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Find video protocols related to scientific articles indexed in Pubmed.
Polymeric Microbubbles as Delivery Vehicles for Sensitisers in Sonodynamic Therapy.
Langmuir
PUBLISHED: 11-20-2014
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Microbubbles (MBs) have recently emerged as promising delivery vehicles for sensitiser drugs in sonodynamic therapy (SDT). The ability to selectively destroy the MB and activate the sensitizer using an external ultrasound trigger could provide a minimally invasive and highly targeted therapy. While lipid MBs have been approved for use as contrast agents in diagnostic ultrasound, the attachment of sensitiser drugs to their surface results in a significant reduction in particle stability. In this manuscript, we prepare both lipid and polymer (PLGA) MBs with rose bengal attached to their surface and demonstrate that PLGA MB conjugates are significantly more stable than their lipid counterparts. In addition, the improved stability offered by the PLGA shell does not hinder their selective destruction using therapeutically acceptable ultrasound intensities. Furthermore, we demonstrate that treatment of ectopic human tumours (BxPC-3) in mice with the PLGA MB-rose bengal conjugate and ultrasound reduced tumour volume by 34% 4 days after treatment while tumours treated with the conjugate alone increased in volume by 48% over the same time period. Therefore, PLGA MBs may offer a more stable alternative to lipid MBs for the site specific delivery of sensitisers in SDT.
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Specific Gene Repression by CRISPRi System Transferred through Bacterial Conjugation.
ACS Synth Biol
PUBLISHED: 11-20-2014
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In microbial communities, bacterial populations are commonly controlled using indiscriminate, broad range antibiotics. There are few ways to target specific strains effectively without disrupting the entire microbiome and local environment. Here we use conjugation, a natural DNA horizontal transfer process among bacterial species, to deliver an engineered CRISPR interference (CRISPRi) system for targeting specific genes in recipient Escherichia coli cells. We show that delivery of the CRISPRi system is successful and can specifically repress a reporter gene in recipient cells, thereby establishing a new tool for gene regulation across bacterial cells and potentially for bacterial population control.
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Effects of TiO2 and Ag Nanoparticles on Polyhydroxybutyrate Biosynthesis By Activated Sludge Bacteria.
Environ. Sci. Technol.
PUBLISHED: 11-20-2014
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Manufactured nanomaterials (MNMs) are increasingly incorporated into consumer products that are disposed into sewage. In wastewater treatment, MNMs adsorb to activated sludge biomass where they may impact biological wastewater treatment performance, including nutrient removal. Here, we studied MNM effects on bacterial polyhydroxyalkanoate (PHA), specifically polyhydroxybutyrate (PHB), biosynthesis because of its importance to enhanced biological phosphorus (P) removal (EBPR). Activated sludge was sampled from an anoxic selector of a municipal wastewater treatment plant (WWTP), and PHB-containing bacteria were concentrated by density gradient centrifugation. After starvation to decrease intracellular PHB stores, bacteria were nutritionally augmented to promote PHB biosynthesis while being exposed to either MNMs (TiO2 or Ag) or to Ag salts (each at a concentration of 5 mg L-1). Cellular PHB concentration and PhyloChip community composition were analyzed. The final bacterial community composition differed from activated sludge, demonstrating that laboratory enrichment was selective. Still, PHB was synthesized to near-activated sludge levels. Ag salts altered final bacterial communities, although MNMs did not. PHB biosynthesis was diminished with Ag (salt or MNMs), indicating the potential for Ag-MNMs to physiologically impact EBPR through the effects of dissolved Ag ions on PHB producers.
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End Stage Renal Disease Among HIV-Infected Adults in North America.
Clin. Infect. Dis.
PUBLISHED: 11-20-2014
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?HIV-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.
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Case 36-2014.
N. Engl. J. Med.
PUBLISHED: 11-20-2014
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An 18-year-old woman was admitted to the hospital because of fever, pharyngitis, facial swelling, and diplopia. Imaging studies showed an abscess in the right parotid gland. Despite antibacterial therapy, her condition worsened. Diagnostic procedures were performed.
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Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B.
N. Engl. J. Med.
PUBLISHED: 11-20-2014
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Background In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity. Methods We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×10(12) vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. Results A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. Conclusions In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238 .).
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Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012.
Commun Dis Intell Q Rep
PUBLISHED: 11-20-2014
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In 2012, the Australian Group on Antimicrobial Resistance (AGAR) conducted a community-onset period-prevalence survey of clinical Staphylococcus aureus isolated from hospital outpatients and general practice patients including nursing homes, long term care facilities and hospice patients. Day surgery and dialysis patients were excluded. Twenty-nine medical microbiology laboratories from all state and mainland territories participated. Isolates were tested by Vitek2® (AST-P612 card). Results were compared with previous AGAR community surveys. Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) increased significantly from 11.5% in 2000 to 17.9% in 2012 (P<0.0001). Resistance to the non-ß-lactam antimicrobials varied between regions. No resistance was detected to vancomycin, teicoplanin or linezolid. Resistance in methicillin susceptible S. aureus was rare apart from erythromycin (12.8%) and was absent for vancomycin, teicoplanin, linezolid and daptomycin. The proportion of S. aureus characterised as health care-associated MRSA (HA-MRSA) was 5.1%. Three HA-MRSA clones were characterised, with 72.9% and 26.4% of HA-MRSA classified as ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA) respectively. Multi-clonal community-associated MRSA (CA-MRSA) accounted for 12.5% of all S. aureus. Regional variation in resistance in MRSA was primarily due to the differential distribution of the 2 major HA-MRSA clones; ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials, and ST22-IV [2B] (EMRSA-15), which is resistant to ciprofloxacin and typically erythromycin. Although the majority of CA-MRSA were non-multi-resistant, a significant expansion of Panton-Valentine leukocidin (PVL) positive CA-MRSA clones has occurred nationally. The mean age of patients (31.7 years, 95% CI 28.9-34.5) with a PVL positive CA-MRSA infection was significantly lower (P<0.0001), than the mean age of patients with a PVL negative CA-MRSA infection (55.7 years, 95% CI 50.7-60.6). This shift in the molecular epidemiology of MRSA clones in the Australian community will potentially increase the number of young Australians with skin and soft tissue infections requiring hospitalisation. Commun Dis Intell 2014;38(1):E59-E69.
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Community-onset Gram-negative Surveillance Program annual report, 2012.
Commun Dis Intell Q Rep
PUBLISHED: 11-20-2014
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The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2012 survey focussed on community-onset infections, examining isolates from urinary tract infections from patients presenting to outpatient clinics, emergency departments or to community practitioners. In 2012, 2,025 Escherichia coli, 538 Klebsiella species and 239 Enterobacter species were tested using a commercial automated method (Vitek 2, BioMérieux) and results were analysed using Clinical and Laboratory Standards Institute breakpoints from January 2012. Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 4.2% of E. coli and 4.6%-6.9% of Klebsiella spp. Non-susceptibility rates to ciprofloxacin were 6.9% for E. coli, 0.0%-3.5% for Klebsiella spp. and 0.8%-1.9% in Enterobacter spp, and resistance rates to piperacillin-tazobactam were 1.7%, 0.7%-9.2%, and 8.8%-11.4% for the same 3 groups respectively. Only 1 Enterobacter cloacae was shown to harbour a carbapenemase (IMP-4). Commun Dis Intell 2014;38(1):E54-E58.
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Hospital-onset Gram-negative Surveillance Program annual report, 2011.
Commun Dis Intell Q Rep
PUBLISHED: 11-20-2014
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The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2011 survey focussed on hospital-onset infections, examining isolates from all specimens presumed to be causing disease. In 2011, 1,827 Escherichia coli, 537 Klebsiella species and 269 Enterobacter species were tested using a commercial automated method (Vitek 2, BioMérieux) and results were analysed using Clinical and Laboratory Standards Institute breakpoints from January 2012. Of the key resistances, non-susceptibilty to the third-generation cephalosporin, ceftriaxone, was found in 9.6% of E. coli and 9.5%-12.1% of Klebsiella spp. Non-susceptibility rates to ciprofloxacin were 10.6% for E. coli, 0.0%-8.3% for Klebsiella spp. and 0.0%-5.0% in Enterobacter spp. Resistance rates to gentamicin were 8.6%, 2.9%-10.9%, and 0.0%-15.6% for the same 3 groups respectively. Eight strains, 5 Klebsiella spp. and 3 Enterobacter spp. were shown to harbour a carbapenemase (IMP-4). Commun Dis Intell 2014;38 (1):E49-E53.
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Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia.
Blood
PUBLISHED: 11-15-2014
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Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of childhood associated with a poor prognosis. Recently, massively parallel sequencing has identified recurrent mutations in the SKI domain of SETBP1 in a variety of myeloid disorders. These lesions were detected in nearly 10% of patients with JMML and have been characterized as secondary events. We hypothesized that rare subclones with SETBP1 mutations are present at diagnosis in a large portion of patients who relapse, but are below the limits of detection for conventional deep sequencing platforms. Using droplet digital polymerase chain reaction (ddPCR) we identified SETBP1 mutations in 17/56 (30%) of patients who were treated on Children's Oncology Group sponsored clinical trial, AAML0122. Five-year event free survival (EFS) in patients with SETBP1 mutations was 18% ± 9% compared to 51% ± 8% for those without mutations (p=0.006).
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The impact of transfer patients on the local Cascade of HIV Care continuum.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 11-14-2014
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The Cascade of Care (COC) visualizes stages of HIV-care progression within a population. It is predicated on a local population model and thus may not address the impact on the COC of HIV-experienced individuals diagnosed and cared for elsewhere who move into the area.
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Australian enterococcal sepsis outcome progamme, 2011.
Commun Dis Intell Q Rep
PUBLISHED: 11-14-2014
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From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ? 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
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Carbon quantum dot-NO photoreleaser nanohybrids for two-photon phototherapy of hypoxic tumors.
Chem. Commun. (Camb.)
PUBLISHED: 11-13-2014
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We report a conjugate between carbon quantum dots and a NO photoreleaser able to photogenerate the anticancer NO radical via an energy transfer mechanism. This nanohybrid proved toxic to cancer cells in vitro and significantly reduced tumor volume in mice bearing human xenograft BxPC-3 pancreatic tumors upon two-photon excitation with the highly biocompatible 800 nm light.
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Prolonged growth of a clinical Staphylococcus aureus strain selects for a stable Small Colony Variant cell-type.
Infect. Immun.
PUBLISHED: 11-12-2014
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An undetermined feature of Staphylococcus aureus pathogenesis is its persistence then relapse of disease. This has been explained by its switch to alternative lifestyles; mainly as biofilm or Small Colony Variants (SCVs). Studying the native characteristics of SCVs has been problematic due to their reversion to the parental lifestyle. We have observed that for a number of S. aureus strains as they switch to a SCV lifestyle there is the formation of an extracellular matrix. We focused our analysis on one strain, WCH-SK2. For bacterial survival in the host, the combination of low nutrients and the prolonged timeframe forms a stress that selects for a specific cell-type from the population. In this context, we used steady-state growth conditions with low nutrients and a controlled low growth rate, for a prolonged time and with methylglyoxal. These conditions induced S. aureus WCH-SK2 into a stable SCV cell-type, they did not revert after sub-culturing. Analysis revealed these cells possessed a metabolic and surface profile that was different from previously described SCVs or biofilm cells. The extracellular matrix was protein and extracellular DNA; but not polysaccharide. The SCV cells induced expression of certain surface proteins (such as Ebh) and lantibiotic synthesis while down-regulating factors that stimulates immune response (leucocidin, capsule, carotenoid). Our data reveal a cell heterogeneity within a S. aureus population and using conditions that resemble long-term survival in the host has identified a previously unnoticed S. aureus cell-type, with a distinctive metabolic and molecular profile.
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Simian Hemorrhagic Fever Virus Cell Entry is Dependent on CD163 and Uses a Clathrin-mediated Endocytosis-like Pathway.
J. Virol.
PUBLISHED: 10-31-2014
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Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques, but is thought to be nonpathogenic for humans. To date, the SHFV lifecycle is almost completely uncharacterized on the molecular level. Here we describe the first steps of the SHFV lifecycle. Our experiments indicate that SHFV enters target cells by low pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-?-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin, and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knock-out study and electron-microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, ?-chymotrypsin, trypsin) abrogated entry, indicating that the SHFV cell-surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component.
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Tenosynovitis Caused by a Novel Nontuberculous Mycobacterium Species Initially Misidentified as a Member of the Mycobacterium tuberculosis Complex.
J. Clin. Microbiol.
PUBLISHED: 09-24-2014
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We present a case of tenosynovitis caused by a novel, slowly growing, nonchromogenic, nontuberculous mycobacterium (NTM). Originally misidentified as Mycobacterium tuberculosis complex, the NTM cross-reacts with the M. tuberculosis complex nucleic acid hybridization probe, a M. tuberculosis gamma interferon release assay, and is closely related to M. tuberculosis by 16S rRNA gene sequencing.
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Recording the sexual orientation of male patients attending general practice.
Fam Pract
PUBLISHED: 09-20-2014
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Determination of a patient's sexual orientation is important to guide appropriate health care. We assessed how frequently sexual orientation is included in the health records of men attending general practice and factors associated with its recording.
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Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies.
PLoS Med.
PUBLISHED: 09-01-2014
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High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
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The induction of Staphylococcus aureus biofilm formation or Small Colony Variants is a strain-specific response to host-generated chemical stresses.
Microbes Infect.
PUBLISHED: 08-04-2014
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Staphylococcus aureus is extremely versatile. It has a capacity to persist within its host by switching to the alternative lifestyles of biofilm or Small Colony Variants (SCV). The induction of this switch has been presumed to be in response to stressed conditions, however the environmental basis has not been thoroughly investigated. We assessed the response of numerous strains to chemicals that are present in human host. There were some that induced a biofilm or SCV phenotype and indeed some inducing both lifestyles. This result illustrates the diversity within a population and a strain-specific adaptation to the presence of host-generated stresses.
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Willingness to use HIV pre-exposure prophylaxis has declined among australian gay and bisexual men: results from repeated national surveys, 2011-2013.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-01-2014
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We surveyed willingness to use pre-exposure prophylaxis (PrEP) and the likelihood of decreased condom use among Australian gay and bisexual men in 2011 and 2013 (n = 2384). Willingness to use PrEP declined from 28.2% to 23.3% [adjusted odds ratio = 0.83, 95% confidence interval (CI): 0.68 to 1.00, P = 0.050]. Willingness to use PrEP was the greatest among men with HIV-positive partners and among those who had taken HIV postexposure prophylaxis. Among men willing to use PrEP, the likelihood of decreased condom use remained stable between 2011 and 2013 (8.0% vs. 11.9%; adjusted odds ratio = 1.40, 95% CI: 0.80 to 2.45, P = 0.23). A minority of men remain willing to use PrEP and appear to be appropriate candidates for it.
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Incidence and risk factors of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma in HIV-infected individuals.
Oral Oncol.
PUBLISHED: 07-29-2014
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To examine the risk and trends of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma (HNSCC) in HIV-infected individuals and assess whether immunosuppression (measured through CD4 cell count) and other risk factors impact HNSCC risk.
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Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates.
J. Clin. Microbiol.
PUBLISHED: 07-16-2014
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An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.
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The practice of clinical pathology: a quantitative description of laboratory director activities at a large academic medical center.
Am. J. Clin. Pathol.
PUBLISHED: 07-13-2014
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The scope of activities performed by clinical laboratory directors is sometimes unfamiliar to other physicians or hospital administrators. Consequently, hospital leadership may undervalue the role and assume that many director level activities could be delegated to a professional manager. In this study, we sought to define the activities of academic laboratory directors, and to determine which activities require doctorate level medical or scientific expertise.
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Intracellular guest exchange between dynamic supramolecular hosts.
J. Am. Chem. Soc.
PUBLISHED: 05-20-2014
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Decyl and oligo(ethylene glycol) chains were appended to the same poly(methacrylate) backbone to generate an amphiphilic polymer with a ratio between hydrophobic and hydrophilic segments of 2.5. At concentrations greater than 10 ?g mL(-1) in neutral buffer, multiple copies of this particular macromolecule assemble into nanoparticles with a hydrodynamic diameter of 15 nm. In the process of assembling, these nanoparticles can capture anthracene donors and borondipyrromethene acceptors within their hydrophobic interior and permit the transfer of excitation energy with an efficiency of 95%. Energy transfer is observed also if nanocarriers containing exclusively the donors are mixed with nanoparticles preloaded separately with the acceptors in aqueous media. The two sets of supramolecular assemblies exchange their guests with fast kinetics upon mixing to co-localize complementary chromophores within the same nanostructured container and enable energy transfer. After guest exchange, the nanoparticles can cross the membrane of cervical cancer cells and bring the co-entrapped donors and acceptors within the intracellular environment. Alternatively, intracellular energy transfer is also established after sequential cell incubation with nanoparticles containing the donors first and then with nanocarriers preloaded with the acceptors or vice versa. Under these conditions, the nanoparticles exchange their cargo only after internalization and allow energy transfer exclusively within the cell interior. Thus, the dynamic character of such supramolecular containers offers the opportunity to transport independently complementary species inside cells and permit their interaction only within the intracellular space.
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Bringing new HIV infections to zero - opportunities and challenges offered by antiretroviral-based prevention in Asia, the Pacific and beyond: An overview of this special issue.
Sex Health
PUBLISHED: 04-08-2014
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This editorial to the special issue of Sexual Health on antiretroviral-based prevention of HIV infection is dedicated to showcasing research and practice in this area. It aims to promote debate regarding the potential of new antiretroviral-based prevention approaches and the challenges encountered in moving prevention innovations into the community. This special issue covers the breadth of innovative HIV prevention research, including that undertaken in the fields of epidemiology, clinical research, social and behavioural science, public health and policy analysis, and with special emphasis on Asia and the Pacific region. Most importantly, it provides an indication of how the region is progressing towards embracing new prevention approaches to combat HIV epidemics across the region.
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Virological characteristics of occult hepatitis B virus in a North American cohort of human immunodeficiency virus type 1-positive patients on dual active anti-HBV/HIV therapy.
J. Clin. Virol.
PUBLISHED: 03-10-2014
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Occult hepatitis B virus infection (OBI) is defined as low-level HBV DNA presence in serum, liver and/or peripheral blood mononuclear cells (PBMC) in individuals that lack serum hepatitis B virus surface antigen (HBsAg). HIV+ patients with OBI may be at risk for HBV reactivation, and often receive dual active anti-HBV/HIV therapy, such as lamivudine (LMV).
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A new three-component formulation for the efficient whitening of teeth (Carbamide Plus).
Clin Oral Investig
PUBLISHED: 03-03-2014
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This study aimed to develop and characterise a new three-component dental whitening formulation which is as effective as the currently used carbamide peroxide but at significantly lower hydrogen peroxide concentrations.
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Minority stress in lesbian, gay, and bisexual young adults in australia: associations with psychological distress, suicidality, and substance use.
Arch Sex Behav
PUBLISHED: 02-27-2014
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Lesbian, gay, bisexual, and other same-sex attracted young people have been shown to be at a higher risk of mental health problems, including depression, anxiety, suicidality, and substance abuse, compared to their heterosexual peers. Homophobic prejudice and stigma are often thought to underlie these disparities. In this study, the relationship between such experiences of social derogation and mental health and substance use in same-sex attracted young people was examined using Meyer's minority stress theory. An online survey recruited 254 young women and 318 young men who identified as same-sex attracted, were aged 18-25 years, and lived in Sydney, Australia. Multivariate logistic regression analyses showed that internalized homophobia, perceived stigma, and experienced homophobic physical abuse were associated with higher levels of psychological distress and self-reported suicidal thoughts in the previous month. Furthermore, perceived stigma and homophobic physical abuse were associated with reporting a lifetime suicide attempt. The association between minority stress and substance use was inconsistent. While, as expected, higher levels of perceived stigma were associated with club drug dependence, there was an inverse association between internalized homophobia and club drug use, and between perceived stigma and hazardous alcohol use. The findings of this study provide support for the minority stress theory proposition that chronic social stress due to sexual orientation is associated with poorer mental health. The high rates of mental health and substance use problems in the current study suggest that same-sex attracted young people should continue to be a priority population for mental health and substance use intervention and prevention.
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Disparities in the quality of HIV care when using US Department of Health and Human Services indicators.
Clin. Infect. Dis.
PUBLISHED: 01-23-2014
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We estimated US Department of Health and Human Services (DHHS)-approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ?200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention- and treatment-related disparities.
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Molecular epidemiology of enterococcal bacteremia in Australia.
J. Clin. Microbiol.
PUBLISHED: 01-03-2014
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Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
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Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases).
Vet. Dermatol.
PUBLISHED: 01-02-2014
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Superficial bacterial folliculitis (SBF) is usually caused by Staphylococcus pseudintermedius and routinely treated with systemic antimicrobial agents. Infection is a consequence of reduced immunity associated with alterations of the skin barrier and underlying diseases that may be difficult to diagnose and resolve; thus, SBF is frequently recurrent and repeated treatment is necessary. The emergence of multiresistant bacteria, particularly meticillin-resistant S. pseudintermedius (MRSP), has focused attention on the need for optimal management of SBF.
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CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
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Methodological Challenges in Collecting Social and Behavioural Data Regarding the HIV Epidemic among Gay and Other Men Who Have Sex with Men in Australia.
PLoS ONE
PUBLISHED: 01-01-2014
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Behavioural surveillance and research among gay and other men who have sex with men (GMSM) commonly relies on non-random recruitment approaches. Methodological challenges limit their ability to accurately represent the population of adult GMSM. We compared the social and behavioural profiles of GMSM recruited via venue-based, online, and respondent-driven sampling (RDS) and discussed their utility for behavioural surveillance.
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Micronutrient deficiency and treatment adherence in a randomized controlled trial of micronutrient supplementation in ART-naïve persons with HIV.
PLoS ONE
PUBLISHED: 01-01-2014
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The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection.
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Comprehensive testing for, and diagnosis of, sexually transmissible infections among Australian gay and bisexual men: findings from repeated, cross-sectional behavioural surveillance, 2003-2012.
Sex Transm Infect
PUBLISHED: 11-14-2013
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To analyse changes in testing for sexually transmissible infections (STI) among gay and bisexual men in Melbourne, Sydney and Queensland, Australia, particularly comprehensive STI testing (at least four tests from different anatomical sites in the previous year), and the characteristics of men who had such testing.
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The cost of antiretroviral drug resistance in HIV-positive patients.
Antivir. Ther. (Lond.)
PUBLISHED: 11-01-2013
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Antiretroviral drug resistance (ARV) limits choices often necessitating the selection of drugs with less desirable pill burdens, toxicity profiles, drug interactions, dosing schedules, and may increase cost. We examine the impact of resistance on the cost of HIV care.
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Invasive cervical cancer risk among HIV-infected women: a North American multicohort collaboration prospective study.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 10-30-2013
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HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic human papillomavirus infection-the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.
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Surviving an epidemic -- Australian GPs on caring for people with HIV and AIDS in the early years.
Aust Fam Physician
PUBLISHED: 10-17-2013
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Although general practitioners (GPs) play a central role in responding to human immunodeficiency virus (HIV) in Australia, the social history of their contribution in the early years has remained largely untold.
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Activation of virus uptake through induction of macropinocytosis with a novel polymerizing peptide.
FASEB J.
PUBLISHED: 10-04-2013
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A 27-aa peptide (P27) was previously shown to decrease the accumulation of human immunodeficiency virus type 1 (HIV-1) in the supernatant of chronically infected cells; however, the mechanism was not understood. Here, we show that P27 prevents virus accumulation by inducing macropinocytosis (MPC). Treatment of HIV-1- and human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells with 2-10 ?M P27 caused cell membrane ruffling and uptake of virus and polymerized forms of the peptide into large vacuoles. As demonstrated by electron microscopy, activation of MPC did not require virus or cells infected with virus, as P27 initiated its own uptake in the absence of virus. Inhibitors of MPC, Cytochalasin D and amiloride, decreased P27-mediated uptake of soluble dextran and inhibited P27-induced virus uptake by >60%, which provides further evidence that P27 induces MPC. In CD4(+) HeLa cells, HIV-1 infection was enhanced by P27 up to 4-fold, and P27 increased infection at concentrations as low as 20 nM. The 5-aa C-terminal domain of P27 was necessary for virus uptake and may be responsible for the polymerization of P27 into fibrils. These forms of P27 may play a key role in triggering MPC, making this peptide a useful tool for studying virus uptake and infection, as well as MPC of other macromolecules.-Daniels, S.I., Soule, E.E., Davidoff, K.S., Bernbaum, J.G., Hu, D., Maeda, K., Stahl, S.J., Naiman, N.E., Waheed, A.E., Freed, E.O., Wingfield, P., Yarchoan, R., Davis. D.A. Activation of virus uptake through induction of macropinocytosis with a novel polymerizing peptide.
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Comparative cost-effectiveness of two-tiered testing strategies for serodiagnosis of lyme disease with noncutaneous manifestations.
J. Clin. Microbiol.
PUBLISHED: 09-25-2013
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The mainstay of laboratory diagnosis for Lyme disease is two-tiered serological testing, in which a reactive first-tier enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay is supplemented by separate IgM and IgG immunoblots. Recent data suggest that the C6 ELISA can be substituted for immunoblots without a reduction in either sensitivity or specificity. In this study, the costs of 4 different two-tiered testing strategies for Lyme disease were compared using the median charges for these tests at 6 commercial diagnostic laboratories in 2012. The study found that a whole-cell sonicate ELISA followed by the C6 ELISA was the most cost-effective two-tiered testing strategy for Lyme disease with acute-phase serum samples. We conclude that the C6 ELISA can substitute for immunoblots in the two-tiered testing protocol for Lyme disease without a loss of sensitivity or specificity and is less expensive.
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The effect of churn on "community viral load" in a well-defined regional population.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 09-20-2013
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The concept of community viral load (CVL) was introduced to quantify the pool of transmissible HIV within a community and to monitor the potential impact of highly active antiretroviral therapy (HAART) on reducing new infections. The implications of churn (patient movement in/out of care in a community) on CVL have not been studied.
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Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival.
Blood
PUBLISHED: 09-16-2013
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Hematopoietic stem cells are both necessary and sufficient to sustain the complete blood system of vertebrates. Here we show that Nfix, a member of the nuclear factor I (Nfi) family of transcription factors, is highly expressed by hematopoietic stem and progenitor cells (HSPCs) of murine adult bone marrow. Although short hairpin RNA-mediated knockdown of Nfix expression in Lineage(-)Sca-1(+)c-Kit(+) HSPCs had no effect on in vitro cell growth or viability, Nfix-depleted HSPCs displayed a significant loss of colony-forming potential, as well as short- and long-term in vivo hematopoietic repopulating activity. Analysis of recipient mice at 4 to 20 days posttransplant revealed that Nfix-depleted HSPCs are established in the bone marrow, but fail to persist due to increased apoptotic cell death. Gene expression profiling of Nfix-depleted HSPCs reveals that loss of Nfix expression in HSPCs is concomitant with a decrease in the expression of multiple genes known to be important for HSPCs survival, such as Erg, Mecom, and Mpl. These data reveal that Nfix is a novel regulator of HSPCs survival posttransplantation and establish a role for Nfi genes in the regulation of this cellular compartment.
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HIV-negative and HIV-positive gay mens attitudes to medicines, HIV treatments and antiretroviral-based prevention.
AIDS Behav
PUBLISHED: 08-31-2013
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We assessed attitudes to medicines, HIV treatments and antiretroviral-based prevention in a national, online survey of 1,041 Australian gay men (88.3% HIV-negative and 11.7% HIV-positive). Multivariate analysis of variance was used to identify the effect of HIV status on attitudes. HIV-negative men disagreed with the idea that HIV drugs should be restricted to HIV-positive people. HIV-positive men agreed and HIV-negative men disagreed that taking HIV treatments was straightforward and HIV-negative men were more sceptical about whether HIV treatment or an undetectable viral load prevented HIV transmission. HIV-negative and HIV-positive men had similar attitudes to pre-exposure prophylaxis but divergent views about treatment as prevention.
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Extending the tissue penetration capability of conventional photosensitisers: a carbon quantum dot-protoporphyrin IX conjugate for use in two-photon excited photodynamic therapy.
Chem. Commun. (Camb.)
PUBLISHED: 08-24-2013
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A carbon quantum dot (CQD)-protoporphyrin (IX) sensitisier conjugate was designed to exploit the large two-photon absorption cross section of CQDs and enable the indirect excitation of the sensitiser with 800 nm irradiation via FRET.
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The informal use of antiretrovirals for preexposure prophylaxis of HIV infection among gay men in Australia.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-21-2013
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We aimed to describe the current use of antiretrovirals(ARVs) before unprotected anal intercourse (UAI) among Australian gay men, which may represent informal HIV preexposure prophylaxis (PrEP).
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Regional resistance surveillance program results for 12 Asia-Pacific nations (2011).
Antimicrob. Agents Chemother.
PUBLISHED: 08-19-2013
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The Regional Resistance Surveillance program monitored susceptibility rates and developing resistance by geographic region, including 12 Asia-Pacific (APAC) countries. Reference broth microdilution methods for susceptibility/interpretations were applied, processing 5,053 strains. Among Staphylococcus aureus isolates (37% methicillin-resistant S. aureus [MRSA], highest in South Korea [73%]), linezolid (LZD), tigecycline (TIG), and vancomycin were 100% active, but 33 and 34% of strains were levofloxacin (LEV) or macrolide resistant, respectively. Streptococcus pneumoniae was most resistant to ?-lactams and macrolides (45%) but was LZD, LEV, and TIG susceptible (>98%). Extended-spectrum ?-lactamase (ESBL) phenotype rates in Escherichia coli and Klebsiella spp. were 48 and 47%, respectively, and were highest in Taiwan, at 75 to 91%. The best anti-ESBL-phenotype agents were amikacin (81 to 96% susceptible), colistin (COL; >98%), TIG (>98%), and carbapenems (81 to 97%). Pseudomonas aeruginosa showed ?20% resistance to all drugs except COL (99% susceptible). In conclusion, endemic evolving antimicrobial resistances in APAC nations show compromised roles for many commonly used antimicrobials.
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Intimate Partner Violence and HIV: A Review.
Curr HIV/AIDS Rep
PUBLISHED: 08-15-2013
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Intimate partner violence (IPV) is a common and negative social determinant of health. IPV also increases vulnerability to risks associated with HIV transmission and contributes to HIV transmission. IPV is therefore predictably common among people living with HIV. It is increasingly being recognized as an important predictor of poor outcomes for those living with HIV by affecting retention to care, mental health, adherence to therapy, frequency of follow-up; all of which lead to more hospitalizations and progression to AIDS. HIV care providers can safely and effectively screen all HIV patients for IPV. Screening offers the opportunity to identify those at risk for poor outcomes and mitigate its effects. Further research is required in further defining the risk factors and outcomes of IPV and optimizing interventions. We review the association between HIV infection and IPV and make recommendations for IPV screening of HIV-positive individuals and those at high risk for HIV.
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Utilization management in microbiology.
Clin. Chim. Acta
PUBLISHED: 08-10-2013
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The available literature concerning utilization management in the clinical microbiology laboratory is relatively limited compared with that for high-volume, automated testing in the central Core Laboratory. However, the same strategies employed elsewhere in the clinical laboratory operation can be applied to utilization management challenges in microbiology, including decision support systems, application of evidence-based medicine, screening algorithms and gatekeeper functions. The results of testing in the microbiology laboratory have significant effects on the cost of clinical care, especially costs related to antimicrobial agents and infection control practices. Consequently many of the successful utilization management interventions described in clinical microbiology have targeted not just the volume of tests performed in the laboratory, but also the downstream costs of care. This article will review utilization management strategies in clinical microbiology, including specific examples from our institution and other healthcare organizations.
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Hepatitis C viremia and the risk of chronic kidney disease in HIV-infected individuals.
J. Infect. Dis.
PUBLISHED: 07-31-2013
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?The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified.
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The Impact of Long-Term Health Goals on Sexual Risk Decisions in Impulsive and Reflective Cognitive States.
Arch Sex Behav
PUBLISHED: 06-29-2013
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In the heat of the moment, people often impulsively take risks. Having unprotected sex, for example, can result in sexually transmitted infections. In three studies, we investigated a possible explanation for the increased sexual risk propensity of people in an impulsive state. In contrast to the intuitively appealing notion that they are less influenced by their long-term goals, we hypothesized and showed that people in both impulsive and reflective states make less risky sexual decisions when health goals are important. We further showed that, when sexual health goals are important, people in a reflective state make riskier sexual decisions as temptations become stronger, while decisions of people in an impulsive state were not influenced by temptation strength. This supports the counterintuitive prediction that people in an impulsive state are better able to cope with strong temptations than people in a reflective state.
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Performance of the Vitek MS v2.0 system in distinguishing Streptococcus pneumoniae from nonpneumococcal species of the Streptococcus mitis group.
J. Clin. Microbiol.
PUBLISHED: 06-19-2013
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The Vitek MS v2.0 matrix-assisted laser desorption ionization-time of flight mass spectrometry system accurately distinguished Streptococcus pneumoniae from nonpneumococcal S. mitis group species. Only 1 of 116 nonpneumococcal isolates (<1%) was misidentified as S. pneumoniae. None of 95 pneumococcal isolates was misidentified. This method provides a rapid, simple means of discriminating among these challenging organisms.
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Evaluation of brief screening tools for neurocognitive impairment in HIV/AIDS: a systematic review of the literature.
AIDS
PUBLISHED: 06-12-2013
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To systematically review literature on brief screening tools used to detect and differentiate between normal cognition and neurocognitive impairment and HIV-associated neurocognitive disorders (HANDs) in adult populations of persons with HIV.
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Multicenter validation of the VITEK MS v2.0 MALDI-TOF mass spectrometry system for the identification of fastidious gram-negative bacteria.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 06-07-2013
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The VITEK MS v2.0 MALDI-TOF mass spectrometry systems performance in identifying fastidious gram-negative bacteria was evaluated in a multicenter study. Compared with the reference method (DNA sequencing), the VITEK MS system provided an accurate, species-level identification for 96% of 226 isolates; an additional 1% were accurately identified to the genus level.
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The clinical implications of high rates of intimate partner violence against HIV-positive women.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-30-2013
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Intimate partner violence (IPV) is associated with increased risk of HIV infection among women, however, whether IPV affects outcomes after HIV infection is uncertain. We assess the impact of IPV on HIV-positive women.
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Gender differences in patterns of experienced sexual coercion and associated vulnerability factors among young people in the Netherlands.
J Interpers Violence
PUBLISHED: 05-27-2013
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The development of effective policies and programs to prevent sexual coercion among young people requires thorough understanding of the diversity of coercive sexual experiences, patterns in such types of experiences, and similarities and differences between subgroups, especially by gender, in patterns of coercive sexual experiences and associations with potential vulnerability factors. The present online self-report study assessed a wide range of coercive sexual experiences and potential vulnerability factors among a sociodemographically diverse sample of 1,319 young people (16-25 years old) in The Netherlands. Findings confirm that sexual coercion comprises a diversity of experiences, with rates differing substantially across types of coercion. Latent class analysis revealed distinct patterns of coercive sexual experiences for young women and young men. Among young men, three patterns of experiences were found: no coercive sexual experiences, experience with verbal pressure, and experience with verbal pressure as well as coercion related to alcohol intoxication. Among young women, four patterns of coercive experiences were identified. In addition to the three patterns observed among young men, a fourth pattern encompassed experiences with verbal pressure as well as the use of force or violence. Higher numbers of sexual partners, lower levels of sexual refusal skills, and higher levels of token resistance were consistently associated with increased vulnerability. Findings illustrate the importance of communication skills and suggest that sexual communication training should be an integral part of sexuality education.
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Fluorescence turn-on sensor for F- derived from vitamin B6 cofactor.
Analyst
PUBLISHED: 05-23-2013
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A novel vitamin B6 Schiff base analog (L) was synthesized by combining vitamin B6 cofactor pyridoxal with 2-aminophenol. Receptor L displays a color change detectable by the naked-eye from yellow to red in the presence of fluoride and acetate due to the formation of hydrogen bonding host-guest complexes in 1 : 1 stoichiometry. Importantly, receptor L showed fluoride-selective turn-on fluorescent response with a detection limit (3?) of 7.39 × 10(-8) M.
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The effects of integrating instrumental and affective arguments in rhetorical and testimonial health messages.
J Health Commun
PUBLISHED: 05-09-2013
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Recent research highlights the superior influence of affect over cognition in health decision making. The present study examined the independent and combined effects of 2 message characteristics that are thought to tap into the cognition-affect distinction: message format (rhetorical vs. testimonial) and argument type (instrumental vs. affective). In this 2 × 2 experiment, 81 college students were randomly assigned to 1 of 4 health messages discouraging binge drinking. The results indicated that messages containing affective arguments were judged more positively and perceived as more effective than were messages containing instrumental arguments. The results further revealed an interaction effect between message format and argument type. Testimonials were more persuasive when they contained affective arguments than when they contained instrumental arguments. Type of arguments did not influence the efficacy of rhetorical messages. Mediation analyses revealed that instrumental arguments reduce the efficacy of testimonials because they prevent individuals from being transported into the story, and increase psychological reactance. In conclusion, testimonial messages more effectively discourage binge drinking among college students when they contain affective, as opposed to instrumental, arguments.
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Multicenter study evaluating the Vitek MS system for identification of medically important yeasts.
J. Clin. Microbiol.
PUBLISHED: 05-08-2013
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The optimal management of fungal infections is correlated with timely organism identification. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is revolutionizing the identification of yeasts isolated from clinical specimens. We present a multicenter study assessing the performance of the Vitek MS system (bioMérieux) in identifying medically important yeasts. A collection of 852 isolates was tested, including 20 Candida species (626 isolates, including 58 C. albicans, 62 C. glabrata, and 53 C. krusei isolates), 35 Cryptococcus neoformans isolates, and 191 other clinically relevant yeast isolates; in total, 31 different species were evaluated. Isolates were directly applied to a target plate, followed by a formic acid overlay. Mass spectra were acquired using the Vitek MS system and were analyzed using the Vitek MS v2.0 database. The gold standard for identification was sequence analysis of the D2 region of the 26S rRNA gene. In total, 823 isolates (96.6%) were identified to the genus level and 819 isolates (96.1%) were identified to the species level. Twenty-four isolates (2.8%) were not identified, and five isolates (0.6%) were misidentified. Misidentified isolates included one isolate of C. albicans (n = 58) identified as Candida dubliniensis, one isolate of Candida parapsilosis (n = 73) identified as Candida pelliculosa, and three isolates of Geotrichum klebahnii (n = 6) identified as Geotrichum candidum. The identification of clinically relevant yeasts using MS is superior to the phenotypic identification systems currently employed in clinical microbiology laboratories.
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Multicenter evaluation of the Vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of Gram-positive aerobic bacteria.
J. Clin. Microbiol.
PUBLISHED: 05-08-2013
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Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) is gaining momentum as a tool for bacterial identification in the clinical microbiology laboratory. Compared with conventional methods, this technology can more readily and conveniently identify a wide range of organisms. Here, we report the findings from a multicenter study to evaluate the Vitek MS v2.0 system (bioMérieux, Inc.) for the identification of aerobic Gram-positive bacteria. A total of 1,146 unique isolates, representing 13 genera and 42 species, were analyzed, and results were compared to those obtained by nucleic acid sequence-based identification as the reference method. For 1,063 of 1,146 isolates (92.8%), the Vitek MS provided a single identification that was accurate to the species level. For an additional 31 isolates (2.7%), multiple possible identifications were provided, all correct at the genus level. Mixed-genus or single-choice incorrect identifications were provided for 18 isolates (1.6%). Although no identification was obtained for 33 isolates (2.9%), there was no specific bacterial species for which the Vitek MS consistently failed to provide identification. In a subset of 463 isolates representing commonly encountered important pathogens, 95% were accurately identified to the species level and there were no misidentifications. Also, in all but one instance, the Vitek MS correctly differentiated Streptococcus pneumoniae from other viridans group streptococci. The findings demonstrate that the Vitek MS system is highly accurate for the identification of Gram-positive aerobic bacteria in the clinical laboratory setting.
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Out of sight, out of mind: cognitive states alter the focus of attention.
Exp Psychol
PUBLISHED: 05-01-2013
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People in an impulsive state are influenced mainly by the immediate incentive value of appetitive stimuli, whereas people in a reflective state usually also consider the (sometimes negative) long-term consequences of such stimuli. In order to consider all information, we hypothesize that, people in reflective states distribute their attention over all available information, whereas people in impulsive states focus their attention on the most salient information. We measured cognitive states using eye-blink rate (Experiment 1) or induced them with a procedural priming manipulation (Experiments 2 and 3). In eye-tracking Experiments 1 and 2, we established that people in an impulsive state indeed focus their attention on the salient information, whereas people in a reflective state distribute their attention. Moreover, we show that this attentional difference extends to evaluative judgments (Experiment 3), which could potentially contribute to peoples increased propensity to risk in impulsive states.
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The NK receptor NKp30 mediates direct fungal recognition and killing and is diminished in NK cells from HIV-infected patients.
Cell Host Microbe
PUBLISHED: 04-25-2013
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Natural killer (NK) cells are a subset of immune effectors that directly bind and kill fungi via a perforin-dependent mechanism. The receptor mediating this activity and its potential role in disease remain unknown. Using an unbiased approach, we determined that NKp30 is responsible for recognition and killing of the fungal pathogens Cryptococcus and Candida. NKp30 was required for NK cell-fungal conjugate formation, phosphatidylinositol 3-kinase (PI3K) signaling, and perforin release. Because fungal infections are a leading cause of death in AIDS patients, we examined NKp30 expression in HIV-infected patients. NK cells from these patients had diminished NKp30 expression, defective perforin release, and blunted microbicidal activity. Surprisingly, interleukin-12 (IL-12) restored NKp30 expression and fungal killing. Thus, the NKp30 receptor plays a critical role in NK cell antifungal cytotoxicity, and diminished expression of NKp30 is responsible for defective antifungal activity of NK cells from HIV-infected patients, which can be corrected with IL-12.
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Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).
Int J Epidemiol
PUBLISHED: 04-18-2013
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The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).
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Performance of United States serologic assays in the diagnosis of Lyme borreliosis acquired in Europe.
Clin. Infect. Dis.
PUBLISHED: 04-16-2013
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Physicians in the United States sometimes need to evaluate a patient for suspected Lyme borreliosis (LB) who may have acquired the infection in Europe. Using serum samples from European LB patients, we compared the performance of European and US serodiagnostic tests, including newer-generation assays containing Vmp-like sequence, expressed or its C6 peptide.
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The impact of living with HIV: differences in experiences of stigma for heterosexual and homosexual people living with HIV in Australia.
Sex Health
PUBLISHED: 04-02-2013
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Background HIV in Australia has been closely aligned with the gay community and continues to disproportionately affect members of this community. Although heterosexual transmission remains low, recently there has been an increase in new HIV diagnoses attributable to heterosexual sex. This highlights the need to address the health and social consequences for heterosexual people living with HIV (PLHIV). This subanalysis of a larger study compared the experiences of stigma, health and wellbeing of a sample of gay and heterosexual PLHIV. Methods: Data were drawn from a study of experiences of stigma among PLHIV in Australia. All 49 participants who reported being heterosexual were included, as were 49 participants randomly selected from the 611 gay participants. The samples were compared on perceived HIV stigma, HIV treatment-related stigma, perceived negative reactions of others, HIV status disclosure, and health and wellbeing measures. Results: The findings illustrate that heterosexual PLHIV have more negative experiences in terms of both general HIV stigma and treatment-related stigma than gay PLHIV. The heterosexual PLHIV also perceived greater negative reactions in relation to their HIV status by different people in their social environment and were less likely to access treatment than the gay PLHIV. There were no differences between the two groups in any of the health and wellbeing measures. Conclusions: This study shows that in the Australian context, heterosexual PLHIV may feel more stigmatised than gay PLHIV. In view of lower HIV treatment uptake in heterosexual PLHIV, addressing HIV-related stigma could contribute to increasing access to HIV treatment.
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Distress, Need for Help, and Positive Feelings Derived from Participation in Sex Research: Findings of a Population Study in the Netherlands.
J Sex Res
PUBLISHED: 03-29-2013
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To inform cost-benefit analyses of potential harms and benefits for participants in sex research, the current study investigated potential effects of completing a self-report sex survey. The data stem from a sexual health study in a population sample in the Netherlands (N = 8,064; 15 to 70 years old). Three measures assessed potential effects of participation: distress, need for help, and positive feelings related to research participation. Analyses showed that levels of experienced distress and need for help resulting from participation in a self-report sex survey were low, while participants reported positive feelings to a considerable extent. Only few participants reported levels of positive experiences that were lower than the levels of distress (4.8%) or need for help (1.7%) they experienced. Although differences were found according to sociodemographic characteristics and sexual experiences, the proportion of variance explained by these variables was generally small. While the findings of this study show that the balance between potential harm and positive outcomes seems disturbed for few participants, researchers should provide participants with the details of care providers in case they experience any distress or need for help.
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HIV and hepatitis C virus co-infection among men who have sex with men in Sydney, and associations with sexual and drug use practices.
Sex Health
PUBLISHED: 03-26-2013
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In recent years there has been an increase in the incidence of acute hepatitis C virus (HCV) in men who have sex with men (MSM). The aim of the present study was to examine the prevalence of HIV/HCV co-infection among MSM in Sydney, and to compare sexual and drug use risk practices of HIV/HCV co-infected MSM with HIV and HCV mono-infected MSM.
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Expert perspectives on the contribution of HIV general practice nursing to the extraordinary story of HIV medicine in Australia.
Prim Health Care Res Dev
PUBLISHED: 03-14-2013
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Aim This paper explores cultural and professional dynamics of HIV general practice nursing in Australia. It highlights specific contributions that HIV general practice nurses make to HIV medicine and considers how nurses clinical practice has been shaped by past experiences of the AIDS crisis and subsequent developments in HIV medicine. BACKGROUND: In international contexts, nurses in HIV medicine commonly work as part of shared-care teams. In recent years, HIV general practice nursing has become a prioritised area for primary health care in Australia. METHODS: Data for this analysis were drawn from 45 in-depth, semi-structured interviews conducted with nurses and general practitioners (GPs) who provide HIV care in general practice, and key informants who work in policy, advocacy or education and training of the HIV general practice workforce. Findings Viewed through a socio-ecological framework of social capital, descriptive content analysis highlights a unique and strong HIV health professional identity, which emerged out of the adverse conditions experienced by nurses, GPs and allied health professionals during the 1980s AIDS crisis. Participants reported that today, HIV general practice nursing includes information provision, HIV treatment side-effect management, teaching patients methods to increase adherence to HIV treatments and capacity building with allied health professionals. Participants reported that HIV general practice nurses can reduce the clinical burden on GPs, ameliorate patients exposure to HIV health care-related stigma and discrimination and facilitate the emergence of a comprehensive and personalised model of shared primary health care based on trust and rapport, which is desired by people with HIV. This studys findings support the future expansion of the role of HIV general practice nurses in Australia and internationally. General practice nursing will become increasingly important in the scaling up of HIV testing and in caring for increasing numbers of people living with HIV.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.