Poly(β-Amino Ester)-Nanoparticle Mediated Transfection of Retinal Pigment Epithelial Cells In Vitro and In Vivo

A variety of genetic diseases in the retina, including retinitis pigmentosa and leber congenital amaurosis, might be excellent targets for gene delivery as treatment. A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Poly(beta-amino ester)s (PBAEs) have shown great potential as gene delivery reagents because they are easily synthesized and they transfect a wide variety of cell types with high efficacy in vitro. We synthesized a combinatorial library of PBAEs and evaluated them for transfection efficacy and toxicity in retinal pigment epithelial (ARPE-19) cells to identify lead polymer structures and transfection formulations. Our optimal polymer (B5-S5-E7 at 60 w/w polymer∶DNA ratio) transfected ARPE-19 cells with 44±5% transfection efficacy, significantly higher than with optimized formulations of leading commercially available reagents Lipofectamine 2000 (26±7%) and X-tremeGENE HP DNA (22±6%); (p<0.001 for both). Ten formulations exceeded 30% transfection efficacy. This high non-viral efficacy was achieved with comparable cytotoxicity (23±6%) to controls; optimized formulations of Lipofectamine 2000 and X-tremeGENE HP DNA showed 15±3% and 32±9% toxicity respectively (p>0.05 for both). Our optimal polymer was also significantly better than a gold standard polymeric transfection reagent, branched 25 kDa polyethyleneimine (PEI), which achieved only 8±1% transfection efficacy with 25±6% cytotoxicity. Subretinal injections using lyophilized GFP-PBAE nanoparticles resulted in 1.1±1×103-fold and 1.5±0.7×103-fold increased GFP expression in the retinal pigment epithelium (RPE)/choroid and neural retina respectively, compared to injection of DNA alone (p = 0.003 for RPE/choroid, p<0.001 for neural retina). The successful transfection of the RPE in vivo suggests that these nanoparticles could be used to study a number of genetic diseases in the laboratory with the potential to treat debilitating eye diseases

Nursing teamwork and time to respond to call lights: an exploratory study

AIM: The aim of this exploratory study was to determine whether the level of nursing teamwork is correlated to call light answering time in acute care hospital patient care units. Background: Teamwork has been shown to improve productivity. In this study, we examine the relationship between unit call light response time as a measure of productivity and the level of teamwork on the unit. METHOD: The Nursing Teamwork Survey was administered to nursing staff on 18 inpatient units in 3 hospitals. In addition to the overall teamwork score, the NTS has 5 subscales. Call light response times were collected from electronic systems which measures the time it takes for nursing staff on a given unit to respond to patient call lights. RESULTS: There was no significant relationship between call light response time and teamwork overall or on the five subscales. Shared mental models, which comprise the conceptual understanding of the roles and responsibilities of each team member, however was moderately correlated with call-light answering times. CONCLUSIONS: It is logical that shared mental models would be associated with call light response time since a common problem in patient units is the "it's not my job syndrome" where nursing staff do not answer call lights for patients assigned to someone else. More research with a larger number of patient units is needed to validate these findings

Impacts of MicroRNA Gene Polymorphisms on the Susceptibility of Environmental Factors Leading to Carcinogenesis in Oral Cancer

BACKGROUND: MicroRNAs (miRNAs) have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC) remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC. METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48) of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94) and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79) in younger patients (age<60). CONCLUSIONS: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese

Marine Incursion: The Freshwater Herring of Lake Tanganyika Are the Product of a Marine Invasion into West Africa

The spectacular marine-like diversity of the endemic fauna of Lake Tanganyika, the oldest of the African Great Lakes, led early researchers to suggest that the lake must have once been connected to the ocean. Recent geophysical reconstructions clearly indicate that Lake Tanganyika formed by rifting in the African subcontinent and was never directly linked to the sea. Although the Lake has a high proportion of specialized endemics, the absence of close relatives outside Tanganyika has complicated phylogeographic reconstructions of the timing of lake colonization and intralacustrine diversification. The freshwater herring of Lake Tanganyika are members of a large group of pellonuline herring found in western and southern Africa, offering one of the best opportunities to trace the evolutionary history of members of Tanganyika's biota. Molecular phylogenetic reconstructions indicate that herring colonized West Africa 25–50MYA, at the end of a major marine incursion in the region. Pellonuline herring subsequently experienced an evolutionary radiation in West Africa, spreading across the continent and reaching East Africa's Lake Tanganyika during its early formation. While Lake Tanganyika has never been directly connected with the sea, the endemic freshwater herring of the lake are the descendents of an ancient marine incursion, a scenario which may also explain the origin of other Tanganyikan endemics

Neuronal hemoglobin affects dopaminergic cells' response to stress

Hemoglobin (Hb) is the major protein in erythrocytes and carries oxygen (O2) throughout the body. Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson's disease (PD). Here we show that Hb confers DA cells' susceptibility to 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O2 binding and is associated with insoluble aggregate formation in the nucleolus. Neurochemical stress induces epigenetic modifications, nucleolar alterations and autophagy inhibition that depend on Hb expression. When adeno-associated viruses carrying \u3b1- and \u3b2-chains of Hb are stereotaxically injected into mouse SN, Hb forms aggregates and causes motor learning impairment. These results position Hb as a potential player in DA cells' homeostasis and dysfunction in PD. Copyright The Author(s) 201

Work satisfaction of professional nurses in South Africa: a comparative analysis of the public and private sectors

<p>Abstract</p> <p>Background</p> <p>Work satisfaction of nurses is important, as there is sufficient empirical evidence to show that it tends to affect individual, organizational and greater health and social outcomes. Although there have been several studies of job satisfaction among nurses in South Africa, these are limited because they relate to studies of individual organizations or regions, use small samples or are dated. This paper presents a national study that compares and contrasts satisfaction levels of nurses in both public and private sectors.</p> <p>Methods</p> <p>This was a cross-sectional survey of professional nurses conducted throughout South Africa using a pretested and self-administered questionnaire. Univariate and bivariate statistical models were used to evaluate levels of satisfaction with various facets of work and to elicit the differences in satisfaction levels between different groups of nurses. A total of 569 professional nurses participated in the study.</p> <p>Results</p> <p>Private-sector nurses were generally satisfied, while public-sector nurses were generally dissatisfied. Public-sector nurses were most dissatisfied with their pay, the workload and the resources available to them. They were satisfied only with the social context of the work. Private-sector nurses were dissatisfied only with their pay and career development opportunities. Professional nurses in the more rural provinces, those intending to change sectors and those more likely not to be in their current positions within the next five years were also more likely to be dissatisfied with all facets of their work.</p> <p>Conclusion</p> <p>This study highlighted the overall dissatisfaction among South African nurses and confirmed the disparity between the levels of job satisfaction between the public and private sectors. Health managers should address those factors that affect job satisfaction, and therefore retention, of nurses in South Africa. Improving the work environment so that it provides a context congruent with the aspirations and values systems of nurses is more likely to increase the satisfaction of nurses and consequently have a positive effect on individual, organizational and health outcomes.</p

Conserved community structure and simultaneous divergence events in the fig wasps associated with Ficus benjamina in Australia and China

Localised patterns of species diversity can be influenced by many factors, including regional species pools, biogeographic features and interspecific interactions. Despite recognition of these issues, we still know surprisingly little about how invertebrate biodiversity is structured across geographic scales. In particular, there have been few studies of how insect communities vary geographically while using the same plant host. We compared the composition (species, genera) and functional structure (guilds) of the chalcid wasp communities associated with the widespread fig tree, Ficus benjamina, towards the northern (Hainan province, China) and southern (Queensland, Australia) edges of its natural range. Sequence data were generated for nuclear and mtDNA markers and used to delimit species, and Bayesian divergence analyses were used to test patterns of community cohesion through evolutionary time. Both communities host at least 14 fig wasp species, but no species are shared across continents. Community composition is similar at the genus level, with six genera shared although some differ in species diversity between China and Australia; a further three genera occur in only China or Australia. Community functional structure remains very similar in terms of numbers of species in each ecological guild despite community composition differing a little (genera) or a lot (species), depending on taxonomic level. Bayesian clustering analyses favour a single community divergence event across continents over multiple events for different ecological guilds. Molecular dating estimates of lineage splits between nearest inter-continental species pairs are broadly consistent with a scenario of synchronous community divergence from a shared "ancestral community". Fig wasp community structure and genus-level composition are largely conserved in a wide geographic comparison between China and Australia. Moreover, dating analyses suggest that the functional community structure has remained stable for long periods during historic range expansions. This suggests that ecological interactions between species may play a persistent role in shaping these communities, in contrast to findings in some comparable temperate systems

Use frequency of traditional Chinese medicine in Taiwan

BACKGROUND: Use of Traditional Chinese medicine (TCM), an important category of complementary and alternative medicine (CAM), has increased substantially in Western countries during the past decade. Use of TCM is also widespread in the Chinese population. However, few informative data have been obtained to date by large-scale investigations of TCM use in the Chinese population. This study was aimed at elucidating the demographics and patterns of TCM use in Taiwan. METHODS: We employed the complete datasets of TCM outpatient reimbursement claims from 1996 to 2001, including the use of Chinese herbal remedies, acupuncture and traumatology manipulative therapy, to analyse use frequencies, the characteristics of TCM users, and the disease categories that were treated by TCM in Taiwan. RESULTS: At the end of 2001, 6,142,829 (28.4%) among the 21,653,555 valid beneficiaries of the National Health Insurance in Taiwan had used TCM during the year. However, 13,536,266 subjects (62.5%) had used TCM at least once during the whole 6-year period from 1996 to 2001, with a total of 156,224,266 visits (mean 11.5 visits per user). The mean number of TCM users per annum was 5,733,602, with a mean increment of 1,671,476 (29.2%) of new users yearly. Among TCM users, female was higher than male (female:male = 1.13:1), and the age distribution displayed a peak at around the 30s, followed by the 20s and 40s. Chinese herbal remedies (85.9%) were the most common TCM modality used by this population, followed by acupuncture (11.0%) and traumatology manipulative therapies (3.1%). Private TCM clinics provided most of the TCM care (82.6%), followed by private TCM hospitals (12.0%). The top ten major disease categories for TCM visits were diseases of the respiratory system, musculoskeletal system and connective tissue; symptoms, signs and ill-defined conditions; injury and poisoning; diseases of the digestive system, genitourinary system, skin and subcutaneous tissue, nervous system and sense organs, circulatory and endocrine system; nutritional and metabolic diseases; and immunological disorders. CONCLUSION: TCM was popular among the Chinese population in Taiwan during the period studied. More than 60% of all subjects had used TCM during the 6-year interval. TCM was widely used by the Chinese population to treat problems and diseases of major human organ systems recognised by western medicine. This study provides information about the use frequencies of TCM and the disease categories treated by TCM, which should be useful for health policy makers and for those considering the integration of TCM and Western medicine