Graphene oxide coated aluminium as an efficient antibacterial surface

Antimicrobial coatings on metallic surfaces are rapidly emerging to combat bacterial pathogens. The excess use of conventional antibiotics increases the number of resistant strains at an alarming rate, which in turn leads to detrimental implications in the healthcare sector. Hence, it is of great importance in developing a new class of material with inherent bactericidal activity and good biocompatibility. In the present study, we have modified the aluminium surfaces by a coating of graphene oxide (GO) due to its excellent physicochemical properties, water dispersity and low cytotoxicity. Coatings were developed through facile and enviornment-friendly transfer method. The antimicrobial properties of GO coated aluminium are investigated against Gram-negative strain E. coli through agar plate counting and ‘Live/Dead’ fluorescence staining. Further, to shed light into the mechanism of antibacterial activity of GO at the molecular level, we have performed X-ray reflectivity (XRR) study considering a phospholipid multilayer as a model system to mimic bacteria cell membrane. Results show a significant bactericidal activity of the GO coatings compared to uncoated aluminium with lower concentration showing slightly better antibacterial property due to higher roughness. The obtained results may pave the way for engineering graphene-based antimicrobial coatings on a material surface using an easy, environment-friendly, cost-effective and straight forward processing route

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site

Silent but Not Static: Accelerated Base-Pair Substitution in Silenced Chromatin of Budding Yeasts

Subtelomeric DNA in budding yeasts, like metazoan heterochromatin, is gene poor, repetitive, transiently silenced, and highly dynamic. The rapid evolution of subtelomeric regions is commonly thought to arise from transposon activity and increased recombination between repetitive elements. However, we found evidence of an additional factor in this diversification. We observed a surprising level of nucleotide divergence in transcriptionally silenced regions in inter-species comparisons of Saccharomyces yeasts. Likewise, intra-species analysis of polymorphisms also revealed increased SNP frequencies in both intergenic and synonymous coding positions of silenced DNA. This analysis suggested that silenced DNA in Saccharomyces cerevisiae and closely related species had increased single base-pair substitution that was likely due to the effects of the silencing machinery on DNA replication or repair

How participatory is parental consent in low literacy rural settings in low income countries? Lessons learned from a community based study of infants in South India

<p>Abstract</p> <p>Background</p> <p>A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed.</p> <p>Aims</p> <p>The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation.</p> <p>Methods</p> <p>In an observational cohort study of tuberculosis in infants in South India, field supervisors who were responsible for obtaining informed consent noted down questions asked during the informed consent discussions for 4,382 infants who were enrolled in the study. These questions were post-coded by topic. Bivariate and multivariate analysis was conducted to examine factors associated with asking at least one question during the informed consent process.</p> <p>Results</p> <p>In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process. We found that the likelihood of parents asking questions during the informed consent process was significantly associated with education level of either parent both parents being present, and location.</p> <p>Conclusions</p> <p>The findings have implications for planning the informed consent process in a largely rural setting with low levels of literacy. Greater effort needs to be directed towards developing simple participatory communication materials for the informed consent process. Furthermore, including both parents in a discussion about a child's participation in a research study may increase the extent to which consent is truly informed. Finally, continuing efforts need to be made to improve the communication skills of research workers with regard to explaining research processes and putting potential research participants at ease.</p

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion

Transgenic Overexpression of LARGE Induces α-Dystroglycan Hyperglycosylation in Skeletal and Cardiac Muscle

BACKGROUND: LARGE is one of seven putative or demonstrated glycosyltransferase enzymes defective in a common group of muscular dystrophies with reduced glycosylation of α-dystroglycan. Overexpression of LARGE induces hyperglycosylation of α-dystroglycan in both wild type and in cells from dystroglycanopathy patients, irrespective of their primary gene defect, restoring functional glycosylation. Viral delivery of LARGE to skeletal muscle in animal models of dystroglycanopathy has identical effects in vivo, suggesting that the restoration of functional glycosylation could have therapeutic applications in these disorders. Pharmacological strategies to upregulate Large expression are also being explored. METHODOLOGY/PRINCIPAL FINDINGS: In order to asses the safety and efficacy of long term LARGE over-expression in vivo, we have generated four mouse lines expressing a human LARGE transgene. On observation, LARGE transgenic mice were indistinguishable from the wild type littermates. Tissue analysis from young mice of all four lines showed a variable pattern of transgene expression: highest in skeletal and cardiac muscles, and lower in brain, kidney and liver. Transgene expression in striated muscles correlated with α-dystroglycan hyperglycosylation, as determined by immunoreactivity to antibody IIH6 and increased laminin binding on an overlay assay. Other components of the dystroglycan complex and extracellular matrix ligands were normally expressed, and general muscle histology was indistinguishable from wild type controls. Further detailed muscle physiological analysis demonstrated a loss of force in response to eccentric exercise in the older, but not in the younger mice, suggesting this deficit developed over time. However this remained a subclinical feature as no pathology was observed in older mice in any muscles including the diaphragm, which is sensitive to mechanical load-induced damage. CONCLUSIONS/SIGNIFICANCE: This work shows that potential therapies in the dystroglycanopathies based on LARGE upregulation and α-dystroglycan hyperglycosylation in muscle should be safe

Food choices and practices during pregnancy of immigrant women with high-risk pregnancies in Canada: a pilot study

Background: Immigrant women may be regarded as a vulnerable population with respect to access and navigation of maternity care services. They may encounter difficulties when accessing culturally safe and appropriate maternity care, which may be further exacerbated by language difficulties and discriminatory practices or attitudes. The project aimed to understand ethnocultural food and health practices and how these intersect in a particular social context of cultural adaptation and adjustment in order to improve the care-giving capacities of health practitioners working in multicultural perinatal clinics. Methods: This four-phase study employed a case study design allowing for multiple means of data collection and different units of analysis. Phase one consists of a scoping review of the literature. Phases two and three incorporate pictorial representations of food choices with semi-structured photo-elicited interviews. This study was undertaken at a Prenatal and Obstetric Clinic, in an urban Canadian city. In phase four, the research team will inform the development of culturally appropriate visual tools for health promotion. Results: Five themes were identified: (a) Perceptions of Health, (b) Social Support (c) Antenatal Foods (d) Postnatal Foods and (e) Role of Health Education. These themes provide practitioners with an understanding of the cultural differences that affect women’s dietary choices during pregnancy. The project identified building collaborations between practitioners and families of pregnant immigrant women to be of utmost importance in supporting healthy pregnancies, along with facilitating social support for pregnant and breastfeeding mothers. Conclusion: In a multicultural society that contemporary Canada is, it is challenging for health practitioners to understand various ethnocultural dietary norms and practices. Practitioners need to be aware of customary practices of the ethnocultural groups that they work with, while simultaneously recognizing the variation within—not everyone follows customary practices, individuals may pick and choose which customary guidelines they follow. What women choose to eat is also influenced by their own experiences, access to particular foods, socioeconomic status, family context, and so on. The pilot study demonstrated the efficacy of the employed research strategies and we subsequently acquired funding for a national study

No long-term impact of low-energy distal radius fracture on health-related quality of life and global quality of life: a case-control study

<p>Abstract</p> <p>Background</p> <p>Changes in patient-reported outcomes like health related quality of life (HRQOL) and global quality of life (GQOL) in patients with low-energy distal radius fracture might be related to fracture, or be within the normal range of variation in an elderly population. Hence, the present study aims to examine: Whether patients with low-energy distal radius fracture attain their pre-fracture levels in HRQOL and GQOL one year after the fracture and compare these levels with age- and sex-matched controls; and whether objective factors predict changes in HRQOL and GQOL during the same one year period.</p> <p>Methods</p> <p>We examined 160 patients and 169 age- and sex matched controls, respectively (mean ± SD) 67 ± 9 and 66 ± 9 years of age. HRQOL was assessed by the Modified Health Assessment Questionnaire (MHAQ) and the Short–Form 36 (SF-36). The Quality of Life Scale (QOLS) assessed GQOL. Paired sample t-tests and multiple linear regression analyses were applied.</p> <p>Results</p> <p>After one year no differences were found in HRQOL (assessed as arm functions, physical health and mental health) compared to pre-fracture level in the patient group. Both patients with distal radius fracture and controls reported a reduced GQOL after one year (p < 0.001). Low-energy distal radius fracture did not predict worsened HRQOL or GQOL one year after inclusion, and few predictors of changes were identified. Worsened arm function was predicted by low BMI (B = -0.20, p = 0.019) at baseline, worsened physical health was predicted by low education (B = 1.37, p = 0.017) at baseline, and living with someone predicted worsened mental health (B = 2.85, p = 0.009)</p> <p>Conclusion</p> <p>Patients with a distal radius fracture seem to manage well despite the fracture, and distal radius fracture is not an independent predictor of worsened HRQOL and GQOL.</p

Immigrant women’s experiences of maternity-care services in Canada: a systematic review using a narrative synthesis

Background: Canada’s diverse society and its statutory commitment to multiculturalism means that a synthesis of knowledge related to the healthcare experiences of immigrants is essential to realise the health potential for future Canadians. Although concerns about the maternity experiences of immigrants in Canada are relatively new, recent national guidelines explicitly call for the tailoring of services to user needs. We therefore assessed the experiences of immigrant women accessing maternity-care services in Canada. In particular, we investigated the experiences of immigrant women in Canada in accessing and navigating maternity and related healthcare services from conception to 6 months postpartum in Canada. Our focus was on (a) the accessibility and acceptability of maternity-care services for immigrant women and (b) the effects of the perceptions and experiences of these women on their birth and postnatal outcomes. Methods: We conducted a systematic review using a systematic search and narrative synthesis of peer-reviewed and non-peer-reviewed reports of empirical research, with the aim of providing stakeholders with perspectives on maternity-care services as experienced by immigrant women. We partnered with key stakeholders (‘integrated knowledge users’) to ensure the relevancy of topics and to tailor recommendations for effective translation into future policy, practice and programming. Two search phases and a three-stage selection process for published and grey literature were conducted prior to appraisal of literature quality and narrative synthesis of the findings. Results: Our knowledge synthesis of maternity care among immigrants to Canada provided a coherent evidence base for (a) eliciting a better understanding of the factors that generate disparities in accessibility, acceptability and outcomes during maternity care; and (b) improving culturally based competency in maternity care. Our synthesis also identified pertinent issues in multiple sectors that should be addressed to configure maternity services and programs appropriately. Conclusions: Although immigrant women in Canada are generally given the opportunity to obtain necessary services, they face many barriers in accessing and utilising these services. These barriers include lack of information about or awareness of the services, insufficient supports to access these services and discordant expectations between the women and their service providers. Systematic review registration: PROSPERO registration number: CRD42012002185