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Abstract: Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester because of the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester and about the impact of stopping just before pregnancy. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and evaluates the impact on perinatal outcomes. The Registry of Pregnancy and Cardiac Disease is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. ACE-Is (n = 35) and/or ARBs (n = 8) were used in 42 (0.7%) of the 5,739 Registry of Pregnancy and Cardiac Disease pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p = 0.021), had chronic hypertension (31% vs 6%, p <0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p <0.001). In the multivariable analysis, ACE-I use during the first trimester was associated with an increased risk of congenital anomaly (odds ratio 3.2, 95% confidence interval 1.0 to 9.6). Therefore, ACE-Is should be avoided during pregnancy, also in the first trimester, because of a higher risk of congenital anomalies. However, there is no need to stop long before pregnancy. Preconception counseling is crucial to discuss the potential risks of these medications, to evaluate the clinical condition and, if possible, to change or stop the medication.
Keywords: ACE inhibitor, angiotensin receptor blocker, preconception, pregnancy
Published in DiRROS: 16.12.2025; Views: 4; Downloads: 4
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Abstract: In this work, we fabricate a facile de novo synthesis route to prepare bio-functionalized carbon nitride-reduced graphene oxide with chitosan (Chi) nanocomposite (C3N4/RGO/Chi). The nitrogen-rich C3N4 has been synthesized through facile and low-cost thermal oxidation and offers a metal-free and highly active surface for synergistic modification with RGO and Chi. Moreover, the synergistically incorporated C3N4/RGO and biopolymer improve the electrocatalytic activity, provide surface functionalities, and enhance electroconductivity for immunosensing applications. Consequently, the bio-functionalized C3N4/RGO nanocomposite provides a suitable substrate for the immobilization of SARS-CoV-2 RBD spike protein. The immunosensor detects SARS-CoV-2 antibodies in a wide detection range from 10 zg mL−1 (10 × 10−21 g mL−1) to 100 ng mL−1 with an ultra-low detection limit (LOD) of 3.31 zg mL−1. The validation of the immunosensor was also carried out on spiked serum samples, which show a linear detection range of 100 ag mL−1 to 100 ng mL−1 and a LOD of 1.73 ag mL−1. Nevertheless, the clinical diagnostic application of the immunosensor is validated through the examination of real serum samples from COVID-19 patients. The results suggest that the immunosensor can be efficiently used as a screening platform to distinguish between positive and negative samples with high accuracy. The findings of the work have the potential to translate the immunosensing strategy into next-generation point-of-care testing (POCT) of various infectious diseases.
Keywords: SARS-CoV-2, detection, nanomaterials
Published in DiRROS: 16.12.2025; Views: 12; Downloads: 6
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Abstract: Background: The differential diagnosis of cardiac myxomas (CM), the most common benign primary cardiac tumors, is broad and a thorough diagnostic workup is required to establish accurate diagnosis prior to surgical resection. Transthoracic echocardiography (TTE) is usually the first imaging modality used for diagnosis of suspected CM. In a single tertiary centre study, we sought to determine the accuracy, sensitivity, and specificity of TTE in the diagnosis of CM and to determine echocardiographic characteristics indicative of CM. Patients and methods: We retrospectively analyzed clinical, echocardiographic, and pathohistological findings of 73 patients consecutively admitted for suspected CM. Results: After diagnostic workup, 53 (73%) patients were treated surgically at our institution. Based on preoperative TTE, patients were divided into a CM group (n=45, 85%) and non-myxoma (NM) group. Of the 53 pathohistological specimens obtained during surgery, 39 (73%) were CM. The sensitivity and specificity of preoperative echocardiography were 97% and 50%, respectively. The overall accuracy was 85%. All NM tumors were found in an atypical location and 72% of CM were found in a typical position in the left atrium (p < 0.001). Tumors in NM group were significantly smaller than CM (24.3 ± 13.2 mm vs. 37.9 ± 18.3 mm, p = 0.017). Conclusions: Our study confirms very good accuracy of TTE in the diagnosis of CM. The most important echocardiographic characteristics to differentiate between CM and tumors of different etiology are tumor location and size. Smaller tumors presenting at an atypical location are less likely to be diagnosed as CM, and these require additional imaging modalities for accurate diagnosis.
Keywords: cardiac mass, cardiac myxoma, cardiovascular imaging, echocardiography
Published in DiRROS: 16.12.2025; Views: 4; Downloads: 4
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Abstract: Purpose: Effective intercellular communication among lens epithelial cells (LECs) is essential for lens homeostasis, and its disruption has been implicated in cataract formation. This study investigates the mechanisms of calcium (Ca²⁺) wave propagation in the human lens epithelium, focusing on the respective roles of gap-junctional coupling and ATP-mediated paracrine signaling. Methods: We performed multicellular Ca²⁺ imaging on human postoperative anterior lens capsule preparations obtained from cataractous lenses during cataract surgery which retained intact monolayers containing viable LECs. Mechanically induced Ca²⁺ waves were recorded, and the contribution of specific signaling pathways was evaluated by pharmacological intervention using apyrase (an ATP-hydrolyzing enzyme) and carbenoxolone (CBX; a gap-junctional blocker). To interpret the experimental results, we developed a biophysically detailed computational model of the LEC monolayer, incorporating intracellular Ca²⁺ dynamics, gap-junctional IP₃/Ca²⁺ diffusion, and extracellular ATP signaling. Results: Apyrase moderately reduced the spatial extent, amplitude, and duration of Ca²⁺ waves without affecting propagation speed. In contrast, CBX significantly suppressed wave transmission, limiting activation to cells directly adjacent to the stimulation site. Simulations reproduced key experimental features and indicated that neither pure gap-junctional nor purely paracrine signaling mechanisms alone could explain the observed dynamics. Instead, a hybrid mechanism combining gap-junctional communication and partially regenerative ATP release was required. Conclusions: Our results highlight the cooperative roles of gap-junctional and ATP-based paracrine signaling in mediating mechanically induced Ca²⁺ wave propagation in the human lens epithelium. This dual-pathway mechanism may be critical for coordinated cellular responses that support physiological processes such as ion homeostasis and transparency maintenance in the human lens.
Keywords: human lens epithelium, calcium signaling, intercellular communication, calcium imaging, computational model
Published in DiRROS: 16.12.2025; Views: 4; Downloads: 4
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Abstract: The current study aims to improve clarithromycin bioavailability and effectiveness in complicated intra-abdominal infection management. Therefore, clarithromycin-loaded submicron dual lipid carriers (CLA-DLCs) were developed via hot high shear homogenization technique and evaluated for colloidal parameters, release behavior, stability study, and in-vitro antibiofilm activity. Bioavailability and therapeutic efficacy of optimized formulation on hampering cytokines storm induction was determined in E. coli-induced peritonitis. The developed CLA-DLCs (particle size 326.19 ± 24.14 nm, zeta potential −31.34 ± 2.81 mV, and entrapment efficiency 85.78 ± 4.01%) exhibited smooth spherical shapes and sustained in vitro release profiles. Long-term stability study of optimized CLA-DLCs ensured maintenance of colloidal parameters for 1 year at room temperature. In vitro antimicrobial studies revealed 3.43-fold higher anti-biofilm activity of CLA-DLCs compared with clarithromycin. In addition, the relative bioavailability of CLA-DLCs was enhanced 5.89-fold compared to pure drug in rats. The remarkable decrease in microbial burden in blood as well as tissues, along with oxidative stress markers (lipid peroxidation, myeloperoxidase activity, and carbonylated protein level) and immunological markers (total leukocyte count, neutrophil migration, NO, TNF-, and IL-6) on treatment with CLA-DLCs enhanced the survival in a rat model of peritonitis compared with the pure drug and untreated groups. In conclusion, CLA-DLCs hold promising potential in management of intra-abdominal infections and prevention of associated complications.
Keywords: clarithromycin, E. coli, peritonitis, submicron dual lipid carriers
Published in DiRROS: 16.12.2025; Views: 7; Downloads: 7
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