Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk

Efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 Ctenocephalides felis flea strain infesting cats

<p>Abstract</p> <p>Background</p> <p>Two studies were conducted to evaluate and compare the efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 flea strain infesting cats. In both studies the treatment groups were comprised of non-treated controls, 6% w/v selamectin (Revolution^®; Pfizer Animal Health) topical solution and 10% w/v imidacloprid + 1% w/v moxidectin (Advantage <it>Multi</it>^®for Cats, Bayer Animal Health) topical solution. All cats were infested with 100 fleas on Days -2, 7, 14, 21, and 28. The difference in the studies was that in study #1 efficacy evaluations were conducted at 24 and 48 hours post-treatment or post-infestation, and in study #2 evaluations were conducted at 12 and 24 hours.</p> <p>Results</p> <p>In study #1 imidacloprid + moxidectin and the selamectin formulation provided 99.8% and 99.0% efficacy at 24 hours post-treatment. On day 28, the 24 hour efficacy of the selamectin formulation dropped to 87.1%, whereas the imidacloprid + moxidectin formulation provided 98.9% efficacy. At the 48 hour assessments following the 28 day infestations, efficacy of the imidacloprid + moxidectin and selamectin formulations was 96.8% and 98.3% respectively. In study # 2 the efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after treatment was 100% and 69.4%, respectively. On day 28, efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after infestation was 90.2% and 57.3%, respectively. In study #2 both formulations provided high levels of efficacy at the 24 hour post-infestation assessments, with selamectin and imidacloprid + moxidectin providing 95.3% and 97.5% efficacy, following infestations on day 28.</p> <p>Conclusions</p> <p>At the 24 and 48 hour residual efficacy assessments, the imidacloprid + moxidectin and selamectin formulations were similarly highly efficacious. However, the imidacloprid + moxidectin formulation provided a significantly higher rate of flea kill against the KS1 flea strain infesting cats at every 12 hour post-infestation residual efficacy assessment. Both formulations should provide excellent flea control for an entire month on cats.</p

Laparoscopic Video Analysis for Training and Image Guided Surgery

Automatic analysis of Minimally Invasive Surgical video has the potential to drive new solutions for alleviating needs of safe and reproducible training programs, objective and transparent evaluation systems and navigation tools to assist surgeons and improve patient safety. Surgical video is an always available source of information, which can be used without any additional intrusive hardware in the operating room. This paper is focused on surgical video analysis methods and techniques. It describes authors' contributions in two key aspects, the 3D reconstruction of the surgical field and the segmentation and tracking of tools and organs based on laparoscopic video images. Results are given to illustrate the potential of this field of research, like the calculi of the 3D position and orientation of a tool from its 2D image, or the translation of a preoperative resection plan into a hepatectomy surgical procedure using the shading information of the image. Research efforts are required to further develop these technologies in order to harness all the valuable information available in any video-based surgery

Characterization of the SNAG and SLUG Domains of Snail2 in the Repression of E-Cadherin and EMT Induction: Modulation by Serine 4 Phosphorylation

Snail1 and Snail2, two highly related members of the Snail superfamily, are direct transcriptional repressors of E-cadherin and EMT inducers. Previous comparative gene profiling analyses have revealed important differences in the gene expression pattern regulated by Snail1 and Snail2, indicating functional differences between both factors. The molecular mechanism of Snail1-mediated repression has been elucidated to some extent, but very little is presently known on the repression mediated by Snail2. In the present work, we report on the characterization of Snail2 repression of E-cadherin and its regulation by phosphorylation. Both the N-terminal SNAG and the central SLUG domains of Snail2 are required for efficient repression of the E-cadherin promoter. The co-repressor NCoR interacts with Snail2 through the SNAG domain, while CtBP1 is recruited through the SLUG domain. Interestingly, the SNAG domain is absolutely required for EMT induction while the SLUG domain plays a negative modulation of Snail2 mediated EMT. Additionally, we identify here novel in vivo phosphorylation sites at serine 4 and serine 88 of Snail2 and demonstrate the functional implication of serine 4 in the regulation of Snail2-mediated repressor activity of E-cadherin and in Snail2 induction of EMT

Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins.</p> <p>Results</p> <p>We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes.</p> <p>Conclusion</p> <p>Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.</p

Aerosolized BC-819 Inhibits Primary but Not Secondary Lung Cancer Growth

Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed >90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819