178 research outputs found
Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy
Craniectomy for Malignant Cerebral Infarction: Prevalence and Outcomes in US Hospitals
Randomized trials have demonstrated the efficacy of craniectomy for the treatment of malignant cerebral edema following ischemic stroke. We sought to determine the prevalence and outcomes related to this by using a national database.Patient discharges with ischemic stroke as the primary diagnosis undergoing craniectomy were queried from the US Nationwide Inpatient Sample from 1999 to 2008. A subpopulation of patients was identified that underwent thrombolysis. Two primary end points were examined: in-hospital mortality and discharge to home/routine care. To facilitate interpretations, adjusted prevalence was calculated from the overall prevalence and two age-specific logistic regression models. The predictive margin was then generated using a multivariate logistic regression model to estimate the probability of in-hospital mortality after adjustment for admission type, admission source, length of stay, total hospital charges, chronic comorbidities, and medical complications.After excluding 71,996 patients with the diagnosis of intracranial hemorrhage and posterior intracranial circulation occlusion, we identified 4,248,955 adult hospitalizations with ischemic stroke as a primary diagnosis. The estimated rates of hospitalizations in craniectomy per 10,000 hospitalizations with ischemic stroke increased from 3.9 in 1999-2000 to 14.46 in 2007-2008 (p for linear trend<0.001). Patients 60+ years of age had in-hospital mortality of 44% while the 18-59 year old group was found to be 24% (p = 0.14). Outcomes were comparable if recombinant tissue plasminogen activator had been administered.Craniectomy is being increasingly performed for malignant cerebral edema following large territory cerebral ischemia. We suspect that the increase in the annual incidence of DC for malignant cerebral edema is directly related to the expanding collection of evidence in randomized trials that the operation is efficacious when performed in the correct patient population. In hospital mortality is high for all patients undergoing this procedure
The reach and impact of social marketing and reproductive health communication campaigns in Zambia
Background: Like many sub-Saharan African countries, Zambia is dealing with major health issues, including HIV/AIDS, family planning, and reproductive health. To address reproductive health problems and the HIV/AIDS epidemic in Zambia, several social marketing and health communication programs focusing on reproductive and HIV/AIDS prevention programs are being implemented. This paper describes the reach of these programs and assesses their impact on condom use. Methods: This paper assesses the reach of selected radio and television programs about family planning and HIV/AIDS and of communications about the socially marketed Maximum condoms in Zambia, as well as their impact on condom use, using data from the 2001-2002 Zambia Demographic and Health Survey. To control for self-selection and endogeneity, we use a two-stage regression model to estimate the effect of program exposure on the behavioural outcomes. Results: Those who were exposed to radio and television programs about family planning and HIV/AIDS were more likely to have ever used a condom (OR = 1.16 for men and 1.06 for women). Men highly exposed to Maximum condoms social marketing communication were more likely than those with low exposure to the program to have ever used a condom (OR = 1.48), and to have used a condom at their last sexual intercourse (OR = 1.23). Conclusion: Findings suggest that the reproductive health and social marketing campaigns in Zambia reached a large portion of the population and had a significant impact on condom use. The results suggest that future reproductive health communication campaigns that invest in radio programming may be more effective than those investing in television programming, and that future campaigns should seek to increase their impact among women, perhaps by focusing on the specific constrains that prevent females from using condoms
PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer
Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell’s responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention
In Vivo CD8+ T-Cell Suppression of SIV Viremia Is Not Mediated by CTL Clearance of Productively Infected Cells
The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV
One size does not fit all: local determinants of measles vaccination in four districts of Pakistan
Common factors are associated with vaccination. However, despite common factors the pattern of variables related to measles vaccination differs between and within districts. In this study children were more likely to receive measles vaccination if their mother had any formal education, if she knew at least one vaccine preventable disease, and if she had not heard of any bad effects of vaccination. In rural areas, living within 5 km of a vaccination facility or in a community visited by a vaccination team were factors associated with vaccination, as was the mother receiving information about vaccinations
Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs
MicroRNAs (miRNAs) are 19–22-nucleotide noncoding RNAs that post-transcriptionally regulate mRNA targets. We have identified endogenous miRNA binding sites in mouse embryonic stem cells (mESCs), by performing photo-cross-linking immunoprecipitation using antibodies to Argonaute (Ago2) followed by deep sequencing of RNAs (CLIP-seq). We also performed CLIP-seq in Dicer[superscript −/−] mESCs that lack mature miRNAs, allowing us to define whether the association of Ago2 with the identified sites was miRNA dependent. A significantly enriched motif, GCACUU, was identified only in wild-type mESCs in 3′ untranslated and coding regions. This motif matches the seed of a miRNA family that constitutes ~68% of the mESC miRNA population. Unexpectedly, a G-rich motif was enriched in sequences cross-linked to Ago2 in both the presence and absence of miRNAs. Expression analysis and reporter assays confirmed that the seed-related motif confers miRNA-directed regulation on host mRNAs and that the G-rich motif can modulate this regulation.Leukemia & Lymphoma Society of AmericaUnited States. Public Health Service (Grant R01-GM34277)United States. Public Health Service (Grant R01-CA133404)National Cancer Institute (U.S.) (Grant P01-CA42063)National Cancer Institute (U.S.) Cancer Center Support (Grant P30-CA14051
Three-dimensional spectral domain optical coherence tomography and light microscopy of an intravitreal parasite
BACKGROUND: Various imaging modalities play a role in diagnosing parasitic infections of the eye. We describe the spectral domain optical coherence tomography (SD-OCT) findings of an intravitreal parasite with subsequent evaluation by light microscopy. FINDINGS: This is a case report of a 37-year-old Ecuadorian man who presented with uveitic glaucoma and a new floater in his left eye for 1 week’s duration. Full ophthalmic examination revealed an intravitreal parasite. Color fundus photography, fluorescein angiography (FA), ocular ultrasonography (US), and SD-OCT were performed. The parasite was removed via 23-gauge pars plana vitrectomy and sent to pathology for evaluation. Color fundus photography and ocular ultrasonography demonstrated an elongated foreign body within the vitreous above the retina. FA demonstrated minimal vascular changes in the vicinity of the parasite. SD-OCT was utilized to visualize the parasite and to create a three-dimensional (3D) image. The parasite was determined to be most consistent with Gnathostoma spp. by morphologic analysis. CONCLUSIONS: This is the first reported case of SD-OCT of an intravitreal parasite with corresponding evaluation by pathology. SD-OCT allows non-invasive, high-resolution visualization and 3D reconstruction of parasitic anatomy which may help establish tomographic criteria for species identification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12348-015-0064-x) contains supplementary material, which is available to authorized users
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