Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect.

ABSTRACT: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.

Coherent beam combining of femtosecond third-harmonic generators: towards high-power, high-beam-quality UV light generation.

Coherent beam combining (CBC) of two femtosecond third-harmonic (TH) generators is proposed and demonstrated. By applying phase modulation to one of the fundamental laser pulses, the feedback loop effectively eliminates both phase and pointing errors between the two TH femtosecond laser beams. The system delivers 345-nm femtosecond laser pulses with 22-W average power at 1-MHz repetition rate. The average combining efficiency is 91.5% over approximately 1 h of testing. The beam quality of the combined ultraviolet (UV) laser beam is near-diffraction-limited with M2 factors of M X2=1.36, M Y2=1.24, which are similar to those of the individual channels. This scheme exhibits promising potential for increasing high-beam-quality UV laser power.

Rectal malakoplakia mimicking advanced rectal cancer: A case report.

Background: Malakoplakia is a rare acquired chronic infectious granulomatous condition, that is characterized by the accumulation of large granular macrophages containing basophilic inclusion bodies in the cytoplasm termed Michaelis-Gutmann (MG) bodies. Malakoplakia most commonly involves the genitourinary system, and the second most commonly affected site is the gastrointestinal tract. Rectal malakoplakia is an unusual entity that is difficult to diagnose due to its diverse clinical manifestations and radiological findings that are similar to different diseases and advanced cancers. Case description: A 61-year-old male patient presented with difficulty in urination and defecation that started 4 months prior, along with a weight loss of 10 kg. Abdominal computerized tomography (CT) scanning revealed diffuse lesions of the perirectal region with multiple lymphadenopathies and involvement of the bladder, prostate, bilateral seminal vesicles, and left ureter. 18F-FDG PET/CT MIP showed intense FDG uptake in the rectal region, and a diagnosis of an occupying lesion was proposed. Colonoscopy and histological examination of rectal lesion biopsies showed the characteristic features of malakoplakia. Conclusion: Malakoplakia of the rectum with lymph node involvement and adjacent organ extension has been extensively misdiagnosed in clinical practice, and mimics malignancy radiologically. It is of great importance for radiologists to be aware of malakoplakia when making the differential diagnosis of benign and malignant mass lesions of the rectum, although the radiologic findings are nonspecific. Endoscopic evaluation and pathologic examination of a biopsy should be recommended to make the correct diagnosis, which may prevent unnecessary surgical resection.