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In the diagnosis of infective endocarditis (IE), Modified Duke's criteria, coupled with clinical suspicion, serve as the guiding framework. For cases involving prosthetic valve endocarditis and infections affecting implantable devices, the use of metabolic imaging with 18 F-FDG PET/CT scans has gained prominence, as per the recommendations of the European Society of Cardiology guidelines. This imaging modality enhances sensitivity and specificity by identifying infective foci within the heart and extracardiac locations. Early utilization of these scans is crucial for confirming or ruling out IE, although caution is required to mitigate false positive responses, especially in the presence of ongoing inflammatory activity. A standardized ratio of ≥2.0 between FDG uptake around infected tissues and the blood pool has demonstrated a sensitivity of 100 % and specificity of 91 %. It is noteworthy that the sensitivity of FDG PET/CT varies, being lower for native valve and lead infections but considerably higher for prosthetic valve and pulse generator infections. This review provides a comprehensive overview of the advantages offered by FDG PET/CT in achieving a definitive diagnosis of IE., Competing Interests: Declaration of competing interest The authors have none to declare., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Diagnostic value of fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (F18-FDG PET/CT) in the assessment of myocardial viable segments is well known; hence, it can identify patients with left ventricular (LV) systolic dysfunction who may benefit from revascularization. The presence of significant myocardial viable segments before revascularization will offer better prognosis with reduced mortality and morbidity. However, the usage of F18-FDG PET/CT myocardial viability study in the presurgical risk stratification is limited., Objective: The objective of the study is to predict perioperative mortality with hibernating viable myocardial (HVM) segments established by F18-FDG PET/CT in comparison with EuroSCORE II in patients with LV dysfunction undergoing coronary artery bypass grafting surgery., Materials and Methods: A prospective, observational study included 75 patients of chronic ischemic coronary artery disease with ejection fraction ≤40%. Tc-99m sesta-methoxyisobutylisonitrile myocardial perfusion single photon emission CT/CT and myocardial viability with F18-FDG PET/CT at rest were performed. Mortality risk stratification was done according to the EuroSCORE II. Patients were followed for post-coronary artery bypass graft surgery (CABG) 30-day mortality. Mortality observed by HVM segment groups were compared with EuroSCORE II predicted mortality., Results: Receiver operating curve for 30-day mortality prediction with HVM segments and EuroSCORE II was constructed. It showed that a cutoff of <4 HVM segments (area under the curve [AUC] = 0.7) had a sensitivity of 85%, whereas EuroSCORE II (AUC = 0.4) had only 28.6% sensitivity. EuroSCORE II underestimated perioperative risk in patients with <4 viable segments, that is 5 times higher risk was observed in patients with <4 viable segments., Conclusions: HVM segments established by F18-FDG PET/CT had independently predicted mortality postoperatively. Hence, including F18-FDG PET/CT for viability assessment along with EuroSCORE II in preoperative risk assessment for revascularization by CABG in patients with LV dysfunction provided better risk stratification., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)

Whole pancreatic transplant and islet cells transplantation are currently available strategies aiming toward diabetes cure. Beta cell specific noninvasive functional imaging using novel PET radiotracers are now available and can be used for beta cell imaging and quantification. Herein we describe a spectrum of 2 cases demonstrating beta cell targeted imaging using Ga-DOTA-exendin-4 PET/CT in patients with diabetes after simultaneous pancreas-kidney transplantation.

99m Tc diethylenetriaminepentaacetic acid (DTPA) renogram is a commonly performed evaluation postrenal transplant to assess graft function and for early detection of suspected immediate and late transplant-associated complications. Although several modalities can be utilized to detect perinephric collection in posttransplant period, the utility of 99m Tc DTPA single-photon emission-computed tomography (SPECT-CT) is not recognized. Herein, we discuss the incremental role of seldom considered SPECT-CT in early detection, leading to timely appropriate management and graft salvage in a case of posttransplant deteriorating renal allograft as a result of subcapsular hematoma., Competing Interests: There are no conflicts of interest.

Previously, we have reported that Fos-related antigen-1 (Fra-1) transcription factor promotes LPS-induced acute lung injury and mortality, and that LPS-induced Fra-1 expression in the lung occurs predominantly in alveolar macrophages. Nuclear factor-κB (NF-κB) and c-Jun transcription factors play key roles in modulating inflammatory and immune responses induced by infectious and non-infectious insults. Here, we report that NF-κB and c-Jun coregulate Fra-1 induction by LPS in alveolar macrophages and that this regulation occurs through both the NF-κB and the extracellular signal-regulated protein kinase (ERK) signaling pathways. Transient transfections with Fra-1 promoter-reporter constructs and inhibitor studies revealed that the transcriptional activation of Fra-1 by LPS in alveolar macrophages is mediated by NF-κB and ERK1/2 signaling. Importantly, chromatin immunoprecipitation assays revealed the recruitment of c-Jun and NF-κB to the endogenous Fra-1 promoter after LPS stimulation. We found that inhibition of ERK1/2 signaling reduced LPS-stimulated c-Jun and NF-κB recruitment to the promoter. Likewise, NF-κB inhibitor blocked LPS-induced NF-κB and c-Jun binding to the promoter. ERK1/2 inhibition had no effect on c-Jun activation but suppressed LPS-stimulated NF-κB phosphorylation. Finally, functional assays showed reduced levels of LPS-stimulated NF-κB regulated proinflammatory IL-1β and macrophage inflammatory protein-1α expression and increased antiinflammatory IL-10 expression in lung alveolar macrophages of Fra-1-null mice in vivo. Thus, our studies indicate that NF-κB and c-Jun coregulate LPS-induced Fra-1 transcription and that Fra-1 selectively modulates LPS-stimulated inflammatory cytokine expression in lung alveolar macrophages during inflammatory lung injury.

Background: To evaluate the advantages of contrast enhanced F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-contrast enhanced CT [CECT]) when used as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin (MUO)., Materials and Methods: A total of 243 patients with fine needle aspiration cytology/biopsy proven MUO were included in this prospective study. Patients who were thoroughly evaluated for primary or primary tumor was detected by any other investigation were excluded from the analysis. Totally, 163 patients with pathological diagnosis of malignancy but no apparent sites of the primary tumor were finally selected for analysis. The site of probable primary malignancy suggested by PET-CECT was confirmed by biopsy/follow-up., Results: PET-CECT suggested probable site of primary in 128/163 (78.52%) patients. In 30/35 remaining patients, primary tumor was not detected even after extensive work-up. In 5 patients, where PET-CECT was negative, primary was found on further extensive investigations or follow-up. The sensitivity, specificity, positive predictive value and negative predictive value of the study were 95.76%, 66.67%, 88.28% and 85.71% respectively., Conclusions: F-18 FDG PET-CECT aptly serves the purpose of initial imaging modality owing to high sensitivity, negative and positive predictive value. PET-CECT not only surveys the whole body for the primary malignancy but also stages the disease accurately. Use of contrast improves the diagnostic utility of modality as well as help in staging of the primary tumor. Although benefits of using PET-CECT as initial diagnostic modality are obvious from this study, there is a need for a larger study comparing conventional methods for diagnosing primary in patients with MUO versus PET-CECT.

Colon cancer is one of the deadliest cancers worldwide because of its metastasis to other essential organs. Metastasis of colon cancer involves a complex set of events, including epithelial-to-mesenchymal transition (EMT) that increases invasiveness of the tumor cells. Here, we show that the xeroderma pigmentosum group E (XPE) gene product, damaged DNA-binding protein (DDB)-2, is downregulated in high-grade colon cancers, and it plays a dominant role in the suppression of EMT of the colon cancer cells. Depletion of DDB2 promotes mesenchymal phenotype, whereas expression of DDB2 promotes epithelial phenotype. DDB2 constitutively represses genes that are the key activators of EMT, indicating that DDB2 is a master regulator of EMT of the colon cancer cells. Moreover, we observed evidence that DDB2 functions as a barrier for EMT induced by hypoxia and TGF-β. Also, we provide evidence that DDB2 inhibits metastasis of colon cancer. The results presented here identify a transcriptional regulatory pathway of DDB2 that is directly linked to the mechanisms that suppress metastasis of colon cancer., (©2013 AACR.)

Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent commonly found in edible cruciferous vegetables. It has been implicated also for therapy, and is in clinical trial for lung cancer. Here, we provide evidence that the tumor suppressive effect of PEITC is related to its ability to induce expression of damaged DNA binding protein 2 (DDB2), a DNA repair protein involved also in apoptosis and premature senescence. DDB2 expression is attenuated in a wide variety of cancers including the aggressive colon cancers. We show that, in colon cancer cells, reactive oxygen species, which are induced by PEITC, augment expression of DDB2 through the p38MAPK/JNK pathway, independently of p53. PEITC-induced expression of DDB2 is critical for inhibition of tumor progression by PEITC. Tumors derived from DDB2-deficient colon cancer cells are refractory to PEITC-treatments, resulting from deficiencies in apoptosis and senescence. The DDB2-proficient tumors, on the other hand, respond effectively to PEITC. The results show that PEITC can be used to induce expression of DDB2, and that expression of DDB2 is critical for effective response of tumors to PEITC.

Expression of receptor for advanced glycation end products (RAGE) plays a key role in the progression of prostate cancer. However, the therapeutic potential of targeting RAGE expression in prostate cancer is not yet evaluated. Therefore in this study, we have investigated the effects of silencing the expression of RAGE by RNAi approach both in vitro and in vivo. The results of this study showed that down regulation of RAGE expression by RNAi inhibited the cell proliferation of androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells. Furthermore, targeting RAGE expression resulted in apoptotic elimination of these prostate cancer cells by activation of caspase-8 and caspase-3 death signaling. Of note, the levels of prostate specific antigen (PSA) were also reduced in LNCaP cells transfected with RAGE RNAi constructs. Importantly, the RAGE RNAi constructs when administered in nude mice bearing prostate tumors, inhibited the tumor growth by targeting the expression of RAGE, and its physiological ligand, HMGB1 and by up regulating death receptors DR4 and DR5 expression. Collectively, the results of this study for the first time show that targeting RAGE by RNAi may be a promising alternative therapeutic strategy for treating prostate cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Although environmental lead exposure is associated with significant deficits in cognition, executive functions, social behaviors, and motor abilities, the neuroanatomical basis for these impairments remains poorly understood. In this study, we examined the relationship between childhood lead exposure and adult brain volume using magnetic resonance imaging (MRI). We also explored how volume changes correlate with historic neuropsychological assessments., Methods and Findings: Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead concentrations. Using conservative, minimum contiguous cluster size and statistical criteria (700 voxels, unadjusted p < 0.001), approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead concentration. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex (ACC). Areas of lead-associated gray matter volume loss were much larger and more significant in men than women. We found that fine motor factor scores positively correlated with gray matter volume in the cerebellar hemispheres; adding blood lead concentrations as a variable to the model attenuated this correlation., Conclusions: Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and ACC responsible for executive functions, mood regulation, and decision-making. These neuroanatomical findings were more pronounced for males, suggesting that lead-related atrophic changes have a disparate impact across sexes. This analysis suggests that adverse cognitive and behavioral outcomes may be related to lead's effect on brain development producing persistent alterations in structure. Using a simple model, we found that blood lead concentration mediates brain volume and fine motor function.