Symptomatic Developmental Venous Anomaly: State-of-the-Art Review on Genetics, Pathophysiology, and Imaging Approach to Diagnosis.

Developmental venous anomalies (DVAs) are the most common slow-flow venous malformation in the brain. Most DVAs are benign. Uncommonly, DVAs can become symptomatic, leading to a variety of different pathologies. DVAs can vary significantly in size, location, and angioarchitecture, and imaging evaluation of symptomatic developmental venous anomalies requires a systematic approach. In this review, we aimed to provide neuroradiologists with a succinct overview of the genetics and categorization of symptomatic DVAs based on the pathogenesis, which forms the foundation for a tailored neuroimaging approach to assist in diagnosis and management.

Evaluation of functional recovery in the intrinsic and flexor muscles after nerve transfer for ulnar nerve lesion. A new measurement method: The Cha method.

"Supercharge" end-to-side (SETS) nerve transfer for lesions of the proximal ulnar nerve is a recognized novel option, but improvement in motor function after surgery has not been properly evaluated. We therefore propose a modified method for quantitative evaluation of improvement in the intrinsic hand strength. We screened 216 patients with proximal ulnar nerve lesions who presented to our outpatient department from 2012 to 2020. Of these, 101 met our inclusion/exclusion criteria and were evaluated just before surgery. We used a novel method to measure finger abduction ("2nd-abd"), adduction ("5th-add"), and ring and little finger flexion strength ("4,5 grip"), and analyzed correlations with established pinch strength data. The male:female sex ratio was 86:15, and the ratio dominant to nondominant arm involvement was 68:33. All strength measurements were analyzed as percentage affected to contralateral normal side. On Pearson correlation analysis, the strength ratios for "4,5 grip", "2nd-abd", and "5th-add", but not "5 fingers (total) grip", showed significant positive correlation with key and oppositional pinch strength (all p < 0.001). Additionally, linear regression analysis showed identical results for each strength correlation with key/oppositional pinch, except for "5 fingers total) grip" (all, p < 0.001). SETS is a reasonable alternative for lesions of the proximal ulnar nerve. The measurement method we propose is feasible for specific assessment of intrinsic muscle strength, which improves after surgery. LEVEL OF EVIDENCE: Diagnostic, level IV.

Supplementation with heat-inactivated Lacticaseibacillus paracasei K47 ameliorates allergic asthma in mice by regulating the Th1/Th2 balance.

Asthma is a chronic inflammatory disease related to the immune response of type 2 T helper cells (Th2), which affects all age groups. The incidence of asthma is increasing worldwide, and it has become a significant public health problem. This study aimed to investigate the immunomodulatory effects of Lacticaseibacillus (formerly Lactobacillus) paracasei K47 on mice with ovalbumin (OVA)-induced allergy. The consequences of orally administered heat-inactivated K47 in OVA-sensitised/challenged BALB/c mice were evaluated by assessing the serum levels of immunoglobulins (Igs), airway hyperresponsiveness (AHR), and bronchoalveolar lavage fluid (BALF) cytokine. In addition, the effect of K47 on type 1 T helper cells (Th1)/Th2 cytokine production in splenocytes from OVA-sensitised mice was evaluated. The results revealed that supplementation with K47 remarkably reduced serum levels of total IgE, OVA-specific IgE, and OVA-specific IgG1 in OVA-sensitised/challenged mice. In addition, K47 intervention ameliorated AHR and suppressed the accumulation of inflammatory cells in the BALF of OVA-sensitised/challenged mice. Furthermore, the immunomodulatory ability of K47 was mediated by regulation of the cytokine profile toward the Th1 response in the BALF, and splenocytes of OVA-sensitised mice. Taken together, these results suggested that K47 can modulate the host immune response to ameliorate AHR and inflammation in allergic asthma.

Dual-Layer Spectral CT Imaging of Upper Aerodigestive Tract Cancer: Analysis of Spectral Imaging Parameters and Impact on Tumor Staging.

BACKGROUND AND PURPOSE: Dual-layer spectral CT is a novel technology that utilized conventional single-tube CT acquisition with a dual-layer detector for the separation of high and low-energy photons to create spectral data for material decomposition. We evaluated the spectral parameters of iodine density and Z-effective values in primary head and neck squamous cell carcinoma and determined its impact on local tumor staging. MATERIALS AND METHODS: Twenty-one patients with primary head and neck squamous cell carcinoma and 15 healthy controls were retrospectively evaluated. Iodine density (milligram/milliliter) and Z-effective values were compared quantitatively between head and neck squamous cell carcinoma and normal neck mucosa. The receiver operating characteristic area under the curve determined the diagnostic performance of the spectral data for local staging. We compared conventional CT images without and with iodine density and Z-effective images to determine its impact on local tumor staging. RESULTS: Primary head and neck squamous cell carcinoma showed higher mean iodine density (2.01 [SD, 0.26] mg/mL, P < .001) and Z-effective values (8.21 [SD, 0.36], P < .001). A high interobserver correlation was demonstrated for ROI measurements for both the control group (iodine density, κ = 0.71, and Z-effective values, κ = 0.78) and head and neck squamous cell carcinoma (iodine density, κ = 0.84, and Z-effective values, κ = 0.75) group. The area under the curve for iodine density and Z-effective values was 0.98 and 0.93, respectively. Optimal thresholds were identified as 1.58 mg/mL (95% CI, 1.45-1.71 mg/mL; P < .001; sensitivity = 1.0; specificity = .0.93) for iodine density and 8.08 (95% CI, 7.96-8.19; P < .001; sensitivity = 0.86; specificity = 0.93) for Z-effective values. Conventional CT with the addition of dual-layer spectral data (iodine density and Z-effective values) improved the accuracy of local tumor staging in 3 of 21 patients (14%) with head and neck squamous cell carcinoma compared with the criterion standard surgical staging/histopathology. CONCLUSIONS: Dual-layer spectral iodine density and Z-effective values provided increased quantitative and qualitative differentiation between upper aerodigestive head and neck squamous cell carcinoma and normal mucosa. Increased tissue differentiation improved the local tumor staging accuracy.

The effect of plaque control in the treatment of Oral Lichen Planus with gingival manifestations: a Systematic Review.

BACKGROUND: Oral lichen planus (OLP) is a chronic autoimmune disease that frequently affects the oral mucosa. Patients with OLP tend to present with plaque accumulation which may further exacerbate the lichenoid lesion, thus plaque control may improve the quality of life of patients. The aim of this review was to test the effect of plaque control on OLP with gingival manifestations. METHODS: Systematic review following the PRISMA checklist. A search was conducted through Medline, Embase and the Cochrane Library Database up to March 2020 and complemented by a manual search in some relevant journals. Randomised Controlled Trials (RCTs) reporting plaque interventions and their effects in populations with gingival manifestations of OLP, with a follow-up period of at least 3 months were included. Risk of Bias was assessed using the Cochrane Collaboration Tool in Randomised Trials. RESULTS: The initial search generated 89 sources, resulting in final inclusion of three RCTs following full-text reading. The control groups were asked to continue their regular oral hygiene routine, while test groups received additional tailored oral hygiene advice as the intervention. Two of the included papers had sufficiently similar design to be included in meta-analysis. The oral hygiene intervention was associated with improvements in clinical disease status (Escudier index) and patient-reported outcomes (OHIP-14) from baseline compared with the control group. Differences in visual analogue scores for pain between groups were not statistically different between test and control groups. Two studies were judged to have low risk of bias, while one (not included in meta-analysis) had high risk of bias. CONCLUSION: Improvements in disease and patient-reported outcomes can occur as a result of oral hygiene instruction in patients with gingival manifestations of OLP.

Inter-relationship of risk factors and pathways associated with chronic kidney disease in patients with type 2 diabetes mellitus: a structural equation modelling analysis.

OBJECTIVES: Diabetes mellitus is the most common cause of chronic kidney disease (CKD); however, the inter-relationships and pathogenetic mechanisms among risk factors are still largely unknown. Structural equation modelling (SEM) was applied to test a hypothesis of causal pathways related to CKD in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: This is a prospective observational study. METHODS: A total of 3395 patients with T2DM were enrolled in this study. A hypothesised SEM was applied to assess associations among demographic data, diabetic self-management behaviours, diabetes control, lifestyle, psycho-social, chronic inflammation factors, anthropometric and metabolic variables simultaneously and the risk of CKD. RESULTS: Demographic data (including education, marital status and mini-mental state examination score) (-0.075), white blood cell count (0.084), high blood pressure (0.144), World Health Organisation (WHO) 5 well-being index (-0.082), diabetes control (0.099), triglyceride (0.091) and uric acid (0.282) levels had direct effects on the risk of CKD. The final model could explain 26% of the variability in baseline CKD status. In addition, the same direct and specific indirect factors at baseline CKD status analysis contributed to the risk of CKD at the 12-month follow-up. The final model could explain 31% of the variability in the risk of CKD at the 12-month follow-up. CONCLUSIONS: This study investigates associations between factors obtained from real-world daily practice and CKD status simultaneously and delineates the potential pathways and inter-relationships of the risk factors that contribute to the development of CKD in patients with T2DM.

Quantifying Tissue Properties of the Optic Radiations Using Strategically Acquired Gradient Echo Imaging and Enhancing the Contrast Using Diamagnetic Susceptibility Weighted Imaging.

Visualization of the optic radiations is of clinical importance for diagnosing many diseases and depicting their anatomic structures for neurosurgical interventions. In this study, we quantify proton density, T1, T2*, and susceptibility of the optic radiation fiber bundles in a series of 10 healthy control participants using strategically acquired gradient echo imaging. Furthermore, we introduce a novel means to enhance the contrast of the optic radiations using diamagnetic susceptibility weighted imaging.

The relationship between resting heart rate and new-onset microalbuminuria in people with type 2 diabetes: An 8-year follow-up study.

AIMS: Microalbuminuria is an indicator of adverse cardiovascular events and chronic kidney disease. Studies have described an elevated resting heart rate as a risk factor for microalbuminuria in people with cardiovascular disease, but none have clarified its role in microalbuminuria development in people with type 2 diabetes. Therefore, this study investigated the relationship between resting heart rate and new-onset microalbuminuria in type 2 diabetes. METHODS: A total of 788 people from a glycaemic control trial in Taiwan were enrolled. Microalbuminuria was defined as a fasting urine albumin-to-creatinine ratio ≥30 mg/g in two consecutive urine tests. Resting heart rate and other covariates were measured at baseline. The quartile of resting heart rates, categorized as <70, 70-74, 75-80 and >80 beats/min, was used for analysis. Cox proportional hazard models were used to evaluate the association between resting heart rate and risk of microalbuminuria. RESULTS: During the follow-up period, 244 people (31%) developed microalbuminuria. Those who developed microalbuminuria had a longer diabetes duration (median = 3.0 vs. 2.0 years, p < 0.001), higher rate of hypertension (77% vs. 66%, p = 0.003), higher rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment (50% vs. 38%, p = 0.001) and higher baseline HbA1c level (70 vs. 64 mmol/mol, 8.6 vs. 8.0%, p < 0.001). After adjusting for demographics, metabolic profiles and inflammatory markers, developing microalbuminuria was significantly associated with baseline resting heart rate of 70-74, 75-80 and >80 beats/min (with hazard ratios [95% CI] of 2.05 [1.32, 3.18], 2.10 [1.32, 3.32] and 1.62 [1.01, 2.59], respectively) compared to resting heart rates <70 beats/min. An average increased risk of microalbuminuria for increment of 10 beats/min was about 24% among those with hypertension (with hazard ratios of 1.24 [1.05, 1.47] in the multivariable Cox model). CONCLUSIONS: This prospective cohort study showed that resting heart rate may be an associative risk factor for developing microalbuminuria in type 2 diabetes.

Tumefactive Primary Central Nervous System Vasculitis: Imaging Findings of a Rare and Underrecognized Neuroinflammatory Disease.

Primary central nervous system vasculitis (PCNSV) is a poorly understood neuroinflammatory disease of the CNS affecting the intracranial vasculature. Although PCNSV classically manifests as a multifocal beaded narrowing of the intracranial vessels, some patients may not have angiographic abnormalities. A rare subset of patients with PCNSV present with masslike brain lesions mimicking a neoplasm. In this article, we retrospectively review 10 biopsy-confirmed cases of tumefactive PCNSV (t-PCNSV). All cases of t-PCNSV in our series that underwent CTA or MRA were found to have normal large and medium-sized vessels. T-PCNSV had a variable MR imaging appearance with most cases showing cortical/subcortical enhancing masslike lesion (70%), often with microhemorrhages (80%). Diffusion restriction was absent in all lesions. In summary, normal vascular imaging does not exclude the diagnosis of t-PCNSV. Advanced imaging techniques including MR perfusion and MR spectroscopy failed to demonstrate specific findings for t-PCNSV but assisted in excluding neoplasm in the differential diagnosis. Biopsy remains mandatory for definitive diagnosis.

Nanoscale strain engineering of giant pseudo-magnetic fields, valley polarization, and topological channels in graphene.

The existence of nontrivial Berry phases associated with two inequivalent valleys in graphene provides interesting opportunities for investigating the valley-projected topological states. Examples of such studies include observation of anomalous quantum Hall effect in monolayer graphene, demonstration of topological zero modes in "molecular graphene" assembled by scanning tunneling microscopy, and detection of topological valley transport either in graphene superlattices or at bilayer graphene domain walls. However, all aforementioned experiments involved nonscalable approaches of either mechanically exfoliated flakes or atom-by-atom constructions. Here, we report an approach to manipulating the topological states in monolayer graphene via nanoscale strain engineering at room temperature. By placing strain-free monolayer graphene on architected nanostructures to induce global inversion symmetry breaking, we demonstrate the development of giant pseudo-magnetic fields (up to ~800 T), valley polarization, and periodic one-dimensional topological channels for protected propagation of chiral modes in strained graphene, thus paving a pathway toward scalable graphene-based valleytronics.

Lactobacillus paracasei PS23 reduced early-life stress abnormalities in maternal separation mouse model.

Maternal separation (MS) has been developed as a model for inducing stress and depression in studies using rodents. The concept of the gut-brain axis suggests that gut health is essential for brain health. Here, we present the effects of administration of a probiotic, Lactobacillus paracasei PS23 (PS23), to MS mice against psychological traits including anxiety and depression. The administration of live and heat-killed PS23 cells showed positive behavioural effects on MS animals, where exploratory tendencies and mobility were increased in behavioural tests, indicating reduced anxiety and depression compared to the negative control mice (P<0.05). Mice administered with both live and heat-killed PS23 cells also showed lower serum corticosterone levels accompanied by higher serum anti-inflammatory interleukin 10 (IL-10) levels, compared to MS separated mice (P<0.05), indicating a stress-elicited response affiliated with increased immunomodulatory properties. Assessment of neurotransmitters in the brain hippocampal region revealed that PS23 affected the concentrations of dopaminergic metabolites differently than the control, suggesting that PS23 may have improved MS-induced stress levels via neurotransmitter pathways, such as dopamine or other mechanisms not addressed in the current study. Our study illustrates the potential of a probiotic in reversing abnormalities induced by early life stress and could be an alternative for brain health along the gut-brain axis.

Investigation of the antiphase dynamics of the orthogonally polarized passively Q-switched Nd:YLF laser.

The antiphase dynamics of Q-switched orthogonally polarized emissions have been thoroughly investigated. A Nd:YLF crystal with the anisotropic thermal lensing effect is used as the gain medium for achieving dual polarized laser. By using the Cr4+:YAG saturable absorber, the passively Q-switched output shows intriguing switching dynamics, where the number of pulses for both polarized components within one switching period is directly determined by the power ratio between the orthogonally polarized emissions. Experimental results reveal that the pulse energies of every single pulse for both orthogonally polarized states are equal with the maximum value of 223 µJ. The pulse durations for π- and σ-polarization are measured to be 15 ns and 11 ns and the corresponding peak power levels are up to 15.0 kW and 20.3 kW, respectively.

AFP role in predicting recurrence of hepatocellular carcinoma after living donor liver transplantation in HCV patients.

HCC is one of the leading causes of death worldwide. Liver transplantation including living donor transplantation is the best available treatment. We have analyzed our experience with LDLT in patients with HCC and HCV in order to determine if alpha feto-protein (AFP) is a better predictor of recurrence than the tumor burden. We have identified all patients with HCV related liver disease and HCC who have undergone LDLT in one center during the period from December 2000 to December 2014. Outcomes from the prospective database were compared for patients who met Milan criteria (single tumor ≤5 cm, maximum of 3 total tumors with none >3 cm) or not. Uni- and multi-variable analyses of factors influencing recurrence free survival (RFS) were performed. A total of 142 patients with HCC and HCV associated liver disease underwent LDTL during the study period. RFS was 96.4% at 1 years, 91.8% at 3 years and 91.8% at 5 years. Gender, model for End-Stage Liver disease (MELD), pre-transplant therapy, AFP level, tumor number, total tumor size were predictors of recurrence on univariable analysis. On multivariable analysis MELD score (Hazard ratio (HR) 1.16) and Log10 AFP (HR 3.14) were predictors of RFS. In the ROC curve analysis with an AUC of 0.76 the optimal cut-off value of AFP was 26ng/mL. In conclusion MELD score and pre-transplant AFP predict recurrence after LDLT for HCC with HCV infection.

Arsenic and five metal concentrations in the muscle tissue of bigeye tuna (Thunnus obesus) in the Atlantic and Indian Oceans.

White muscle concentrations of As, Cd, Cu, Fe, Se, and Zn were investigated in Atlantic- and Indian-bigeye tuna (BET) (Thunnus obesus) from 6 regions. As and Cd muscle concentrations were significantly higher in the Indian-BET than in the Atlantic-BET, whereas the Indian-BET caught in the waters off South Africa revealed the highest As, Se, and Zn muscle concentrations. Accordingly, multidimensional scaling separated them into two oceanic groups. Positive linear relationships between muscle Cd concentration and fork length (FL) were established in both oceans. For the other elements, only muscle-Fe and FL relationship was found in the Atlantic-BET. 10.3% of BET > 145 cm FL from both oceans possessed muscle Cd concentrations exceeding the food safety limit (0.1 µg g-1 wet weight) set by the European Commission. Increased Cd, Cu and Zn pollution was found in the Atlantic Ocean compared with previous data, with higher levels found in the Indian Ocean.

HARMless: Transient Cortical and Sulcal Hyperintensity on Gadolinium-Enhanced FLAIR after Elective Endovascular Coiling of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR has been increasingly recognized after iodinated contrast medium exposure during angiographic procedures. The goal of this study was to assess the relationship of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR against various variables in patients following elective endovascular treatment of intracranial aneurysms. MATERIALS AND METHODS: We performed a retrospective review of 58 patients with 62 MR imaging studies performed within 72 hours following endovascular treatment of intracranial aneurysms. Patient demographics, aneurysm location, and vascular territory distribution of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR were documented. Analysis of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated contrast medium volume, procedural duration, number of angiographic runs, and DWI lesions was performed. RESULTS: Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR was found in 32/62 (51.61%) post-endovascular treatment MR imaging studies, with complete resolution of findings in all patients on the available follow-up studies (27/27). Angiographic iodinated contrast medium injection and arterial anatomy matched the vascular distribution of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR. No significant association was found between cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated contrast medium volume (P = .56 value) and the presence of DWI lesions (P = .68). However, a significant association was found with procedural time (P = .001) and the number of angiographic runs (P = .019). No adverse clinical outcomes were documented. CONCLUSIONS: Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR is a transient observation in the arterial territory exposed to iodinated contrast medium during endovascular treatment of intracranial aneurysms. Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR is significantly associated with procedural time, and the frequency of angiographic runs suggesting a potential technical influence on the breakdown of the BBB, but no reported adverse clinical outcome or association with both iodinated contrast medium volume and DWI lesions was found. Recognition of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR as a benign incidental finding is vital to avoid unnecessary investigation.

A Point-based Mortality Prediction System for Older Adults with Diabetes.

The mortality prediction models for the general diabetic population have been well established, but the corresponding elderly-specific model is still lacking. This study aims to develop a mortality prediction model for the elderly with diabetes. The data used for model establishment were derived from the nationwide adult health screening program in Taiwan in 2007-2010, from which we applied a 10-fold cross-validation method for model construction and internal validation. The external validation was tested on the MJ health screening database collected in 2004-2007. Multivariable Cox proportional hazards models were used to predict five-year mortality for diabetic patients ≥65 years. A total of 220,832 older subjects with diabetes were selected for model construction, of whom 23,241 (10.5%) died by the end of follow-up (December 31, 2011). The significant predictors retained in the final model included age, gender, smoking status, body mass index (BMI), fasting glucose, systolic and diastolic blood pressure, leukocyte count, liver and renal function, total cholesterol, hemoglobin, albumin, and uric acid. The Harrell's C in the development, internal-, and external-validation datasets were 0.737, 0.746, and 0.685, respectively. We established an easy-to-use point-based model that could accurately predict five-year mortality risk in older adults with diabetes.

ARHGEF10 knockout inhibits platelet aggregation and protects mice from thrombus formation.

Essentials ARHGEF10 single-nucleotide polymorphism provides risk of ischemic and atherothrombotic stroke. The role of ARHGEF10 in platelet function was examined using ARHGEF10 knockout mice. ARHGEF10 deficiency inhibits platelet function and arterial thrombus formation. ARHGEF10 knockout protects mice from stroke-induced infarction. SUMMARY: Background ARHGEF10, a member of the Rho guanine nucleotide exchange factor (GEF) family, stimulates Rho GTPases. Rho GTPases have been reported to regulate a variety of cellular behaviors, such as cell polarity, cytoskeletal organization, and gene transcription. ARHGEF10 single-nucleotide polymorphisms are linked to the risk of ischemic stroke. However, the role of ARHGEF10 in platelet function remains unknown. Objective To examine the role of ARHGEF10 in platelet function. Methods ARHGEF10-/- were generated. We examined the in vitro and in vivo effects of ARHGEF10 knockout on platelet function and arterial thrombosis formation. Results ARHGEF10-/- mice had normal platelet counts, but showed altered aggregation in response to thrombin, collagen, ADP, protease-activated receptor-4 peptide, and U46619 stimulation. ARHGEF10 knockout influenced platelet spreading on fibrinogen-coated surfaces, and caused the platelets to show less lamellipodia-like extension than wild-type platelets. ARHGEF10 knockout also inhibited platelet clot retraction induced by thrombin stimulation. ARHGEF10 knockout resulted in prolonged tail bleeding time and inhibited the stable thrombus formation induced by FeCl3 in the carotid artery. Conclusions ARHGEF10 serves as an important regulator in platelet shape change, spreading, and aggregation. Moreover, ARHGEF10 also plays an important role in arterial thrombosis formation.

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.