Triple-component nanocomposite films prepared using a casting method: Its potential in drug delivery

The purpose of this study was to fabricate a triple-component nanocomposite system consisting of chitosan, polyethylene glycol (PEG), and drug for assessing the application of chitosan–PEG nanocomposites in drug delivery and also to assess the effect of different molecular weights of PEG on nanocomposite characteristics. The casting/solvent evaporation method was used to prepare chitosan–PEG nanocomposite films incorporating piroxicam-β-cyclodextrin. In order to characterize the morphology and structure of nanocomposites, X-ray diffraction technique, scanning electron microscopy, thermogravimetric analysis, and Fourier transmission infrared spectroscopy were used. Drug content uniformity test, swelling studies, water content, erosion studies, dissolution studies, and anti-inflammatory activity were also performed. The permeation studies across rat skin were also performed on nanocomposite films using Franz diffusion cell. The release behavior of films was found to be sensitive to pH and ionic strength of release medium. The maximum swelling ratio and water content was found in HCl buffer pH 1.2 as compared to acetate buffer of pH 4.5 and phosphate buffer pH 7.4. The release rate constants obtained from kinetic modeling and flux values of ex vivo permeation studies showed that release of piroxicam-β-cyclodextrin increased with an increase in concentration of PEG. The formulation F10 containing 75% concentration of PEG showed the highest swelling ratio (3.42 ± 0.02) in HCl buffer pH 1.2, water content (47.89 ± 1.53%) in HCl buffer pH 1.2, maximum cumulative drug permeation through rat skin (2405.15 ± 10.97 μg/cm²) in phosphate buffer pH 7.4, and in vitro drug release (35.51 ± 0.26%) in sequential pH change mediums, and showed a significantly (p < 0.0001) higher anti-inflammatory effect (0.4 cm). It can be concluded from the results that film composition had a particular impact on drug release properties. The different molecular weights of PEG have a strong influence on swelling, drug release, and permeation rate. The developed films can act as successful drug delivery approach for localized drug delivery through the skin.     

Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease

Neurodegeneration, a complex disease state, comprises several pathways that contribute to cell death. Conventional approach of targeting only one of these pathways has not been proven to be entirely successful and has demanded a hypothetical change as to how researchers design and develop new drugs. In this study, effects of a series of α, β‐unsaturated carbonyl‐based tetralone derivatives against Alzheimer's disease (AD) were investigated. Moreover, their activity toward amyloid β‐induced cytotoxicity was also studied. Six compounds including 3f , 3o , 3u , 3ae , 3af , and 3ag were discovered to be most protective against Aβ‐induced neuronal cell death in PC12 cells. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO‐B, AChE, and self‐induced Aβ_1–42 aggregation. The compound 3f exhibited best AChE (IC₅₀ = 0.045 ± 0.02 μm ) inhibitory potential in addition to potent inhibition of MAO‐B (IC₅₀ = 0.88 ± 0.12 μm ). Furthermore, compound 3f disassembled the Aβ fibrils produced by self‐induced Aβ aggregation by 78.2 ± 4.8%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.     

Effect of the Source-to-Substrate Distance on Structural,Optoelectronic, and Thermoelectric Properties of Zinc Sulfide Thin Films

Zinc sulfide (ZnS) thin films with variable structural, optical, electrical, and thermoelectric properties were obtained by changing the source-to-substrate (SSD) distance in the physical-vapor-thermal-coating (PVTC) system. The films crystallized into a zinc-blende cubic structure with (111) preferred orientation. The films had a wide 3.54 eV optical band gap. High-quality homogenous thin films were obtained at 60 mm SSD. The sheet resistance and resistivity of the films decreased from 10¹¹ to 10¹⁰ Ω/Sq. and from 10⁶ to 10⁵ Ω-cm, when SSD was increased from 20 mm to 60 mm, respectively. The phase and band gap were also verified by first principles that were in agreement with the experimental results. Thermoelectric characteristics were studied by using the semi-classical Boltzmann transport theory. The high quality, wide band gap, and reduced electrical resistance make ZnS a suitable candidate for the window layer in solar cells.     

Fabrication and Characterization of Au-Decorated MCM-41 Mesoporous Spheres Using Laser-Ablation Technique

This study reports the synthesis of Au-decorated MCM-41 mesoporous nanoparticles using a laser-ablation technique. It was observed that the number of Au attached to MCM-41 nanostructures was dependent on the amount of encapsulated Cationic surfactant (cetyl ammonium bromide (CTAB) volume. The chemical group of the prepared nanoparticles was analyzed by FT-IR spectroscopy, where different absorption peaks corresponding to Au and MCM-41 were observed. The observed band region was ∼1090, 966, 801, 2918, and 1847 cm⁻¹ for different samples, clearly confirming the successful preparation of MCM-41 with CTAB and Au-decorated MCM-41 nanoparticles using environmentally friendly laser-ablation approach. The surface morphology of the prepared nanoparticles were performed using TEM techniques. The TEM analysis of the MCM-41 specimen showed silica spheres with an average size of around 200 nm. Furthermore, Raman spectroscopy was done to evaluate the chemical structure of the prepared nanoparticles. It was seen that the prepared Au NPs decorated the MCM-41 system facilitated strong Raman peaks of CTAB. In addition, eight distinct Raman peaks were observed in the presence of Au NPs. This new functionalized method using the laser-ablation approach for mesoporous nanoparticles will participate effectively in multiple applications, especially the encapsulated molecule sensing and detection.     

Effectiveness of Therapeutic Patient Education Interventions in Obesity and Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis present a critical synthesis of the development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus qualitatively synthesized. Out of these, 47 were included in the quantitative synthesis. There was substantial heterogeneity in the reporting of these outcomes (I² = 88.35%, Q = 317.64), with a significant improvement noted in serum HbA1c levels (standardized mean difference (SMD) = 0.272, 95% CI: 0.118 to 0.525, n = 7360) and body weight (SMD = 0.526, 95% CI: 0.205 to 0.846, n = 1082) in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (p < 0.001). These interventions should be implemented in healthcare and community settings to improve the health outcomes in patients suffering from obesity and DM.     

Increased Perviousness on CT for Acute Ischemic Stroke is Associated with Fibrin/Platelet-Rich Clots

BACKGROUND AND PURPOSE:Clot perviousness in acute ischemic stroke is a potential CT imaging biomarker for mechanical thrombectomy efficacy. We investigated the association among perviousness, clot cellular composition, and first-pass effect.MATERIALS AND METHODS:In 40 mechanical thrombectomy–treated cases of acute ischemic stroke, we calculated perviousness as the difference in clot density on CT angiography and noncontrast CT. We assessed the proportion of fibrin/platelet aggregates, red blood cells, and white blood cells on clot histopathology. We tested for linear correlation between histologic components and perviousness, differences in components between “high” and “low” pervious clots defined by median perviousness, and differences in perviousness/composition between cases that did and did not achieve a first-pass effect.RESULTS:Perviousness significantly positively and negatively correlated with the percentage of fibrin/platelet aggregates (P = .001) and the percentage of red blood cells (P = .001), respectively. Higher pervious clots had significantly greater fibrin/platelet aggregate content (P = .042). Cases that achieved a first-pass effect (n = 14) had lower perviousness, though not significantly (P = .055). The percentage of red blood cells was significantly higher (P = .028) and the percentage of fibrin/platelet aggregates was significantly lower (P = .016) in cases with a first-pass effect. There was no association between clot density on NCCT and clot composition or first-pass effect. Receiver operating characteristic analysis indicated that clot composition was the best predictor of first-pass effect (area under receiver operating characteristic curve: percentage of fibrin/platelet aggregates  = 0.731, percentage of red blood cells  = 0.706, perviousness = 0.668).CONCLUSIONS:Clot perviousness on CT is associated with a higher percentage of fibrin/platelet aggregate content. Histologic data and, to a lesser degree, perviousness may have value in predicting first-pass outcome. Imaging metrics that more strongly reflect clot biology than perviousness may be needed to predict a first-pass effect with high accuracy.

CT is the most common imaging technique used to evaluate patients with acute ischemic stroke (AIS). Together, NCCT and CTA can provide valuable information about the occlusive clot, such as its location, length, and density.^1-3 One parameter derived from these images is clot permeability, or perviousness, which indicates the amount of contrast that diffuses through the clot tissue.^1,4 Several clinical studies have claimed that perviousness may be an important indicator of how easily occlusive clots can be treated by tPA or mechanical thrombectomy (MT).^1,5 However, the underlying biology behind why some clots are more pervious than others remains largely unknown.The advent of MT for the treatment of AIS has enabled the biologic investigation of retrieved clots by histopathology.⁶ Recent studies have shown large-scale heterogeneity in the composition of retrieved clots, in terms of the percentage of fibrin/platelet aggregates (FP), red blood cell (RBC), and white blood cells (WBC).⁷ Differences in clot composition have been associated with stroke etiology and MT treatment outcomes. In several studies, FP-rich clots have been found to be cardioembolic in origin^8-10 and less responsive to revascularization attempts.^6,10,11 Intrinsically, perviousness is likely to be related to the cellular composition of a clot because different biologic components have different densities and thus alter how soluble molecules diffuse through them.^4,5 Experimental studies have shown that thrombi composed of higher fibrin fractions allowed greater contrast agent permeation than those packed with RBC.¹² Nevertheless, this association has not been established in clinical studies.To this end, the goal of this study was to investigate the relationship between clot perviousness calculated at the time of admission CT and its histopathologic composition after retrieval by MT. Furthermore, to explore whether perviousness could be used to indicate MT effectiveness, we also explored the relationships among perviousness, composition, and MT outcome, measured by the first-pass effect (FPE).¹³ Characterization of the occlusive clot based on pretreatment NCCT/CTA could impact the clinical management of patients with AIS.     

Effect of early allograft dysfunction on outcomes following liver transplantation

Early allograft dysfunction (EAD) following liver transplantation (LT) remains a challenge for patients and clinicians. We retrospectively analyzed the effect of pre‐defined EAD on outcomes in a 10‐year cohort of deceased‐donor LT recipients with clearly defined exclusion criteria. EAD was defined by at least one of the following: AST or ALT >2000 IU/L within first‐week post‐LT, total bilirubin ≥10 mg/dL, and/or INR ≥1.6 on post‐operative day 7. Ten patients developed primary graft failure and were analyzed separately. EAD occurred in 86 (36%) recipients in a final cohort of 239 patients. In univariate and multivariate analyses, EAD was significantly associated with mechanical ventilation ≥2 days or death on days 0, 1, PACU/SICU stay >2 days or death on days 0‐2 and renal failure (RF) at time of hospital discharge (all P<.05). EAD was also significantly associated with higher one‐year graft loss in both uni‐ and multivariate Cox hazard analyses (P=.0203 and .0248, respectively). There was no difference in patient mortality between groups in either of the Cox proportional hazard models. In conclusion, we observed significant effects of EAD on short‐term post‐LT outcomes and lower graft survival.