In this study, spectrofluorimetric and resonance Rayleigh scattering techniques were applied for the first time for determination of rupatadine through two validated methods. The proposed methods were based on a facile association complex formation between rupatadine and erythrosin B reagent in acidic medium. Spectrofluorimetric determination relied on the quenching effect of rupatadine on the fluorescence intensity of erythrosin B at 556 nm (excitation = 530 nm). Conversely, the resonance Rayleigh scattering (RRS) method relied on enhancement in the resonance Rayleigh scattering spectrum of erythrosin B at 344 nm after the addition of rupatadine. The developed methods produced linear results over ranges 0.15-2.0 μg/ml and 0.1-1.5 μg/ml, with detection limits of 0.030 μg/ml and 0.018 μg/ml for the spectrofluorimetric method and the RRS method, respectively. All reaction conditions for rupatadine-erythrosin B formation were optimized experimentally and both methods were validated according to International Council for Harmonisation guidelines. The developed methods were applied to estimate rupatadine content in its pharmaceutical tablet dosage form with acceptable recoveries. Furthermore, a content uniformity test for the commercial rupatadine tablets was successfully applied by the suggested spectroscopic methods according to United States Pharmacopeia guidelines.
Down syndrome (DS) is a chromosomal disorder that causes intellectual disability. Few studies have been conducted on functional connectivity using resting-state fMRI (functional magnetic resonance imaging) signals or more specifically, on the relevant structure and density of the default mode network (DMN). Although data on this issue have been reported in adult DS individuals (age >45years), the DMN properties in young DS individuals have not been studied. The aim of this study was to describe the density and structure of the DMN network from fMRI signals in young DS (age <36years).

A sample of 22 young people with DS between the ages of 16 and 35 (M=25.5 and SD=5.1) was recruited in various centers for people with intellectual disability (ID). In addition to sociodemographic data, a six-minute fMRI session was recorded with a 3. T Philips Ingenia scanner. A control group of 22 young people, matched by age and gender, was obtained from the Human Connectome Project (to compare the networks properties between groups).

The values of the 48 ROIs that configured the DMN were obtained, and the connectivity graphs for each subject, the average connectivity graph for each group, the clustering and degree values for each ROI, and the average functional connectivity network were estimated.

A higher density of overactivation was identified in DS group in the ventral, sensorimotor, and visual DMN networks, although within a framework of a wide variability of connectivity patterns in comparison with the control group network. These results extend our understanding of the functional connectivity networks pattern and intrasubject variability in DS.
A higher density of overactivation was identified in DS group in the ventral, sensorimotor, and visual DMN networks, although within a framework of a wide variability of connectivity patterns in comparison with the control group network. These results extend our understanding of the functional connectivity networks pattern and intrasubject variability in DS.Osteosarcoma is a cancer of pathological bone remodeling with high mortality and severe comorbidity. New therapies are urgently needed. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, has been suggested to stimulate proliferation and invasion of osteosarcoma cells in vitro, thus representing a potential therapeutic target. In this study, inhibition of the activin receptor signaling pathway was explored as a therapy for osteosarcoma. In a murine intratibial osteosarcoma xenograft model, two types of inhibitors were tested (a) a soluble activin type IIA decoy receptor (ActRIIA-mFc), or (b) a modified variant of follistatin (FSTΔHBS -hFc), either alone or in combination with a bisphosphonate. Both inhibitors reduced primary tumor development by nearly 50% compared to vehicle treatment. When ActRIIA-mFc was combined with bisphosphonate, the effect on tumor size became even more pronounced (78% reduction vs. vehicle). Moreover, FSTΔHBS -hFc increased body weight in the face of tumor progression (14% increase vs. vehicle), and ActRIIA-mFc reduced the number of lung metastases when combined with bisphosphonate. The present study demonstrates a novel approach to treating osteosarcoma and encourages further investigation of inhibition of the activin receptor signaling pathway as an intervention against the disease.
To compare the long-term clinical outcomes after self-expandable bare nitinol stent (BNS) implantation between hemodialysis (HD) and non-HD patients with femoropopliteal (FP) disease.

Although a BNS has been commonly used in patients with FP disease, the long-term efficacy of BNSs in HD patients remains unknown.

In total, 427 HD patients treated with a BNS for FP disease were enrolled, along with 157 non-HD patients as a control group. Over the following 5 years, the incidence of target lesion revascularization (TLR), major amputation and mortality was investigated. We also performed propensity-score matching analysis.

The 5-year TLR rate (45.2 vs. 32.5%, p = .013) and mortality rate (39.3 vs. 14.0%, p = .0002) were significantly higher in the HD group than in the non-HD group. The major amputation rate was comparable between the groups (7.2% in the HD group vs. 2.8% in the non-HD group, p = .16). In the propensity-score-matched cohort, the TLR rate, and mortality rate were remained higher in the HD group than in the non-HD group (48.9 vs. 34.1%, hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.30-3.49, p = .0024, and 47.9 vs. 12.0%, HR 3.38, 95% CI 1.86-6.56, p < .0001, respectively). The adjusted amputation rate was consistently similar between the groups (1.7% in the HD group vs. 2.7% in the non-HD group, HR 0.90, 95% CI 0.26-2.99, p = .86).

The TLR rate and mortality at 5 years post BNS implantation for FP disease were significantly higher in HD patients than in non-HD patients, though the limb salvage rate was similar.
The TLR rate and mortality at 5 years post BNS implantation for FP disease were significantly higher in HD patients than in non-HD patients, though the limb salvage rate was similar.
To present 1 year clinical and echocardiographic outcomes of the randomized DIRECT (Pre-dilatation in Transcatheter Aortic Valve Implantation Trial) trial.

Intermediate-term data from randomized studies investigating the safety and efficacy of direct implantation are lacking.

DIRECT trial randomized 171 consecutive patients with severe aortic stenosis at four tertiary centers to undergo TAVI with the use of self-expanding prostheses with (pre-BAV) or without pre-dilatation (no-BAV). The primary endpoint was device success according to the VARC-2 criteria. https://www.selleckchem.com/products/nazartinib-egf816-nvs-816.html All patients underwent a clinical and echocardiographic follow-up at 1 year. All-cause and cardiac mortality, stroke, heart failure hospitalization, and new pacemaker implantation were recorded.

At 1 year, four deaths were recorded in pre-BAV group (4.7%) and three deaths in no-BAV group (3.5%). There was no difference in Kaplan-Meier plots between the two groups in all-cause mortality at 1 year (log-rank p = .72). Similarly, there was no difference in the incidence of permanent pacemaker implantation between the two groups at 1 year (27/67-40.3% in no-BAV group versus 20/69-29% in pre-BAV group, log-rank p = .24). There was no significant difference between pre-BAV and no BAV group in aortic valve area (1.84 ± 0.39 cm
vs. 1.85 ± 0.44 cm
, p = .90), mean aortic valve gradient (8.36 ± 5.04 vs. 8.00 ± 4.04 mmHg, p = .65) and moderate or severe paravalvular regurgitation (5-6.6 vs. 4-5.7%, respectively) at 1 year. The same applied independently from the performance of post-dilatation at baseline.

Direct, without pre-dilatation, implantation of a self-expanding valve has no impact on one-year clinical and echocardiographic outcomes, independently also from the baseline performance of post-dilatation.
Direct, without pre-dilatation, implantation of a self-expanding valve has no impact on one-year clinical and echocardiographic outcomes, independently also from the baseline performance of post-dilatation.
There is a high prevalence of HIV (5.2% in 2018) among men who have sex with men (MSM) in Ukraine. HIV testing, condom provision and facilitated linkage to HIV treatment have been funded by various bodies through non-governmental organizations (NGOs). We investigated whether contact with these NGOs was associated with improved prevention and treatment outcomes among MSM in Ukraine.

Data were taken from four rounds of integrated bio-behavioural surveys among MSM in Ukraine (2011,N=5950; 2013,N=8101; 2015,N=4550; 2018,N=5971) including HIV testing combined with questionnaire responses. Data were analysed using mixed-effect regression models, which estimated associations between being an NGO client and behavioural, HIV testing and HIV treatment outcomes, adjusted for demographic factors.

Those MSM who were NGO clients were more likely than non-clients to have been HIV tested in the last year [adjusted odds ratio (aOR) = 7.01, 95% confidence interval (CI) 6.45-7.62] or ever (aOR = 11.00, 95% CI 9.77-12.38), to have used a condom for the last anal sex act (aOR = 1.32, 95% CI 1.21-1.43), and to have recently either bought or received condoms (aOR = 21.27, 95% CI 18.01-25.12). HIV-positive MSM were more likely to have contact with NGOs (aOR = 1.61, 95% CI 1.39-1.86). Among the HIV-positive MSM, those who were NGO clients were more likely to be registered at an AIDS centre (aOR = 2.24, 95% CI 1.61-3.11) and to be on antiretroviral treatment (aOR = 2.20, 95% CI 1.51-3.20).

In Ukraine, being in contact with MSM-targeted NGOs is associated with better outcomes for HIV prevention, testing and treatment, suggesting that NGO harm reduction projects for MSM have had a beneficial impact on reducing HIV transmission and morbidity.
In Ukraine, being in contact with MSM-targeted NGOs is associated with better outcomes for HIV prevention, testing and treatment, suggesting that NGO harm reduction projects for MSM have had a beneficial impact on reducing HIV transmission and morbidity.The treatment of cancer has been one of the most significant challenges for the medical field. Further research on the signal transduction pathway of tumor cells is driving the rapid development of antitumor agents targeting tyrosine kinases. However, most of the currently approved tyrosine kinase inhibitors based on the "single target/single drug" design are becoming less and less effective in the treatment of complex, heterogeneous, and multigenic cancers; this also results in resistance to chemotherapy. In contrast, multitargeted tyrosine kinase inhibitors (MT-TKIs) can effectively block multiple pathways of intracellular signal transduction. Therefore, they have therapeutic advantages over single-targeted inhibitors and have become a hotspot in antitumor drug research in recent years. This minireview summarizes recent advances in the discovery of MT-TKIs based on their chemical structures. In particular, we describe the kinase inhibitory and antitumor activity of promising compounds, as well as their structure - activity relationships (SARs).