Search

Introduction: Inappropriate use of direct oral anticoagulants (DOACs) is common, affecting up to 30% of atrial fibrillation (AF) population receiving treatment for stroke prevention. This study assessed appropriateness of anticoagulation in anticoagulation-naive AF patients treated with DOACs during a 12-month prospective follow-up., Methods: This prospective cohort study included all anticoagulation-naive AF patients referred for anticoagulation for stroke prevention at a tertiary cardiovascular center. Participants were prospectively followed through phone call interviews by a dedicated nurse at 1, 3, 6, 9, and 12 months after enrollment., Results: Of 403 anticoagulation-naive AF patients, rivaroxaban was prescribed for 325 patients (80.7%) and apixaban for 78 (19.3%). Inappropriate therapy was observed in 23% (76/325) and 46% (36/78) of patients treated with rivaroxaban and apixaban, respectively. Undertreatment was predominant scenario for both drugs, detected in 78.5% (78/112) of patients treated inappropriately, and was more frequently observed with apixaban versus rivaroxaban (44.8% vs 16.3%). During 12 months, inappropriate treatment was corrected in only 13% of all patients. The multivariate regression model identified creatinine clearance ≤ 49 mL/min (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.12 to 4.21), female sex (OR, 1.81; 95% CI, 1.11 to 2.97), and age ≥ 80 years (OR, 1.85; 95% CI, 1.22 to 2.83) as independent covariates associated with inappropriate dosing., Conclusions: Inappropriate therapy with DOACs for stroke prevention in patients with AF is common, and the dosage were corrected in few patients during the 12-month follow-up. Our findings highlight the persistent lack of knowledge regarding appropriate DOAC dosage and need for continuous education., Competing Interests: Declarations. Competing interests: Dr. Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally.  He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multi morbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation program me under grant agreement No 899871., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Conventional chemotherapy has significant limitations for colorectal cancer (CRC) treatment, especially those who have developed metastatic recurrence CRC. A growing number of studies have investigated the potential use of monoclonal antibodies (mAbs) for CRC therapy. mAbs showing clinical benefits for CRC, making the treatment more selective with lower side effects without significant immunogenicity. In addition, recent advancements in antibody engineering strategies and the development of bifunctional or even trifunctional drugs have helped to overcome heterogeneity as the main challenge in cancer treatment. The current review discusses advances in applying mAbs for CRC therapy alone, combined, or with small molecules., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A U-shaped contraction pattern was shown to be associated with a better Cardiac resynchronization therapy (CRT) response. The main goal of this study is to automatically recognize left ventricular contractile patterns using machine learning algorithms trained on conventional quantitative features (ConQuaFea) and radiomic features extracted from Gated single-photon emission computed tomography myocardial perfusion imaging (GSPECT MPI). Among 98 patients with standard resting GSPECT MPI included in this study, 29 received CRT therapy and 69 did not (also had CRT inclusion criteria but did not receive treatment yet at the time of data collection, or refused treatment). A total of 69 non-CRT patients were employed for training, and the 29 were employed for testing. The models were built utilizing features from three distinct feature sets (ConQuaFea, radiomics, and ConQuaFea + radiomics (combined)), which were chosen using Recursive feature elimination (RFE) feature selection (FS), and then trained using seven different machine learning (ML) classifiers. In addition, CRT outcome prediction was assessed by different treatment inclusion criteria as the study's final phase. The MLP classifier had the highest performance among ConQuaFea models (AUC, SEN, SPE = 0.80, 0.85, 0.76). RF achieved the best performance in terms of AUC, SEN, and SPE with values of 0.65, 0.62, and 0.68, respectively, among radiomic models. GB and RF approaches achieved the best AUC, SEN, and SPE values of 0.78, 0.92, and 0.63 and 0.74, 0.93, and 0.56, respectively, among the combined models. A promising outcome was obtained when using radiomic and ConQuaFea from GSPECT MPI to detect left ventricular contractile patterns by machine learning., (© 2022. The Author(s).)

Different molecular signaling pathways have been involved in the incidence and progression of CRC. We aimed to examine the correlation between eight candidate genes, including TFGβ, SMAD2, SMAD4, RhoA, EGFR, MAP2K1, MTA1, and LEF1 in the progression of colorectal cancer (CRC) and their association with clinicopathological variables and CRC patients prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) analysis 2 -ΔΔct , were performed to assess the expression of eight genes in 64 and 122 patients with CRC, respectively and 20 normal samples were added for verification. We showed a positive correlation between SMAD2 and MAP2K1 (r = 0.337, P < 0.001), MAP2K1 and LEF1 (r = 0.187, P = 0.03), SMAD4 and RhoA (r = 0.214, P = 0.01) and as well, a negative correlation between SMAD2 and TGFβ (r =  - 0.197, P = 0.02), and RhoA and LEF1 (r =  - 0.180, P = 0.04) in tumor tissues. A decrease in RhoA mRNA expression was associated with the advanced TNM stage (P = 0.01), while the EGFR and SMAD2 mRNA expression upregulated in advanced stages (P = 0.03, P = 0.03), respectively. Also, an increase in EGFR and SMAD4 protein expression was significantly associated with the advanced TNM stage (P = 0.000) (P = .002), respectively. Perceiving the connections between canonical and non-canonical Transforming growth factor (TGF-β) signaling pathway along with the epidermal growth factor receptor (EGFR) and WNT cascades may trigger the development of novel approaches for CRC prediction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Spermatogonial stem cells (SSCs) are essential to the initiation of spermatogenesis. Cryopreservation, long-term maintenance, and auto-transplantation of SSCs could be a new treatment for infertility. The aim of this study was to add melatonin to the basic freezing medium and to evaluate its effect on the efficiency of the thawed SSCs after transplantation into the testicles of azoospermic mice. SSCs were isolated from newborn NMRI mice, and the cells were enriched to assess morphological features. The thawed SSCs were evaluated for survival, apoptosis, and ROS level before transplantation, and the proliferation (MVH and ID4) and differentiation (c-Kit, SCP3, TP1, TP2, and Prm1) markers of SSCs were examined using immunofluorescence, western blot, and quantitative real-time polymerase chain reaction (PCR) after transplantation. It was found that the survival rate of SSCs after thawing was significantly higher in the melatonin group compared with the cryopreservation group containing basic freezing medium, and the rate of apoptosis and level of ROS production also decreased significantly in the cryopreservation group with melatonin (p < 0.05). The expression of proliferation and differentiation markers after transplantation was significantly higher in the cryopreservation group with melatonin compared to the cryopreservation group (p < 0.05). The results suggest that adding melatonin to the basic freezing medium can effectively protect the SSCs by increasing the viability and reducing the ROS production and apoptosis and improve the transplantation efficiency of SSCs after cryopreservation, which will provide a significant suggestion for fertility protection in the clinic.

Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary manipulation to reduce calorie intake which has been shown to improve neuroprotection and attenuate neurodegenerative disorders. Here, we evaluated the effect of 33% CR regimen for 4 weeks on the remyelination capacity of Cuprizone (CPZ) induced demyelination in a mouse model of MS. Results showed that CR induced a significant increase in motor coordination and balance performance in CPZ mice. Also, luxol fast blue (LFB) staining showed that CR regimen significantly improved the remyelination in the corpus callosum of CPZ + CR mice compared to the CPZ group. In addition, CR regimen significantly increased the transcript expression levels of BDNF, Sox2, and Sirt1 in the corpus callosum of CPZ mice, while decreasing the p53 levels. Moreover, CR regimen significantly decreased the apoptosis rate. Furthermore, astrogliosis (GFAP + astrocytes) and microgliosis (Iba-1 + microglia) were significantly decreased by CR regimen while oligodendrogenesis (Olig2+) and Sirt1 + cell expression were significantly increased in the corpus callosum of CPZ + CR mice compared to the CPZ group. In conclusion, CR regimen can promote remyelination potential in a CPZ-demyelinating mouse model of MS by increasing oligodendrocyte generation while decreasing their apoptosis.

Accurate determination of microRNA expression levels is a prerequisite in using these small non-coding RNA molecules as novel biomarkers in disease diagnosis and prognosis. Quantitative PCR is the method of choice for measuring the expression levels of microRNAs. However, a major obstacle that affects the reliability of results is the lack of validated reference controls for data normalization. Various non-coding RNAs have previously been used as reference controls, but their use may lead to variations and lack of comparability of microRNA data among the studies. Despite the growing number of studies investigating microRNA profiles to discriminate between healthy and disease stages, robust reference controls for data normalization have so far not been established. In the present article, we provide an overview of different reference controls used in various diseases, and highlight the urgent need for the identification of suitable reference controls to produce reliable data. Our analysis shows, among others, that RNU6 is not an ideal normalizer in studies using patient material from different diseases. Finally, our article tries to disclose the challenges to find a reference control which is uniformly and stably expressed across all body tissues, fluids, and diseases.

Chronic demyelination in the central nervous system (CNS) is accompanied by an increase in the number of reactive astrocytes and astrogliosis. There are controversial issues regarding astrocytes and their roles in demyelinating diseases in particular for multiple sclerosis (MS). We aimed to evaluate possible roles for pharmacologic astrocyte ablation strategy using La-aminoadipate (L-AAA) on remyelination in a cuprizone model of demyelination. Male C57BL/6 mice were fed with 0.2% cuprizone for 12 weeks followed by 2-week administration of L-AAA through a cannula inserted 1 mm above the corpus callosum. Rotarod test showed a significant decrease in the range of motor coordination deficits after ablation of astrocytes in mice receiving cuprizone. Results of Luxol fast blue (LFB) and transmission electron microscopy (TEM) for evaluation of myelin content within the corpus callosum revealed a noticeable rise in the percentage of myelinated areas and in the number of myelinated fibers after L-AAA administration in the animals. Astrocyte ablation reduced protein expressions for GFAP (an astrocyte marker) and Iba-1 (a microglial marker), but increased expression of Olig2 (an oligodendrocyte marker) assessed by immunofluorescence. Finally, expression of genes related to recruitment of microglia (astrocyte chemokines CXCL10 and CXCL12) and suppression of oligodendrocyte progenitor cell (OPC) differentiation (astrocyte peptides ET-1 and EDNRB) showed a considerable decrease after administration of L-AAA (for all p < 0.05). These results are indicative of improved remyelination after ablation of astrocytes possibly through hampering microgliosis and astrogliosis and a further rise in the number of matured Olig2 + cells.