BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.
- MeSH
- AIDS * epidemiologie MeSH
- dospělí MeSH
- HIV infekce * prevence a kontrola MeSH
- HIV MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prevalence MeSH
- séroepidemiologické studie MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- subsaharská Afrika MeSH
In this study, a sensitive platform was designed for the electrocatalytical oxidation and recognition of ascorbic acid (AA) based on poly(β-cyclodextrin) modified glassy carbon electrode (p(β-CD-GCE). Electropolymerization of β-CD on the surface of GCE was performed on the potential range of -1 to 1.5 V. So, a novel biopolymer was prepared on the surface of GCE towards sensitive recognition of AA in human plasma samples. The developed platform has good sensitivity and accuracy for electrooxidation and detection of AA with lower limit of quantification (LLOQ) of 1 nM and linear range of 1 nM to 100 mM. Moreover, the designed electrochemical sensor was employed for the analysis of AA on human plasma samples with high sensitivity. Based on advantages of p(β-CD) prepared by electropolymerization procedure (green, fast, homogeny, and efficient eletrocatalytical behaviour), this conductive biopolymer showed excellent analytical behaviour towards electrooxidation of AA. It is expected that the prepared polymeric interface is able to use in the analysis of biological species in clinical samples.
- MeSH
- beta-cyklodextriny MeSH
- biokompatibilní materiály MeSH
- biopolymery MeSH
- elektrochemické techniky * metody MeSH
- kyselina askorbová * MeSH
- lidé MeSH
- propylenglykoly MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Mounting evidence indicated the capability of various microorganisms in biosynthesis of exopolysaccharides (EPSs). A wide range of evidence extensively investigated the ability of bacterial species for EPS synthesis and their favorable effects, so little is known regarding yeast species. Many factors like composition of growth media and fermentation conditions are related to the structural and physical properties of EPSs. The EPS protects the producer yeast strain against extreme environment. Researchers proposed that yeast EPSs have priority over bacterial EPSs because of high yields of EPS biosynthesis and easy separation methods from growth media. Besides, they have drawn increasing attention due to their interesting biological activities, food, pharmaceutical, and cosmetics applications. Although a limited number of studies exist, this review aims to highlight the EPS structure and various applications of known yeast species in detail.
Induction of selective thrombosis and infarction in tumor-feeding vessels represents an attractive strategy to combat cancer. Here we took advantage of the unique coagulation properties of staphylocoagulase and genetically engineered it to generate a new fusion protein with novel anti-cancer properties. This novel bi-functional protein consists of truncated coagulase (tCoa) and an NGR (GNGRAHA) motif that recognizes CD13 and αvβ3 integrin receptors, targeting it to tumor endothelial cells. Herein, we report that tCoa coupled by its C-terminus to an NGR sequence retained its normal binding activity with prothrombin and avβ3 integrins, as confirmed in silico and in vitro. Moreover, in vivo biodistribution studies demonstrated selective accumulation of FITC-labeled tCoa-NGR fusion proteins at the site of subcutaneously implanted PC3 tumor xenografts in nude mice. Notably, systemic administration of tCoa-NGR to mice bearing 4T1 mouse mammary xenografts or PC3 human prostate tumors resulted in a significant reduction in tumor growth. These anti-tumor effects were accompanied by massive thrombotic occlusion of small and large tumor vessels, tumor infarction and tumor cell death. From these findings, we propose tCoa-NGR mediated tumor infarction as a novel and promising anti-cancer strategy targeting both CD13 and integrin αvβ3 positive tumor neovasculature.
- MeSH
- antigeny CD13 metabolismus MeSH
- buněčná smrt fyziologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- integrin alfaVbeta3 metabolismus MeSH
- koagulasa metabolismus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory mléčné žlázy u zvířat metabolismus patologie MeSH
- nádory prostaty metabolismus patologie MeSH
- oligopeptidy metabolismus MeSH
- patologická angiogeneze metabolismus patologie MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The Global Alliance for Infections in Surgery appreciates the great effort of the task force who derived and validated the Sepsis-3 definitions and considers the new definitions an important step forward in the evolution of our understanding of sepsis. Nevertheless, more than a year after their publication, we have a few concerns regarding the use of the Sepsis-3 definitions.
- MeSH
- arteriální tlak MeSH
- Glasgowská stupnice kómat MeSH
- konsensus MeSH
- lidé MeSH
- senzitivita a specificita MeSH
- sepse klasifikace mortalita MeSH
- správnost dat * MeSH
- stupeň závažnosti nemoci * MeSH
- vyhodnocení orgánové dysfunkce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any significant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and afforded favorable interaction of fusion proteins with prothrombin and αvβ3 endothelial cell receptors, as verified by in silico, in vitro, and in vivo experiments. Although free coagulase elicited robust coagulase activity in vitro, only targeted coagulase (tCoa-RGD) was capable of producing extensive thrombosis, and subsequent infarction and massive necrosis of CT26 mouse colon, 4T1 mouse mammary and SKOV3 human ovarian tumors in mice. Additionally, systemic injections of lower doses of tCoa-RGD produced striking tumor growth inhibition of CT26, 4T1 and SKOV3 solid tumors in animals. Altogether, the nontoxic nature, unique shortcut mechanism, minimal effective dose, wide therapeutic window, efficient induction of thrombosis, local effects and susceptibility of human blood to coagulase suggest tCoa-RGD fusion proteins as a novel and promising anticancer therapy for human trials.
- MeSH
- bakteriální proteiny genetika metabolismus MeSH
- infarkt patologie MeSH
- koagulasa genetika metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mutace MeSH
- myši inbrední C57BL MeSH
- myši nahé MeSH
- nádorové buněčné linie MeSH
- nádory genetika metabolismus terapie MeSH
- oligopeptidy genetika MeSH
- patologická angiogeneze genetika metabolismus patologie MeSH
- rekombinantní fúzní proteiny genetika metabolismus MeSH
- trombóza genetika metabolismus MeSH
- tumor burden genetika MeSH
- xenogenní modely - testy protinádorové aktivity metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. METHODS: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. RESULTS: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p < 0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). CONCLUSION: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.
- MeSH
- antibiotická politika metody MeSH
- antiinfekční látky terapeutické užití MeSH
- celosvětové zdraví trendy MeSH
- lidé MeSH
- nitrobřišní infekce farmakoterapie MeSH
- pooperační komplikace farmakoterapie MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH