A Scoping Review of Measurement Tools Evaluating Awareness and Disease-Related Knowledge in Peripheral Arterial Disease Patients.

BACKGROUND: Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic cardiovascular morbidity worldwide, with high prevalence and associated complications, and is often overlooked and undertreated. Research has shown that there is a profound lack of PAD-related knowledge and awareness; additionally, information sources are not often reliable and accessible. The objective of this scoping review was: (1) to identify and critically appraise instruments that measure patients' disease-related knowledge/awareness about PAD, and (2) to characterize the current state of knowledge/awareness levels among these patients. METHODS: This systematic review was conducted and reported in accordance with the PRISMA statement. Six databases (APA PsycInfo, CINAHL Ultimate, Embase, Emcare Nursing, Medline ALL and Web of Science Core Collection) were searched, and search strategies were developed utilizing the PICO framework. Potential studies of any methodological design were considered for inclusion through a snowball hand search. Data from the included articles were extracted by a reviewer, and the extraction accuracy was independently cross-checked by another author. RESULTS: The initial database search yielded 9832 records, of which sixteen studies (thirteen quantitative and three qualitative) were included. Only three questionnaires had their psychometric properties assessed. Questionnaire items focused on the following topics: definition/characteristics, risk factors/causes, treatment, complications, and personal issues regarding the perception/management of the disease. Overall, knowledge/awareness about PAD was low among patients. CONCLUSIONS: This study identified major gaps in PAD education, including the lack of availability of a validated measurement tool addressing all educational topics relevant to care and low knowledge/awareness of patients about their condition.

Translation, cross-cultural adaptation, and psychometric properties of the Brazilian Portuguese version of the DiAbeTes Education Questionnaire (DATE-Q).

BACKGROUND: The DiAbeTes Education Questionnaire (DATE-Q) is a self-administered tool developed to evaluate disease-related knowledge and to assess knowledge of five core components of rehabilitation programs: physical exercise, diet, psychosocial well-being, disease self-management, and complications. OBJECTIVE: To translate and cross-culturally adapt into Brazilian Portuguese, and to test the psychometric properties of the DATE-Q for its use in Brazil. METHODS: The process of translation and cross-cultural adaptation consisted of five steps: translation into Brazilian Portuguese, synthesis of translation, back translation, expert committee, and pilot test of pre-final version. The pre-final version was applied to a sample of 30 patients with diabetes. Psychometric properties (internal consistency, reliability, construct validity, and ceiling and floor effects) of the final version of the Brazilian Portuguese version of the DATE-Q were tested in a sample of 200 adults with diabetes. RESULTS: There was no conceptual divergence between the original and the translated versions. Ten (50%) items of the DATE-Q were culturally adapted. Internal consistency (Cronbach's alpha coefficient = 0.6), reliability (intraclass correlation coefficient = 0.5), and construct validity (correlation between Diabetes Knowledge Scales and DATE-Q total scores: ρ = 0.7; P < 0.001) were confirmed. Ceiling or floor effects were not identified. The highest scoring item was about healthy eating. The average time for completion of the DATE-Q was 5 min and 51 s, and the completion rate was 100% for all items. CONCLUSION: The Brazilian Portuguese version of the DATE-Q showed adequate psychometric properties, and results suggested that the tool can be used to assess disease-related knowledge in adults with diabetes in Brazil.

An overview of human leptospirosis vaccine design and future perspectives.

Introduction: It's been 20 years since the first report of a recombinant vaccine that protected against leptospirosis. Since then, numerous recombinant vaccines have been evaluated; however, no recombinant vaccine candidate has advanced to clinical trials. With the ever-increasing burden of leptospirosis, there is an urgent need for a universal vaccine against leptospirosis.Areas covered: This review covers the most promising vaccine candidates that induced significant, reproducible, protection and how advances in the field of bioinformatics has led to the discovery of hundreds of novel protein targets. The authors also discuss the most recent findings regarding the innate immune response and host-pathogen interactions and their impact on the discovery of novel vaccine candidates. In addition, the authors have identified what they believe are the most challenging problems for the discovery and development of a universal vaccine and their potential solutions.Expert opinion: A universal vaccine for leptospirosis will likely only be achieved using a recombinant vaccine as the bacterins are of limited use due to the lack of a cross-protective immune response. Although there are hundreds of novel targets, due to the lack of immune correlates and the need for more research into the basic microbiology of Leptospira spp., a universal vaccine is 10-15 years away.

Plakinamine P, A Steroidal Alkaloid with Bactericidal Activity against Mycobacterium tuberculosis.

Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus Plakina revealed the presence of a new steroidal alkaloid of the plakinamine class, which we have given the common name plakinamine P. Its structure is most similar to plakinamine L, which also has an acyclic side chain. Careful dissection of the nuclear magnetic resonance data, collected in multiple solvents, suggests that the dimethyl amino group at the 3 position is in an equatorial rather than axial position unlike previously reported plakinamines. Plakinamine P was bactericidal against M. tuberculosis, and exhibited moderate activity against other mycobacterial pathogens, such as M. abscessus and M. avium. Furthermore, it had low toxicity against J774 macrophages, yielding a selectivity index (SI, or IC50/MIC) of 8.4. In conclusion, this work provides a promising scaffold to the tuberculosis drug discovery pipeline. Future work to determine the molecular target of this compound may reveal a pathway essential for M. tuberculosis survival during infection.

Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus.

Mycobacterium tuberculosis and the fast-growing species Mycobacterium abscessus are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant M. tuberculosis strains and the high level of intrinsic resistance of M. abscessus call for novel drug scaffolds that effectively target both pathogens. In this study, we evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase types I and II (Topo1 and Topo2), against M. abscessus and M. tuberculosis We identified a total of 5 noncytotoxic compounds active against both mycobacterial pathogens under replicating in vitro conditions. We chose one of these hits, compound 14, for detailed analysis due to its potent bactericidal mode of inhibition and scalable synthesis. The clinical relevance of this compound was demonstrated by its ability to inhibit a panel of diverse M. tuberculosis and M. abscessus clinical isolates. Prompted by previous data suggesting that compound 14 may target topoisomerase/gyrase enzymes, we demonstrated that it lacked cross-resistance with fluoroquinolones, which target the M. tuberculosis gyrase. In vitro enzyme assays confirmed the potent activity of compound 14 against bacterial topoisomerase 1A (Topo1) enzymes but not gyrase. Novel scaffolds like compound 14 with potent, selective bactericidal activity against M. tuberculosis and M. abscessus that act on validated but underexploited targets like Topo1 represent a promising starting point for the development of novel therapeutics for infections by pathogenic mycobacteria.

Selective Killing of Dormant Mycobacterium tuberculosis by Marine Natural Products.

The dormant phenotype acquired by Mycobacterium tuberculosis during infection poses a major challenge in disease treatment, since these bacilli show tolerance to front-line drugs. Therefore, it is imperative to find novel compounds that effectively kill dormant bacteria. By screening 4,400 marine natural product samples against dual-fluorescent M. tuberculosis under both replicating and nonreplicating conditions, we have identified compounds that are selectively active against dormant M. tuberculosis This validates our strategy of screening all compounds in both assays as opposed to using the dormancy model as a secondary screen. Bioassay-guided deconvolution enabled the identification of unique pharmacophores active in each screening model. To confirm the activity of samples against dormant M. tuberculosis, we used a luciferase reporter assay and enumerated CFU. The structures of five purified active compounds were defined by nuclear magnetic resonance (NMR) and mass spectrometry. We identified two lipid compounds with potent activity toward dormant and actively growing M. tuberculosis strains. One of these was commercially obtained and showed similar activity against M. tuberculosis in both screening models. Furthermore, puupehenone-like molecules were purified with potent and selective activity against dormant M. tuberculosis In conclusion, we have identified and characterized antimycobacterial compounds from marine organisms with novel activity profiles which appear to target M. tuberculosis pathways that are conditionally essential for dormancy survival.

Dragmacidin G, a Bioactive Bis-Indole Alkaloid from a Deep-Water Sponge of the Genus Spongosorites.

A deep-water sponge of the genus Spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in the patent literature and has recently been reported by Hitora et al. from a sponge of the genus Lipastrotheya. Dragmacidin G is the first in this series of compounds to have a pyrazine ring linking the two indole rings. It also has a rare N-(2-mercaptoethyl)-guanidine side chain. Dragmacidin G shows a broad spectrum of biological activity including inhibition of methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, Plasmodium falciparum, and a panel of pancreatic cancer cell lines.

Small-Molecule Inhibitors Targeting Topoisomerase I as Novel Antituberculosis Agents.

Bacterial topoisomerase functions are required for regulation of DNA supercoiling and overcoming the DNA topological barriers that are encountered during many vital cellular processes. DNA gyrase and topoisomerase IV of the type IIA bacterial topoisomerase family are important clinical targets for antibacterial therapy. Topoisomerase I, belonging to the type IA topoisomerase family, has recently been validated as a potential antitubercular target. The topoisomerase I activity has been shown to be essential for bacterial viability and infection in a murine model of tuberculosis. Mixture-based combinatorial libraries were screened in this study to identify novel bacterial topoisomerase I inhibitors. Using positional-scanning deconvolution, selective small-molecule inhibitors of bacterial topoisomerase I were identified starting from a polyamine scaffold. Antibacterial assays demonstrated that four of these small-molecule inhibitors of bacterial topoisomerase I are bactericidal against Mycobacterium smegmatis and Mycobacterium tuberculosis The MICs for growth inhibition of M. smegmatis increased with overexpression of recombinant M. tuberculosis topoisomerase I, consistent with inhibition of intracellular topoisomerase I activity being involved in the antimycobacterial mode of action.

Bioactive Lipidic Extracts from Octopus (Paraoctopus limaculatus): Antimutagenicity and Antiproliferative Studies.

Fractions from an organic extract from fresh octopus (Paraoctopus limaculatus) were studied for biological activities such as antimutagenic and antiproliferative properties using Salmonella tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line (B-cell lymphoma), respectively. A chloroform extract obtained from octopus tentacles was sequentially fractionated using thin layer chromatography (TLC), and each fraction was tested for antimutagenic and antiproliferative activities. Organic extract reduced the number of revertants caused by aflatoxin B(1) showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. Based on the results obtained, the isolated fractions obtained from octopus contain compounds with chemoprotective properties that reduce the mutagenicity of AFB(1) and proliferation of cancer cell lines.

Antimutagenicity and antiproliferative studies of lipidic extracts from white shrimp (Litopenaeus vannamei).

An organic extract from fresh shrimp (Litopenaeus vannamei) was studied for antimutagenic and antiproliferative properties using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line (B-cell lymphoma), respectively. Shrimp extract was sequentially fractionated by thin layer chromatography (TLC) and each fraction was tested for antimutagenic and antiproliferative activities. Crude organic extracts obtained from shrimp reduced the number of revertants caused by aflatoxina B(1), showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. These results suggested that the lipid fraction of the tested species contained compounds with chemoprotective properties that reduce the mutagenicity of AFB(1) and proliferation of a cancer cell line.

Fitness study of the RDRio lineage and Latin American-Mediterranean family of Mycobacterium tuberculosis in the city of Rio Grande, Brazil.

RD(Rio) is a novel Mycobacterium tuberculosis lineage of the Latin American-Mediterranean (LAM) family. LAM has been found worldwide but is more predominant in South America. The aim of this study was to assess the presence of the RD(Rio) lineage and LAM family in the city of Rio Grande, Brazil, and to investigate the fitness of these strains based on determination of their growth rate. Fifty clinical isolates of M. tuberculosis were genotyped and 43 different patterns were found by spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats. The predominant genotypes belonged to the LAM family (54% of the strains) followed by clade T (22%) and Haarlem (16%). The RD(Rio) lineage represented 38% of the total strains and 70.4% of the LAM strains found in this study. Strains belonging to the LAM family showed a fitness advantage when comparing their rate of growth with that of non-LAM strains, but a significant difference between RD(Rio) and non-RD(Rio) strains was not confirmed.

Clonal diversity of M. tuberculosis isolated in a sea port city in Brazil.

Genotyping tools have been widely used to study the occurrence of outbreaks and to identify the patterns of transmission of Mycobacterium tuberculosis strains. The clonal diversity of 65 clinical isolates of M. tuberculosis was determined by PCR methods. The Double Repeat Element method (DRE-PCR) and spoligotyping identified 45 and 26 distinct patterns respectively. Among these, LAM (38%) was the most frequent lineage, followed by Haarlem (31%) and T (20%). Five orphan patterns were not present in the SITVIT database. Mycobacterial interspersed repetitive units (MIRU) using 12 loci revealed 46 distinct patterns. MIRU loci 10, 23, 26 and 40 had the highest discriminatory power. The high genetic diversity found among M. tuberculosis isolates in this study suggests a high level of recent TB transmission, indicating an endemic mode of TB transmission and a putative importation of new TB genotypes. In addition, the high diversity among the isolates could indicate early detection of the infection in patients and an efficient rate of cure.

Qualidade higiênico-sanitária de formulações ministradas a neonatos / Hygienic-sanitary quality of infant formulas given to neonates

Premature babies hospitalized at the Neonatal Intensive Care Units,particularly those with low weight and that are not allowed to be normallyfed, often need nutritional support of Infant Formulas (IF). These formulas,when contaminated, can be the source of nosocomial infections, the mostprobable way of contamination being the inadequate handling andstorage of these formulas. Evaluate the Hygienic-Sanitary quality and thesusceptibility profi le of the bacteria isolated from Ifs prepared in the lactary in the city of Rio Grande-RS to antimicrobial agents. IF samples were collected during 6 months by hospital employees working in the morning (Group A) and afternoon (group B) shifts, totalizing 72 analyzed samples. The Most Probable Number method (MPN/ml) was utilized to measure the amount of thermo-resistant and total coliforms. For mesophilic microorganisms the number of Colony-forming Units (CFU/ml) was counted. Also, samples were cultured in Blood and MacConkey Agar media and the isolates were identifi ed by 16S rRNA sequencing and submitted to antibiogram by the Kirby-Bauer method. The samples from groups A and B presented, respectively, 88.9% and 55.5% of contamination by total coliforms and 61.1% e 38.8% by thermo-resistant coliforms. Concerning the count of mesophilic microorganisms, groups A and B presented, respectively, 69.4% and 52.7% of the samples with results above the allowed limit. The identified microorganisms were Escherichia coli, Acinetobacter spp., Pseudomonas spp. and Enterobacter spp. The antimicrobial susceptibility test showed that all isolates presented resistance to at least three tested antimicrobials and that all of the isolates were resistant to tetracycline and one of them was also resistant to a carbapenem (imipinem).

Los recién nacidos prematuros hospitalizados en Unidades de Cuidados Intensivos, principalmente aquellos con bajo peso y poca habilidad para alimentarse naturalmente, necesitan el soporte nutricional de preparadospara lactantes (PL). Los PL, cuando contaminados, son fuente de infecciones hospitalaria, siendo la manipulación y el almacenamiento inadecuados las causas más frecuentes de los brotes de infección. Evaluar la calidad higiénico-sanitaria y el perfi l de susceptibilidad a los antimicrobianos de bacterias aisladas en PL. Las muestras se recogieron durante el período de 6 meses con dos grupos de trabajo: matutino (Grupo A) y vespertino (grupo B) del lactario del hospital, totalizando 72 muestras analizadas. Se realizó el recuento de número más probable (NMP / ml)de termotolerantes y coliformes totales y el recuento de unidades formadoras de colonias (UFC / ml) de los microorganismos mesófi los. Lasmuestras fueron cultivadas en Agar Sangre y MacConkey Agar y los aislados fueron identifi cados por la secuenciación del 16S rRNAy sometidos al antibiograma por el método Kirby-Bauer. Las muestras de los grupos A y B, presentaron, 88,9 y 55,5% y 61,1 y 38,8% decontaminación por coliformes totales y coliformes termotolerantes respectivamente. En cuanto a los mesófi los el recuento de microorganismos de los grupos A y B, presento, respectivamente,69,4 y 52,7% de las muestras con valores arriba del límite permitido. Los microorganismos identificados fueron Escher ichia coli , Acinetobacter spp., Pseudomonas spp. y Enterobacter spp. El antibiograma mostró quelos aislados presentaban resistencia por lo menos a tres de los antimicrobianos, todos fueron resistentes a tetraciclina y uno de ellos también fue resistente a un carbapenem (imipinem).

Prematuros que se encontram em Unidades de Tratamento Intensivo Neonatal, particularmente aqueles com baixo peso e com difi culdades parareceber a alimentação natural, necessitam frequentemente de suporte nutricional por meio de fórmulas infantis (FI). As FI, quando contaminadas, podem ser fontes de infecção hospitalar, sendo a manipulação e oarmazenamento inadequados os prováveis meios de contaminação. O estudo objetivou avaliar a qualidade higiênico-sanitária e o perfilde suscetibilidade aos antimicrobianos das bactérias isoladas em FI preparadas no lactário de um hospital da cidade de Rio Grande-RS.Amostras de FI reconstituídas por lactaristas do turno da manhã (grupo A) e da tarde (grupo B) foram coletadas durante 6 meses, totalizando72 amostras analisadas. Foi realizada a contagem do Número Mais Provável (NMP/ml) de coliformes totais e termotolerantes e a contagem das Unidades Formadoras de Colônias (UFC/ml) de microrganismos mesófi los. Além disso, amostras foram semeadas em Ágar Sangue e MacConkey e os isolados foram identificados por meio de sequenciamento do 16S rRNA e submetidos ao antibiograma através de método de Kirby-Bauer. As amostras dos grupos A e B apresentaram, respectivamente, 88,9 e 55,5% de contaminação por coliformes totais e 61,1 e 38,8% por coliformes termotolerantes. Na contagem de microrganismos mesófilos, os grupos A e B apresentaram, respectivamente, 69,4 e 52,7% das amostras com contagem acima do limite permitido. Os microrganismos identificadosforam Escherichia coli, Acinetobacter spp., Pseudomonas spp. e Enterobacter spp. O teste de suscetibilidade antimicrobiana mostrou quetodos os isolados apresentavam resistência a pelo menos três antimicrobianos testados e que todos foram resistentes à tetraciclina e um também foi resistente a um carbapenem (imipinem).