Influence of chitosan coating on the oral bioavailability of gold nanoparticles in rats

Gold nanoparticles are one of the most extensively investigated metallic nanoparticles for several applications. It is less toxic than other metallic nanolattices. The exceptional electrical and thermal conductivity of gold make it possible to be administered as non-invasive radiofrequency irradiation therapy that produces sufficient heat to kill tumor cells. Nanoparticles are generally administered intravenously instead of orally due to negligible oral absorption and cellular uptake. This study evaluated the oral bioavailability of gold nanoparticles coated with chitosan (C-AuNPs), a natural mucoadhesive polymer. We employed traditional method of evaluating bioavailability that involve estimation of maximum concentrations and area under the curve of 3?nm chitosan coated gold nanoparticles (C-AuNPs) in the rat plasma following intravenous and oral administrations (0.8?mg and 8?mg/kg body weight respectively). The oral bioavailability of C-AuNPs was found to be 2.46% (approximately 25 folds higher than polyethylene glycol (PEG) coated gold nanoparticles, reported earlier). These findings suggest that chitosan coating could be better than PEG coating for the enhancement of oral bioavailability of nanoparticles.     

Formulation of sustained release bioadhesive minitablets containing solid dispersion of levofloxacin for once daily ocular use

This study aimed to increase ocular residence time of levofloxacin by formulation into zero-order sustained release mucoadhesive minitablets for once daily administration using a hydrophobic–hydrophilic polymeric matrix. Levofloxacin was first formulated into solid dispersion with different ratios of Eudragit^® RS then the resulting solid dispersion was mixed with different concentrations of Carbopol^® and other excipients to be finally compressed into minitablets. A 2⁴ full factorial design was employed to estimate the effects and interactions of two formulation factors, and to establish their relationships with selected responses in the developed minitablets. The studied factors were: drug to Eudragit^® RS ratio, and percent of Carbopol^® in the minitablets. Sixteen ocular minitablets formulations were prepared and evaluated for the cumulative percentages drug release at 6, 12, and 24?h, as well as mucoadhesion time, mucoadhesive strength, and swelling index as response variables. After optimizing the responses, the optimized formulation was found to be stable on sterilization using gamma-irradiation and storage at 40?°C/75% RH for six months. In vivo testing of the optimized formulation showed that the minitablets extended levofloxacin release up to 24?h without causing any ocular irritation. The optimized formulation exhibited superior microbiological activity compared to the commercial product.     

Epidemiology of Metastatic Hepatocellular Carcinoma,A Nationwide Perspective

Background

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver.

Aims

The aim of this study was to describe the prevalence, trends, and predictors of metastatic HCC on a national scale.

Methods

We used two nationwide datasets for our study: the University Health Consortium (UHC) and the Nationwide Inpatient Sample (NIS) databases. We included adults with a primary diagnosis of HCC from 2000 to 2011. We collected information regarding demographics, insurance, HCC risk factors, liver decompensation, and the sites and frequencies of metastases. Multivariable regression analysis was used to examine predictors of metastatic HCC. Trend analysis was performed to examine the change in metastatic HCC prevalence over time.

Results

We included 25,671 and 26,054 HCC patients from UHC and NIS, respectively. Prevalence of metastatic HCC was 18 % with lung being the most frequent site (31 %). Compared with Caucasian, African American ethnicity was an independent predictor of metastasis in both the NIS [OR 1.13 (1.02–1.25)] and UHC [OR 1.4 (1.3–1.6)] databases. Lack of long-term insurance was associated with significantly higher prevalence of metastasis in both the NIS [OR 1.6 (1.4–1.9)] and UHC [OR 1.9 (1.6–2.2)] databases. There has been an increased prevalence of metastatic HCC over the last decade with an annual percentage change of +1.25 and +1.60 % (p = 0.03 and p = 0.08) for the NIS and UHC databases, respectively.

Conclusions

Metastasis is not rare among HCC patients and is rising in prevalence over the last decade. Lungs were the most common metastatic site. Ethnicity and insurance status are independent predictors of metastasis.     

Towards enhanced community genetic literacy among a minority ethnic community: a participatory action research project

BackgroundInfant mortality is a key public health outcome showing substantial socioeconomic and ethnic inequalities in the UK. The UK Pakistani population has an infant mortality rate of over nine per 1000 livebirths, more than twice that for the population as a whole. Increased risk is partly attributable to rare autosomal recessive genetic disorders linked to the practice of customary consanguineous marriage. WHO recommends community-level action to raise genetic literacy combined with enhanced genetics services. However, UK interventions are in their infancy, with varied local initiatives and no national response. A combination of a valued social practice affecting marginalised communities, complicated patterns of risk, and low professional awareness, makes this a complex and contentious issue. Indeed, some previous intervention has generated considerable backlash. This study in Sheffield, a northern English city, aimed to develop a community-level genetic literacy intervention that would be sensitive and responsive to local information needs.MethodsA participatory approach was used, drawing on a user-centred design and engaging local people as coresearchers. Two phases of insight gathering made use of group discussions, interviews, and participatory exercises to describe current understanding, gaps in knowledge, and trusted networks of communication. A series of testing-and-refinement cycles were then undertaken to coproduce a set of communication materials tailored to subgroups, with materials being tested for acceptability, appeal, and comprehension.FindingsSix local people were trained as coresearchers. Over 200 people participated in the insight and testing work. Information needs and preferred communication channels varied widely, confirming population heterogeneity and diverse perspectives to the issue. Despite some resistance, there was strong demand for information and willingness to discuss the topic. Conveying accurate and consistent information was challenging, as was meeting differing demands for detail within generic materials. Key areas of confusion and mistrust were addressed. Narrative, real life audio (for local radio) and video (for social media) were recommended and developed, supported by factual information in leaflet and website form, and contained links to religious resources plus genetics services.InterpretationDevelopment of appropriate community-level genetic literacy interventions can be achieved through participatory action research. Evaluative work is now needed to assess the effect on knowledge and service uptake.FundingGenetics Disorders UK funded the study. SS is a Senior Research Fellow funded by the National Institute for Health Research (NIHR) School for Public Health Research. Preparatory work was funded by NIHR Collaboration for Leadership in Applied Health Research & Care for South Yorkshire.     

Burden of asthma among children in a developing megacity: childhood asthma study,Pakistan

Objectives: Global burden of childhood asthma has increased in the past few decades, particularly in low-income countries. In Pakistan, there is a lack of community-based epidemiological studies estimating the burden of asthma among children. This study determined the prevalence and predictors of asthma among children 3–17 years of age in Karachi, Pakistan. Methods: A two-stage community-based representative cross-sectional survey was conducted in Karachi from March 2012 to April 2013 comprising 1046 children aged 3–17 years. Of 7500 clusters, 80 were randomly selected, and of these, 15 children per cluster were enrolled randomly. A translated and pre-tested version of International Study of Asthma and Allergies in Children questionnaire was administered. Results: The overall prevalence of asthma among study participants was 10.2% (95% CI: 8.4–12.0). Asthma was more likely to occur among boys (adj. OR: 2.5, 95% CI: 1.6–4.0), children in the younger age group (3–7 years) (adj. OR: 2.9, 95% CI: 1.7–4.8), those living in households with ill-ventilated kitchens (adj. OR: 1.8, 95% CI: 1.1–3.1), having family history of asthma (adj. OR: 2.3, 95% CI: 1.3–3.9) and those of the Sindhi ethnicity (adj. OR: 2.2, 95% CI: 1.1–4.4). Conclusion: This study is the first robust evidence regarding asthma among children in Pakistan, reporting a high burden in this group. Family history, male gender, Sindhi ethnicity and ill-ventilated kitchen were identified as important predictors of asthma. Targeted preventive measures and intervention studies are required to better understand and reduce the burden of asthma among children in Pakistan.     

COVID-19 and the heart: An update for clinicians

SARS-CoV-2, the cause of the COVID-19 pandemic has significantly impacted cardiovascular healthcare. Patients with pre-existing cardiovascular disease are at higher risk of morbidity and mortality. The virus may affect the heart directly and indirectly with clinical syndromes of acute myocardial injury, myocarditis, acute coronary syndromes, heart failure, arrhythmias, and venous thromboembolism. Some therapeutics under investigation for COVID-19 may also have adverse cardiac effects. The involvement of the RAAS system in viral entry makes it pertinent to consider the effects of medications that modulate the system. Comprehensive knowledge of peculiar cardiovascular manifestations of COVID-19 and the role of RAAS in the prognosis of COVID-19 disease is needed for optimal patient management.