Explore the vast range of titles available.

Background Atypical antipsychotic agents, such as clozapine, are used to treat schizophrenia and other psychiatric disorders by a mechanism that is believed to involve modulating the immune system. Multiple sclerosis is an immune-mediated neurological disease, and recently, clozapine was shown to reduce disease severity in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). However, the mode of action by which clozapine reduces disease in this model is poorly understood. Methods Because the mode of action by which clozapine reduces neuroinflammation is poorly understood, we used the EAE model to elucidate the in vivo and in vitro effects of clozapine. Results In this study, we report that clozapine treatment reduced the infiltration of peripheral immune cells into the central nervous system (CNS) and that this correlated with reduced expression of the chemokines CCL2 and CCL5 transcripts in the brain and spinal cord. We assessed to what extent immune cell populations were affected by clozapine treatment and we found that clozapine targets the expression of chemokines by macrophages and primary microglia. Furthermore, in addition to decreasing CNS infiltration by reducing chemokine expression, we found that clozapine directly inhibits chemokine-induced migration of immune cells. This direct target on the immune cells was not mediated by a change in receptor expression on the immune cell surface but by decreasing downstream signaling via these receptors leading to a reduced migration. Conclusions Taken together, our study indicates that clozapine protects against EAE by two different mechanisms; first, by reducing the chemoattractant proteins in the CNS; and second, by direct targeting the migration potential of peripheral immune cells.

Glioblastoma has been recognized as a most complex and highly malignant type of primary brain tumor. The rapid progression brain tumor model was developed by direct intracranial administration of ENU at the different focal brain points in the rat brains. The GQD was synthesized by bottom-up technique and functionalized with Trastuzumab and Caspase-8 antibody by Carbodiimide-amidation activation. The in-vitro cytotoxicity MTT assay was performed with all the GQD conjugates in SK-N-SH and N2a cell lines. The acute and chronic toxicity of synthesized GQD was performed in healthy rats and evaluated the hemolytic activity and CRP levels. A synthesized quasi-spherical 2D tiny GQD has a particle size of less than 10 nm and a 12.7% quantum yield. DSL, TEM, AFM, FTIR, and fluorescence spectroscopy characterized the GQD conjugates. In-silico molecular docking was a conformed static interaction between GQD and antibodies. GQD-conjugates showed dose-dependent toxicity in both cell lines and mild acute toxicity in rat blood. The GBM tumor-bearing rats were assessed for the anticancer and neuroprotective activity of the GQD conjugates. Histopathology, immunohistochemistry, metabolic, and inflammatory tumor biomarker estimation showed that the GQD_Caspase-8 conjugate showed better anti-tumor and neuroprotective effects than other conjugates.

Conventional hydroelectric turbines use the potential energy of the water as a primary source of energy. However, the hydrokinetic turbines use the kinetic energy of the flowing water to generate power output. It is also one of the best clean energy generation technologies. Out of many hydrokinetic turbines, the Savonius hydrokinetic turbine is very simple in design and easy to manufacture. The ratio of the gap between the two vanes to the turbine diameter is known as the overlap ratio. The effect of the positive overlap has been extensively investigated for the Savonius turbine. However, for the first time in the present investigation, the effect of the negative overlap ratio on the hydrodynamic performance of the Savonius turbine is investigated. The highest value of negative overlap ratios is obtained for two, three, and four numbers of blades of Savonius hydrokinetic turbines. With the present investigation, the best-suited range of the negative overlap ratio is obtained for each case. The present investigation also concludes that the Savonius turbine with three and four vanes, with a negative overlap ratio, maintains its good performance for a wide variation in the turbine load. Also, the best-obtained design through numerical analysis was cross-verified by experiments.

The reduced therapeutic efficacy of rizatriptan in migraine treatment is primarily due to low oral bioavailability and extensive first pass metabolism. The purpose of this investigation was to optimize the thin mucoadhesive buccal film of rizatriptan and assess the practicability of its development as a potential substitute for conventional migraine treatment. Buccal films (FR1–FR10) were fabricated by a conventional solvent casting method utilizing a combination of polymers (Proloc, hydroxypropyl methylcellulose and Eudragit RS 100). Drug-loaded buccal films (F1–F4) were examined for mechanical, mucoadhesive, swelling and release characteristics. In vivo pharmacokinetics parameters of selected buccal film (F1) in rabbits were compared to oral administration. Films F1–F4 displayed optimal physicomechanical properties including mucoadhesive strength, which can prolong the buccal residence time. A biphasic, complete and higher drug release was seen in films F1 and F4, which followed Weibull model kinetics. The optimized film, F1, exhibited significantly higher (p < 0.005) rizatriptan buccal flux (71.94 ± 8.26 µg/cm2/h) with a short lag time. Film features suggested the drug particles were in an amorphous form, compatible with the polymers used and had an appropriate surface morphology suitable for buccal application. Pharmacokinetic data indicated a significantly higher rizatriptan plasma level (p < 0.005) and Cmax (p < 0.0001) upon buccal film application as compared to oral solution. The observed AUC0–12h (994.86 ± 95.79 ng.h/mL) in buccal treatment was two-fold higher (p < 0.0001) than the control, and the relative bioavailability judged was 245%. This investigation demonstrates the prospective of buccal films as a viable and alternative approach for effective rizatriptan delivery.

PurposeMRI is the current imaging gold standard to diagnose adenomyosis, but access is often limited by high costs and availability. Transvaginal ultrasound provides a cost-effective, accurate and readily available alternative. The objective of our study was to determine the diagnostic accuracy of commonly described sonographic findings in predicting uterine adenomyosis.MethodsThis retrospective study evaluated 649 MRI studies performed to investigate adenomyosis with a preceding transvaginal ultrasound within 12 months between 2013 and 2018. Two blinded reviewers assessed the presence or absence of six sonographic features: bulky uterus, heterogeneous myometrium, streaky myometrium, myometrial cysts, endometrial–myometrial interface ill-definition, and echogenic linear striations. The sensitivity, specificity, positive and negative predictive values of these features were calculated individually and in combination when compared to MRI as the standard of reference.ResultsAdenomyosis was found in 315 (48.5%) cases on MRI. Ultrasound had a high specificity of 91.8% (95% CI 88.4 to 94.6%) but was less sensitive (36.8% (95% CI 31.5 to 42.4%)) for detecting adenomyosis. Comorbid fibroids or focal adenomyosis did not affect diagnostic accuracy. All six variables were significantly more common in patients with adenomyosis compared to those without. Individually, ‘bulky uterus’ and ‘heterogenous myometrium’ each demonstrated a mean sensitivity and specificity > 50%. The best dual combined variables were ‘bulky uterus’ + ‘ill definition of the endometrial–myometrial interface’ (sensitivity 39%, specificity 91%). The best triple combined variables were ‘bulky uterus’, ‘heterogeneous myometrium’ + ‘ill definition of the endometrial-myometrial interface’ (sensitivity 38%, specificity 93%).ConclusionTransvaginal ultrasound is highly specific for diagnosing uterine adenomyosis, providing a cost-effective and readily available alternative to MRI.

The human brain maintains billions of neurons functional across the lifespan of the individual. The glial, supportive cells of the brain are indispensable to neuron elasticity. They undergo various states (active, reactive, macrophage, primed, resting) and carefully impose either quick repair or the cleaning of injured neurons to avoid damage extension. Identifying the failure of these interactions involving the relation of the input of glial cells to the inception and/or progression of chronic neurodegenerative diseases (ND) is crucial in identifying therapeutic options, given the well-built neuro-immune module of these diseases. In the present review, we scrutinize different interactions and important factors including direct cell–cell contact, intervention by the CD200 system, various receptors present on their surfaces, CXC3RI and TREM2, and chemokines and cytokines with special reference to Alzheimer’s disease (AD). The present review of the available literature will elucidate the contribution of microglia and astrocytes to the pathophysiology of AD, thus evidencing glial cells as obligatory transducers of pathology and superlative targets for interference.

Background The intersubject variability which was related to the genetic makeup was the major cause of change in pharmacological and pharmacokinetic behavior of same dosage form in varied human being. 3D printing technology will help therapy evolve and eliminate the limitations of conventional technologies. Nebivolol's (NBL)-limited oral bioavailability is mainly due to its poor aqueous solubility. The research aims to combine advanced 3D printing technology and nanotechnology to design customized therapy and enhance the functionality of NBL using a statistical approach. Results and discussion The results of the phase solubility indicated that NBL was a poorly aqueous soluble drug. Its solubility was increased by employing nanoparticle drug delivery, which is a promising solubility enhancement technique. The 3 2 full factorial design was employed to develop and optimize bionanoparticles (BNPs) by solvent evaporation technique using poly (lactic-co-glycolic acid 50:50) (PLGA 50:50) and poloxamer-407 as a surfactant. The BNPs were characterized by % encapsulation efficiency (% EE), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC), transmission electron microscope (TEM), zeta potential, polydispersity index (PDI), particle size, in vitro drug release, etc. The BNPs loaded of NBL were further incorporated into the multichannel 3D-controlled release tablets made by PVA filaments employing fused deposition modeling (FDM) technology optimized by central composite design (CCD). Multichannel 3D-printed bionanoparticles-loaded tablet (M3DPBT) was optimized using CCD. All designed M3DPBTs were evaluated for post-fabrication parameters. The optimized M3DPBT could release more than 85% NBL within 10 h. Conclusions The newly fabricated M3DPBT was found stable. The amount of PLGA 50:50 and Polaxomer was significant for developing BNPs. % infill and layer height were observed as critical for the designing M3DPBT. The combined novel 3D printing and nanotechnology technology will open a new direction for patient compliance and better therapeutic effects. Graphical abstract Designing and developing of M3DPBT is substantially improve the patient compliance and therapeutic effectiveness of Nebivolol.

Background Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension. Methods In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers. Results Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m 2 ; female > 78 g/m 2 ). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16 ). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06 ). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001 ). Conclusion In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.

The objective of this study was to define the characteristic imaging appearances of the common renal cell carcinoma (RCC) subtypes. The Institutional Review Board approval was obtained for this HIPAA-compliant retrospective study, and informed consent was waived. 520 patients (336 men, 184 women; age range, 22-88 years) underwent preoperative cross-sectional imaging of 544 RCCs from 2008 to 2013. The imaging appearances of the RCCs and clinical information were reviewed. Data analysis was performed using parametric and nonparametric statistics, descriptive statistics, and receiver operating characteristic analysis. The RCC subtypes showed significant differences ( < 0.001) in several imaging parameters such as tumor margins, tumor consistency, tumor homogeneity, the presence of a central stellate scar, T2 signal intensity, and the degree of tumor enhancement. Low T2 signal intensity on magnetic resonance imaging (MRI) allowed differentiation of papillary RCC from clear cell and chromophobe RCCs with 90.9% sensitivity and 93.1% specificity. A tumor-to-cortex ratio ≥1 on the corticomedullary phase had 98% specificity for clear cell RCC. The T2 signal intensity of the tumor on MRI and its degree of enhancement are useful imaging parameters for discriminating between the RCC subtypes while gross morphological findings offer additional value in RCC profiling.

III-VI semiconductor compounds are interesting materials for the fabrication of such devices as ionizing radiation detectors, solid-state electrodes, ion batteries, as well as photosensitive heterostructures and solar cells. The structural complexity of In-Se family has motivated us to examine an unexplored composition (In2Se3) and its properties with antimony doping (Sb). The purpose of the present work is to study the influence of antimony on the novel configuration In2Se3. Ternary semiconductor compounds in the form of single crystals or thin films have attracted considerable interest because of their structural, optical and electrical properties, which allow them to be widely used in many electronic and optoelectronic devices. As the global energy market seeks applications that offer more efficient electronic systems, In2Se2.7Sb0.3 single crystals synthesized by the modified vertical Bridgeman technique pave the way for exciting innovations in solid-state photovoltaic systems and clean energy sectors. We have grown In2Se2.7Sb0.3 single crystal using the Bridgman-Stockbarger technique. The temperature gradient of the system was kept at 60 C/cm with a growth rate of 0.35 cm/h. Hardness testing is of significant importance in interpreting the mechanical behavior of materials and correlates with other physical properties. Hardness to deformation of as-grown crystals depends on the bond strength and structural perfection. The microhardness measurements of as-cleaved and quenched samples were made by using a Vickers projection microscope. In this paper, the results have been discussed and reported in detail.