Deep learning-based k-space-to-image reconstruction and super resolution for diffusion-weighted imaging in whole-spine MRI.

PURPOSE: To assess the feasibility of deep learning (DL)-based k-space-to-image reconstruction and super resolution for whole-spine diffusion-weighted imaging (DWI). METHOD: This retrospective study included 97 consecutive patients with hematologic and/or oncologic diseases who underwent DL-processed whole-spine MRI from July 2022 to March 2023. For each patient, conventional (CONV) axial single-shot echo-planar DWI (b = 50, 800 s/mm2) was performed, followed by DL reconstruction and super resolution processing. The presence of malignant lesions and qualitative (overall image quality and diagnostic confidence) and quantitative (nonuniformity [NU], lesion contrast, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and ADC values) parameters were assessed for DL and CONV DWI. RESULTS: Ultimately, 67 patients (mean age, 63.0 years; 35 females) were analyzed. The proportions of vertebrae with malignant lesions for both protocols were not significantly different (P: [0.55-0.99]). The overall image quality and diagnostic confidence scores were higher for DL DWI (all P ≤ 0.002) than CONV DWI. The NU, lesion contrast, SNR, and CNR of each vertebral segment (P ≤ 0.04) but not the NU of the sacral segment (P = 0.51) showed significant differences between protocols. For DL DWI, the NU was lower, and lesion contrast, SNR, and CNR were higher than those of CONV DWI (median values of all segments; 19.8 vs. 22.2, 5.4 vs. 4.3, 7.3 vs. 5.5, and 0.8 vs. 0.7). Mean ADC values of the lesions did not significantly differ between the protocols (P: [0.16-0.89]). CONCLUSIONS: DL reconstruction can improve the image quality of whole-spine diffusion imaging.

Value of Edema-like Marrow Signal Intensity in Diagnosis of Joint Pain: Radiologists' Perspective.

Musculoskeletal pain is a significant contributor to disability. The mechanism and target of the treatment should be optimized by imaging, but currently no accepted gold standard exists to image pain. In addition to end-organ pathology, other mediators also contribute to nociception, such as angiogenesis, axonal extension, immunologic modulation, and central sensitization. Recent research indicates that local inflammation is a significant contributor to pain in the extremities; therefore, we focus here on edema-like marrow signal intensity (ELMSI). We examine both the relevance of ELMSI for pain and novel imaging techniques.

Development of a Semiquantitative Whole-Body MRI Scoring System for Multiple Myeloma.

Background In patients with multiple myeloma (MM), the serum marker ß2-microglobulin does not always accurately reflect tumor load. In contrast, whole-body (WB) MRI has shown high sensitivity for detecting bone lesions. Purpose To develop and validate a semiquantitative WB MRI scoring system for newly diagnosed MM and to compare it with the International Staging System (ISS) and Revised ISS (R-ISS). Materials and Methods This study included two retrospective groups (group 1, July 2015 to September 2021; group 2, February 2020 to September 2021) and one prospective group (group 3, October 2021 to February 2022) of patients with newly diagnosed MM. A new scoring system for MM was developed using spine MRI scans in group 1 and WB MRI scans in group 2 that integrated three features: (a) background marrow pattern, (b) number of focal bone lesions, and (c) presence of extramedullary or paramedullary lesions. The summed total score ranged from zero to nine. The interobserver agreement for each feature was assessed using Fleiss or Cohen weighted κ. WB MRI total scores in group 3 were compared across ISS and R-ISS stages using two-way analysis of variance. Results Groups 1, 2, and 3 included 103 patients (mean age, 62.1 years ± 9.1 [SD]; 60 men), 36 patients (mean age 65.4 years ± 11.3 [SD]; 19 women), and 39 participants (mean age, 62.0 years ± 11.7 [SD]; 20 men), respectively. The interobserver agreements for the three features composing the scoring system were substantial (κ range, 0.69-0.80). WB MRI total score increased with increasing ISS stage (mean score for ISS 1, 2, and 3 was 2.2, 4.2, and 5.8, respectively; P = .009) and R-ISS stage (mean score for R-ISS 1, 2, and 3 was 2.1, 3.8, and 5.9, respectively; P = .005). Conclusion The developed WB MRI scoring system for MM demonstrated substantial observer agreement and corresponded well with ISS and R-ISS stages. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Dragan and Messiou in this issue.

[Clinical Application and Limitations of Myeloma Response Assessment and Diagnosis System (MY-RADS)]. / ê³¨ìˆ˜ì¢ ë°˜ì‘í‰ê°€ì™€ 진단체계의 ìž„ìƒì ìš© 및 ì œí•œì .

Multiple myeloma, which is a proliferative disease of plasma cells that originate from a single clone, is the second most common hematologic malignancy following non-Hodgkin lymphoma. In the past, its diagnosis was made based on clinical findings (so-called "CRAB") and a skeletal survey using radiographs. However, since the implementation of the International Myeloma Working Group's revised guideline regarding the radiologic diagnosis of multiple myeloma, whole-body (WB) MRI has emerged to play a central role in the early diagnosis of multiple myeloma. Diffusion-weighted imaging and fat quantification using Dixon methods enable treatment response assessment by MRI. In keeping with the trend, a multi-institutional and multidisciplinary consensus for standardized image acquisition and reporting known as the Myeloma Response Assessment and Diagnostic System (MY-RADS) has recently been proposed. This review aims to describe the clinical application of WB-MRI based on MY-RADS in multiple myeloma, discuss its limitations, and suggest future directions for improvement.

Solid Pseudopapillary Neoplasm of the Pancreas with Lymph Node Metastasis in a Young Male Patient.

Solid pseudopapillary pancreatic neoplasms are rare. The male-to-female ratio is 1:9, and metastasis occurs only in a few cases. A 39-year-old male with a solid pseudopapillary neoplasm (SPN) with lymph node metastasis underwent ultrasonography, CT, and MRI, which revealed a mass (8 cm) in the pancreatic head. Fluorodeoxyglucose (FDG)-PET showed a hypermetabolic lymph node in the root area of the superior mesenteric artery (SMA). The patient underwent pylorus-preserving pancreaticoduodenectomy, which confirmed a peripancreatic lymph node metastasis. The lymph node of the SMA root area remained because of the encasing of the superior mesenteric artery. After 14 months of follow-up (with no adjuvant therapy initiated), the residual metastatic lymph nodes showed no change and no recurrence. In conclusion, surgery of the primary tumor for patients with SPN is recommended, even in cases with metastatic lymph nodes remaining.

Unenhanced computed tomography for non-invasive diagnosis of hepatic steatosis with low tube potential protocol.

BACKGROUND: Lowering kVp affects the image contrast and computed tomography (CT) attenuation values of low kVp CT is different from those of conventional 120-kVp scans. The purpose of this study is to determine the diagnostic performance and to establish the reference range of low-kVp unenhanced CT for the assessment of hepatic steatosis in liver transplantation donors using magnetic resonance (MR) spectroscopy as a reference standard. METHODS: This retrospective study included 165 potential donors (male:female =114:51, 36.5±12.0 years old) who underwent 100-kVp single-slice unenhanced CT scan and MR spectroscopy. The difference between hepatic and splenic attenuation (CTL-S) and liver-to-spleen attenuation ratio (CTL/S) were calculated. Reference standard was the fat signal fraction measured by MR spectroscopy. Limits of agreement between CT measurements and the reference standard were calculated. Areas under receiver operating characteristic curves (AUROCs) of CTL-S and CTL/S were compared for the diagnosis of moderate to severe steatosis. Cut-off values of CTL-S and CTL/S that provided a balance between sensitivity and specificity and the highest specificity using the lower limit of the reference range were calculated. RESULTS: Eighty-seven subjects had a non-steatotic liver. Sixty-one subjects had mild steatosis and 17 subjects had moderate to severe steatosis based on MR spectroscopy. CTL-S and CTL/S values were negatively correlated with the fat signal fraction (P<0.001) and limits of agreement were -8.4% to 8.4% for CTL-S and -9.6% to 9.6% for CTL/S. AUROCs of CTL-S and CTL/S for diagnosing moderate to severe steatosis were 0.956 and 0.957, respectively. Cut-off values of CTL-S and CTL/S for diagnosis of moderate to severe steatosis by the Youden index were -0.5 HU for CTL-S and 0.99 for CTL/S. Reference ranges of non-steatotic liver were -6.90 to 31.40 HU for CTL-S and 0.89 to 1.77 for CTL/S. Using -6.9 HU for CTL-S and 0.89 for CTL/S as cut-off values, the sensitivity and specificity for diagnosing moderate to severe steatosis were 70.59% and 90.54% (CTL-S) and 76.47% and 90.54% (CTL/S), respectively. CONCLUSIONS: Measurements from a low-kVp unenhanced CT scan were negatively correlated with the degree of hepatic steatosis. Low-kVp unenhanced CT is a robust technique with reduced radiation exposure for diagnosing moderate to severe hepatic steatosis.

[Inflammatory Myofibroblastic Tumor Misdiagnosed as Intrahepatic Cholangiocarcinoma].

An inflammatory myofibroblastic tumor (IMT) is a rare tumor that is currently classified as an intermediate cancer according to the World Health Organization classification system. The pathophysiology of its occurrence is still unknown. Imaging tests, such as CT or MRI, can be helpful in diagnosis, but the final diagnosis is confirmed by a pathological examination through a biopsy and immunohistochemistry stain. The patient, in this case, presented an asymptomatic intrahepatic mass discovered incidentally on an imaging examination. Initially, intrahepatic cholangiocarcinoma was suspected, but she was finally diagnosed with IMT through a histological examination after a liver resection.

The impact of face shields on the quality of gastrointestinal endoscopy during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic, with healthcare workers at a high risk of exposure. During this pandemic, endoscopists must wear personal protective equipment (PPE), including face shields, to prevent COVID-19 transmission; however, few studies have reported the impact of face shields on the quality of gastrointestinal (GI) endoscopy. We aimed to determine whether the use of PPE, including face shields, affected the quality of GI endoscopy during the COVID-19 pandemic. METHODS: The medical records of patients who had undergone screening or surveillance colonoscopy and gastric endoscopic submucosal dissection (ESD) at Dong-A University Hospital between June 2020 and March 2021 were retrospectively reviewed. Endoscopists wore isolation gowns, disposable gloves, and KF94 masks from June 2020 to October 2020. From November 2020, endoscopists also wore face shields. We compared GI endoscopy quality indicators between the first five months (no face shields) and the second five months (with face shields). In the non-face shield and face shield groups, we calculated the overall adenoma detection rates (ADRs), polyp detection rate (PDR), sessile serrated lesion detection rate (SSLDR), advanced neoplasia detection rate (ANDR), complete resection rate (CRR), number of polyps and/or adenomas per colonoscopy, and gastric ESD procedure time. RESULTS: In total, 1359 study patients had undergone screening or surveillance colonoscopy (face shield group, n = 679; non-face shield group, n = 680). No statistically significant between-group differences were observed (PDR, 49.04 vs. 52.50%, p = 0.202; ADR, 38.59 vs. 38.97%, p = 0.884; SSPDR, 1.91 vs. 1.32%, p = 0.388; ANDR, 3.98 vs. 3.97%, p = 0.991, respectively). No difference was found in colonoscopy quality indicators between patients examined by experienced and trainee endoscopists with and without face shields. Of 144 study patients who had undergone gastric ESD for gastric neoplasms, there were 72 patients in each group. No statistically significant differences were found in the CRR (94.44 vs 93.05%, p = 1.000) and procedure times (19.22 ± 9.33 vs. 19.03 ± 11.49, p = 0.911). CONCLUSIONS: Wearing face shields during the COVID-19 pandemic did not affect the quality indicators for GI endoscopy.

Endoscopic Removal Through a Gastrostomy of Swallowed Acupuncture Needles.

Acupuncture is a representative treatment field in oriental medicine that is used widely in various medical conditions. Although acupuncture is considered a safe procedure, it can cause complications. This paper reports the case of a 44-year-old quadriplegic woman who received a percutaneous gastrostomy (PEG) tube and was referred for the endoscopic removal of swallowed acupuncture needles. The needles were removed successfully by endoscopy through the PEG tube using the rendezvous technique without significant complications.

In Vitro Interaction of AB-FUBINACA with Human Cytochrome P450, UDP-Glucuronosyltransferase Enzymes and Drug Transporters.

AB-FUBINACA, a synthetic indazole carboxamide cannabinoid, has been used worldwide as a new psychoactive substance. Because drug abusers take various drugs concomitantly, it is necessary to explore potential AB-FUBINACA-induced drug-drug interactions caused by modulation of drug-metabolizing enzymes and transporters. In this study, the inhibitory effects of AB-FUBINACA on eight major human cytochrome P450s (CYPs) and six uridine 5'-diphospho-glucuronosyltransferases (UGTs) of human liver microsomes, and on eight clinically important transport activities including organic cation transporters (OCT)1 and OCT2, organic anion transporters (OAT)1 and OAT3, organic anion transporting polypeptide transporters (OATP)1B1 and OATP1B3, P-glycoprotein, and breast cancer resistance protein (BCRP) in transporter-overexpressing cells were investigated. AB-FUBINACA inhibited CYP2B6-mediated bupropion hydroxylation via mixed inhibition with Ki value of 15.0 µM and competitively inhibited CYP2C8-catalyzed amodiaquine N-de-ethylation, CYP2C9-catalyzed diclofenac 4'-hydroxylation, CYP2C19-catalyzed [S]-mephenytoin 4'-hydroxylation, and CYP2D6-catalyzed bufuralol 1'-hydroxylation with Ki values of 19.9, 13.1, 6.3, and 20.8 µM, respectively. AB-FUBINACA inhibited OCT2-mediated MPP+ uptake via mixed inhibition (Ki, 54.2 µM) and competitively inhibited OATP1B1-mediated estrone-3-sulfate uptake (Ki, 94.4 µM). However, AB-FUBINACA did not significantly inhibit CYP1A2, CYP2A6, CYP3A4, UGT1A1, UGT1A3, UGT1A4, UGT1A6, or UGT2B7 enzyme activities at concentrations up to 100 µM. AB-FUBINACA did not significantly inhibit the transport activities of OCT1, OAT1/3, OATP1B3, P-glycoprotein, or BCRP at concentrations up to 250 µM. As the pharmacokinetics of AB-FUBINACA in humans and animals remain unknown, it is necessary to clinically evaluate potential in vivo pharmacokinetic drug-drug interactions induced by AB-FUBINACA-mediated inhibition of CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, OCT2, and OATP1B1 activities.

Mertansine Inhibits mRNA Expression and Enzyme Activities of Cytochrome P450s and Uridine 5'-Diphospho-Glucuronosyltransferases in Human Hepatocytes and Liver Microsomes.

Mertansine, a tubulin inhibitor, is used as the cytotoxic component of antibody-drug conjugates (ADCs) for cancer therapy. The effects of mertansine on uridine 5'-diphospho-glucuronosyltransferase (UGT) activities in human liver microsomes and its effects on the mRNA expression of cytochrome P450s (CYPs) and UGTs in human hepatocytes were evaluated to assess the potential for drug-drug interactions (DDIs). Mertansine potently inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-ß-glucuronidation, and UGT1A4-catalyzed trifluoperazine N-ß-d-glucuronidation, with Ki values of 13.5 µM, 4.3 µM, and 21.2 µM, respectively, but no inhibition of UGT1A6, UGT1A9, and UGT2B7 enzyme activities was observed in human liver microsomes. A 48 h treatment of mertansine (1.25-2500 nM) in human hepatocytes resulted in the dose-dependent suppression of mRNA levels of CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C9, CYP2C19, UGT1A1, and UGT1A9, with IC50 values of 93.7 109.1, 36.8 18.3, 160.6 167.4, 32.1 14.9, 578.4 452.0, 539.5 233.4, 856.7 781.9, and 54.1 29.1 nM, respectively, and decreased the activities of CYP1A2-mediated phenacetin O-deethylase, CYP2B6-mediated bupropion hydroxylase, and CYP3A4-mediated midazolam 1-hydroxylase. These in vitro DDI potentials of mertansine with CYP1A2, CYP2B6, CYP2C8/9/19, CYP3A4, UGT1A1, and UGT1A9 substrates suggest that it is necessary to carefully characterize the DDI potentials of ADC candidates with mertansine as a payload in the clinic.

Liquid Chromatography-Tandem Mass Spectrometry for the Simultaneous Determination of Doxorubicin and its Metabolites Doxorubicinol, Doxorubicinone, Doxorubicinolone, and 7-Deoxydoxorubicinone in Mouse Plasma.

Doxorubicin, an anthracycline antitumor antibiotic, acts as a cancer treatment by interfering with the function of DNA. Herein, liquid chromatography-tandem mass spectrometry was for the first time developed and validated for the simultaneous determination of doxorubicin and its major metabolites doxorubicinol, doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinone in mouse plasma. The liquid-liquid extraction of a 10 µL mouse plasma sample with chloroform:methanol (4:1, v/v) and use of the selected reaction monitoring mode led to less matrix effect and better sensitivity. The lower limits of quantification levels were 0.5 ng/mL for doxorubicin, 0.1 ng/mL for doxorubicinol, and 0.01 ng/mL for doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinone. The standard curves were linear over the range of 0.5-200 ng/mL for doxorubicin; 0.1-200 ng/mL for doxorubicinol; and 0.01-50 ng/mL for doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinone in mouse plasma. The intra and inter-day relative standard deviation and relative errors for doxorubicin and its four metabolites at four quality control concentrations were 0.9-13.6% and -13.0% to 14.9%, respectively. This method was successfully applied to the pharmacokinetic study of doxorubicin and its metabolites after intravenous administration of doxorubicin at a dose of 1.3 mg/kg to female BALB/c nude mice.

Single-Port Laparoscopic and Robotic Cholecystectomy in Obesity (>25 kg/m2).

BACKGROUND AND OBJECTIVES: Single-port cholecystectomy has emerged as an alternative technique to reduce the number of ports and improve cosmesis. Few previous studies have assessed obesity-related surgical outcomes following single-port cholecystectomy. In this study, technical feasibility and surgical outcomes of single-port laparoscopic cholecystectomy (SPLC) and robotic single-site cholecystectomy (RSSC) in obese patients were investigated. METHODS: We conducted a two-center collaborative study and retrospectively reviewed initial experiences of RSSC and SPLC in patients whose body mass index was over 25 kg/m2. Medical records of patients were reviewed. Clinical characteristics and short-term oncologic outcomes were considered and compared between SPLC and RSSC groups. RESULTS: RSSC and SPLC were performed in 39 and 78 patients, respectively. In comparative analysis, the total operative time was longer in the RSSC group (109.92 minutes vs. 60.99 minutes; P < .001).However, requiring additional port for completion of surgical procedure was less frequent in the RSSC group (0% vs. 12.8%; P = .029). Immediate postoperative pain score was not significantly different between the two groups (4.95 vs. 5.00; P = .882). However, pain score was significantly lower in the RSSC group at the time of discharge (1.79 vs. 2.38; P = .010). Conversion to conventional multiport cholecystectomy, intraoperative bile spillage, or complication rate was not significantly different between the two groups (P > .05). CONCLUSIONS: SPLC and RSSC could be safely performed in selected patients with high body mass index, showing no significant clinical differences.

Analysis of intrahepatic sarcomatoid cholangiocarcinoma: Experience from 11 cases within 17 years.

BACKGROUND: Intrahepatic sarcomatoid chonalgiocarcinoma (s-CCC) is an extremely rare disease, accounting for less than 1% of hepatobiliary system malignancies, and its pathophysiology is not well known. On the hypothesis that its clinical, serologic, or radiologic diagnosis are not fully understood and its prognosis is poor, we investigated the distinguishing features of s-CCC compared with those of intrahepatic bile duct adenocarcinoma [cholangiocellular carcinoma (CCC)] in patients from a single center. AIM: To analyze the clinical, serologic, imaging, and histopathologic characteristics of intrahepatic s-CCC patients diagnosed in a single center. METHODS: The clinical, serologic, imaging, and histopathologic features of 227 patients diagnosed with intrahepatic cholangiocarcinoma (IHCC) in a single medical center during the last 17 years were analyzed. The characteristics of 11 patients with s-CCC were compared with those of 216 patients with CCC. RESULTS: The number of patients with s-CCC who presented fever and abdominal pain and past history of chronic viral hepatitis or liver cirrhosis (LC) was higher than that of patients with CCC. In imaging studies, patients with s-CCC showed relatively aggressive features. However, no clear distinction was observed between s-CCC and CCC based on other clinical, serologic or radiologic examination results. An accurate diagnosis could be made only via a histopathologic examination through immunohistochemical staining. The clinical course of s-CCC was generally aggressive, and patients had a relatively poor prognosis. CONCLUSION: In patients with s-CCC, early diagnosis through biopsy and aggressive treatment, including surgical resection, are important.

[Endoscopic Diagnosis of Aortoesophageal Fistula Not Presenting Hematemesis].

Aortoesophageal fistula (AEF) is an extremely rare but lethal cause of massive gastrointestinal hemorrhage. Characteristic symptoms are mid-thoracic pain, sentinel minor hemorrhage, and massive hemorrhage after a symptom-free interval. Prompt diagnosis and immediate treatments are necessary to reduce mortality. However, AEF is difficult to diagnose because it is uncommon and often leads to death with massive bleeding before proper evaluation. We report a case of endoscopic diagnosis of AEF that did not present with hematemesis; it was treated with thoracic endovascular aortic repair (TEVAR) and surgery. A 71-year-old female presented to the emergency department with epigastric discomfort. Endoscopy demonstrated a submucosal tumor-like protrusion and pulsating mass with blood clots. Contrast-enhanced chest CT confirmed AEF due to descending thoracic aortic aneurysm. The patient immediately underwent TEVAR to prevent massive bleeding and subsequently underwent surgery. Endoscopists should consider AEF if they see a submucosal tumor-like mass with a central ulcerative lesion or a pulsating protrusion covered with blood clots in mid-esophagus during an endoscopy.

YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer.

PURPOSE: Given that osimertinib is the only approved third-generation EGFR-TKI against EGFR activating and resistant T790M mutated non-small cell lung cancer (NSCLC), additional mutant-selective inhibitors with a higher efficacy, especially for brain metastases, with favorable toxicity profile are still needed. In this study, we investigated the antitumor efficacy of YH25448, an oral, mutant-selective, irreversible third-generation EGFR-TKI in preclinical models. EXPERIMENTAL DESIGN: Antitumor activity of YH25448 was investigated in vitro using mutant EGFR-expressing Ba/F3 cells and various lung cancer cell lines. In vivo antitumor efficacy, ability to penetrate the blood-brain barrier (BBB), and skin toxicity of YH25448 were examined and compared with those of osimertinib using cell lines and PDX model. RESULTS: Compared with osimertinib, YH25448 showed a higher selectivity and potency in kinase assay and mutant EGFR-expressing Ba/F3 cells. In various cell line models harboring EGFR activating and T790M mutation, YH25448 effectively inhibited EGFR downstream signaling pathways, leading to cellular apoptosis. When compared in vivo at equimolar concentrations, YH25448 produced significantly better tumor regression than osimertinib. Importantly, YH25448 induced profound tumor regression in brain metastasis model with excellent brain/plasma and tumor/brain area under the concentration-time curve value. YH25448 rarely suppressed the levels of p-EGFR in hair follicles, leading to less keratosis than osimertinib in animal model. The potent systemic and intracranial activity of YH25448 has been shown in an ongoing phase I/II clinical trial for advanced EGFR T790M mutated NSCLC (NCT03046992). CONCLUSIONS: Our findings suggest that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib.

Direct visualization of single-molecule membrane protein interactions in living cells.

Interactions between membrane proteins are poorly understood despite their importance in cell signaling and drug development. Here, we present a co-immunoimmobilization assay (Co-II) enabling the direct observation of membrane protein interactions in single living cells that overcomes the limitations of currently prevalent proximity-based indirect methods. Using Co-II, we investigated the transient homodimerizations of epidermal growth factor receptor (EGFR) and beta-2 adrenergic receptor (ß2-AR) in living cells, revealing the differential regulation of these receptors' dimerizations by molecular conformations and microenvironment in a plasma membrane. Co-II should provide a simple, rapid, and robust platform for visualizing both weak and strong protein interactions in the plasma membrane of living cells.

Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes.

Synthetic cannabinoids, a new class of psychoactive substances, are potent agonists of cannabinoid receptors, which mimic the psychoactive effects of the principal psychoactive component of cannabis, ∆9-tetrahydrocannabinol. Despite governmental scheduling as illicit drugs, new synthetic cannabinoids are being produced. The abuse of synthetic cannabinoids with several drugs containing different chemical groups has resulted in large numbers of poisonings. This has increased the urgency for forensic and public health laboratories to identify the metabolites of synthetic cannabinoids and apply this knowledge to the development of analytical methods and for toxicity prediction. It is necessary to determine whether synthetic cannabinoids are involved in drug-metabolizing enzyme-mediated drug-drug interactions. This review describes the metabolic pathways of 13 prevalent synthetic cannabinoids and various drug-metabolizing enzymes responsible for their metabolism, including cytochrome P450 (CYP), UDP-glucuronosyltransferases (UGTs), and carboxylesterases. The inhibitory effects of synthetic cannabinoids on CYP and UGT activities are also reviewed to predict the potential of synthetic cannabinoids for drug-drug interactions. The drug-metabolizing enzymes responsible for metabolism of synthetic cannabinoids should be characterized and the effects of synthetic cannabinoids on CYP and UGT activities should be determined to predict the pharmacokinetics of synthetic cannabinoids and synthetic cannabinoid-induced drug-drug interactions in the clinic.

Prediction of Posthepatectomy Liver Failure: MRI With Hepatocyte-Specific Contrast Agent Versus Indocyanine Green Clearance Test.

OBJECTIVE: The objective of our study was to identify whether quantitative measurements from gadoxetic acid-enhanced MRI are useful for predicting posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) compared with and in combination with future remnant liver volume (FRLV) and an indocyanine green (ICG) clearance test. MATERIALS AND METHODS: Preoperative gadoxetic acid-enhanced MR images were retrospectively evaluated in 73 patients who underwent anatomic liver resection for HCC between 2011 and 2013. For quantitative measurement of hepatocyte function, relative liver enhancement (RLE) and remnant hepatocyte uptake index (rHUI) were measured using hepatobiliary phase MR images. FRLV was determined using measurements from preoperative CT scans. Univariate and multivariate analyses of measurements from gadoxetic acid-enhanced MRI, ICG clearance tests, and FRLV for finding predictors of PHLF were performed. To compare the diagnostic performance of predictors, ROC analyses were also performed. RESULTS: Eighteen (25%) of 73 patients met the criteria for PHLF. Univariate analysis revealed that all measurements related to MRI including RLE, rHUI, ICG clearance, and FRLV were significantly associated with PHLF. Multivariate analysis showed that RLE, FRLV, ICG-plasma disappearance rate (ICG-PDR), rHUI, and rHUI corrected for body weight (rHUI-BW) were independent predictors of PHLF (p = 0.011, p = 0.034, p = 0.003, p < 0.001, and p = 0.001, respectively). In ROC analyses, AUCs of rHUI and rHUI-BW were larger than those of other independent predictors; the differences were statistically significant (for rHUI-BW vs RLE, ICG-PDR, and FRLV, p = 0.016, 0.007, and 0.046, respectively; for rHUI vs RLE and ICG-PDR, p = 0.045 and 0.016, respectively). CONCLUSION: Measurements from gadoxetic acid-enhanced MRI predicted PHLF better than the ICG clearance test in patients with HCC who underwent hepatectomy.

Ectopic RING zinc finger gene from hot pepper induces totally different genes in lettuce and tobacco.

Advances in molecular biology have improved crops through transferring genes from one organism to new hosts, and these efforts have raised concerns about potential unexpected outcomes. Here, we provide evidence that a gene with a specific function in one organism can yield completely different effects in a new host. CaRZFP1 is a C3HC4-type RING zinc finger protein gene previously isolated from a cDNA library for heat-stressed hot pepper. In our previous work investigating in vivo CaRZFP1 function, we transferred CaRZFP1 into tobacco; transgenic tobacco exhibited enhanced growth and tolerance to abiotic stresses. As further analysis of CaRZFP1 ectopic expression in a heterologous host plant, here we mobilized and constitutively overexpressed CaRZFP1 in lettuce. In contrast to tobacco, transgenic lettuce exhibited poorer growth and delayed flowering compared with vector-only controls. To identify genes that might be involved in this phenotypic effect, transcriptome analyses on transgenic plants of both species were performed, uncovering dozens of genes that reflect the different outcomes between tobacco and lettuce. These included protein kinase, transcriptional factor, transporter protein, hormone and metabolism-related genes, and some unannotated genes. The opposite effects of CaRZFP1 ectopic expression in lettuce and tobacco address concerns of unexpectedly different outcomes in different host species.