RESUMEN
Hospital Dentistry is an inclusive synergism of the recognized dental specialties in an emergency/hospital atmosphere. This perspective composition serves to display the breadth of Hospital Dentistry from an observational and creative viewpoint while elucidating the role of the Hospital Dentist in the dynamic large university hospital setting. It calls for increased awareness of the field of Hospital Dentistry and the potential for its specialized role in the future of dental medicine. Hospital-based General Practice Residencies (GPR) expose trainees to Hospital Dentistry and its integrated role in medicine. Exploring the ventures of Hospital Dentistry highlight the need to increase Hospital Dentistry-focused student groups while encouraging advanced dental education through GPR programs. The rising geriatric community, complex patient caseload, and population growth call for the need to expand the field of Hospital Dentistry through its recognition as a specialty in the future of dental medicine.
Asunto(s)
Internado y Residencia , Medicina , Anciano , Odontología , Hospitales , HumanosRESUMEN
This paper presents an analysis of the symbolic conditions which govern health care provision in the Scottish prison system. The paper considers the wider context of Scottish prisons, where health care provision follows a similar structure both in juvenile and adult prisons. Our intention is to provoke a debate about the doxa (Bourdieu, 1977), which underlies decision making in respect of health care in prison, in a political environment where pragmatism, allied to the 'pathologisation' of social policies, health and criminal justice has been a hegemonic force.
Asunto(s)
Toma de Decisiones , Atención a la Salud/organización & administración , Prisioneros , Prisiones/organización & administración , Adolescente , Adulto , Política de Salud , Humanos , Delincuencia Juvenil , Política , Rehabilitación , Escocia , ViolenciaRESUMEN
Abstract This paper presents an analysis of the symbolic conditions which govern health care provision in the Scottish prison system. The paper considers the wider context of Scottish prisons, where health care provision follows a similar structure both in juvenile and adult prisons. Our intention is to provoke a debate about the doxa (Bourdieu, 1977), which underlies decision making in respect of health care in prison, in a political environment where pragmatism, allied to the 'pathologisation' of social policies, health and criminal justice has been a hegemonic force.
Resumo Este artigo apresenta uma análise das condições simbólicas que governam a provisão de saúde nos sistemas prisional escocês. O artigo considera o contexto ampliado do sistema prisonal escocês, onde a provisão de saúde segue uma estrutura similar tanto nas unidades juvenis quanto nas de adultos. Nossa intenção é provocar um debate sobre a doxa (Bourdieu, 1977) que sustenta as tomadas de decisão sobre provisão de saúde nas prisões, onde o contexto político marcado pelo pragmatismo, aliado à 'patologização' das políticas sociais, de saúde e de justiça criminal, tem sido uma força hegemônica.
Asunto(s)
Humanos , Adolescente , Adulto , Prisiones/organización & administración , Prisioneros , Toma de Decisiones , Atención a la Salud/organización & administración , Política , Rehabilitación , Escocia , Violencia , Política de Salud , Delincuencia JuvenilRESUMEN
The partitioning of pharmaceuticals in the environment can be assessed by measuring their adsorption coefficients (Kd) between aqueous and solid phases. Measuring this coefficient in sewage sludge gives an indication of their partitioning behaviour in a wastewater treatment plant and hence contributes to an understanding of their subsequent fate. The regulatory approved method for measuring Kd in sewage sludge is the US Environmental Protection Agency's Office of Prevention, Pesticides and Toxic Substances (OPPTS) guideline 835.1110, which is labour intensive and time consuming. We describe an alternative method for measuring the Kd of pharmaceuticals in sewage sludge using a modified solid-phase extraction (SPE) technique. SPE cartridges were packed at different sludge/PTFE ratios (0.4, 6.0, 24.0 and 40.0% w/w sludge) and eluted with phosphate buffer at pH 7.4. The approach was tested initially using three pharmaceuticals (clofibric acid, diclofenac and oxytetracycline) that covered a range of Kd values. Subsequently, the sorption behaviour of ten further pharmaceuticals with varying physico-chemical properties was evaluated. Results from the SPE method were comparable to those of the OPPTS test, with a correlation coefficient of 0.93 between the two approaches. SPE cartridges packed with sludge and PTFE were stable for up to one year; use within one month reduced variability in measurements (to a maximum of 0.6 log units). The SPE method is low-cost, easy to use and enables the rapid measurement of Kd values for a large number of chemicals. It can be used as an alternative to the more laborious full OPPTS test in environmental fate studies and risk assessments.
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Preparaciones Farmacéuticas/análisis , Aguas del Alcantarillado/química , Extracción en Fase Sólida/métodos , Eliminación de Residuos Líquidos/métodos , Adsorción , Cromatografía Líquida de Alta Presión , Ácido Clofíbrico/química , Diclofenaco/química , Modelos Químicos , Estructura Molecular , Oxitetraciclina/química , Preparaciones Farmacéuticas/químicaRESUMEN
The Organisation for Economic Co-operation and Development (OECD) 308 water-sediment transformation test has been routinely conducted in Phase II Tier A testing of the environmental risk assessment (ERA) for all human pharmaceutical marketing authorization applications in Europe, since finalization of Environmental Medicines Agency (EMA) ERA guidance in June 2006. In addition to the "Ready Biodegradation" test, it is the only transformation test for the aquatic/sediment compartment that supports the classification of the drug substance for its potential persistence in the environment and characterizes the fate of the test material in a water-sediment environment. Presented is an overview of 31 OECD 308 studies conducted by 4 companies with a focus on how pharmaceuticals behave in these water-sediment systems. The geometric mean (gm) parent total system half-life for the 31 pharmaceuticals was 30 days with 10th/90th percentile (10/90%ile) of 14.0/121.6 d respectively, with cationic substances having a half-life approximately 2 times that of neutral and anionic substances. The formation of nonextractable residues (NER) was considerable, with gm (10/90%ile) of 38% (20.5/81.4) of the applied radioactivity: cationic substances 50.8% (27.7/87.6), neutral substances 31.9% (15.3/52.3), and anionic substances 16.7% (9.5/30.6). In general, cationic substances had fewer transformation products and more unchanged parent remaining at day 100 of the study. A review of whether a simplified 1-point analysis could reasonably estimate the parent total system half-life showed that the total amount of parent remaining in the water and sediment extracts at day 100 followed first-order kinetics and that the theoretical half-life and the measured total system half-life values agreed to within a factor of 1.68. Recommendations from this 4-company collaboration addressed: 1) the need to develop a more relevant water-sediment transformation test reflecting the conditions of the discharge scenario more representative of human pharmaceuticals, 2) potential use of a 1-point estimate of parent total system half-life in the EMA ERA screening phase of testing, 3) the need for a more consistent and transparent interpretation of the results from the transformation study; consistent use of terminology such as dissipation, transformation, depletion, and degradation in describing their respective processes in the ERA, 4) use of the parent total system dissipation half-life in hazard classification schemes and in revising predicted environmental concentration in ERA, and 5) further research into cationic pharmaceuticals to assess whether their classification as such serves as a structural alert to high levels of NER; and whether this results in reduced bioavailability of those residues.
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Preparaciones Farmacéuticas/análisis , Medición de Riesgo/métodos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Aniones , Biodegradación Ambiental , Cationes , Monitoreo del Ambiente/métodos , Sedimentos Geológicos , Guías como Asunto , Semivida , Humanos , Preparaciones Farmacéuticas/metabolismo , Aguas del Alcantarillado , Eliminación de Residuos LíquidosRESUMEN
It is important to understand the adsorption mechanism of chemicals and active pharmaceutical ingredients (API) on sewage sludge since wastewater treatment plants are the last barrier before the release of these compounds to the environment. Adsorption models were developed considering mostly hydrophobic API-sludge interaction. They have poor predictive ability, especially with ionisable compounds. This work proposes a solid-phase extraction (SPE) approach to estimate rapidly the API-sludge interaction. Sludge-filled SPE cartridges could not be percolated with API spiked mobile phases so different powders were tested as SPE sludge supports. Polytetrafluoroethylene (PTFE) was selected and tested at different PTFE/sludge ratios under eight different adsorption conditions with three API ionisable compounds. The PTFE/sludge mixtures with 50% or less sludge could be used in SPE mode for API sorption studies with methanol/water liquid phases. The results gave insights into API-sludge interactions. It was found that π-π, hydrogen-bonding and charge-charge interactions were as important as hydrophobicity in the adsorption mechanism of charged APIs on sludge.
RESUMEN
It is important to understand the adsorption mechanism of chemicals and active pharmaceu-tical ingredients (API) on sewage sludge since wastewater treatment plants are the last barrier before the release of these compounds to the environment. Adsorption models were developed considering mostly hydrophobic API-sludge interaction. They have poor predictive ability, especially with ionisable compounds. This work proposes a solid-phase extraction (SPE) approach to estimate rapidly the API-sludge interaction. Sludge-filled SPE cartridges could not be percolated with API spiked mobile phases so different powders were tested as SPE sludge supports. Polytetrafluoroethylene (PTFE) was selected and tested at different PTFE/sludge ratios under eight different adsorption conditions with three API ionisable compounds. The PTFE/sludge mixtures with 50% or less sludge could be used in SPE mode for API sorption studies with methanol/water liquid phases. The results gave insights into API-sludge interactions. It was found that π-π, hydrogen-bonding and charge-charge interactions were as important as hydrophobicity in the adsorption mechanism of charged APIs on sludge.
RESUMEN
BACKGROUND: Here, we present to practicing spine surgeons and an even broader professional audience a case in which one spine surgeon, operating in his own outpatient surgery facility, performed a staggering number of procedures or "multiple operations on the same patient" (MOSP). In the vacuum of information regarding the multiply operated patient, the authors are without any guidance or even knowledge as to whether or not MOSP is a complete aberration or occurs with some documentable frequency within the medical/surgical profession. CASE REPORT: The authors report a very extraordinary case of a woman, who, between April 4, 2000, and April 17, 2002, underwent 27 operative procedures on various parts of her spine. Within this same time frame, she additionally had one operation on each shoulder and an arthroscopy of the left knee. Each operation was performed at the same outpatient spine surgery center by the same surgeon and each was accompanied by a full operative report. CONCLUSIONS: As there is little information regarding MOSP, future documentation and reports are required so that the extent and degree of MOSP can be better evaluated. Furthermore, it is critical to examine multiple quality concerns, including indications for surgery, examination of patients' personality traits in order to understand why one individual would subject herself to such a multitude of operations in such a short period of time, and some examination of the surgeon's motivations and practice patterns.
RESUMEN
The single-component RcoM transcription factor couples an N-terminally bound heme cofactor with a C-terminal "LytTR" DNA-binding domain. Here the RcoM(Bx)-1 protein from Burkholderia xenovorans LB400 was heterologously expressed and then purified in a form with minimal bound CO (~10%) and was found to stably bind this effector with a nanomolar affinity. DNase I protection assays demonstrated that the CO-associated form binds with a micromolar affinity to two ~60-bp DNA regions, each comprised of a novel set of three direct-repeat binding sites spaced 21 bp apart on center. Binding to each region was independent, while binding to the triplet binding sites within a region was cooperative, depended upon spacing and sequence, and was marked by phased DNase I hyperactivity and protection patterns consistent with considerable changes in the DNA conformation of the nucleoprotein complex. Each protected binding site spanned a conserved motif (5'-TTnnnG-3') that was present, in triplicate, in putative RcoM-binding regions of more than a dozen organisms. In vivo screens confirmed the functional importance of the conserved "TTnnnG" motif residues and their triplet arrangement and were also used to determine an improved binding motif [5'-CnnC(C/A)(G/A)TTCAnG-3'] that more closely corresponds to canonical LytTR domain/DNA-binding sites. A low-affinity but CO-dependent binding of RcoM(Bx)-1 to a variety of DNA probes was demonstrated in vitro. We posit that for the RcoM(Bx)-1 protein, the high CO affinity combined with multiple low-affinity DNA-binding events constitutes a transcriptional "accumulating switch" that senses low but persistent CO levels.
Asunto(s)
Proteínas Bacterianas/metabolismo , Burkholderia/metabolismo , Monóxido de Carbono/metabolismo , Factores de Transcripción/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Burkholderia/genética , Clonación Molecular , Huella de ADN , ADN Bacteriano/metabolismo , Expresión Génica , Regulación Bacteriana de la Expresión Génica , Unión Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/aislamiento & purificaciónRESUMEN
The CO-responsive transcriptional regulator RcoM from Burkholderia xenovorans (BxRcoM) was recently identified as a Cys(thiolate)-ligated heme protein that undergoes a redox-mediated ligand switch; however, the Cys bound to the Fe(III) heme was not identified. To that end, we generated and purified three Cys-to-Ser variants of BxRcoM-2--C94S, C127S, and C130S--and examined their spectroscopic properties in order to identify the native Cys(thiolate) ligand. Electronic absorption, resonance Raman, and electron paramagnetic resonance (EPR) spectroscopies demonstrate that the C127S and C130S variants, like wild-type BxRcoM-2, bind a six-coordinate low-spin Fe(III) heme using a Cys/His ligation motif. In contrast, electronic absorption and resonance Raman spectra of the C94S variant are most consistent with a mixture of five-coordinate high-spin and six-coordinate low-spin Fe(III) heme, neither of which are ligated by a Cys(thiolate) ligand. The EPR spectrum of C94S is dominated by a large, axial high-spin Fe(III) signal, confirming that the native ligation motif is not maintained in this variant. Together, these data reveal that Cys(94) is the distal Fe(III) heme ligand in BxRcoM-2; by sequence alignment, Cys(94) is also implicated as the distal Fe(III) heme ligand in BxRcoM-1, another homologue found in the same organism.
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Burkholderia/química , Cisteína/química , Hemoproteínas/química , Elementos Reguladores de la Transcripción/genética , Secuencia de Aminoácidos , Burkholderia/genética , Cisteína/genética , Variación Genética , Hemoproteínas/genética , Ligandos , Datos de Secuencia Molecular , Estructura Molecular , Alineación de Secuencia , Espectrometría RamanRESUMEN
The intentional misuse of psychotropic drugs is recognized as a significant public health concern in Canada, although there is a lack of empirical research detailing this. Even less research has been documented on the misuse of prescription drugs among First Nations in Canada. In the past, Western biomedical and individual-based approaches to researching Indigenous health have been applied, whereas First Nations' understandings of health are founded on a holistic view of wellbeing. Recognition of this disjuncture, alongside the protective influence of First Nations traditional culture, is foundational to establishing an empirical understanding of and comprehensive response to prescription drug misuse. We propose health promotion as a framework from which to begin to explore this. Our work with a health promotion framework has conveyed its potential to support the consideration of Western and Indigenous worldviews together in an 'ethical space', with illustrations provided. Health promotion also allots for the consideration of Canada's colonial history of knowledge production in public health and supports First Nations' self-determination. Based on this, we recommend three immediate ways in which a health promotion framework can advance research on prescription drug misuse among First Nations in Canada.
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Rhodospirillum rubrum (Esmarch 1887) Molisch 1907 is the type species of the genus Rhodospirillum, which is the type genus of the family Rhodospirillaceae in the class Alphaproteobacteria. The species is of special interest because it is an anoxygenic phototroph that produces extracellular elemental sulfur (instead of oxygen) while harvesting light. It contains one of the most simple photosynthetic systems currently known, lacking light harvesting complex 2. Strain S1(T) can grow on carbon monoxide as sole energy source. With currently over 1,750 PubMed entries, R. rubrum is one of the most intensively studied microbial species, in particular for physiological and genetic studies. Next to R. centenum strain SW, the genome sequence of strain S1(T) is only the second genome of a member of the genus Rhodospirillum to be published, but the first type strain genome from the genus. The 4,352,825 bp long chromosome and 53,732 bp plasmid with a total of 3,850 protein-coding and 83 RNA genes were sequenced as part of the DOE Joint Genome Institute Program DOEM 2002.
RESUMEN
Vfr, a transcription factor homologous to the Escherichia coli cyclic AMP (cAMP) receptor protein (CRP), regulates many aspects of virulence in Pseudomonas aeruginosa. Vfr, like CRP, binds to cAMP and then recognizes its target DNA and activates transcription. Here we report that Vfr has important functional differences from CRP in terms of ligand sensing and response. First, Vfr has a significantly higher cAMP affinity than does CRP, which might explain the mysteriously unidirectional functional complementation between the two proteins (S. E. H. West et al., J. Bacteriol. 176:7532-7542, 1994). Second, Vfr is activated by both cAMP and cGMP, while CRP is specific to cAMP. Mutagenic analyses show that Thr133 (analogous to Ser128 of CRP) is the key residue for both of these distinct Vfr properties. On the other hand, substitutions that cause cAMP-independent activity in Vfr are similar to those seen in CRP, suggesting that a common cAMP activation mechanism is present. In the course of these analyses, we found a remarkable class of Vfr variants that have completely reversed the regulatory logic of the protein: they are active in DNA binding without cAMP and are strongly inhibited by cAMP. The physiological impact of Vfr's ligand sensing and response is discussed, as is a plausible basis for the fundamental change in protein allostery in the novel group of Vfr variants.
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Proteínas Bacterianas/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Regulación Bacteriana de la Expresión Génica , Pseudomonas aeruginosa/fisiología , Proteínas Bacterianas/genética , Proteína Receptora de AMP Cíclico/genética , Análisis Mutacional de ADN , Cinética , Unión Proteica , Pseudomonas aeruginosa/genética , Factores de Virulencia/biosíntesisRESUMEN
Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) catalyzes the first step of CO(2) fixation in the Calvin-Benson-Bassham (CBB) cycle. Besides its function in fixing CO(2) to support photoautotrophic growth, the CBB cycle is also important under photoheterotrophic growth conditions in purple nonsulfur photosynthetic bacteria. It has been assumed that the poor photoheterotrophic growth of RubisCO-deficient strains was due to the accumulation of excess intracellular reductant, which implied that the CBB cycle is important for maintaining the redox balance under these conditions. However, we present analyses of cbbM mutants in Rhodospirillum rubrum that indicate that toxicity is the result of an elevated intracellular pool of ribulose-1,5-bisphosphate (RuBP). There is a redox effect on growth, but it is apparently an indirect effect on the accumulation of RuBP, perhaps by the regulation of the activities of enzymes involved in RuBP regeneration. Our studies also show that the CBB cycle is not essential for R. rubrum to grow under photoheterotrophic conditions and that its role in controlling the redox balance needs to be further elucidated. Finally, we also show that CbbR is a positive transcriptional regulator of the cbb operon (cbbEFPT) in R. rubrum, as seen with related organisms, and define the transcriptional organization of the cbb genes.
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Rhodospirillum rubrum/enzimología , Ribulosa-Bifosfato Carboxilasa/metabolismo , Ribulosafosfatos/metabolismo , Eliminación de Gen , Rhodospirillum rubrum/genética , Rhodospirillum rubrum/crecimiento & desarrollo , Ribulosa-Bifosfato Carboxilasa/deficiencia , Ribulosa-Bifosfato Carboxilasa/genética , Ribulosafosfatos/toxicidadRESUMEN
Low levels of carbon monoxide inhibit the N(2)-dependent growth of Rhodospirillum rubrum unless the â¼100-residue CowN protein is expressed. Expression requires the CO-responsive regulator RcoM and is maximal in cells grown in the presence of CO and a poor nitrogen source, consistent with the role of CowN in N(2) fixation.
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Monóxido de Carbono/metabolismo , Nitrógeno/metabolismo , Rhodospirillum rubrum/crecimiento & desarrollo , Rhodospirillum rubrum/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/biosíntesis , Expresión Génica , Datos de Secuencia Molecular , Fijación del Nitrógeno , Homología de Secuencia de Aminoácido , Factores de Transcripción/metabolismoRESUMEN
Nitrogenase not only reduces atmospheric nitrogen to ammonia, but also reduces protons to hydrogen (H(2)). The nitrogenase system is the primary means of H(2) production under photosynthetic and nitrogen-limiting conditions in many photosynthetic bacteria, including Rhodospirillum rubrum. The efficiency of this biological H(2) production largely depends on the nitrogenase enzyme and the availability of ATP and electrons in the cell. Previous studies showed that blockage of the CO(2) fixation pathway in R. rubrum induced nitrogenase activity even in the presence of ammonium, presumably to remove excess reductant in the cell. We report here the re-characterization of cbbM mutants in R. rubrum to study the effect of Rubisco on H(2) production. Our newly constructed cbbM mutants grew poorly in malate medium under anaerobic conditions. However, the introduction of constitutively active NifA (NifA*), the transcriptional activator of the nitrogen fixation (nif) genes, allows cbbM mutants to dissipate the excess reductant through the nitrogenase system and improves their growth. Interestingly, we found that the deletion of cbbM alters the posttranslational regulation of nitrogenase activity, resulting in partially active nitrogenase in the presence of ammonium. The combination of mutations in nifA, draT and cbbM greatly increased H(2) production of R. rubrum, especially in the presence of excess of ammonium. Furthermore, these mutants are able to produce H(2) over a much longer time frame than the wild type, increasing the potential of these recombinant strains for the biological production of H(2).
RESUMEN
GlnD is a bifunctional uridylyltransferase/uridylyl-removing enzyme (UTase/UR) and is believed to be the primary sensor of nitrogen status in the cell by sensing the level of glutamine in enteric bacteria. It plays an important role in nitrogen assimilation and metabolism by reversibly regulating the modification of P(II) protein; P(II) in turn regulates a variety of other proteins. GlnD appears to have four distinct domains: an N-terminal nucleotidyltransferase (NT) domain; a central HD domain, named after conserved histidine and aspartate residues; and two C-terminal ACT domains, named after three of the allosterically regulated enzymes in which this domain is found. Here we report the functional analysis of these domains of GlnD from Escherichia coli and Rhodospirillum rubrum. We confirm the assignment of UTase activity to the NT domain and show that the UR activity is a property specifically of the HD domain: substitutions in this domain eliminated UR activity, and a truncated protein lacking the NT domain displayed UR activity. The deletion of C-terminal ACT domains had little effect on UR activity itself but eliminated the ability of glutamine to stimulate that activity, suggesting a role for glutamine sensing by these domains. The deletion of C-terminal ACT domains also dramatically decreased UTase activity under all conditions tested, but some of these effects are due to the competition of UTase activity with unregulated UR activity in these variants.
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Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Mutagénesis/genética , Nucleotidiltransferasas/química , Nucleotidiltransferasas/metabolismo , Proteínas PII Reguladoras del Nitrógeno/química , Proteínas PII Reguladoras del Nitrógeno/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Electroforesis en Gel de Poliacrilamida , Escherichia coli/genética , Escherichia coli/metabolismo , Immunoblotting , Datos de Secuencia Molecular , Nucleotidiltransferasas/genética , Proteínas PII Reguladoras del Nitrógeno/genética , Estructura Terciaria de Proteína/genética , Estructura Terciaria de Proteína/fisiología , Rhodospirillum rubrum/genética , Rhodospirillum rubrum/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
What are the dangers of swallowing foreign bodies of dental origin? How do we recognize when a patient has actually swallowed a dental appliance? How far should we pursue the retrieval of the appliance? We report a case of a patient with unnoticed ingestion of a dislodged fixed partial denture while undergoing general anesthesia and review the literature on dangers of swallowing foreign bodies of dental origin. Anesthesiologists should understand the dangers and recognize this complication when it happens, so that appropriate treatment can be pursued if necessary.
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Anestesia General/efectos adversos , Dentadura Parcial Fija/efectos adversos , Cuerpos Extraños/etiología , Intubación Intratraqueal/efectos adversos , Adulto , Humanos , Masculino , Resultado del TratamientoRESUMEN
The protein Clp from Xanthomonas axonopodis pv. citri regulates pathogenesis and is a member of the CRP (cyclic AMP receptor protein) superfamily. We show that unlike the DNA-binding activity of other members of this family, the DNA-binding activity of Clp is allosterically inhibited by its effector and that cyclic di-GMP serves as that effector at physiological concentrations.