Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Electron paramagnetic resonance and other properties of hydrogenases isolated from Desulfovibrio vulgaris (strain Hildenborough) and Megasphaera elsdenii

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65872/1/j.1432-1033.1983.tb07727.x.pd

Microbial Maintenance: A Critical Review on Its Quantification

Microbial maintenance is an important concept in microbiology. Its quantification, however, is a subject of continuous debate, which seems to be caused by (1) its definition, which includes nongrowth components other than maintenance; (2) the existence of partly overlapping concepts; (3) the evolution of variables as constants; and (4) the neglect of cell death in microbial dynamics. The two historically most important parameters describing maintenance, the specific maintenance rate and the maintenance coefficient, are based on partly different nongrowth components. There is thus no constant relation between these parameters and previous equations on this subject are wrong. In addition, the partial overlap between these parameters does not allow the use of a simple combination of these parameters. This also applies for combinations of a threshold concentration with one of the other estimates of maintenance. Maintenance estimates should ideally explicitly describe each nongrowth component. A conceptual model is introduced that describes their relative importance and reconciles the various concepts and definitions. The sensitivity of maintenance on underlying components was analyzed and indicated that overall maintenance depends nonlinearly on relative death rates, relative growth rates, growth yield, and endogenous metabolism. This quantitative sensitivity analysis explains the felt need to develop growth-dependent adaptations of existing maintenance parameters, and indicates the importance of distinguishing the various nongrowth components. Future experiments should verify the sensitivity of maintenance components under cellular and environmental conditions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Cooperativity between electrons and protons in a monomeric Cytochrome c3: the importance of mechano-chemical coupling for energy transduction

To fully understand the structural bases for the mechanisms of biological energy transduction, it is essential to determine the microscopic thermodynamic parameters which describe the properties of each centre involved in the reactions, as well as its interactions with the others. These interactions between centres can then be interpreted in the light of structural features of the proteins. Redox titrations of cytochrome c(3), from Desulfovibrio desulfuricans ATCC27774 followed by NMR and visible spectroscopy were analysed by using an equilibrium thermodynamic model. The network of homotropic and heterotropic cooperativities results in the coupled transfer of electrons and protons under physiological conditions. The microscopic characterisation allows the identification of several pairs of centres for which there are clear conformational (non-Coulombic) contributions to their coupling energies, thus establishing the existence of localised redox- and acid - base-linked structural modifications in the protein (mechano-chemical coupling). The modulation of interactions between centres observed for this cytochrome may be an important general phenomenon and is discussed in the framework of its physiological function and of the current focus of energy, transduction research

Functional properties of cytochrome c(7) isolated from Desulfuromonas acetoxidans

Abstract poster presentation (G)

Single Photon Emission Computerized Tomography in the Evaluation of the Osteoblastic Activities of a New Bone Regeneration Technique, Analysis of 12 Mandibular Sites in six Experimental Pigs

Objectives: To utilize single photon emission computerized tomography performed in sequence to determine the osseo-integrating capabilities and osteoblastic activities of a new bone regeneration technique called the membrane – sandwich technique (Ogunsalu sandwich bone regenerating technique) and to compare the quality and quantity of bone formed by this bone regeneration unit to bone regeneration obtained by using the same particulate bone grafting material covered with interceed® (another type of bio-resorbable membrane). Design and Method: Single photon emission computerized tomography bone imaging was performed in sequence on the mandible of a total of 6 pigs on both the right and left side (total of 12 sites) at two and a half hours following the injection of technetium 99m methylene diphosphate. Imaging was performed using a Siemen Orbitar II gamma camera. The projection data was acquired in a 128 x 128 matrix over 180 arc and SPECT reconstruction was performed using a filtered back projector method with a Shepp-Logan Hanning filter and a cut-off frequency of 0.4. The surgical defect on one side of the jaw was treated with the sandwich unit with Bio-oss particulate bone within it, while the other side contained the same quantity of Bio-oss as in the left side but just covered with interceed® membrane. The osteoblastic uptake on the side with the classical sandwich was compared to the side with the particulate bone covered with interceed® membrane for dynamic physiological activities. The average activity for both sides was calculated and compared. Result: For all the 12 sites, osteoblastic activities were recorded and indicated that vascularized bone was formed at all the experimental sites. Autogenous bone graft was confirmed to be superior to xenograft using this sandwich technique. Furthermore, the osteoblastic activities on the sandwich side were seen to be more when compared with the control side (Interceed® side). Conclusion: The Ogunsalu sandwich bone regeneration technique has been successfully evaluated with SPECT which shows osteoblastic activity with formation of vascularized bone which integrates with the surrounding bone. La Tomografía Computarizada por Emisión de fotón único en la Evaluación de las Actividades Osteoblásticas de una nueva Técnica de Regeneración ósea RESUMEN Objetivos: Utilizar la tomografía computarizada por emisión de fotón único (TCEFU) realizada en secuencia, a fin de determinar la capacidad óseo-integradora y las actividades osteoblásticas de una nueva técnica de regeneración del hueso, denominada técnica de membrana-sándwich, y comparar la calidad y cantidad de hueso formado por esta unidad de regeneración ósea con la regeneración ósea obtenida mediante el mismo material de injerto de hueso particulado cubierto con interceed® (otro tipo de membrana bioreabsorbible). Diseño y Método: Mediante TCEFU, se realizó un estudio de imágenes óseas en secuencia, de la mandíbula de un total de 6 cerdos, a los lados izquierdo y derecho (un total de 12 sitios) a las dos horas y media, luego de una inyección de difosfato de metileno marcado con tecnecio 99 m. El examen de imágenes fue realizado usando una cámara gamma Siemens Orbiter tipo II. Los datos de la proyección fueron adquiridos en una matriz de 128 x 128 sobre un arco de 180 y la reconstrucción con TCEFU se realizó usando un método de retroproyección filtrada, con un filtro Shepp-Logan-Hanning y una frecuencia de corte de 0.4. El defecto quirúrgico en un lado de la mandíbula fue tratado con la unidad de sándwich con hueso particulado bio-oss dentro, mientras que el otro lado contenía la misma cantidad de Bio-oss del lado izquierdo, pero cubierto con una membrana de interceed®. La respuesta osteoblástica en el lado con el sándwich clásico fue comparada con el lado del hueso particulado cubierto con la membrana de interceed® en cuanto a actividades fisiológicas dinámicas. La actividad promedio de ambos lados fue calculada y comparada. Resultado: En los 12 sitios, las actividades osteoblásticas fueron registradas de forma indicando que se formó hueso vascularizado en todos los sitios experimentales. Se confirmó que el injerto óseo autógeno es superior al xenoinjerto que usa esta técnica de sándwich. Además, se observó que las actividades osteoblásticas en el lado del sándwich eran más en comparación con el lado control (lado del interceed®). Conclusión: La técnica de Ogunsalu para la regeneración ósea por “sándwich” o membrana interposicional, ha sido exitosamente evaluada mediante TCEFU, concluyéndose que la misma consiste en la actividad osteoblástica con formación de hueso vascularizado que se integra al hueso circundante