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Incidental liver masses are commonly identified on imaging performed for other indications. Since the prevalence of benign focal liver lesions in adults is high, even in patients with primary malignancy, accurate characterization of incidentally detected lesions is of paramount clinical importance. This document reviews utilization of various imaging modalities for characterization of incidentally detected liver lesions, discussed in the context of several clinical scenarios. For each clinical scenario, a summary of current evidence supporting the use of a given diagnostic modality is reported. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Incidental liver masses are commonly identified on imaging performed for other indications. Since the prevalence of benign focal liver lesions in adults is high, even in patients with primary malignancy, accurate characterization of incidentally detected lesions is of paramount clinical importance. This document reviews utilization of various imaging modalities for characterization of incidentally detected liver lesions, discussed in the context of several clinical scenarios. For each clinical scenario, a summary of current evidence supporting the use of a given diagnostic modality is reported. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

The liver fibrosis stage is the most important clinical determinate of morbidity and mortality in patients with chronic liver diseases. With newer therapies, liver fibrosis can be stabilized and possibly reversed, thus accurate diagnosis and staging of liver fibrosis are clinically important. Ultrasound, CT, and conventional MRI can be used to establish the diagnosis of advanced fibrosis/cirrhosis but have limited utility for assessing earlier stages of fibrosis. Elastography-based ultrasound and MRI techniques are more useful for assessment of precirrhotic hepatic fibrosis. In patients with advanced fibrosis at risk for hepatocellular carcinoma (HCC), ultrasound is the surveillance modality recommended by international guidelines in nearly all circumstances. However, in patients in whom ultrasound does not assess the liver well, including those with severe steatosis or obesity, multiphase CT or MRI may have a role in surveillance for HCC. Both multiphase CT and MRI can be used for continued surveillance in patients with a history of HCC, and contrast-enhanced ultrasound may have an emerging role in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Incidental pancreatic cysts are increasingly detected on imaging studies performed for unrelated indications and may be incompletely characterized on these studies. Adequate morphological characterization is critical due to the small risk of malignant degeneration associated with neoplastic pancreatic cysts, as well as the risk of associated pancreatic adenocarcinoma. For all pancreatic cysts, both size and morphology determine management. Specifically, imaging detection of features, such as pancreatic ductal communication and presence or absence of worrisome features or high-risk stigmata, have important management implications. The recommendations in this publication determine the appropriate initial imaging study to further evaluate a pancreatic cyst that was incidentally detected on a nondedicated imaging study. The recommendations are designed to maximize the yield of diagnostic information in order to better risk-stratify pancreatic cysts and assist in guiding future management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

The liver fibrosis stage is the most important clinical determinate of morbidity and mortality in patients with chronic liver diseases. With newer therapies, liver fibrosis can be stabilized and possibly reversed, thus accurate diagnosis and staging of liver fibrosis are clinically important. Ultrasound, CT, and conventional MRI can be used to establish the diagnosis of advanced fibrosis/cirrhosis but have limited utility for assessing earlier stages of fibrosis. Elastography-based ultrasound and MRI techniques are more useful for assessment of precirrhotic hepatic fibrosis. In patients with advanced fibrosis at risk for hepatocellular carcinoma (HCC), ultrasound is the surveillance modality recommended by international guidelines in nearly all circumstances. However, in patients in whom ultrasound does not assess the liver well, including those with severe steatosis or obesity, multiphase CT or MRI may have a role in surveillance for HCC. Both multiphase CT and MRI can be used for continued surveillance in patients with a history of HCC, and contrast-enhanced ultrasound may have an emerging role in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Incidental pancreatic cysts are increasingly detected on imaging studies performed for unrelated indications and may be incompletely characterized on these studies. Adequate morphological characterization is critical due to the small risk of malignant degeneration associated with neoplastic pancreatic cysts, as well as the risk of associated pancreatic adenocarcinoma. For all pancreatic cysts, both size and morphology determine management. Specifically, imaging detection of features, such as pancreatic ductal communication and presence or absence of worrisome features or high-risk stigmata, have important management implications. The recommendations in this publication determine the appropriate initial imaging study to further evaluate a pancreatic cyst that was incidentally detected on a nondedicated imaging study. The recommendations are designed to maximize the yield of diagnostic information in order to better risk-stratify pancreatic cysts and assist in guiding future management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Novel hybrids N-(4-phenoxybenzyl)aniline were designed, synthesized, and evaluated for their potential AChE inhibitory activity along with antioxidant potential. The inhibitory potential (IC 50) of synthesized analogs was evaluated against human cholinesterases (hAChE and hBChE) using Ellman's method. Among all the tested compounds, 42 with trimethoxybenzene substituent showed maximum hAChE inhibition with the competitive type of enzyme inhibition (IC 50 = 1.32 µM; Ki = 0.879 µM). Further, parallel artificial membrane permeation assay (PAMPA-BBB) showed favorable BBB permeability by most of the synthesized compounds. Meanwhile, compound 42 also inhibited AChE-induced Aβ aggregation (39.5–66.9%) in thioflavin T assay. The in vivo behavioral studies showed dose-dependent improvement in learning and memory by compound 42. The ex vivo studies also affirmed the significant AChE inhibition and antioxidant potential of compound 42 in brain homogenates. [ABSTRACT FROM AUTHOR]

Although right upper quadrant pain is a very common clinical presentation, it can be nonspecific. However, acute cholecystitis is very often the diagnosis of exclusion. This review focuses on the recommended imaging evaluation in the most commonly encountered clinical scenarios presenting with right upper quadrant abdominal pain, including suspected biliary disease, suspected acute cholecystitis, and suspected acalculous cholecystitis. This document hopes to clarify the appropriate utilization of the many imaging procedures that are available and commonly employed in these clinical settings. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Jaundice is the end result of myriad causes, which makes the role of imaging in this setting particularly challenging. In the United States, the most common causes of all types of jaundice fall into four categories including hepatitis, alcoholic liver disease, blockage of the common bile duct by a gallstone or tumor, and toxic reaction to a drug or medicinal herb. Clinically, differentiating between the various potential etiologies of jaundice requires a detailed history, targeted physical examination, and pertinent laboratory studies, the results of which allow the physician to categorize the type of jaundice into mechanical or nonmechanical causes. Imaging modalities used to evaluate the jaundiced patient (all etiologies) include abdominal ultrasound (US), CT, MR cholangiopancreatography, endoscopic retrograde cholangiopancreatography and endoscopic US. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Novel hybrids bearing a 2-aminopyrimidine (2-AP) moiety linked to substituted 1,3,4-oxadiazoles were designed, synthesized and biologically evaluated. Among the developed compounds, 28 noncompetitively inhibited human acetylcholinesterase (hAChE; pIC 50 = 6.52; Ki = 0.17 µM) and showed potential in vitro antioxidant activity (60.0%) when evaluated using the Ellman's and DPPH assays, respectively. Compound 28 competitively displaced propidium iodide (PI) from the peripheral anionic site (PAS) of hAChE (17.6%) and showed high blood-brain barrier (BBB) permeability, as observed in the PAMPA-BBB assay. Additionally, compound 28 inhibited hAChE-induced Aβ aggregation in a concentration-dependent manner according to the thioflavin T assay and was devoid of neurotoxic liability towards SH-SY5Y cell lines, as demonstrated by the MTT assay. The behavioral studies of compound 28 in mice showed a significant reversal of scopolamine-induced amnesia, as observed in Y-maze and passive avoidance tests. Furthermore, compound 28 exhibited significant AChE inhibition in the brain in ex vivo studies. An evaluation of oxidative stress biomarkers revealed the antioxidant potential of 28. Moreover, in silico molecular docking and dynamics simulation studies were used as a computational tool to evaluate the interactions of compound 28 with the active site residues of hAChE. [ABSTRACT FROM AUTHOR]

Highlights • The pathophysiological roles and underlying mechanisms of several hypotheses involved in AD are extensively reviewed. • A detailed investigation of all the conventional and novel therapeutic targets. • The identification of structural and functional motifs with a comprehensive framework of the active sites involved. • To elucidate and simplify the complexity and call for attention on the crucial areas to discover innovative therapeutics. Abstract AD is a progressive neurodegenerative disorder and a leading cause of dementia in an aging population worldwide. The enormous challenge which AD possesses to global healthcare makes it as urgent as ever for the researchers to develop innovative treatment strategies to fight this disease. An in-depth analysis of the extensive available data associated with the AD is needed for a more comprehensive understanding of underlying molecular mechanisms and pathophysiological pathways associated with the onset and progression of the AD. The currently understood pathological and biochemical manifestations include cholinergic, Aβ, tau, excitotoxicity, oxidative stress, ApoE, CREB signaling pathways, insulin resistance, etc. However, these hypotheses have been criticized with several conflicting reports for their involvement in the disease progression. Several issues need to be addressed such as benefits to cost ratio with cholinesterase therapy, the dilemma of AChE selectivity over BChE, BBB permeability of peptidic BACE-1 inhibitors, hurdles related to the implementation of vaccination and immunization therapy, and clinical failure of candidates related to newly available targets. The present review provides an insight to the different molecular mechanisms involved in the development and progression of the AD and potential therapeutic strategies, enlightening perceptions into structural information of conventional and novel targets along with the successful applications of computational approaches for the design of target-specific inhibitors. [ABSTRACT FROM AUTHOR]

Some novel indolizine derivatives were synthesized by bioisosteric modification of imidazo[1,2- a ]pyridine for anti-inflammatory activity. The physicochemical characterization and structure of compounds were elucidated by state of the art spectroscopic technique. Induced fit docking was performed for initial screening to elucidate the interactions with corresponding amino acids of cyclooxygenase (COX-1, COX-2) and lipoxygenase (LOX) enzymes. The target compounds 53 – 60 were then evaluated against in vivo carrageenan and arachidonic acid induced rat paw edema models for anti-inflammatory activity. Amongst all the synthesized derivatives, compound 56 showed the significant anti-inflammatory activity in both rat paw edema models with very less ulcerogenic liability in comparison to standard diclofenac, celecoxib, and zileuton. The compounds 56 was further assessed to observe in vitro enzyme inhibition assay on both cyclooxygenase and lipoxygenase enzyme where it showed a preferential and selective non-competitive enzyme inhibition towards the COX-2 (IC 50 = 14.91 μM, Ki = 0.72 µM) over COX-1 (IC 50 > 50 μM) and a significant non-competitive inhibition of soybean lipoxygenase enzyme (IC 50 = 13.09 μM, Ki = 0.92 µM). Thus, in silico, in vivo , and in vitro findings suggested that the synthesized indolizine compound 56 has a dual COX-2 and LOX inhibition characteristic and parallel in vivo anti-inflammatory activity in comparison to the standard drugs. [ABSTRACT FROM AUTHOR]

Series of some 3,5-dimethoxy- N -methylenebenzenamine and 4-(methyleneamino)benzoic acid derivatives comprising of N -methylenebenzenamine nucleus were designed, synthesized, characterized, and assessed for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory, and antioxidant activity thereby improving learning and memory in rats. The IC 50 values of all the compound along with standard were determined on AChE and BChE enzyme. The free radical scavenging activity was also assessed by in vitro DPPH (2,2-diphenyl-1-picryl-hydrazyl) and hydrogen peroxide radical scavenging assay. The selective inhibitions of all compounds were observed against AChE in comparison with standard donepezil. The enzyme kinetic study of the most active compound 4 indicated uncompetitive AChE inhibition. The docking studies of compound 4 exhibited the worthy interaction on active-site gorge residues Phe330 and Trp279 responsible for its high affinity towards AChE, whereas lacking of the BChE inhibition was observed due to a wider gorge binding site and absence of important aromatic amino acids interactions. The ex vivo study confirmed AChE inhibition abilities of compound 4 at brain site. Further, a considerable decrease in escape latency period of the compound was observed in comparison with standard donepezil through in vivo Spatial Reference Memory (SRM) and Spatial Working Memory (SWM) models which showed the cognition-enhancing potential of compound 4 . The in vivo reduced glutathione (GSH) estimation on rat brain tissue homogenate was also performed to evaluate free radical scavenging activity substantiated the antioxidant activity in learning and memory. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma is associated with poor overall prognosis. Complete surgical resection is the only possible option for cure. As such, increasingly complex surgical techniques including sophisticated vascular reconstruction are being used. Continued advances in surgical techniques, in conjunction with use of combination systemic therapies, and radiation therapy have been suggested to improve outcomes. A key aspect to surgical success is reporting of pivotal findings beyond absence of distant metastases, such as tumor size, location, and degree of tumor involvement of specific vessels associated with potential perineural tumor spread. Multiphase contrast-enhanced multidetector CT and MRI are the imaging modalities of choice for pretreatment staging and presurgical determination of resectability. Imaging modalities such as endoscopic ultrasound and fluorine-18-2-fluoro-2-deoxy-D-glucose imaging with PET/CT are indicated for specific scenarios such as biopsy guidance and confirmation of distant metastases, respectively. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Abstract The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N -benzylpiperidine analogs (17 – 31 and 32 – 46) were designed and synthesized as multi-functional inhibitors of acetylcholinesterase (AChE) and β-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets. Compounds 40 and 41 exhibited high brain permeability in the PAMPA-BBB assay, significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE, and were devoid of neurotoxicity towards SH-SY5Y neuroblastoma cell lines up to the maximum tested concentration of 80 μM. Meanwhile, both these compounds inhibited self- and AChE-induced Aβ aggregation in thioflavin T assay, which was also re-affirmed by morphological characterization of Aβ aggregates using atomic force microscopy (AFM). Moreover, 40 and 41 ameliorated the scopolamine-induced cognitive impairment in elevated plus and Y-maze experiments. Ex vivo and biochemical analysis established the brain AChE inhibitory potential and antioxidant properties of these compounds. Further, improvement in Aβ 1-42 -induced cognitive impairment was also observed by compound 41 in the Morris water maze experiment with significant oral absorption characteristics ascertained by the pharmacokinetic studies. Graphical abstract Image 1 Highlights • Design and synthesis of a series of N -benzylpiperidine analogs (17 – 46). • Compounds 25, 26, 40, and 41 exhibited balanced inhibition of AChE and BACE-1. • Propidium iodide displacement and inhibition of Aβ aggregation by 40 and 41. • Biochemical analysis of rat brain homogenates suggested antioxidant potential. • Amelioration of scopolamine- and Aβ-induced cognitive impairment in AD rat models. [ABSTRACT FROM AUTHOR]