Ethnobotanical, phytochemical and pharmacological aspects of daphne mucronata (thymeleaceae)

Daphne mucronata is a shrub well known as a medicinal plant in different regions of Asia. Ethnobotanical, phytochemical and pharmacological studies have revealed strong anti-cancer potential of the plant. Literature reports the evaluation of the initial bioactivity profile and extraction of the plant followed by different chromatographic techniques to obtain fractions. As an outcome,  isolation and identification of coumarins, flavonoids, triterpenoids, lignin  cumarinolignans, glucosides, daphnecin, aquillochin, daphnine and umbelliferone from the plant have been reported. Of these compounds, a diterpene, named gnidilatimonoein, has shown promising anticancer potency in in vitro tests on various cancer cell lines. This review article is an effort to summarize literature published in recent years on the bioactivity of Daphne mucronata

Are interventions to increase the uptake of screening for cardiovascular disease risk factors effective? A systematic review and meta-analysis

Abstract Background Cardiovascular disease (CVD) is the leading cause of death globally. However, many individuals are unaware of their CVD risk factors. The objective of this systematic review is to determine the effectiveness of existing intervention strategies to increase uptake of CVD risk factors screening. Methods A systematic search was conducted through Pubmed, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials. Additional articles were located through cross-checking of the references list and bibliography citations of the included studies and previous review papers. We included intervention studies with controlled or baseline comparison groups that were conducted in primary care practices or the community, targeted at adult populations (randomized controlled trials, non-randomized trials with controlled groups and pre- and post-intervention studies). The interventions were targeted either at individuals, communities, health care professionals or the health-care system. The main outcome of interest was the relative risk (RR) of screening uptake rates due to the intervention. Results We included 21 studies in the meta-analysis. The risk of bias for randomization was low to medium in the randomized controlled trials, except for one, and high in the non-randomized trials. Two analyses were performed; optimistic (using the highest effect sizes) and pessimistic (using the lowest effect sizes). Overall, interventions were shown to increase the uptake of screening for CVD risk factors (RR 1.443; 95% CI 1.264 to 1.648 for pessimistic analysis and RR 1.680; 95% CI 1.420 to 1.988 for optimistic analysis). Effective interventions that increased screening participation included: use of physician reminders (RR ranged between 1.392; 95% CI 1.192 to 1.625, and 1.471; 95% CI 1.304 to 1.660), use of dedicated personnel (RR ranged between 1.510; 95% CI 1.014 to 2.247, and 2.536; 95% CI 1.297 to 4.960) and provision of financial incentives for screening (RR 1.462; 95% CI 1.068 to 2.000). Meta-regression analysis showed that the effect of CVD risk factors screening uptake was not associated with study design, types of population nor types of interventions. Conclusions Interventions using physician reminders, using dedicated personnel to deliver screening, and provision of financial incentives were found to be effective in increasing CVD risk factors screening uptake

NOMA Enhanced Backscatter Communication for Green IoT Networks

Backscatter communication has recently emerged as a promising technology to enable the passive sensing-based Internet-of-things (IoT) applications. In a backscatter communication network, uplink transmissions of multiple nodes are usually multiplexed in time- or frequency-domain to avoid collisions, yet it is desirable to improve the uplink capacity further. In this paper, we study a wireless-powered backscatter communication system, where the sensors use a hybrid channel access scheme by combining time division multiplexing access (TDMA) with power-domain non-orthogonal multiple access (PD-NOMA) to enhance the system performance in terms of outage probability and throughput. Our analysis shows that the proposed PD-NOMA increases both the spectrum efficiency and the throughput of the system

Combating Sale of Counterfeit and Falsified Medicines Online: A Losing Battle

No abstract available

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Inhibition of Macrophage Migration Inhibitory Factor Ameliorates Ocular Pseudomonas aeruginosa-Induced Keratitis

Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa-induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications

Heterogeneity of O6-alkylguanine DNA-alkyltransferase expression in human breast tumours

An important determinant of cellular resistance to chemotherapeutic O6-alkylating agents, which comprise methylating and chloroethylating agents, is the ability of cells to repair alkylation damage at the O6-position of guanine in DNA. This is achieved by a specific DNA repair enzyme O6-alkylguanine DNA-alkyltransferase. In this study O6-alkylguanine DNA-alkyltransferase expression was measured in human breast tumours using both biochemical and immunohistochemical techniques. O6-alkylguanine DNA-alkyltransferase activity was then compared with known clinical prognostic indices to assess the potential role of O6-alkylguanine DNA-alkyltransferase in predicting the behaviour of this common malignancy. The application of both biochemical and immunohistochemical techniques was feasible and practical. Most breast tumours expressed high levels of O6-alkylguanine DNA-alkyltransferase. Immunohistochemical analysis showed marked variation in expression not only between individuals but also within individual tumours, and in the same patient, between metastases and between primary tumour and metastatic site. O6-alkylguanine DNA-alkyltransferase activity in tissue extracts significantly correlated not only with immunohistochemical staining intensity determined by subjective quantitation, but also with measures of protein levels using a computerised image analysis system including mean grey (P<0.001), percentage of cells positive for O6-alkylguanine DNA-alkyltransferase (P<0.001), and integrated optical density (P<0.001). O6-alkylguanine DNA-alkyltransferase expression did not correlate with any of the established clinical prognostic indicators for current treatment regimens. However, immunohistochemical offers a rapid and convenient method for assessing potential utility of O6-alkylating agents or O6-alkylguanine DNA-alkyltransferase inactivating agents in future studies of breast cancer treatment

Serology based disease status of Pakistani population infected with Hepatitis B virus

<p>Abstract</p> <p>Background</p> <p>The infection rate of hepatitis B virus is continuously increasing in Pakistan. Therefore, a comprehensive study of epidemiological data is the need of time.</p> <p>Methods</p> <p>A total of 1300 individuals were screened for HBV infection markers including HBsAg, anti-HBsAg, HBeAg and anti-HBcAg. The association of these disease indicators was compared with patients' epidemiological characteristics like age, socio-economic status and residential area to analyze and find out the possible correlation among these variables and the patients disease status.</p> <p>Results</p> <p>52 (4%) individuals were found positive for HBsAg with mean age 23.5 ± 3.7 years. 9.30%, 33.47% and 12% individuals had HBeAg, antibodies for HBsAg, and antibodies for HBcAg respectively. HBsAg seropositivity rate was significantly associated (<it>p </it>= 0.03) with the residing locality indicating high infection in rural areas. Antibodies titer against HBsAg decreased with the increasing age reflecting an inverse correlation.</p> <p>Conclusion</p> <p>Our results indicate high prevalence rate of Hepatitis B virus infection and nationwide vaccination campaigns along with public awareness and educational programs are needed to be practiced urgently.</p

Molecular epidemiology of Hepatitis B virus genotypes in Pakistan

<p>Abstract</p> <p>Background</p> <p>Eight genotypes of Hepatitis B virus designated A-H, have been known but in Pakistan, no such data is available on the prevalent HBV genotypes. Therefore, the subject study was conducted to determine HBV genotypes in the indigenous Pakistani population.</p> <p>Methods</p> <p>A total of 690 individuals were enrolled for HBV screening with EIA and nested PCR. Positive samples were further analyzed to determine HBV genotypes (A-F) by multiplex-PCR using type specific primers.</p> <p>Results</p> <p>110 (15.94%) individuals were positive for HBV, including 64% males and 36% females. Out of these, 66 samples (65.34%) were classified into genotype D, 27 (26.73%) were of genotype B while 5(4.95%) had genotype A. In 3 (2.98%) samples, multiple genotypes were detected (genotype A+B; 2(1.99%) and genotypes B+D; 1(0.99%). Nine (8.18%) samples remained untyable.</p> <p>Conclusion</p> <p>In Asia, genotypes B and C are the most prevalent but our study reveals that genotype D is predominant and HBV infection constitutes a significant health problem in Pakistan.</p