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INTRODUCTION: Burn registers can provide high-quality clinical data that can be used for surveillance, research, planning service provision and clinical quality assessment. Many countrywide and intercountry burn registers now exist. The variables collected by burn registers are not standardised internationally. Few international burn register data comparisons are completed beyond basic morbidity and mortality statistics. Data comparisons across registers require analysis of homogenous variables. Little work has been done to understand whether burn registers have sufficiently similar variables to enable useful comparisons. The aim of this project is to compare the variables collected in countrywide and intercountry burn registers internationally to understand their similarities and differences. METHODS AND ANALYSIS: Burn register custodians will be invited to participate in the study and to share their register data dictionaries. Study objectives are to compare patient inclusion and exclusion criteria of each participating burn register; determine which variables are collected by each register, and if variables are required or optional, identify common variable themes; and compare a sample of variables to understand how they are defined and measured. All variable names will be extracted from each register and common themes will be identified. Detailed information will be extracted for a sample of variables to give a deeper insight into similarities and differences between registers. ETHICS AND DISSEMINATION: No patient data will be used in this project. Permission to use each register's data dictionary will be sought from respective register custodians. Results will be presented at international meetings and published in open access journals. These results will be of interest to register custodians and researchers wishing to explore international data comparisons, and countries wishing to establish their own burn register.
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Quemaduras , Humanos , Quemaduras/epidemiología , Exactitud de los Datos , InvestigadoresRESUMEN
Burn injuries have decreased markedly in high-income countries while the incidence of burns remains high in Low- and Middle-Income Countries (LMICs) where more than 90% of burns are thought to occur. However, the cause of burns in LMIC is poorly documented. The aim was to document the causes of severe burns and the changes over time. A cross-sectional survey was completed for 2014 and 2019 in eight burn centers across Africa, Asia, and Latin America: Cairo, Nairobi, Ibadan, Johannesburg, Dhaka, Kathmandu, Sao Paulo, and Guadalajara. The information summarised included demographics of burn patients, location, cause, and outcomes of burns. In total, 15,344 patients were admitted across all centers, 37% of burns were women and 36% of burns were children. Burns occurred mostly in household settings (43-79%). In Dhaka and Kathmandu, occupational burns were also common (32 and 43%, respectively). Hot liquid and flame burns were most common while electric burns were also common in Dhaka and Sao Paulo. The type of flame burns varies by center and year, in Dhaka, 77% resulted from solid fuel in 2014 while 74% of burns resulted from Liquefied Petroleum Gas in 2019. In Nairobi, a large proportion (32%) of burns were intentional self-harm or assault. The average length of stay in hospitals decreased from 2014 to 2019. The percentage of deaths ranged from 5% to 24%. Our data provide important information on the causes of severe burns which can provide guidance in how to approach the development of burn injury prevention programs in LMIC.
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Quemaduras , Países en Desarrollo , Niño , Humanos , Femenino , Masculino , Estudios Transversales , Bangladesh/epidemiología , Brasil , Sudáfrica , Nigeria , Kenia , Quemaduras/epidemiología , Unidades de Quemados , Tiempo de InternaciónRESUMEN
Group I Clostridium botulinum and Clostridium sporogenes are physiologically and genetically closely related. Both are widely distributed in the environment and can cause foodborne botulism. In this work, a physiological study was conducted with 37 isolates from spoiled canned food and five referenced strains of C. sporogenes (three isolates) and Group I C. botulinum (two isolates). Growth limits of vegetative cells were established as a function of pH and NaCl concentration in PYG modified medium (PYGm) at 30 °C for 48 days. The heat resistance of the spores was studied for 2 min and 10 min at 102 °C and 110 °C. This physiological study (pH, NaCl growth limits and heat resistance) allowed the selection of 14 isolates of C. sporogenes (twelve isolates) and Group I C. botulinum (two isolates) representative of the diversity found. This panel of 14 selected isolates (11 isolated from spoiled canned food and three reference strains), were whole genome sequenced, but no association of physiological and genetic characteristics could be detected. Finally, we studied the ability of spores to germinate and grow from 5 isolates (four C. sporogenes and one Group I C. botulinum), under stress conditions generated by pH and NaCl following a low intensity heat treatment. The accumulation of these 3 stresses creates synergies that will strongly reduce the probability of spore growth in pH and salt conditions where they usually proliferate. The effect is progressive as the conditions become drastic: the number of decimal reduction observed increases translating a probability of growth which decreases. This study provides a better understanding of the behaviour of C. sporogenes and Group I C. botulinum isolates and shows how the combination of pH, NaCl and heat treatment can help prevent or minimise foodborne botulism outbreaks.
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Botulismo , Clostridium botulinum , Clostridium , Clostridium botulinum/genética , Microbiología de Alimentos , Calor , Humanos , Concentración de Iones de Hidrógeno , Cloruro de Sodio/farmacología , Esporas BacterianasRESUMEN
BACKGROUND: Burn injuries are a leading cause of morbidity and disability, with the burden of disease being disproportionately higher in low- and middle-income countries (LMIC). Burn prevention programmes have led to significant reductions in the incidence of burns in high-income countries. However, a previous systematic review published in 2015 highlighted that implementation and evaluation of similar programmes has been limited in LMIC. The objective of this scoping review and narrative synthesis was to summarise and understand the initiatives that have been carried out to reduce burn injuries in LMIC and their effectiveness. METHODS: We aimed to identify publications that described studies of effectiveness of burn prevention interventions applied to any population within a LMIC and measured burn incidence or burns-related outcomes. Suitable publications were identified from three sources. Firstly, data was extracted from manuscripts identified in the systematic review published by Rybarczyk et al. We then performed a search for manuscripts on burn prevention interventions published between January 2015 and September 2020. Finally, we extracted data from two systematic reviews where burn evidence was not the primary outcome, which were identified by senior authors. A quality assessment and narrative synthesis of included manuscripts were performed. RESULTS: In total, 24 manuscripts were identified and categorized according to intervention type. The majority of manuscripts (n = 16) described education-based interventions. Four manuscripts focused on environmental modification interventions and four adopted a mixed-methods approach. All of the education-based initiatives demonstrated improvements in knowledge relating to burn safety or first aid, however few measured the impact of their intervention on burn incidence. Four manuscripts described population-based educational interventions and noted reductions in burn incidence. Only one of the four manuscripts describing environmental modification interventions reported burns as a primary outcome measure, noting a reduction in burn incidence. All mixed-method interventions demonstrated some positive improvements in either burn incidence or burns-related safety practices. CONCLUSION: There is a lack of published literature describing large-scale burn prevention programmes in LMIC that can demonstrate sustained reductions in burn incidence. Population-level, collaborative projects are necessary to drive forward burn prevention through specific environmental or legislative changes and supplementary educational programmes.
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Clostridium botulinum Group I and Clostridium sporogenes are closely related bacteria responsible for foodborne, infant and wound botulism. A comparative genomic study with 556 highly diverse strains of C. botulinum Group I and C. sporogenes (including 417 newly sequenced strains) has been carried out to characterise the genetic diversity and spread of these bacteria and their neurotoxin genes. Core genome single-nucleotide polymorphism (SNP) analysis revealed two major lineages; C. botulinum Group I (most strains possessed botulinum neurotoxin gene(s) of types A, B and/or F) and C. sporogenes (some strains possessed a type B botulinum neurotoxin gene). Both lineages contained strains responsible for foodborne, infant and wound botulism. A new C. sporogenes cluster was identified that included five strains with a gene encoding botulinum neurotoxin sub-type B1. There was significant evidence of horizontal transfer of botulinum neurotoxin genes between distantly related bacteria. Population structure/diversity have been characterised, and novel associations discovered between whole genome lineage, botulinum neurotoxin sub-type variant, epidemiological links to foodborne, infant and wound botulism, and geographic origin. The impact of genomic and physiological variability on the botulism risk has been assessed. The genome sequences are a valuable resource for future research (e.g., pathogen biology, evolution of C. botulinum and its neurotoxin genes, improved pathogen detection and discrimination), and support enhanced risk assessments and the prevention of botulism.
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Toxinas Botulínicas/genética , Botulismo/microbiología , Clostridium botulinum/genética , Clostridium/genética , Genoma Bacteriano , Polimorfismo de Nucleótido Simple , Infección de Heridas/microbiología , Toxinas Botulínicas/metabolismo , Botulismo/diagnóstico , Botulismo/epidemiología , Clostridium/metabolismo , Clostridium/patogenicidad , Clostridium botulinum/metabolismo , Clostridium botulinum/patogenicidad , Genotipo , Humanos , Lactante , Epidemiología Molecular , Fenotipo , Filogenia , Secuenciación Completa del Genoma , Infección de Heridas/diagnóstico , Infección de Heridas/epidemiologíaRESUMEN
The safety of current UK industry practice (including shelf-life) for chilled, vacuum/modified atmosphere-packed fresh red meat (beef, lamb and pork) held at 3°C-8°C has been evaluated with respect to non-proteolytic Clostridium botulinum. UK industry typically applies a retail pack shelf-life at 3°C-8°C to 13 days for fresh red meat, with a maximum of 23 days for beef, 27 days for lamb, and 18 days for pork. An exposure assessment established that current commercial practice for fresh red meat provided strong protection with more than 1010 person servings marketed in the UK without association with foodborne botulism. A challenge test demonstrated that spores of non-proteolytic C. botulinum inoculated on chilled vacuum-packed fresh red meat did not lead to detectable neurotoxin at day 50 for beef, day 35 for lamb, or day 25 for pork (i.e. <40 pg type B toxin and type E toxin g-1 of meat). The products were visually spoiled many days before these end points. The exposure assessment and challenge test demonstrated the safety of current UK industry practices for the shelf-life of fresh, vacuum-packed beef, lamb and pork held at 3°C-8°C with respect to C. botulinum, and that botulinum neurotoxin was not detected within their organoleptic shelf-life.
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Botulismo/epidemiología , Exposición Dietética/estadística & datos numéricos , Embalaje de Alimentos/métodos , Almacenamiento de Alimentos/métodos , Carne Roja/microbiología , Animales , Atmósfera , Botulismo/microbiología , Bovinos , Clostridium botulinum/aislamiento & purificación , Frío , Exposición Dietética/análisis , Microbiología de Alimentos , Incidencia , Neurotoxinas/análisis , Carne Roja/análisis , Medición de Riesgo , Ovinos , Olfato , Esporas Bacterianas/aislamiento & purificación , Porcinos , Gusto , VacioRESUMEN
The neurotoxin formed by Clostridium botulinum Group II is a major cause of foodborne botulism, a deadly intoxication. This study aims to understand the genetic diversity and spread of C. botulinum Group II strains and their neurotoxin genes. A comparative genomic study has been conducted with 208 highly diverse C. botulinum Group II strains (180 newly sequenced strains isolated from 16 countries over 80 years, 28 sequences from Genbank). Strains possessed a single type B, E, or F neurotoxin gene or were closely related strains with no neurotoxin gene. Botulinum neurotoxin subtype variants (including novel variants) with a unique amino acid sequence were identified. Core genome single-nucleotide polymorphism (SNP) analysis identified two major lineages-one with type E strains, and the second dominated by subtype B4 strains with subtype F6 strains. This study revealed novel details of population structure/diversity and established relationships between whole-genome lineage, botulinum neurotoxin subtype variant, association with foodborne botulism, epidemiology, and geographical source. Additionally, the genome sequences represent a valuable resource for the research community (e.g., understanding evolution of C. botulinum and its neurotoxin genes, dissecting key aspects of C. botulinum Group II biology). This may contribute to improved risk assessments and the prevention of foodborne botulism.
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Toxinas Botulínicas/genética , Botulismo/microbiología , Clostridium botulinum/genética , Evolución Molecular , Neurotoxinas/genética , Polimorfismo de Nucleótido Simple , Botulismo/epidemiología , Botulismo/prevención & control , Botulismo/transmisión , Clostridium botulinum/clasificación , Clostridium botulinum/aislamiento & purificación , Clostridium botulinum/patogenicidad , Genoma Bacteriano , Genotipo , Fenotipo , Filogenia , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: Spores of psychrotrophic Bacillus cereus may survive the mild heat treatments given to minimally processed chilled foods. Subsequent germination and cell multiplication during refrigerated storage may lead to bacterial concentrations that are hazardous to health. SCOPE AND APPROACH: This review is concerned with the characterisation of factors that prevent psychrotrophic B. cereus reaching hazardous concentrations in minimally processed chilled foods and associated foodborne illness. A risk assessment framework is used to quantify the risk associated with B. cereus and minimally processed chilled foods. KEY FINDINGS AND CONCLUSIONS: Bacillus cereus is responsible for two types of food poisoning, diarrhoeal (an infection) and emetic (an intoxication); however, no reported outbreaks of food poisoning have been associated with B. cereus and correctly stored commercially-produced minimally processed chilled foods. In the UK alone, more than 1010 packs of these foods have been sold in recent years without reported illness, thus the risk presented is very low. Further quantification of the risk is merited, and this requires additional data. The lack of association between diarrhoeal food poisoning and correctly stored commercially-produced minimally processed chilled foods indicates that an infectious dose has not been reached. This may reflect low pathogenicity of psychrotrophic strains. The lack of reported association of psychrotrophic B. cereus with emetic illness and correctly stored commercially-produced minimally processed chilled foods indicates that a toxic dose of the emetic toxin has not been formed. Laboratory studies show that strains form very small quantities of emetic toxin at chilled temperatures.
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BACKGROUND: Pavement-street contact burns are rare. This study compared recent contact burns to those published in "Pavement temperature and burns: Streets of Fire" in 1995. The hypothesis was that there were a significantly increased number of pavement-street burns, as a result of increased ambient temperatures, and that motor vehicle crash (MVC) contact burns were less severe than pavements-street burns. METHODS: This was a retrospective burn center registry study of naturally heated surface contact burns during May to September from 2016 to 2018. Statistical analyses were performed with one-way analysis of variance (ANOVA) and Maximum Likelihood chi-squared for age, percent of total burn surface area (% TBSA), treatment, hospitalization, comorbidities, hospital charges, mortality, ambient, and surface temperatures (pavement, asphalt, rocks). RESULTS: In the 1995 study, median ambient temperatures were 106 (range 100-113) °F compared to the 108 (range 86-119) °F highest noon temperature in the current study. No ambient temperature differences were recorded on days with pavement burn admissions compared to days without these admissions. There were 225 pavement, 27 MVC, 15 road rash, and 103 other contact burns. The major injuries in the pavement group were due to being "down" (unknown reason), falls, and barefoot. Compared to the others, the pavement group was older, 56+ years, p < 0.001, and had smaller burns but similar length of stay. Fifty percent of the 225 pavement group patients with full-thickness burns required skin grafts. There were 13 (6%) fatalities in the pavement group vs 1 (4%) in the MVC group, p = 0.01. Fatalities were secondary to sepsis, shock, cardiac, respiratory, or kidney complications. Compared to survivors, the non-survivors had a significantly higher % TBSA (10% vs 4%), p = 0.01, and lower Glasgow Coma Scores (10 vs 15), p = 0.002. CONCLUSION: There was a median 2 °F increase in ambient temperature since 1995. The increase in pavement burn admissions was multi-factorial: higher temperatures, population, and the number of older patients, with increased metropolis expansion, outreach, and urban heat indices. Pavement group was similar to the MVC group except for significantly older age and increased mortality. Morbidity associated with age contributed to increased mortality.
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Patients with major burn injuries typically require numerous blood transfusions. It is not known if an inhalation injury (INHI) directly influences the need for blood transfusion. The purpose of this study was to determine whether INHI increases the amount of blood transfused to major burn patients. A secondary analysis from the Transfusion Requirement in Burn Care Evaluation (TRIBE) study was conducted. Patients with INHI were compared with patients without INHI. The number of red blood cell (RBC) transfusions per day (RBC per day) between INHI and No INHI was analyzed with a multivariable regression. Patients with INHI (n = 78) had significantly larger burns (P = .0004), larger full-thickness burns (P = .0007), greater admission APACHE score (P < .0001), higher admission multiple organ dysfunction scores (P < .0001), and were transfused more RBC per day (P = .009) than No INHI patients (n = 267). In the multivariable regression analysis, RBC per day was significantly associated with the %TBSA burn (P < .0001), age of the patient (P = .004), the need for more than 1 day of mechanical ventilation (P < .0001), the occurrence of at least one blood stream infection (BSI; P = .044), and being assigned to the liberal transfusion arm of TRIBE (P < .001) but not the presence of INHI (P = .056). The null hypothesis that INHI exerts no influence on the amount of blood transfused could not be rejected. Larger burn size, advanced patient age, mechanical ventilation, and BSIs are important determinants of the blood transfusion rate in major burn patients.
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Quemaduras/terapia , Transfusión de Eritrocitos/estadística & datos numéricos , Lesión por Inhalación de Humo/epidemiología , APACHE , Adulto , Factores de Edad , Bacteriemia/epidemiología , Quemaduras/patología , Femenino , Mortalidad Hospitalaria , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Puntuaciones en la Disfunción de Órganos , Neumonía/epidemiología , Respiración Artificial/estadística & datos numéricosRESUMEN
OBJECTIVES: Studies suggest that a restrictive transfusion strategy is safe in burns, yet the efficacy of a restrictive transfusion policy in massive burn injury is uncertain. Our objective: compare outcomes between massive burn (≥60% total body surface area (TBSA) burn) and major (20-59% TBSA) burn using a restrictive or a liberal blood transfusion strategy. METHODS: Patients with burns ≥20% were block randomized by age and TBSA to a restrictive (transfuse hemoglobin <7 g/dL) or liberal (transfuse hemoglobin <10 g/dL) strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS: Three hundred and forty-five patients received 7,054 units blood, 2,886 in massive and 4,168 in restrictive. Patients were similar in age, TBSA, and inhalation injury. The restrictive group received less blood (45.57 ± 47.63 vs. 77.16 ± 55.0, p < 0.03 massive; 11.0 ± 16.70 vs. 16.78 ± 17.39, p < 0.001) major). In massive burn, the restrictive group had fewer ventilator days (p < 0.05). Median ICU days and LOS were lower in the restrictive group; wound healing, mortality, and infection did not differ. No significant outcome differences occurred in the major (20-59%) group (p > 0.05). CONCLUSIONS: A restrictive transfusion strategy may be beneficial in massive burns in reducing ventilator days, ICU days and blood utilization, but does not decrease infection, mortality, hospital LOS or wound healing.
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Transfusión Sanguínea/métodos , Quemaduras/terapia , Guías como Asunto/normas , Adulto , Transfusión Sanguínea/tendencias , Superficie Corporal , Quemaduras/complicaciones , Femenino , Política de Salud , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVES: Major trials examining storage age of blood transfused to critically ill patients administered relatively few blood transfusions. We sought to determine if the storage age of blood affects outcomes when very large amounts of blood are transfused. DESIGN: A secondary analysis of the multicenter randomized Transfusion Requirement in Burn Care Evaluation study which compared restrictive and liberal transfusion strategies. SETTING: Eighteen tertiary-care burn centers. PATIENTS: Transfusion Requirement in Burn Care Evaluation evaluated 345 adults with burns greater than or equal to 20% of the body surface area. We included only the 303 patients that received blood transfusions. INTERVENTIONS: The storage ages of all transfused red cell units were collected during Transfusion Requirement in Burn Care Evaluation. A priori measures of storage age were the the mean storage age of all transfused blood and the proportion of all transfused blood considered very old (stored ≥ 35 d). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the severity of multiple organ dysfunction. Secondary outcomes included time to wound healing, the duration of mechanical ventilation, and in-hospital mortality. There were 6,786 red cell transfusions with a mean (± SD) storage age of 25.6 ± 10.2 days. Participants received a mean of 23.4 ± 31.2 blood transfusions (range, 1-219) and a mean of 5.3 ± 10.7 units of very old blood. Neither mean storage age nor proportion of very old blood had any influence on multiple organ dysfunction severity, time to wound healing, or mortality. Duration of ventilation was significantly predicted by both mean blood storage age and the proportion of very old blood, but this was of questionable clinical relevance given extreme variability in duration of ventilation (adjusted r ≤ 0.01). CONCLUSIONS: Despite massive blood transfusion, including very old blood, the duration of red cell storage did not influence outcome in burn patients. Provision of the oldest blood first by Blood Banks is rational, even for massive transfusion.
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Conservación de la Sangre/estadística & datos numéricos , Transfusión Sanguínea/estadística & datos numéricos , Quemaduras/terapia , Enfermedad Crítica/terapia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto , Quemaduras/mortalidad , Enfermedad Crítica/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Respiración Artificial/estadística & datos numéricos , Centros de Atención Terciaria , Factores de Tiempo , Índices de Gravedad del Trauma , Cicatrización de Heridas/fisiologíaRESUMEN
Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG.
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Quemaduras/cirugía , Trasplante de Piel , Recolección de Tejidos y Órganos/instrumentación , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Mallas Quirúrgicas , Trasplante Autólogo , Resultado del Tratamiento , Cicatrización de Heridas , Adulto JovenRESUMEN
Clostridium botulinum is an anaerobic spore forming bacterium that produces the potent botulinum neurotoxin that causes a severe and fatal neuro-paralytic disease of humans and animals (botulism). C. botulinum Group II is a psychrotrophic saccharolytic bacterium that forms spores of moderate heat resistance and is a particular hazard in minimally heated chilled foods. Spore germination is a fundamental process that allows the spore to transition to a vegetative cell and typically involves a germinant receptor (GR) that responds to environmental signals. Analysis of C. botulinum Group II genomes shows they contain a single GR cluster (gerX3b), and an additional single gerA subunit (gerXAO). Spores of C. botulinum Group II strain Eklund 17B germinated in response to the addition of L-alanine, but did not germinate following the addition of exogenous Ca2+-DPA. Insertional inactivation experiments in this strain unexpectedly revealed that the orphan GR GerXAO is essential for L-alanine stimulated germination. GerX3bA and GerX3bC affected the germination rate but were unable to induce germination in the absence of GerXAO. No role could be identified for GerX3bB. This is the first study to identify the functional germination receptor of C. botulinum Group II.
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Alanina/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Clostridium botulinum/fisiología , Esporas Bacterianas , Clostridium botulinum/clasificación , FilogeniaRESUMEN
The deadly neurotoxins of Clostridium botulinum (BoNTs) comprise eight serotypes (A-G; X). The neurotoxin gene cluster encoding BoNT and its accessory proteins includes an operon containing an ntnh gene upstream of the boNT gene. Another operon contains either ha (haemagglutinin) or orfX genes (of unknown function). Here we describe a novel boNT gene cluster from Enterococcus sp. 3G1_DIV0629, with a typical ntnh gene and an uncommon orfX arrangement. The neurotoxin (designated putative eBoNT/J) contains a metallopeptidase zinc-binding site, a translocation domain and a target cell attachment domain. Structural properties of the latter suggest a novel targeting mechanism with consequent implications for application by the pharmaceutical industry. This is the first complete boNT gene cluster identified in a non-clostridial genome.
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Enterococcus/metabolismo , Familia de Multigenes , Neurotoxinas/química , Neurotoxinas/genética , Sitios de Unión , Enterococcus/química , Enterococcus/genética , Genes Bacterianos , Metaloproteasas/metabolismo , Modelos Moleculares , Neurotoxinas/metabolismo , Conformación Proteica , Dominios Proteicos , Transporte de ProteínasRESUMEN
Context: One approach to reducing the harm caused by cigarette smoking, at both individual and population level, is to develop, assess and commercialize modified risk alternatives that adult smokers can switch to. Studies to demonstrate the exposure and risk reduction potential of such products generally involve the measuring of biomarkers, of both exposure and effect, sampled in various biological matrices.Objective: In this review, we detail the pros and cons for using several biomarkers as indicators of effects of changing from conventional cigarettes to modified risk products.Materials and methods: English language publications between 2008 and 2017 were retrieved from PubMed using the same search criteria for each of the 25 assessed biomarkers. Nine exclusion criteria were applied to exclude non-relevant publications.Results: A total of 8876 articles were retrieved (of which 7476 were excluded according to the exclusion criteria). The literature indicates that not all assessed biomarkers return to baseline levels following smoking cessation during the study periods but that nine had potential for use in medium to long-term studies.Discussion and conclusion: In clinical studies, it is important to choose biomarkers that show the biological effect of cessation within the duration of the study.
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The Gram-positive spore-forming anaerobe Clostridium sporogenes is a significant cause of food spoilage, and it is also used as a surrogate for C. botulinum spores for testing the efficacy of commercial sterilization. C. sporogenes spores have also been proposed as a vector to deliver drugs to tumor cells for cancer treatments. Such an application of C. sporogenes spores requires their germination and return to life. In this study, Raman spectroscopy and differential interference contrast (DIC) microscopy were used to analyze the germination kinetics of multiple individual C. sporogenes wild-type and germination mutant spores. Most individual C. sporogenes spores germinated with L-alanine began slow leakage of â¼5% of their large Ca-dipicolinic acid (CaDPA) depot at T1, all transitioned to rapid CaDPA release at Tlag1, completed CaDPA release at Trelease, and finished peptidoglycan cortex hydrolysis at Tlys. T1, Tlag1, Trelease, and Tlys times for individual spores were heterogeneous, but ΔTrelease (Trelease - Tlag1) periods were relatively constant. However, variability in T1 (or Tlag1) times appeared to be the major reason for the heterogeneity between individual spores in their germination times. After Trelease, some spores also displayed another lag in rate of change in DIC image intensity before the start of a second obvious DIC image intensity decline of 25-30% at Tlag2 prior to Tlys. This has not been seen with spores of other species. Almost all C. sporogenes spores lacking the cortex-lytic enzyme (CLE) CwlJ spores exhibited a Tlag2 in L-alanine germination. Sublethal heat treatment potentiated C. sporogenes spore germination with L-alanine, primarily by shortening T1 times. Spores without the CLEs SleB or CwlJ exhibited greatly slowed germination with L-alanine, but spores lacking all germinant receptor proteins did not germinate with L-alanine. The absence of these various germination proteins also decreased but did not abolish germination with the non-GR-dependent germinants dodecylamine and CaDPA, but spores without CwlJ exhibited no germination with CaDPA. Finally, C. sporogenes spores displayed commitment in germination, but memory in GR-dependent germination was small, and less than the memory in Bacillus spore germination.
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OBJECTIVE: Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. BACKGROUND: Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. METHODS: This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8âg/dL) or liberal (hemoglobin 10-11âg/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS: Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3â±â32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8â±â44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, χ test). CONCLUSIONS: A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).
Asunto(s)
Transfusión Sanguínea/métodos , Quemaduras/terapia , Adolescente , Adulto , Bacteriemia/epidemiología , Quemaduras/complicaciones , Quemaduras/mortalidad , Humanos , Incidencia , Infecciones/epidemiología , Tiempo de Internación , Persona de Mediana Edad , Insuficiencia Multiorgánica/epidemiología , Estudios Prospectivos , Respiración Artificial , Factores de Tiempo , Resultado del Tratamiento , Cicatrización de Heridas , Adulto JovenRESUMEN
Chronic obstructive pulmonary disease (COPD) is one of the major causes of chronic morbidity and mortality worldwide. The development of markers of COPD onset is hampered by the lack of accessibility to the primary target tissue, and there is a need to consider other sample sources as surrogates for biomarker research. Airborne toxicants pass through the nasal epithelium before reaching the lower airways, and the similarity with bronchial histology makes it an attractive surrogate for lower airways. In this work, we describe the transcriptomics findings from the nasal epithelia of subjects enrolled in a clinical study focusing on the identification of COPD biomarkers. Transcriptomic data were analyzed using the biological network approach that enabled us to pinpoint the biological processes affected in the upper respiratory tract in response to smoking and mild-to-moderate COPD. Our results indicated that nasal and lower airway immune responses were considerably different in COPD subjects and caution should be exercised when using upper airway samples as a surrogate for the lower airway. Nevertheless, the network approach described here could present a sensitive means of identifying smokers at risk of developing COPD.
RESUMEN
As part of the State of Science Meeting, care in elderly was one of the foci. This "white paper" deriving from this meeting indicates advances in the field of burn injuries in the elderly but more importantly areas that are in need of novel insights and investigations. The group created specific segments of a patient's course pre- and postinjury to selectively identify specifics we need to improve on. Tasks were created that were assigned to volunteers of the group and are given in detail in this article. The overarching aim is to initiate substantial momentum among the members of the American Burn Association to improve the outcomes in the elderly burn patients.