Mild Encephalopathy With Reversible Splenial Lesion (MERS) in a Child With Influenza.

Mild encephalopathy with reversible splenial lesion (MERS) is a rare clinical-radiological syndrome with a favorable prognosis that typically presents with central nervous system symptoms such as altered mental status, delirious behavior, seizures, muscle weakness, ophthalmoplegia, and headache. The diagnosis of MERS is based on a constellation of central nervous system symptoms within one week of fever, a lesion in the splenium of the corpus callosum, and complete resolution without sequelae. Both clinical and imaging findings generally resolve within a few months. Treatment is largely supportive care and/or treatment of the primary cause.

Recurrence of pericardial effusion after different procedure modalities in patients with non-small-cell lung cancer.

BACKGROUND: Lung cancer with related pericardial effusion is not rare. Intervention is a crucial step for symptomatic effusion. It is unknown, however, whether the different invasive interventions for pericardial effusion result in different survival outcomes. This study analyzed the clinical characteristics and prognostic factors for patients with non-small-cell lung cancer (NSCLC) who have undergone different procedures. METHODS: From January 2006 to June 2018, we collected data from patients with NSCLC who have received invasive intervention for pericardial effusions. The patients were divided into three categories: simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy. Kaplan-Meier curve and log-rank test were used to analyze the pericardial effusion recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 244 patients were enrolled. Adenocarcinoma (83.6%) was the major NSCLC subtype. Invasive intervention, including simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy, had been carried out on 52, 170, and 22 patients, respectively. The 1-year RFS rates in simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy were 19.2%, 31.2%, and 31.8%, respectively (P = 0.128), and the median RFS was 1.67, 5.03, and 8.32 months, respectively (P = 0.008). There was no significant difference in OS, however, with the median OS at 1.67, 6.43, and 8.32 months, respectively (P = 0.064). According to the multivariable analysis, the gravity in pericardial fluid analysis, receiving systemic therapy after pericardial effusion, and the time period from stage IV lung cancer to the presence of pericardial effusion were independent prognostic factors for pericardial effusion RFS and OS. CONCLUSIONS: Patients who have undergone simple pericardiocentesis alone for the management of NSCLC-related pericardial effusion have lower 1-year RFS rates than those who have undergone balloon pericardiotomy and surgical pericardiectomy. Therefore, balloon pericardiotomy and surgical pericardiectomy should be carried out for patients with NSCLC-related pericardial effusion if tolerable.

Analysis of the small chromosomal Prionium serratum (Cyperid) demonstrates the importance of reliable methods to differentiate between mono- and holocentricity.

For a long time, the Cyperid clade (Thurniceae-Juncaceae-Cyperaceae) was considered a group of species possessing holocentromeres exclusively. The basal phylogenetic position of Prionium serratum (Thunb.) Drège (Thurniceae) within Cyperids makes this species an important specimen to understand the centromere evolution within this clade. In contrast to the expectation, the chromosomal distribution of the centromere-specific histone H3 (CENH3), alpha-tubulin and different centromere-associated post-translational histone modifications (H3S10ph, H3S28ph and H2AT120ph) demonstrate a monocentromeric organisation of P. serratum chromosomes. Analysis of the high-copy repeat composition resulted in the identification of two centromere-localised satellite repeats. Hence, monocentricity was the ancestral condition for the Juncaceae-Cyperaceae-Thurniaceae Cyperid clade, and holocentricity in this clade has independently arisen at least twice after differentiation of the three families, once in Juncaceae and the other one in Cyperaceae. In this context, methods suitable for the identification of holocentromeres are discussed.

Thermoelectric properties of rare-earth doped Fe2VAl Heusler alloys.

The low-temperature electrical transport properties of the rare-earth (RE) Ce, Dy, Sm element doped Fe2VAl Heusler alloys have been investigated. A significant enhancement in the Seebeck coefficient S (peak values of about -125 to -160 µV K-1) is observed as compared to the pure Fe2VAl (peak value of about 40 µV K-1). It is observed that the thermal conductivity reduced by 50% in RE-doped samples. The single parabolic band model has been used to analyze the experimental data and to understand the role of fundamental parameters like the Lorenz number. The lattice contribution to the total thermal conductivity was analyzed through the Callaway model, which in turn provided the insight into the phonon scattering in these alloys. Finally, we demonstrate a significant improvement in power factor and figure of merit at all temperatures for the RE-doped Fe2VAl alloys.

Antibacterial activity of viable and heat-killed probiotic strains against oral pathogens.

Probiotics can stabilize gut flora, regulate intestinal immunity and protect the host from enteric diseases; however, their roles in oral health have received little attention compared to their roles in gut health. Nowadays, the prevalence of sugar-sweetened foods and abuse of antibiotics contribute towards dysbiosis of oral microbiota and drug resistance development in oral pathogens, resulting in various intractable oral diseases. We screened the antibacterial activities of viable and heat-killed probiotic strains against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. The probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 displayed strong antipathogenic activities, whereas heat-killed AP-32, CT-53 and ET-66 displayed high levels of pathogen inhibition. The antibacterial activities of these probiotics were not associated with their H2 O2 production; L. acidophilus TYCA02 produced high levels of H2 O2 but merely exhibited moderate antibacterial activities. Oral tablets containing probiotics showed positive inhibitory effects against oral pathogens, particularly those containing viable probiotics. Our results indicate that probiotics prevent the growth of oral pathogens and improve oral health, providing insights into the antipathogenic efficacy of different probiotic species and their potential role in functional foods that improve oral health. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study provides insights into the antipathogenic efficacy of different probiotic species and their potential roles in developing functional foods to improve oral health. We showed that the probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 have great potential for use in the development of functional foods to improve oral health. Since active probiotics may provide strong and long-term protection, the development of functional food products should favour the use of viable bacteria.

Risk factors outperform intracranial large artery stenosis predicting unfavorable outcomes in patients with stroke.

BACKGROUND: This study examined how intracranial large artery stenosis (ILAS), symptomatic and asymptomatic ILAS, and risk factors affect unfavorable outcome events after medical treatment in routine clinical practice. METHODS: This was a 24-month prospective observational study of consecutively recruited stroke patients. All participants underwent magnetic resonance angiography, and their clinical characteristics were assessed. Outcome events were vascular outcome, recurrent stroke, and death. Cox regression analyses were performed to identify potential factors associated with an unfavorable outcome, which included demographic and clinical characteristics, the risk factors, and stenosis status. RESULTS: The analysis included 686 patients; among them, 371 were assessed as ILAS negative, 231 as symptomatic ILAS, and 84 as asymptomatic ILAS. Body mass index (p < .05), hypertension (p = .01), and old infarction (p = .047) were factors relating to vascular outcomes. Hypertension was the only factor for recurrent stroke (p = .035). Poor glomerular filtration rate (< 30 mL/min/1.73 m2) (p = .011) and baseline National Institutes of Health Stroke Scale scores (p < .001) were significant predictors of death. CONCLUSIONS: This study extended previous results from clinical trials to a community-based cohort study by concurrently looking at the presence/absence of stenosis and a symptomatic/asymptomatic stenotic artery. Substantiated risk factors rather than the stenosis status were predominant determinants of adverse outcome. Although the degree of stenosis is often an indicator for treatment, we suggest risk factors, such as hypertension and renal dysfunction, should be monitored and intensively treated.

Clinical spectrum of glutamic acid decarboxylase antibodies in a Taiwanese population.

BACKGROUND AND PURPOSE: High levels of autoantibodies against glutamic acid decarboxylase (GAD-abs) are associated with stiff-person syndrome (SPS). However, the full clinical spectrum associated with GAD-abs in Asians is unclear. The clinical and immunological features of patients positive for GAD-abs were reviewed in a large Taiwanese series. METHODS: Retrospective case series and immunological investigations were conducted between July 2007 and July 2017 at a tertiary referral centre in Taiwan. Amongst 361 patients with GAD-ab reactivity, 185 with detailed clinical records were included. RESULTS: Twenty-seven patients (14.59%), with a mean age at assessment of 54.8 ± 13.9 years, presented with neurological symptoms. The major neurological presentations (mean GAD-ab concentrations) were SPS (n = 9, 33.3%; 135.45 ± 27.84 U/ml), cerebellar ataxia (n = 3, 11.1%; 95.61 ± 49.63 U/ml), encephalopathy (n = 2, 7.4%; 51.8 ± 49.64 U/ml) and epilepsy (n = 1, 3.7%; 83.3 U/ml). Notably, eight patients fulfilling the clinical diagnosis of multiple system atrophy had relatively lower GAD-ab concentrations (2.57 ± 0.82 U/ml), which has not been reported previously. There was no correlation between disease severity and GAD-ab concentration. Patients presenting with comorbid endocrinopathies (n = 15, 55.5%) had higher GAD-ab concentrations than those without endocrinopathies (n = 12, 44.4%; 104.45 ± 22.51 U/ml vs. 34.08 ± 21.83 U/ml, P = 0.04). Of 158 patients (85.4%) without a neurological presentation, 133 had type 1 diabetes mellitus and 20 had diabetes of other aetiologies (type 2 or gestational diabetes mellitus, or diabetes secondary to pancreatitis); the remaining four patients had pure thyroid disorders. CONCLUSIONS: A clinical and immunological evaluation of East Asian patients positive for GAD-abs is presented and a different clinical spectrum of anti-GAD syndrome is identified compared to Caucasians.

Role of electron-magnon interaction in non-Fermi liquid behavior of SrRuO3.

SrRuO3 is a popular material extensively used as a bottom electrode in various applications, however, a few problems which will certainly change the interface band structure and greatly alter the device's property are still not fully understood, such as the change of carrier types at a certain temperature and the quasiparticle scattering for non-Fermi liquid behavior below ferromagnetic transition temperature. In this study, magnetic, transport (electrical and thermal) properties and x-ray photoemission spectra have been used to understand the role of quasiparticle interactions in the SrRuO3 bulk system. At the Fermi level, the hybridization of Ru4dt 2g ↓ and O2p  bands form a typical two band system. In order to explain the problems as mentioned, our present work reveals that there must be an impurity band that couples with the bands around Fermi level and serves as a charge reservoir. In the present case, the impurity is attributed to the Ru vacancies. As a result, the conduction electrons scatter strongly with the Ru vacancies and couple with the Ru magnons to give rise to a dominant electron-magnon coupling that overwhelms the electron-phonon coupling in the temperature range of 90-150 K.

Benefits and pitfalls of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging in clinical application of the cervical spine MR.

AIM: To evaluate efficacy of T2-weighted (T2W) iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL)-fast spin echo (FSE) imaging of the cervical spine. MATERIALS AND METHODS: The cervical spine of 100 symptomatic patients was imaged using routine magnetic resonance imaging (MRI) versus IDEAL-FSE imaging. The signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), and image quality were analysed. To compare the diagnostic efficiency of degenerative spondylopathy, evaluations of spondylolisthesis, retrolisthesis, disc herniation, myelopathy, disc degeneration, and bone marrow oedema were also performed. RESULTS: IDEAL-FSE showed significantly higher SNRs and CNRs (all p<0.001) than fat-suppressed (FS) T2W-FSE. Sixteen of 100 patients had cervical spine instrumentation; in those patients, IDEAL-FSE provided significantly better uniformity of fat suppression (p<0.001) and fewer metallic artefacts (p<0.001). For patients without instrumentation, FS T2W-FSE showed significantly better overall image quality (p<0.001) and homogeneity of the cerebrospinal fluid (CSF; p<0.001) with fewer motion artefacts (p<0.001). IDEAL-FSE, however, provided significantly better uniformity of fat suppression (p<0.001). There were no significant differences in the diagnoses of spondylolisthesis, retrolisthesis, disc herniation, or myelopathy between IDEAL and FS T2W images. The only significant differences between the IDEAL and FS T2W images were noted when diagnosing degenerative disc disease at the C2-3 and C5-6 disc levels (p=0.019, p=0.002, respectively) and bone marrow oedema at C3 vertebral body (p=0.029). CONCLUSION: T2W IDEAL-FSE imaging should only be considered as an additional sequence to conventional FS T2W images in patients with poor fat suppression or severe metallic artefacts.

Synchronous colorectal carcinoma: predisposing factors and characteristics.

AIM: Whether some diseases are related to the occurrence of synchronous colorectal carcinoma (sCRC) is unknown. Investigating the risk factors and presentation of sCRC could aid in the treatment of patients with colorectal cancer (CRC). The prognosis of sCRC compared with that of solitary CRC remains unclear. METHODS: A total of 17 093 CRC patients were recruited between 1st January 1995 and 31th December 2016. The risk factors of sCRC development were assessed using univariate and multivariate logistic regression. The effect of sCRC on survival was analysed using the multivariate Cox regression model. RESULTS: The prevalence of sCRC was 5.6% in this study. The independent risk factors of sCRC development were advanced age (P < 0.001), male sex (P < 0.001), hereditary cancer (P < 0.001), hypertension (P < 0.001) and liver cirrhosis (P = 0.024). Compared with solitary CRC, a higher number of patients with sCRC presented with an abnormal carcinoembryonic antigen (CEA) level (P = 0.011), anaemia (P < 0.001) and hypoalbuminemia (P < 0.001). Multivariate analysis revealed that sCRC was a significant factor for poor survival in patients at TNM Stage I [hazard ratio (HR) = 1.86; P < 0.001], Stage II (HR = 1.65; P < 0.001) and Stage III (HR = 1.40; P < 0.001). CONCLUSIONS: In addition to hypertension and liver cirrhosis, other risk factors for sCRC were identified in this study. The prognosis of patients with sCRC was significantly worse than that of those with solitary CRC through TNM Stages I to III. Anaemia, abnormal CEA and hypoalbuminemia were more commonly seen in patients with sCRC.

Modelling acute myeloid leukaemia in a continuum of differentiation states.

Here we present a mathematical model of movement in an abstract space representing states of cellular differentiation. We motivate this work with recent examples that demonstrate a continuum of cellular differentiation using single cell RNA sequencing data to characterize cellular states in a high-dimensional space, which is then mapped into ℝ 2 or ℝ 2 with dimension reduction techniques. We represent trajectories in the differentiation space as a graph, and model directed and random movement on the graph with partial differential equations. We hypothesize that flow in this space can be used to model normal and abnormal differentiation processes. We present a mathematical model of hematopoeisis parameterized with publicly available single cell RNA-Seq data and use it to simulate the pathogenesis of acute myeloid leukemia (AML). The model predicts the emergence of cells in novel intermediate states of differentiation consistent with immunophenotypic characterizations of a mouse model of AML.

High-concentration iodinated contrast media for T1-weighted direct magnetic resonance arthrography.

AIM: To quantify in vitro the T1-weighted (T1W) expression of iodinated contrast media (CM), and to compare the in vivo performances of iodinated CM and gadolinium-based CM for T1W direct magnetic resonance imaging (MRI) arthrography. MATERIALS AND METHODS: An in vitro study on a 1.5 T MRI system was performed using Gd-DOTA, a mixture of iopromide and Gd-DOTA, and iopromide alone. The fat-suppressed (FS) T1W signal intensities were measured and analysed. In an in vivo study, 15 normal rabbits were used to compare the expression of iopromide (370 mg iodine/ml), and the mixture of iopromide and diluted Gd-DOTA. In nine of the 15 rabbits, extra-articular administrations of CM were performed to mimic the situation of CM leak. The rabbits were scanned on a 1.5 T MRI system, and the FS T1W sequence and an axial iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T1W sequence were acquired. Signal intensities were measured and signal-to-noise ratios (SNR) were analysed. RESULTS: In the in vitro study, a higher SNR was noted in a higher concentration of iopromide, and the highest SNR of iopromide was 45.9% of that of Gd-DOTA. In the in vivo study, the iopromide and the mixture were well identified in all rabbits. The SNRs of the intra-articular and extra-articular iopromide and the mixture were significantly higher than the SNR of the muscles in the FS T1W images (all, p<0.01) and the IDEAL images (all, p<0.01). CONCLUSIONS: A high-concentration iodinated CM can provide good imaging quality for T1W direct MRI arthrography, and may be an alternative option in certain clinical situations.

Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis.

BACKGROUND: Porphyria cutanea tarda (PCT) is the most common human porphyria. It is caused by hepatic deficiency of uroporphyrinogen decarboxylase activity, which is acquired in the presence of multiple susceptibility factors. PCT presents clinically with cutaneous blistering photosensitivity and is readily treatable with either repeated phlebotomy or 4-aminoquinoline antimalarials. OBJECTIVES: To perform a systematic review and meta-analysis to compare the effectiveness of these quite different treatment approaches, especially on relapse rates (RRs) after achieving remission. METHODS: Published studies that included follow-up for at least 1 year after treatment of PCT were included. The primary study outcome was PCT relapse. Pooled data are reported as the RRs per person-year of follow-up with 95% confidence intervals (CIs). RESULTS: Of 375 articles identified as pertaining to PCT treatment, 12 were eligible for analysis. Of these, five used high-dose 4-aminoquinoline regimens (two combined with phlebotomy and three without phlebotomy), five used low-dose 4-aminoquinoline regimens and three used phlebotomy. RRs during the year after treatment were similar for the high- and low-dose 4-aminoquinoline groups (35-36%) and lower in the phlebotomy group (20%). The pooled RRs with their 95% CIs were 8·6 (3·9-13·3) per 100 person-years in the high-dose 4-aminoquinoline group, 17·1 (8·9-25·3) per 100 person-years in the low-dose 4-aminoquinoline group and 5·1 (0·5-10·6) per 100 person-years in the phlebotomy group. Subgroup and sensitivity analyses showed similar results. CONCLUSIONS: Clinical or biochemical RRs ranged from 5 to 17 per 100 person-years after remission of PCT. Relapses were somewhat more frequent after remission with 4-aminoquinoline regimens than after remission following phlebotomy. Prospective studies are needed to define better how often relapses occur with these treatments after documenting both clinical and biochemical remission of PCT.

Thermoelectric properties of Ag-doped CuS nanocomposites synthesized by a facile polyol method.

We report the first thermoelectric properties of Cu1-xAgxS, x = 0-0.75 nanocomposites, synthesized by using a facile polyol method. Systematic characterizations using powder XRD, Rietveld refinement of XRD, EDAX, XPS and Raman spectroscopy confirmed their single phase, hexagonal crystal structure with the space group P63/mmc, nominal elemental composition, valence states of the constituent elements and stoichiometric nature. The TEM images showing the CuS formation of nearly perfect hexagonal disk-like particles of average thickness 26.7 nm and breadth ranging in a few hundreds of nanometers with nanorods stacked from these hexagonal nanodisks (NDs) elongated along the c axis corroborate the FESEM images. Attributed to structural phase transition, an anomaly at 55 K is clearly observed in both the thermopower and Hall resistivity data. By increasing x, a systematic reduction in thermal conductivity was observed near 300 K. Consequently, a 50% enhancement in figure of merit was observed for Cu0.9Ag0.1S as compared to pure CuS at 300 K. These results therefore are expected to provide a new direction in improving ZT near 300 K.

Association between leukoaraiosis and cerebral blood flow territory alteration in asymptomatic internal carotid artery stenosis.

AIM: To test the hypothesis that leukoaraiosis (also known as white matter lesion) is associated with cerebral blood flow territory change as revealed by territorial arterial spin-labeling (TASL) magnetic resonance imaging (MRI) in patients with asymptomatic internal carotid artery stenosis (aICAS). MATERIALS AND METHODS: The institutional review board approved this study. Thirty-three patients with aICAS were included prospectively and divided into high-grade (ultrasonographic stenosis ≥70%, n=17) and low-grade (n=16) groups; 16 healthy subjects were also included. Cerebral flow territory was delineated for left ICA, right ICA, and vertebral arteries using TASL MRI and fuzzy clustering. Two licensed neuroradiologists independently and dichotomously rated the hemispherical asymmetry of flow territories. Flow territories were finalised by consensus, and when asymmetry was present, these were divided into normal and abnormal areas where the raters separately assessed leukoaraiosis based on fluid-attenuated inversion recovery images and the Fazekas scale. RESULTS: The inter-rater agreement in the evaluation of flow territory asymmetry with TASL imaging in conjunction with time-of-flight angiogram is substantial (Cohen's kappa=0.82). Multinomial logistic regression (reference group=healthy subjects) indicates that global leukoaraiosis is not a predictor of aICAS after controlling for age, whereas in high-grade patients, the deep white matter lesion is more severe in the area receiving collateral circulation than in the area with normal flow territory (Wilcoxon signed-rank test, p=0.03). CONCLUSION: TASL MRI is clinically feasible in aICAS and shows that more severe deep white matter lesions are associated with collateral circulation in high-grade patients.

Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion.

Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia growth-permissive and normal hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Preconditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth. Conversely, disruption of exosome secretion in AML cells through targeting Rab27a, an important regulator involved in exosome release, significantly delayed leukemia development. In BM stromal cells, AML-derived exosomes induced the expression of DKK1, a suppressor of normal hematopoiesis and osteogenesis, thereby contributing to osteoblast loss. Conversely, treatment with a DKK1 inhibitor delayed AML progression and prolonged survival in AML-engrafted mice. In addition, AML-derived exosomes induced a broad downregulation of hematopoietic stem cell-supporting factors (for example, CXCL12, KITL and IGF1) in BM stromal cells and reduced their ability to support normal hematopoiesis. Altogether, this study uncovers novel features of AML pathogenesis and unveils how AML cells create a self-strengthening leukemic niche that promotes leukemic cell proliferation and survival, while suppressing normal hematopoiesis through exosome secretion.

The effect of stoichiometry on the structural, thermal and electronic properties of thermally decomposed nickel oxide.

A thermal decomposition route with different sintering temperatures was employed to prepare non-stoichiometric nickel oxide (Ni1-δ O) from Ni(NO3)2·6H2O as a precursor. The non-stoichiometry of samples was then studied chemically by iodometric titration, wherein the concentration of Ni3+ determined by chemical analysis, which is increasing with increasing excess of oxygen or reducing the sintering temperature from the stoichiometric NiO; it decreases as sintering temperature increases. These results were corroborated by the excess oxygen obtained from the thermo-gravimetric analysis (TGA). X-ray diffraction (XRD) and Fourier transformed infrared (FTIR) techniques indicate the crystalline nature, Ni-O bond vibrations and cubic structural phase of Ni1-δ O. The change in oxidation state of nickel from Ni3+ to Ni2+ were seen in the X-ray photoelectron spectroscopy (XPS) analysis and found to be completely saturated in Ni2+ as the sintering temperature reaches 700 °C. This analysis accounts for the implication of non-stoichiometric on the magnetization data, which indicate a shift in antiferromagnetic ordering temperature (T N) due to associated increased magnetic disorder. A sharp transition in the specific heat capacity at T N and a shift towards lower temperature are also evidenced with respect to the non-stoichiometry of the system.

An αIIb ß3 antagonist prevents thrombosis without causing Fc receptor γ-chain IIa-mediated thrombocytopenia.

Essentials FcγRIIa-mediated thrombocytopenia is associated with drug-dependent antibodies (DDAbs). We investigated the correlation between αIIb ß3 binding epitopes and induction of DDAbs. An FcγRIIa-transgenic mouse model was used to evaluate thrombocytopenia among anti-thrombotics. An antithrombotic with binding motif toward αIIb ß-propeller domain has less bleeding tendency. SUMMARY: Background Thrombocytopenia, a common side effect of Arg-Gly-Asp-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin αIIb ß3 . Objective To explore the correlation between αIIb ß3 binding epitopes and induction of DDAb binding to conformation-altered αIIb ß3 , we examined whether two purified disintegrins, TMV-2 and TMV-7, with distinct binding motifs have different effects on induction of αIIb ß3 conformational change and platelet aggregation in the presence of AP2, an IgG1 inhibitory mAb raised against αIIb ß3 . Methods We investigated the possible mechanisms of intrinsic platelet activation of TMV-2 and TMV-7 in the presence of AP2 by examining the signal cascade, tail bleeding time and immune thrombocytopenia in Fc receptor γ-chain IIa (FcγRIIa) transgenic mice. Results TMV-7 has a binding motif that recognizes the αIIb ß-propeller domain of αIIb ß3 , unlike that of TMV-2. TMV-7 neither primed the platelets to bind ligand, nor caused a conformational change of αIIb ß3 as identified with the ligand-induced binding site mAb AP5. In contrast to eptifibatide and TMV-2, cotreatment of TMV-7 with AP2 did not induce FcγRIIa-mediated platelet aggregation and the downstream activation cascade. Both TMV-2 and TMV-7 efficaciously prevented occlusive thrombosis in vivo. Notably, both eptifibatide and TMV-2 caused severe thrombocytopenia mediated by FcγRIIa, prolonged tail bleeding time in vivo, and repressed human whole blood coagulation indexes, whereas TMV-7 did not impair hemostatic capacity. Conclusions TMV-7 shows antiplatelet and antithrombotic activities resulting from a mechanism different from that of all other tested αIIb ß3 antagonists, and may offer advantages as a therapeutic agent with a better safety profile.