PEGylated Oleic Acid-Lecithin Liposomes (POLL) for anticancer drug delivery

Cancer is a major health issue, conferring to more than 14.5 million deaths worldwide. Liposomes, self-assembly amphiphilic bilayer molecules, served as excellent alternative vehicles due to their ability to encapsulate both hydrophobic and hydrophilic anticancer drugs. Conventional liposomes, comprised mainly phospholipids are cost-ineffective, unstable, and easily degraded by the external environment. In this study, we introduced PEGylated oleic acid-lecithin liposomes constructed by using C-18 monounsaturated fatty acids (oleic acid) and soy lecithin, in the presence of DOPEPEG2000 in pH7.4, above their glass transition temperature, Tg, by employing the simple thin layer lipid hydration method. FTIR spectrum of oleic acid, soy lecithin, and DOPEPEG2000 was studied. The average particle size without further mechanical interference was 1102.3 nm while the zeta potential value was -18 mV, which is compatible with the zeta potential of the red blood cell. The polydispersity index (PDI) was reduced by 46.2% with the incorporation of the DOPEPEG2000. The morphological study using OPM showed the presence of spherical shape liposomes that exhibit the birefringence effect under the light field and Maltese cross under the dark field. Encapsulation of folinic acid, methotrexate, doxorubicin, or irinotecan resulted in greater than 75% encapsulation efficiency (EE). Half-maximal inhibitory concentration, IC50, was significantly reduced in POLL as compared to free anticancer drugs. Our data demonstrate POLL may be a promising alternative vehicle to deliver various anticancer drugs to targeted tumour sites

Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)?

published_or_final_versio

Baryon Washout, Electroweak Phase Transition, and Perturbation Theory

We analyze the conventional perturbative treatment of sphaleron-induced baryon number washout relevant for electroweak baryogenesis and show that it is not gauge-independent due to the failure of consistently implementing the Nielsen identities order-by-order in perturbation theory. We provide a gauge-independent criterion for baryon number preservation in place of the conventional (gauge-dependent) criterion needed for successful electroweak baryogenesis. We also review the arguments leading to the preservation criterion and analyze several sources of theoretical uncertainties in obtaining a numerical bound. In various beyond the standard model scenarios, a realistic perturbative treatment will likely require knowledge of the complete two-loop finite temperature effective potential and the one-loop sphaleron rate.Comment: 25 pages, 9 figures; v2 minor typos correcte

Health and human rights in eastern Myanmar prior to political transition: a population-based assessment using multistaged household cluster sampling

Background: Myanmar/Burma has received increased development and humanitarian assistance since the election in November 2010. Monitoring the impact of foreign assistance and economic development on health and human rights requires knowledge of pre-election conditions. Methods: From October 2008-January 2009, community-based organizations conducted household surveys using three-stage cluster sampling in Shan, Kayin, Bago, Kayah, Mon and Tanintharyi areas of Myanmar. Data was collected from 5,592 heads of household on household demographics, reproductive health, diarrhea, births, deaths, malaria, and acute malnutrition of children 6–59 months and women aged 15–49 years. A human rights focused survey module evaluated human rights violations (HRVs) experienced by household members during the previous year. Results: Estimated infant and under-five rates were 77 (95% CI 56 to 98) and 139 (95% CI 107 to 171) deaths per 1,000 live births; and the crude mortality rate was 13 (95% CI 11 to 15) deaths per thousand persons. The leading respondent-reported cause of death was malaria, followed by acute respiratory infection and diarrhea, causing 21.2% (95% CI 16.5 to 25.8), 16.6% (95% CI 11.8 to 21.4), and 12.3% (95% CI 8.7 to 15.8), respectively. Over a third of households suffered at least one human rights violation in the preceding year (36.2%; 30.7 to 41.7). Household exposure to forced labor increased risk of death among infants (rate ratio (RR) = 2.2; 95% CI 1.1 to 4.4) and children under five (RR = 2.1; 95% CI 1.3 to 3.6). The proportion of children suffering from moderate to severe acute malnutrition was higher among households that were displaced (prevalence ratio (PR) = 3.3; 95% CI 1.9 to 5.6). Conclusions: Prior to the 2010 election, populations of eastern Myanmar experienced high rates of disease and death and high rates of HRVs. These population-based data provide a baseline that can be used to monitor national and international efforts to improve the health and human rights situation in the region

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Postgraduate education for Chinese medicine practitioners: a Hong Kong perspective

<b>Background</b> Despite Hong Kong government's official commitment to the development of traditional Chinese medicine (TCM) over the last ten years, there appears to have been limited progress in public sector initiated career development and postgraduate training (PGT) for public university trained TCM practitioners. Instead, the private TCM sector is expected to play a major role in nurturing the next generation of TCM practitioners. In the present study we evaluated TCM graduates' perspectives on their career prospects and their views regarding PGT.<p></p> <b>Method</b> Three focus group discussions with 19 local TCM graduates who had worked full time in a clinical setting for fewer than 5 years. <p></p> <b>Results</b> Graduates were generally uncertain about how to develop their career pathways in Hong Kong with few postgraduate development opportunities; because of this some were planning to leave the profession altogether. Despite their expressed needs, they were dissatisfied with the current quality of local PGT and suggested various ways for improvement including supervised practice-based learning, competency-based training, and accreditation of training with trainee involvement in design and evaluation. In addition they identified educational needs beyond TCM, in particular a better understanding of western medicine and team working so that primary care provision might be more integrated in the future. <p></p> <b>Conclusion</b> TCM graduates in Hong Kong feel let down by the lack of public PGT opportunities which is hindering career development. To develop a new generation of TCM practitioners with the capacity to provide quality and comprehensive care, a stronger role for the government, including sufficient public funding, in promoting TCM graduates' careers and training development is suggested. Recent British and Australian experiences in prevocational western medicine training reform may serve as a source of references when relevant program for TCM graduates is planned in the futur

Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance.

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe