside hospital imaging and associated reports submitted to us for reinterpretation related to clinical care at our tertiary cancer center. We compared the initial study interpretations to that of interpretations performed by subspecialty-trained abdominal radiologists at our center and whether this resulted in a change in inpatient treatment. MATERIALS AND METHODS: We performed an institutional review board-approved retrospective single-institution study of 915 consecutive outside computed tomography (CT) and magnetic resonance (MR) abdominal imaging studies that had been submitted to our institution between August 1, 2020 and November 30, 2020. The assessed parameters included the quality and accuracy of the report, the technical quality of the imaging compared to that at our institution, the appropriateness of the imaging for staging or restaging, usage of oral and IV contrast, and CT slice thickness. Clinical notes, pathologic findings, and subsequent imaging were used to establish an accurate diagnosis and determine the effect on clinical treatment. Discrepancies between the initial and secondary interpretations were identified independently by a panel of radiologists to assess changes in treatment. The impact of discrepancies on treatment was evaluated based on current treatment guidelines. RESULTS: Of 744 CT (81%) and 171 MR (19%) outside imaging studies, 65% had suboptimal quality compared to the images at our institution, and 31% were inappropriate for oncological care purposes. Only 21% of CT studies had optimal slice thickness of <3 mm. Of 375 (41%) outside reports, 131 (34%) had discrepancies between secondary and initial interpretations. Of the 88 confirmed discrepant studies, 42 patients (48%) had a change in treatment based on the secondary interpretation. CONCLUSIONS: Imaging studies from outside institutions have variable image quality and are often inadequate for oncologic imaging. The secondary interpretations by subspecialty-trained radiologists resulted in treatment change.

Reduced-Dose Deep Learning Reconstruction for Abdominal CT of Liver Metastases.

Background Assessment of liver lesions is constrained as CT radiation doses are lowered; evidence suggests deep learning reconstructions mitigate such effects. Purpose To evaluate liver metastases and image quality between reduced-dose deep learning image reconstruction (DLIR) and standard-dose filtered back projection (FBP) contrast-enhanced abdominal CT. Materials and Methods In this prospective Health Insurance Portability and Accountability Act-compliant study (September 2019 through April 2021), participants with biopsy-proven colorectal cancer and liver metastases at baseline CT underwent standard-dose and reduced-dose portal venous abdominal CT in the same breath hold. Three radiologists detected and characterized lesions at standard-dose FBP and reduced-dose DLIR, reported confidence, and scored image quality. Contrast-to-noise ratios for liver metastases were recorded. Summary statistics were reported, and a generalized linear mixed model was used. Results Fifty-one participants (mean age ± standard deviation, 57 years ± 13; 31 men) were evaluated. The mean volume CT dose index was 65.1% lower with reduced-dose CT (12.2 mGy) than with standard-dose CT (34.9 mGy). A total of 161 lesions (127 metastases, 34 benign lesions) with a mean size of 0.7 cm ± 0.3 were identified. Subjective image quality of reduced-dose DLIR was superior to that of standard-dose FBP (P < .001). The mean contrast-to-noise ratio for liver metastases of reduced-dose DLIR (3.9 ± 1.7) was higher than that of standard-dose FBP (3.5 ± 1.4) (P < .001). Differences in detection were identified only for lesions 0.5 cm or smaller: 63 of 65 lesions detected with standard-dose FBP (96.9%; 95% CI: 89.3, 99.6) and 47 lesions with reduced-dose DLIR (72.3%; 95% CI: 59.8, 82.7). Lesion accuracy with standard-dose FBP and reduced-dose DLIR was 80.1% (95% CI: 73.1, 86.0; 129 of 161 lesions) and 67.1% (95% CI: 59.3, 74.3; 108 of 161 lesions), respectively (P = .01). Lower lesion confidence was reported with a reduced dose (P < .001). Conclusion Deep learning image reconstruction (DLIR) improved CT image quality at 65% radiation dose reduction while preserving detection of liver lesions larger than 0.5 cm. Reduced-dose DLIR demonstrated overall inferior characterization of liver lesions and reader confidence. Clinical trial registration no. NCT03151564 © RSNA, 2022 Online supplemental material is available for this article.

Knockdown of Astrocytic Monocarboxylate Transporter 4 in the Motor Cortex Leads to Loss of Dendritic Spines and a Deficit in Motor Learning.

Monocarboxylate transporters (MCTs) shuttle molecules, including L-lactate, involved in metabolism and cell signaling of the central nervous system. Astrocyte-specific MCT4 is a key component of the astrocyte-neuron lactate shuttle (ANLS) and is important for neuroplasticity and learning of the hippocampus. However, the importance of astrocyte-specific MCT4 in neuroplasticity of the M1 primary motor cortex remains unknown. In this study, we investigated astrocyte-specific MCT4 in motor learning and neuroplasticity of the M1 primary motor cortex using a cell-type specific shRNA knockdown of MCT4. Knockdown of astrocyte-specific MCT4 resulted in impaired motor performance and learning on the accelerating rotarod. In addition, MCT4 knockdown was associated with a reduction of neuronal dendritic spine density and spine width and decreased protein expression of PSD95, Arc, and cFos. Using near-infrared-conjugated 2-deoxyglucose uptake as a surrogate marker for neuronal activity, MCT4 knockdown was also associated with decreased neuronal activity in the M1 primary motor cortex and associated motor regions including the dorsal striatum and ventral thalamus. Our study supports a potential role for astrocyte-specific MCT4 and the ANLS in the neuroplasticity of the M1 primary motor cortex. Targeting MCT4 may serve to enhance neuroplasticity and motor repair in several neurological disorders, including Parkinson's disease and stroke.

Sciatic foramen anatomy and common pathologies: a pictorial review.

This article reviews the relevant anatomy, imaging features on computed tomography, magnetic resonance imaging, and management of common processes involving the sciatic foramen. The anatomy of the sciatic foramen is complex and provides an important conduit between the pelvis, gluteus, and lower extremity. This paper reviewed the anatomy, common pathologies, and imaging features of this region including trauma, infection, nerve entrapment, tumor spread, hernia, and vascular anomaly.

Peer Learning and Operationalizing During COVID-19 Pandemic and Beyond.

The main objective of the article is to describe the changes in managing the peer learning system in the Department of Abdominal Imaging at our institution during the pandemic and its restrictions. The pandemic poses diverse challenges to academic institutions across the country including radiology education and peer learning. The health sector in some areas of the country has been stretched by the number of coronavirus disease 2019 (COVID-19) patients. In March 2020, our institution cancelled all in-person conferences as per guidelines from the Center of Disease Control and Prevention to mitigate the spread of COVID-19 and the conferences were shifted to virtual platforms. Our recent peer learning approach allowed us to practice appropriate social distancing while following the institutional and national guidelines with minimal disruption. Other institutions that are facing similar challenges can adopt or modify our framework of a successful and efficient virtual peer learning process.

CT angiographic evaluation of the V3 vertebral artery course in cases of occipitalized atlas, a study of 25 cases.

OBJECTIVES: To study the relationship of the 3rd segment of the vertebral artery to the posterior arch of the atlas in patients with occipitalized atlas, using CT angiography. METHODS: A retrospective study of 25 cases with complete or partially occipitalized atlas who underwent CT angiography evaluation. Fifty vertebral arteries were analyzed in relation to the respective/related half of the posterior arch of the atlas. RESULTS: Out of 50 vertebral arteries, 35 (70%) were anomalous; 31 (62%) traversed though bony canal between the fused occiput and atlas, and 4 (8%) coursed between C1 and C2 (C2 segmental type of vertebral artery). Except one, all anomalous vertebral arteries were associated with a fused corresponding side of posterior arch of atlas. CONCLUSION: The V3 portion of the vertebral artery assumes an anomalous course at the craniovertebral junction in most cases of occipitalized atlas, and this is strongly determined by the fusion status of the posterior arch of the atlas. Aberrations in its course are still seen despite expectations based on this fusion status. Preprocedural CT Angiography provides accurate information of its course to prevent iatrogenic VA injuries. ADVANCES IN KNOWLEDGE: CT Angiography should be performed before any procedures at the craniovertebral junction in cases of occipitalized atlas to prevent iatrogenic, potentially catastrophic injuries to vertebral artery due to its anomalous course in most of these cases. There are very few such studies in the literature, none in radiology literature. We also describe some rare cases, including a case never described in any literature.

Improved Computed Tomography Contrast Injection Rates Through Implantable Chest Power Ports.

OBJECTIVE: The aim of this study was to optimize chest port contrast injections using stepwise improvements. METHODS: Ex vivo injections were tested. Two hundred scans using power port injections were then evaluated. RESULTS: The highest flow rate was achieved using a 19G access needle, larger diameter tubing, and warmed contrast.The mean injection rates in baseline and postimprovement groups were 2.7 ± 0.4 and 4.8 ± 0.4 mL/s, respectively (P < .0001). CONCLUSION: Component optimization of the port apparatus can maximize contrast flow rates.

Imaging Surveillance of Limited-stage Classic Hodgkin Lymphoma Patients After PET-CT-documented First Remission.

INTRODUCTION: Early stage Hodgkin lymphoma (ESHL) is highly curable; however, 10% to 15% of patients experience relapse. We examined the utilization of follow-up imaging for patients with ESHL who achieved a metabolic complete response after upfront therapy. MATERIALS AND METHODS: The records of adult patients treated at a single institution between 2003 and 2014 were reviewed. Positron emission tomography-computed tomography (PET-CT) and CT scan frequency was quantified during the 2 years following treatment and subsequent visits beyond 2 years. RESULTS: The study cohort contained 179 patients. The median age was 31 years; bulky disease was present in 30%. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or AVD (doxorubicin, vinblastine, and dacarbazine) was given in 97%; 75% received radiation therapy. At a median follow-up of 6.9 years, the 5-year progression-free and overall survival rates were 93.7% and 98.1%, respectively. Relapse occurred in 5% (n = 9) of patients at a median of 9.1 months (range, 4.6-27.2 months) from therapy. Two patients presented with symptoms prompting imaging in follow-up. Within 2 years after therapy, 376 PET-CT scans and 3325 CT scans were performed, yielding an average of 2.1 PET-CTs and 18.6 CTs per patient. Of the initial 179 patients, 113 had follow-up conducted beyond 2 years post-therapy; an average of 2.7 PET-CTs and 33.2 CTs were performed. In the 2-year post-therapy period, 463 scans were performed per relapse detected. CONCLUSION: In this cohort of patients with ESHL who responded completely to frontline therapy, the relapse rate was low. Routine imaging surveillance lacks clinical benefit in this patient population.

Image Quality Assessment of Abdominal CT by Use of New Deep Learning Image Reconstruction: Initial Experience.

OBJECTIVE. The purpose of this study was to perform quantitative and qualitative evaluation of a deep learning image reconstruction (DLIR) algorithm in contrast-enhanced oncologic CT of the abdomen. MATERIALS AND METHODS. Retrospective review (April-May 2019) of the cases of adults undergoing oncologic staging with portal venous phase abdominal CT was conducted for evaluation of standard 30% adaptive statistical iterative reconstruction V (30% ASIR-V) reconstruction compared with DLIR at low, medium, and high strengths. Attenuation and noise measurements were performed. Two radiologists, blinded to examination details, scored six categories while comparing reconstructions for overall image quality, lesion diagnostic confidence, artifacts, image noise and texture, lesion conspicuity, and resolution. RESULTS. DLIR had a better contrast-to-noise ratio than 30% ASIR-V did; high-strength DLIR performed the best. High-strength DLIR was associated with 47% reduction in noise, resulting in a 92-94% increase in contrast-to-noise ratio compared with that of 30% ASIR-V. For overall image quality and image noise and texture, DLIR scored significantly higher than 30% ASIR-V with significantly higher scores as DLIR strength increased. A total of 193 lesions were identified. The lesion diagnostic confidence, conspicuity, and artifact scores were significantly higher for all DLIR levels than for 30% ASIR-V. There was no significant difference in perceived resolution between the reconstruction methods. CONCLUSION. Compared with 30% ASIR-V, DLIR improved CT evaluation of the abdomen in the portal venous phase. DLIR strength should be chosen to balance the degree of desired denoising for a clinical task relative to mild blurring, which increases with progressively higher DLIR strengths.

Investigation of secondary metabolism in the industrial butanol hyper-producer Clostridium saccharoperbutylacetonicum N1-4.

Clostridium saccharoperbutylacetonicum N1-4 (Csa) is a historically significant anaerobic bacterium which can perform saccharolytic fermentations to produce acetone, butanol, and ethanol (ABE). Recent genomic analyses have highlighted this organism's potential to produce polyketide and nonribosomal peptide secondary metabolites, but little is known regarding the identity and function of these metabolites. This study provides a detailed bioinformatic analysis of seven biosynthetic gene clusters (BGCs) present in the Csa genome that are predicted to produce polyketides/nonribosomal peptides. An RNA-seq-based untargeted transcriptomic approach revealed that five of seven BGCs were expressed during ABE fermentation. Additional characterization of a highly expressed nonribosomal peptide synthetase gene led to the discovery of its associated metabolite and its biosynthetic pathway. Transcriptomic analysis suggested an association of this nonribosomal peptide synthetase gene with butanol tolerance, which was supported by butanol challenge assays.

Adrenocortical hyperplasia: a review of clinical presentation and imaging.

Adrenal hyperplasia is non-malignant enlargement of the adrenal glands, which is often bilateral. It can be incidental or related to indolent disease process and may be related to benign or malignant etiologies causing biochemical alterations in the hypothalamic-pituitary-adrenal axis which controls steroidogenesis and in particular cortisol production. Clinical significance of the adrenal hyperplasia is variable ranging from asymptomatic finding to serious manifestations of Cushing syndrome. This is often associated with anatomical changes in the adrenal glands, which typically manifests as diffuse and sometimes nodular enlargement of the adrenal glands radiologically. Approaching adrenal hyperplasia requires careful clinical and biochemical evaluation in correlation with imaging review to differentiate ACTH-dependent and ACTH-independent etiologies. CT is the primary modality of choice for adult adrenal imaging owing to reproducibility, temporal and spatial resolution and broader access, while MRI often serves a complimentary role. Ultrasound and MRI are most commonly used in pediatric cases to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation and imaging features of different types and mimics of adrenal cortical hyperplasia.

Detection of Colorectal Hepatic Metastases Is Superior at Standard Radiation Dose CT versus Reduced Dose CT.

Purpose To evaluate colorectal cancer hepatic metastasis detection and characterization between reduced radiation dose (RD) and standard dose (SD) contrast material-enhanced CT of the abdomen and to qualitatively compare between filtered back projection (FBP) and iterative reconstruction algorithms. Materials and Methods In this prospective study (from May 2017 through November 2017), 52 adults with biopsy-proven colorectal cancer and suspected hepatic metastases at baseline CT underwent two portal venous phase CT scans: SD and RD in the same breath hold. Three radiologists, blinded to examination details, performed detection and characterization of 2-15-mm lesions on the SD FBP and RD adaptive statistical iterative reconstruction (ASIR)-V 60% series images. Readers assessed overall image quality and lesions between SD FBP and seven different iterative reconstructions. Two nonblinded consensus reviewers established the reference standard using the picture archiving and communication system lesion marks of each reader, multiple comparison examinations, and clinical data. Results RD CT resulted in a mean dose reduction of 54% compared with SD. Of the 260 lesions (233 metastatic, 27 benign), 212 (82%; 95% confidence interval [CI]: 76%, 86%) were detected with RD CT, whereas 252 (97%; 95% CI: 94%, 99%) were detected with SD (P < .001); per-lesion sensitivity was 79% (95% CI: 74%, 84%) and 94% (95% CI: 90%, 96%) (P < .001), respectively. Mean qualitative scores ranked SD images as higher quality than RD series images, and ASIR-V ranked higher than ASIR and Veo 3.0. Conclusion CT evaluation of colorectal liver metastases is compromised with modest radiation dose reduction, and the use of iterative reconstructions could not maintain observer performance. © RSNA, 2018.

Comparison of Abdominal Computed Tomographic Enhancement and Organ Lesion Depiction Between Weight-Based Scanner Software Contrast Dosing and a Fixed-Dose Protocol in a Tertiary Care Oncologic Center.

OBJECTIVE: This study aimed to evaluate the quality of enhancement and solid-organ lesion depiction using weight-based intravenous (IV) contrast dosing calculated by injector software versus fixed IV contrast dose in oncologic abdominal computed tomographic (CT) examinations. METHODS: This institutional review board-exempt retrospective cohort study included 134 patients who underwent single-phase abdominal CT before and after implementation of weight-based IV contrast injector software. Patient weight, height, body mass index, and body surface area were determined. Two radiologists qualitatively assessed examinations (4 indicating markedly superior to -4 indicating markedly inferior), and Hounsfield unit measurements were performed. RESULTS: Enhancement (estimated mean, -0.05; 95% confidence interval [CI], -0.19 to 0.09; P = 0.46) and lesion depiction (estimated mean, -0.01; 95% CI, -0.10 to 0.07; P = 0.79) scores did not differ between CT examinations using weight-based IV contrast versus fixed IV contrast dosing when a minimum of 38.5 g of iodine was used. However, the scores using weight-based IV contrast dosing were lower when the injector software calculated and delivered less than 38.5 g of iodine (estimated mean, -0.81; 95% CI, -1.06 to -0.56; P < 0.0001). There were no significant differences in measured Hounsfield units between the CT examinations using weight-based IV contrast dosing versus fixed IV contrast dosing. CONCLUSIONS: Oncologic CT image quality was maintained or improved with weight-based IV contrast dosing using injector software when using a minimum amount of 38.5 g of iodine.

Computed Tomography Image Quality Evaluation of a New Iterative Reconstruction Algorithm in the Abdomen (Adaptive Statistical Iterative Reconstruction-V) a Comparison With Model-Based Iterative Reconstruction, Adaptive Statistical Iterative Reconstruction, and Filtered Back Projection Reconstructions.

OBJECTIVE: The purpose of this study was to compare abdominopelvic computed tomography images reconstructed with adaptive statistical iterative reconstruction-V (ASIR-V) with model-based iterative reconstruction (Veo 3.0), ASIR, and filtered back projection (FBP). METHODS AND MATERIALS: Abdominopelvic computed tomography scans for 36 patients (26 males and 10 females) were reconstructed using FBP, ASIR (80%), Veo 3.0, and ASIR-V (30%, 60%, 90%). Mean ± SD patient age was 32 ± 10 years with mean ± SD body mass index of 26.9 ± 4.4 kg/m. Images were reviewed by 2 independent readers in a blinded, randomized fashion. Hounsfield unit, noise, and contrast-to-noise ratio (CNR) values were calculated for each reconstruction algorithm for further comparison. Phantom evaluation of low-contrast detectability (LCD) and high-contrast resolution was performed. RESULTS: Adaptive statistical iterative reconstruction-V 30%, ASIR-V 60%, and ASIR 80% were generally superior qualitatively compared with ASIR-V 90%, Veo 3.0, and FBP (P < 0.05). Adaptive statistical iterative reconstruction-V 90% showed superior LCD and had the highest CNR in the liver, aorta, and, pancreas, measuring 7.32 ± 3.22, 11.60 ± 4.25, and 4.60 ± 2.31, respectively, compared with the next best series of ASIR-V 60% with respective CNR values of 5.54 ± 2.39, 8.78 ± 3.15, and 3.49 ± 1.77 (P <0.0001). Veo 3.0 and ASIR 80% had the best and worst spatial resolution, respectively. CONCLUSIONS: Adaptive statistical iterative reconstruction-V 30% and ASIR-V 60% provided the best combination of qualitative and quantitative performance. Adaptive statistical iterative reconstruction 80% was equivalent qualitatively, but demonstrated inferior spatial resolution and LCD.

The Oxygen Paradox, the French Paradox, and age-related diseases.

A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen "a toxic environmental poison" could be also indispensable for life (Beckman and Ames Physiol Rev 78(2):547-81, 1998; Stadtman and Berlett Chem Res Toxicol 10(5):485-94, 1997)?: the so-called Oxygen Paradox (Davies and Ursini 1995; Davies Biochem Soc Symp 61:1-31, 1995). How can French people apparently disregard the rule that high dietary intakes of cholesterol and saturated fats (e.g., cheese and paté) will result in an early death from cardiovascular diseases (Renaud and de Lorgeril Lancet 339(8808):1523-6, 1992; Catalgol et al. Front Pharmacol 3:141, 2012; Eisenberg et al. Nat Med 22(12):1428-1438, 2016)?: the so-called, French Paradox. Doubtless, the truth is not a duality and epistemological bias probably generates apparently self-contradictory conclusions. Perhaps nowhere in biology are there so many apparently contradictory views, and even experimental results, affecting human physiology and pathology as in the fields of free radicals and oxidative stress, antioxidants, foods and drinks, and dietary recommendations; this is particularly true when issues such as disease-susceptibility or avoidance, "healthspan," "lifespan," and ageing are involved. Consider, for example, the apparently paradoxical observation that treatment with low doses of a substance that is toxic at high concentrations may actually induce transient adaptations that protect against a subsequent exposure to the same (or similar) toxin. This particular paradox is now mechanistically explained as "Adaptive Homeostasis" (Davies Mol Asp Med 49:1-7, 2016; Pomatto et al. 2017a; Lomeli et al. Clin Sci (Lond) 131(21):2573-2599, 2017; Pomatto and Davies 2017); the non-damaging process by which an apparent toxicant can activate biological signal transduction pathways to increase expression of protective genes, by mechanisms that are completely different from those by which the same agent induces toxicity at high concentrations. In this review, we explore the influences and effects of paradoxes such as the Oxygen Paradox and the French Paradox on the etiology, progression, and outcomes of many of the major human age-related diseases, as well as the basic biological phenomenon of ageing itself.

The industrial anaerobe Clostridium acetobutylicum uses polyketides to regulate cellular differentiation.

Polyketides are an important class of bioactive small molecules valued not only for their diverse therapeutic applications, but also for their role in controlling interesting biological phenotypes in their producing organisms. While numerous polyketides are known to be derived from aerobic organisms, only a single family of polyketides has been identified from anaerobic organisms. Here we uncover a family of polyketides native to the anaerobic bacterium Clostridium acetobutylicum, an organism well-known for its historical use as an industrial producer of the organic solvents acetone, butanol, and ethanol. Through mutational analysis and chemical complementation assays, we demonstrate that these polyketides act as chemical triggers of sporulation and granulose accumulation in this strain. This study represents a significant addition to the body of work demonstrating the existence and importance of polyketides in anaerobes, and showcases a strategy of manipulating the secondary metabolism of an organism to improve traits relevant for industrial applications.

Third version of vendor-specific model-based iterativereconstruction (Veo 3.0): evaluation of CT image quality in the abdomen using new noise reduction presets and varied slice optimization.

OBJECTIVE: To qualitatively and quantitatively compare abdominal CT images reconstructed with a newversion of model-based iterative reconstruction (Veo 3.0; GE Healthcare Waukesha, WI) utilizing varied presetsof resolution preference, noise reduction and slice optimization. METHODS: This retrospective study was approved by our Institutional Review Board and was Health Insurance Portability and Accountability Act compliant. The raw datafrom 30 consecutive patients who had undergone CT abdomen scanning were used to reconstructfour clinical presets of 3.75mm axial images using Veo 3.0: 5% resolution preference (RP05n), 5%noise reduction (NR05) and 40% noise reduction (NR40) with new 3.75mm "sliceoptimization," as well as one set using RP05 with conventional 0.625mm "slice optimization" (RP05c). The images were reviewed by two independent readers in a blinded, randomized manner using a 5-point Likert scale as well as a 5-point comparative scale. Multiple two-dimensional circular regions of interest were defined for noise and contrast-to-noise ratio measurements. Line profiles were drawn across the 7 lp cm-1 bar pattern of the Catphan 600 phantom for evaluation of spatial resolution. RESULTS: The NR05 image set was ranked as the best series in overall image quality (mean difference inrank 0.48, 95% CI [0.081-0.88], p = 0.01) and with specific reference to liver evaluation (meandifference 0.46, 95% CI [0.030-0.89], p = 0.03), when compared with the secondbest series ineach category. RP05n was ranked as the best for bone evaluation. NR40 was ranked assignificantly inferior across all assessed categories. Although the NR05 and RP05c image setshad nearly the same contrast-to-noise ratio and spatial resolution, NR05 was generally preferred. Image noise and spatial resolution increased along a spectrum with RP05n the highest and NR40the lowest. Compared to RP05n, the average noise was 21.01% lower for NR05, 26.88%lower for RP05c and 50.86% lower for NR40. CONCLUSION: Veo 3.0 clinical presets allow for selection of image noise and spatial resolution balance; for contrast-enhanced CT evaluation of the abdomen, the 5% noise reduction preset with 3.75 mm slice optimization (NR05) was generally ranked superior qualitatively and, relative to other series, was in the middle of the spectrum with reference to image noise and spatial resolution. Advances in knowledge: To our knowledge, this is the first study of Veo 3.0 noise reduction presets and varied slice optimization. This study provides insight into the behaviour of slice optimization and documents the degree of noise reduction and spatial resolution changes that users can expect across various Veo 3.0 clinical presets. These results provide important parameters to guide preset selection for both clinical and research purposes.