Health economics-based verification of functional myocardial ischemia evaluation of stable coronary artery disease in Japan: A long-term longitudinal study using propensity score matching.

BACKGROUND: The procedural numbers and medical costs of percutaneous coronary intervention (PCI), mainly elective PCI, have been increasing in Japan. Owing to increased interest in the appropriateness of coronary revascularization, we conducted this medical economics-based evaluation of testing and diagnosis of stable coronary artery disease (CAD). METHODS AND RESULTS: We reviewed patients' medical insurance data to identify stable CAD patients who underwent coronary computed tomography angiography, cardiac single-photon emission computed tomography, coronary angiography, or fractional flow reserve. Subjects were divided into anatomical and functional evaluation groups according to the modality of testing, and background factors were matched by propensity score. The endpoints were major adverse cardiovascular events (MACE), life years (LYs), medical costs, and cost-effectiveness analysis (CEA). The observations were performed for 36 months. MACE, medical costs, and CEA of the functional group in the overall category were trending to be better than the anatomical group (MACE, P = .051; medical costs: 3,105 US$ vs 4,430 US$, P = .007; CEA: 2,431 US$/LY vs 2,902 US$/LY, P = .043). CONCLUSIONS: The functional evaluation approach improved long-term clinical outcomes and reduced cumulative medical costs. As a result, the modality composition of functional myocardial ischemia evaluation was demonstrated to offer superior cost-effectiveness in stable CAD.

Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase.

Plasmodium falciparum's resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.

[A Case of Stage â £ Gastric Cancer with Para-Aortic Lymph Node Metastasis, and Multiple Liver, Lung, and Bone Metastases Leading to Conversion Therapy].

We report a case of unresectable gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases leading to conversion therapy. A 70s-year-old man visited previous doctor with epigastralgia. He was diagnosed as stage Ⅳ gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases by upper gastrointestinal endoscopy, contrast enhanced computer tomography(CT), and positron emission tomography(PET). After a regimen consisting of 6 courses of capecitabine plus cisplatin plus trastuzumab, para-aortic lymph node metastasis and liver, lung, and bone metastases were absent in CT and PET images. So, he visited our department for surgery treatment. We judged curative resection could be achieved for gastric cancer. Total gastrectomy, D2 and paraaortic lymphadenectomy, and cholecystectomy were performed. The histopathological examination of the resected specimen revealed the efficacy of chemotherapy was Grade 2b. The patient was discharge 14 days after the operation, and capecitabine plus trastuzumab was started as adjuvant chemotherapy, and the patient remains alive without recurrence 11 months after surgical treatment.

[Improvement of QOL by Surgery in Two Patients for Brain Metastasis from Esophageal Carcinoma with Paralysis-A Report of Two Cases].

Brain metastasis from esophageal cancer is rare. Symptoms such as paralysis caused a decline in quality of life(QOL)and activity of daily life(ADL)and required emergency treatment. We report 2 cases in which QOL was improved by emergency resection for brain metastasis from esophageal carcinoma with paralysis. Case 1: A 50's male was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N2M0, Stage Ⅲ). Brain metastasis was detected owing to development of left hemiparesis. Craniotomy and tumorectomy were performed, left hemiparesis was improved. He died 10 months after diagnosis of brain metastasis due to progression of other metastatic lesions. Case 2: A 61-year-old female was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N1M0, Stage Ⅲ). She developed right hemiparesis 5 months after esophagectomy, admitted to our hospital. Brain and lung metastases were detected, craniotomy and tumorectomy and were performed, right hemiparesis was improved. Although systemic chemotherapy was administered, she died 10 months after diagnosis of brain metastasis due to progression of lung metastasis. Conclusion: Aggressive surgical treatments for brain metastasis were one good treatment option to maintain QOL and ADL.

Perforated vesicles composed of amphiphilic diblock copolymer: new artificial biomembrane model of nuclear envelope.

With the aim of creating a new artificial model of a biomembrane for the nuclear envelope, perforated vesicles were prepared employing an amphiphilic diblock copolymer of poly(methacrylic acid)-block-poly(methyl methacrylate-random-methacrylic acid-random-2,2,6,6-tetramethyl-4-piperidyl methacrylate), PMAA-b-P(MMA-r-MAA-r-TPMA), by polymerization-induced self-assembly through photo nitroxide-mediated controlled/living radical polymerization (photo NMP). The photo NMP in an aqueous methanol solution produced spherical vesicles perforated with various holes and pores in the surface. The perforation of the vesicles was prevented by trifluoroacetic acid based on the disturbance of the MAA-TPMA interaction in the hydrophobic block chain. The investigation of the morphology changes by the polymerization progress revealed that the perforated spherical vesicles were produced within the membrane of contorted huge vesicles that were formed during the early stage of the polymerization due to the extension of the hydrophobic block chain. The perforated vesicles were found to show a reversible thermo-responsive behavior in the range of 25-50 °C based on dynamic light scattering and transmittance measurements. The vesicles were fused and divided into much smaller vesicles at high temperature, but were restored by cooling. However, the restored vesicles only had a few holes and no pores in the surface. The rearrangement of the MAA-TPMA interaction at high temperature produced more morphologically stable non-perforated vesicles.

[A Successfully Treated Patient Who Underwent Esophageal Bypass Surgery after Undergoing Stent Placement for Unresectable Advanced Esophageal Cancer Stenosed after CRT].

Esophageal bypass surgery is a treatment for oral ingestion in cases of unresectable esophageal cancer with esophageal stricture. Esophageal bypass surgery may be necessary especially in cases of advanced esophageal stricture after CRT because of the high risk of bleeding and perforation due to esophageal stent placement. In recent years, as a safe technique with fewer complications, esophageal bypass surgery using a Y-shaped gastric tube has been increasingly performed. Therefore, we will introduce cases that have undergone esophageal bypass surgery after undergoing stent placement for unresectable advanced esophageal cancer stenosed after CRT.

Impact of Indoxyl Sulfate on Coronary Plaques in Patients on Hemodialysis.

Serum indoxyl sulfate (IS; a uremic toxin) levels, which are significantly higher in patients with chronic kidney disease, including those undergoing hemodialysis, than in the robust, are associated with both cardiovascular disease (CVD) and CVD-related mortality. Furthermore, coronary artery calcium (CAC) is an independent predictor of cardiovascular events in patients undergoing hemodialysis. This study aimed to interpret the association between serum IS levels and coronary plaque burden (CPB) or CAC.A total of 30 consecutive patients on hemodialysis, who underwent 320-row coronary multidetector computed tomography (MDCT) angiography for suspected coronary artery disease, were enrolled in this prospective study. Coronary artery percent atheroma volume (a CPB marker) and percent calcium volume (a CAC marker) assessed using MDCT were evaluated. Furthermore, various oxidative and inflammatory markers typified by serum IS levels at a dialysis-free day were measured. Using these data, we investigated correlation between the inflammatory marker IS and CPB or CAC.Multivariable analysis indicated that serum IS levels were positively correlated with CAC [partial regression coefficient, 2.89; 95% confidence interval (CI), 0.35-5.43; P = 0.03] but not with CPB, even after adjustment for cofounders. Composite cardiovascular events, namely, as all-cause death, non-fatal myocardial infarction, disabling stroke, and hospital admission for other cardiovascular events, were reported to be 50% in all patients (95% CI, 32.1-67.9).In patients undergoing hemodialysis, serum IS levels were significantly associated with CAC but not with CPB.

[A Case of Perforated Gastric Cancer Treated with Curative Resection Following Conservative Medical Management and Chemotherapy].

Perforated gastric cancer typically requires life-saving emergency surgery. However, preoperative diagnosis is difficult, the rate of radical resection is low, and the prognosis remains poor. Perforated gastric cancer is generally treated with 1- or 2- stage gastrectomy, but radical resection is rarely performed after a conservative medical management and chemotherapy for perforated gastric cancer. A 65-year-old man visited another hospital with left upper abdominal pain. He was diagnosed with upper GI perforation, and conservative medical management was selected because peritonitis was limited. After close examination, a Type 3 tumor was found in the cardiac region of the stomach. As the advanced gastric cancer was unresectable, chemotherapy, comprising4 courses of SP plus T-mab, was subsequently administered. As the therapeutic effect was PR, we performed total gastrectomy. The pathological findings were tub2>tub1>por2: pT2N1CY0H0P0M0, pStageⅡ, and we achieved curative resection. Postoperatively, S-1 treatment was performed as an adjuvant chemotherapy. The patient remains alive, without recurrence, for 3 years and 6 months postoperatively.

[A Case of Advanced Gastric Cancer with Peritoneal Dissemination after Gastrectomy Effectively Treated with Combination Chemotherapy of Ramucirumab and Paclitaxel].

The REGARD and RAINBOW trials revealed the effectiveness of ramucirumab(RAM)for advanced gastric cancer patients who had been previously treated with chemotherapy. In the latest Japanese gastric cancer treatment guidelines, PAM plus paclitaxel(PTX)was positioned as a second-line chemotherapy for advanced gastric cancer. We report a case of advanced gastric cancer with peritoneal dissemination after gastrectomy effectively treated with RAM plus PTX. A 66-year-old woman underwent total gastrectomy with D2 lymph node dissection, splenectomy, and distal pancreatectomy. The pathological diagnosis was poorly differentiated adenocarcinoma, pT4b(pancreas), N3b, P1, CY1, Stage Ⅳ. She was treated with postoperative chemotherapy of S-1 plus cisplatin. However, 5 months after surgery, computed tomography(CT)showed ascites and recurrence of peritoneal dissemination. Cytological examination showed adenocarcinoma cells in the ascites. She was treated with combination chemotherapy of RAM and PTX as second line chemotherapy. After 1 course of this therapy, CT revealed complete disappearance of ascites and significant reduction in the size of the peritoneal dissemination. The patient survived without progression for 8 months after the recurrence was detected.

[A Case of Laparoscopic Resection for Locally Advanced Primary Rectal Cancer after Neoadjuvant Chemotherapy].

We treateda 70-year-oldfemale patient with locally advancedrectal cancer accompaniedby metastases to other organs. Three courses of S-1 plus oxaliplatin(SOX)therapy were administered as neoadjuvant chemotherapy(NAC), andthe cancer was subsequently treatedwith laparoscopic rectal resection. She hadvisiteda physician with a chief complaint of melena. A type 2 tumor located in the rectum Rb was found during the lower gastrointestinal endoscopy, which was diagnosed as an adenocarcinoma by biopsy. Vaginal invasion andlymph node metastasis were observedon CT andMRI. After 3 courses of SOX therapy(NAC), her condition was categorized as SD. Laparoscopic rectal amputation(D3)combinedwith resection of the ovary, uterus, and vagina was performed. On histopathological examination, the tumor was an adenocarcinoma, muc> tub2, ypT4b(AI, vaginal wall), int, INF b, ly1, v2, EX(-), PN1a, grade 1, pPM0, pDM0, pRM0 and pStage Ⅲa. The histological analysis demonstrated that the therapeutic effect of chemotherapy was grade 1a. Laparoscopic surgery, which is a relatively safe procedure, may be useful after NAC for an R0 resection.

An Alkyloxyphenyl Group as a Sterically Hindered Substituent on a Triphenylamine Donor Dye for Effective Recombination Inhibition in Dye-Sensitized Solar Cells.

Recombination reactions in dye-sensitized solar cells (DSSCs) may substantially decrease the open-circuit voltage (Voc) with cobalt complex redox electrolyte. Managing steric hindrance in the dye structure is necessary to inhibit recombination reactions and thereby increase the Voc and achieve high power-conversion efficiency (PCE). New dyes with large-sized donors based on triphenylamine and modified with 4-(hexyloxy)phenyl groups were developed to identify an effective inhibitor for the recombination reaction in DSSCs with a cobalt complex redox electrolyte. The 4-(hexyloxy)phenyl tetra-adducts dye MK-123 effectively inhibited the recombination reaction, and the DSSC fabricated using this dye exhibited the highest Voc (greater than 900 mV) among the cells with the investigated dyes. However, the short-circuit current (Jsc) of the MK-123 cell was lower than that of the cell with the simple triphenylamine donor dye, MK-89. In contrast, the cell with bis-adducts dye MK-136 also exhibited an increase in its Voc without a decrease in its Jsc. Among the investigated dyes, MK-136 exhibited the highest PCE of 8.9%. The effects of the steric hindrance of the 4-(hexyloxy)phenyl substituent are discussed.

[Radical Operation Performed on a Gastric Cancer Patient with Cold Agglutinin Disease - A Case Report].

A 56-year-old man with no abnormalmedicalhistory was admitted to our hospitalfor gastric cancer surgery. The preoperative laboratory tests indicated anemia, hyperbilirubinemia, hemagglutinin reaction, and a markedly high cold agglutinin titer; thus, we diagnosed the patient with cold agglutinin disease(CAD). Although perioperative complications caused by cold stimulation were suspected, we decided that it was possible to perform the operation under robust intraoperative conditions avoiding exposure to cold temperatures, and thus performed the radical operation. Intraoperatively, we performed blood transfusion because the anemia of the patient progressed owing to bleeding; however, no other complications were noted. Postoperatively, the clinical course was good without any complications, and the patient was discharged 13 days after the operation. The present case demonstrated that CAD patients requiring surgery can safely be operated on if their conditions, including perioperative body temperature management, are adequately considered during surgical preparation.

[A Case of Laparoscopic Surgery for Rectal Cancer with Synchronous Lung Metastases after Chemotherapy].

A woman in her 70's presented with the predominant complaint of bloody stools. She was diagnosed with rectal cancer, and bilateral lymph node and pulmonary metastases were detected on computed tomography(CT). The patient was diagnosed with cT3N3M1a, cStage IV disease. After undergoing a colostomy, the patient was treated with S-1 plus oxaliplatin (SOX), and bevacizumab(Bev). A second CT scan obtained after completion of 7 courses of chemotherapy revealed that the lung metastases had significantly reduced or disappeared. Approximately 7 months after initial treatment, the patient underwent a laparoscopic Hartmann procedure to remove the tumor. The patient is currently under observation while being administered postoperative adjuvant chemotherapy as an outpatient in our department. There is currently no evidence of the safety of laparoscopic-assisted rectal cancer surgery for first-time Stage IV cases. However, when tumor regression has been achieved with chemotherapy, it may be an effective option.

[A Case of Pathological Complete Response after Neoadjuvant Chemotherapy(S-1 plus Oxaliplatin)and Laparoscopic Low Anterior Resection for Rectal Cancer].

We report a case of pathological complete response after neoadjuvant chemotherapy(NAC)(S-1 plus oxaliplatin)for rectal cancer. The patient was a 50-year-old man who had type 3 circumferential rectal cancer. An abdominal CT scan revealed locally advanced rectal cancer(cT3N2H0P0M0, cStage III b)with severe stenosis and oral-side intestinal dilatation. The patient was treated with NAC after loop-ileostomy. After 3 courses of chemotherapy, a CT scan revealed significant tumor reduction. Laparoscopic low anterior resection and bilateral lymph node dissection were performed 5 weeks after the last course of chemotherapy. The pathological diagnosis was a pathological complete response(no residual cancer cells). This case suggests that laparoscopic low anterior resection after NAC with S-1 plus oxaliplatin for locally advanced rectal cancer is a potentially effective procedure.

[Treatment Strategy for Stage â £ Rectal Cancer].

Eighteen consecutive patients who underwent rectal resection following preoperative chemotherapy for cStage Ⅳ rectal cancer at our institute, between 2009 and 2014, were retrospectively assessed. Preoperative chemotherapy with mFOLFOX6, SOX, XELOX, and other anticancer agents was administered to 8, 5, 3, and 2 patients, respectively. Combined molecular targeted therapy was administered to 12 patients. The response evaluation showed that an antitumor effect was observed in 10 and 8 patients with local tumors who achieved a partial response (PR) and stable disease (SD), respectively, and in 9 and 9 patients with distant metastases who achieved a PR and SD, respectively. The operative procedures included high/low anterior resection (n=12), intersphincteric resection (n=2), and abdominoperineal resection/Hartmann's operation (n=4). An ileostomy was performed in 6 patients before chemotherapy. Postoperative complications occurred in 6 patients. Two patients with an ileostomy had anastomotic insufficiency, but recovered without reoperation. There was no significant difference in overall survival (p=0.382) when these patients were compared with 45 cStage Ⅳ rectal cancer patients who underwent surgery without preoperative chemotherapy. However, the rate of curability B was higher in patients who received preoperative chemotherapy (44.4%) compared to those who did not (26.7%). The results of this study are inconclusive and have not determined whether preoperative chemotherapy results in better long-term survival for cStage Ⅳ rectal cancer patients. However, preoperative chemotherapy might contribute to higher operative curability.

Long-term clinical and functional results of intersphincteric resection for lower rectal cancer.

BACKGROUND: Intersphincteric resection (ISR) is an alternative to abdominoperineal resection (APR) for super-low rectal cancer. The aim of this study was to evaluate the long-term curability after ISR over an average 6-year observational period, to compare the postoperative functional outcomes for ISR with those for low anterior resection (LAR), and to determine whether ISR is a function-preserving surgery. METHODS: Between 2000 and 2007, a total of 77 consecutive patients with low rectal cancer underwent curative ISR. The curability outcomes for ISR, LAR, and APR were compared. We evaluated the postoperative defecation functions, Wexner incontinence score (WIS), and defecation quality of life (QOL) for a between-groups comparison (ISR/LAR). RESULTS: The 5-year survival rate after ISR was 76.4 %, and the outcome was better than for APR (APR 51.2 %, LAR 80.7 %). Local recurrence after ISR occurred in 7.8 % of patients (APR 12.1 %, LAR 11.7 %). The average daily frequency of defecation was 3.7 times for the ISR patients and 3.2 times for the LAR patients, indicating no significant difference between the groups. Moreover, there were no significant differences between the groups for defecation functions. The WIS was 8.1 for ISR and 4.9 for LAR, and the defecation QOL for ISR and LAR was not significantly different (modified fecal incontinence QOL score: ISR 34.3, LAR 26.5). CONCLUSIONS: The long-term clinical and functional results suggest that ISR may be the optimal sphincter-preserving surgery for patients with lower rectal cancers who cannot be treated with a double-stapling technique.

Noninvasive Computed Tomography-Based Deep Learning Model Predicts In Vitro Chemosensitivity Assay Results in Pancreatic Cancer.

OBJECTIVES: We aimed to predict in vitro chemosensitivity assay results from computed tomography (CT) images by applying deep learning (DL) to optimize chemotherapy for pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Preoperative enhanced abdominal CT images and the histoculture drug response assay (HDRA) results were collected from 33 PDAC patients undergoing surgery. Deep learning was performed using CT images of both the HDRA-positive and HDRA-negative groups. We trimmed small patches from the entire tumor area. We established various prediction labels for HDRA results with 5-fluorouracil (FU), gemcitabine (GEM), and paclitaxel (PTX). We built a predictive model using a residual convolutional neural network and used 3-fold cross-validation. RESULTS: Of the 33 patients, effective response to FU, GEM, and PTX by HDRA was observed in 19 (57.6%), 11 (33.3%), and 23 (88.5%) patients, respectively. The average accuracy and the area under the receiver operating characteristic curve (AUC) of the model for predicting the effective response to FU were 93.4% and 0.979, respectively. In the prediction of GEM, the models demonstrated high accuracy (92.8%) and AUC (0.969). Likewise, the model for predicting response to PTX had a high performance (accuracy, 95.9%; AUC, 0.979). CONCLUSIONS: Our CT patch-based DL model exhibited high predictive performance in projecting HDRA results. Our study suggests that the DL approach could possibly provide a noninvasive means for the optimization of chemotherapy.

Incidence and predictors for late target lesion revascularization after sirolimus-eluting stent implantation.

BACKGROUND: In long-term follow-up after drug-eluting stents (DES) implantation, late target lesion revascularization (TLR) is occasionally required. However, the incidence and predictors for late TLR with DES have not been fully investigated. METHODS AND RESULTS: Between August 2004 and March 2005, 249 consecutive patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES) at our institution. Angiographic follow-up data were obtained in 228 patients (91.6%) with 274 lesions (91.6%) at 8 months. TLR incidence was evaluated up to 5 years. The 5-year clinical follow-up data were obtained in 222 patients (97.4%) with 264 lesions (96.4%). The incidence of early TLR before 1 year was 16.7%, and that of late TLR (1-5 years) was 8.3% (2.1% per year). Multivariate analysis indicated that significant predictors for late TLR were insulin-treated diabetes mellitus (DM) (odds ratio (OR) 10.88, P=0.001), stent fracture (OR 27.24, P=0.012), and age (OR 0.94, P=0.026). No association was observed between late TLR and lesion characteristics, including parameters measured by quantitative coronary angiography other than stent fracture, at baseline, post procedure, and follow-up. CONCLUSIONS: Late TLR after SES implantation occurred in approximately 2.1% of lesions per year after the first year without attenuation up to 5 years. Significant predictors for late TLR were insulin-treated DM, stent fracture and younger age. Careful long-term follow-up after SES implantation might be recommended.

[Surgical outcomes and prognostic factors of primary colorectal cancer with peritoneal dissemination].

We evaluated the surgical outcomes and prognostic factors of primary colorectal cancer with peritoneal dissemination. Between 1990 and 2012, a total of 81 cases of operated primary colorectal cancer with peritoneal dissemination were reviewed. According to the classification by the degree of peritoneal dissemination, the 3-year overall survival rate of patients with P1, P2, and P3 were 22%, 14%, and 16%, respectively. A significant difference was not observed between these 3 groups. According to the degree of surgical curability, the 1-year and 3-year overall survival rates of the patients with curability B were 75% and 30%, respectively. The overall survival rate of patients with curability B was higher than those of curability C (p< 0.01). Multivariate analysis showed that the curability of operation (p=0.03) and the existence of hepatic metastases (p=0.01) were significant prognostic factors affecting overall survival. The median relapse-free survival time of patients with curability B was 7.8 months. Nevertheless, long-term survivor cases existed in this group. These findings suggest that complete resection of the primary tumor and metastatic lesions is important to prolong survival term.

Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase.

Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previously been reported to exhibit in vitro antimalarial activity against P. falciparum and in vivo activity against P. berghei. Despite these initial promising results, the active compound from A. altilis is yet to be identified. Here, we have identified 2-geranyl-2', 4', 3, 4-tetrahydroxy-dihydrochalcone (1) from A. altilis leaves as the active constituent of its antimalarial activity. Since natural chalcones have been reported to inhibit food vacuole and mitochondrial electron transport chain (ETC), the morphological changes in food vacuole and biochemical inhibition of ETC enzymes of (1) were investigated. In the presence of (1), intraerythrocytic asexual development was impaired, and according to the TEM analysis, this clearly affected the ultrastructure of food vacuoles. Amongst the ETC enzymes, (1) inhibited the mitochondrial malate: quinone oxidoreductase (PfMQO), and no inhibition could be observed on dihydroorotate dehydrogenase (DHODH) as well as bc1 complex activities. Our study suggests that (1) has a dual mechanism of action affecting the food vacuole and inhibition of PfMQO-related pathways in mitochondria.