Charge regulation mechanism in end-tethered weak polyampholytes.

Weak polyampholytes, containing oppositely charged dissociable groups, are expected to be responsive to changes in ionic conditions. Here, we determine structural and thermodynamic properties, including the charged groups' degrees of dissociation, of end-tethered weak polyampholyte layers as a function of salt concentration, pH, and the solvent quality. For diblock weak polyampholytes grafted by their acidic blocks, we find that the acidic monomers increase their charge while the basic monomers decrease their charge with decreasing salt concentration for pH values less than the pKa value of both monomers and vice versa when the pH > pKa. This complex charge regulation occurs because the electrostatic attraction between oppositely charged blocks is stronger than the repulsion between monomers with the same charge in both good and poor solvents when the screening by salt ions is weak. This is evidenced by the retraction of the top block into the bottom layer. In the case of poor solvent conditions to the basic block (the top block), we find lateral segregation of basic monomers into micelles, forming a two-dimensional hexagonal pattern on the surface at intermediate and high pH values for monovalent salt concentrations from 0.01 to 0.1 M. When the solvent is poor to both blocks, we find lateral segregation of the grafted acidic block into lamellae with longitudinal undulations of low and high acidic monomer density. By exploiting weak block polyampholytes, our work expands the parameter space for creating responsive surfaces stable over a wide range of pH and salt concentration.

A Rare Cause of Persistent Blood Loss after Continuous Ambulatory Peritoneal Dialysis Catheter Placement.

The laparoscopic placement of a continuous ambulatory peritoneal dialysis (CAPD) catheter is a widely used method in patients with end stage renal disease (ESRD). The potential complications of this procedure include perforation of intra-abdominal organs, surgical site infection, peritonitis, catheter migration, catheter blockage, port site herniation, and bleeding. In most cases, bleeding is considered to be an early-onset complication because it mostly occurs within the first seven days after surgery. We report a case of a 68-year-old female patient with a previous history of diabetes mellitus, myelodysplastic syndrome, extensive collateral varices, anaemia, and ESRD due to obstructive uropathy caused by retroperitoneal fibrosis, who presented with persistent blood loss after the laparoscopic placement of a CAPD catheter. Duplex ultrasonography showed that the CAPD catheter was transfixing a superficial epigastric varicose vein, a collateral vein, due to the occlusion of the left external iliac vein. Persistent blood loss after inserting a CAPD catheter without previous imaging of abdominal wall vessels is an indication for further diagnostics.

Prevalence and co-occurrence of hip dysplasia and elbow dysplasia in Dutch pure-bred dogs.

Hip as well as elbow dysplasia (HD, ED) are developmental disorders leading to malformation of their respective joints. For a long time both disorders have been scored and targeted for improvement using selective breeding in several Dutch dog populations. In this paper all scores for both HD and ED, given to pure bred dogs in the Netherlands from 2002 to 2010, were analyzed. Heritabilities and correlations between HD and ED were calculated for the 4 most frequently scored breeds. Heritabilities ranged from 0.0 to 0.37 for HD related traits (FCI-score, osteoarthritis, congruity, shape and laxity (Norberg angle); FCI: Fédération Cynologique Internationale) and from 0.0 to 0.39 for ED related traits (IEWG score, osteoarthritis, sclerosis and indentation; IEWG: International Elbow Working Group). HD related traits showed high genetic and residual correlations among each other but were only to a minor extent correlated with ED related traits, which also showed high correlations among each other. Genetic correlations were higher than residual correlations. Phenotypic and genetic trends since 2001 for the four most scored breeds were slightly positive but decreasing over time, indicating that selection over the past decade has not been effective.

Born energy, acid-base equilibrium, structure and interactions of end-grafted weak polyelectrolyte layers.

This work addresses the effect of the Born self-energy contribution in the modeling of the structural and thermodynamical properties of weak polyelectrolytes confined to planar and curved surfaces. The theoretical framework is based on a theory that explicitly includes the conformations, size, shape, and charge distribution of all molecular species and considers the acid-base equilibrium of the weak polyelectrolyte. Namely, the degree of charge in the polymers is not imposed but it is a local varying property that results from the minimization of the total free energy. Inclusion of the dielectric properties of the polyelectrolyte is important as the environment of a polymer layer is very different from that in the adjacent aqueous solution. The main effect of the Born energy contribution on the molecular organization of an end-grafted weak polyacid layer is uncharging the weak acid (or basic) groups and consequently decreasing the concentration of mobile ions within the layer. The magnitude of the effect increases with polymer density and, in the case of the average degree of charge, it is qualitatively equivalent to a small shift in the equilibrium constant for the acid-base equilibrium of the weak polyelectrolyte monomers. The degree of charge is established by the competition between electrostatic interactions, the polymer conformational entropy, the excluded volume interactions, the translational entropy of the counterions and the acid-base chemical equilibrium. Consideration of the Born energy introduces an additional energetic penalty to the presence of charged groups in the polyelectrolyte layer, whose effect is mitigated by down-regulating the amount of charge, i.e., by shifting the local-acid base equilibrium towards its uncharged state. Shifting of the local acid-base equilibrium and its effect on the properties of the polyelectrolyte layer, without considering the Born energy, have been theoretically predicted previously. Account of the Born energy leads to systematic, but in general small, corrections to earlier theoretical predictions describing the behavior of weak polyelectrolyte layers. However, polyelectrolyte uncharging results in a decrease in the concentration of counterions and inclusion of the Born Energy can result in a substantial decrease of the counterion concentration. The effect of considering the Born energy contribution is explored for end-grafted weak polyelectrolyte layers by calculating experimental observables which are known to depend on the presence of charges within the polyelectrolyte layer: inclusion of the Born energy contribution leads to a decrease in the capacitance of polyelectrolyte-modified electrodes, a decrease of conductivity of polyelectrolyte-modified nanopores and an increase in the repulsion exerted by a planar polyelectrolyte layer confined by an opposing wall.

Hypocitraturia: a common but not well-known cause of nephrolithiasis.

Nephrolithiasis is a frequent problem that can cause serious morbidity. When associated with an underlying metabolic disorder the recurrence rate is higher. Hypocitraturia is estimated to be present in 20-60% of cases. Several secondary causes are known. Potassium citrate is the primary treatment. In the case we present here we emphasise the need for metabolic screening, focussing on hypocitraturia, a less well-known cause of nephrolithiasis.

How to Optimize Binding of Coated Nanoparticles: Coupling of Physical Interactions, Molecular Organization and Chemical State.

One of the key challenges in the development of nano carriers for drug delivery and imaging is the design of a system that selectively binds to target cells. A common strategy is to coat the delivery device with specific ligands that bind strongly to overexpressed receptors. However such devices are usually unable to discriminate between receptors found on benign and malignant cells. We demonstrate, theoretically, how one can achieve enhanced binding to target cells by using multiple physical and chemical interactions. We study the effective interactions between a polymer decorated nano micelle or nanoparticle with three types of model lipid membranes that differ in the composition of their outer leaflet. They are: i) lipid membranes with overexpressed receptors, ii) membranes with a given fraction of negatively charged lipids and iii) membranes with both overexpressed receptors and negatively charged lipids. The coating contains a mixtures of two short polymers, one neutral for protection and the other a polybase with a functional end-group to optimize specific binding with the overexpressed receptors and electrostatic interactions with charged lipid head-groups. The strength of the binding for the combined system is much larger than the sum of the independent electrostatic or specific interactions binding. We find a range of distances where the addition of two effective repulsive interactions become an attraction in the combined case. The changes in the strength and shape of the effective interaction are due to the coupling that exists between molecular organization, physical interactions and chemical state, e.g., protonation. The predictions provide guidelines for the design of carrier devices for targeted drug and nanoparticle delivery and give insight in the competing and highly non-additive nature of the different effective interactions in nanoscale systems in constrained environments that are ubiquitous in synthetic and biological systems.

Relationship between mortality and first-day events index from routinely gathered physiological variables in ICU patients

Objective: To test the hypothesis that the degree and duration of alterations in physiological variables routinely gathered by intensive care unit (ICU) monitoring systems during the first day of admission to the ICU, together with a few additional routinely recorded data, yield information similar to that obtained by traditional mortality prediction systems. Design: A prospective observational multicenter study (EURICUS II) was carried out. Setting: Fifty-five European ICUs. Patients: A total of 17,598 consecutive patients admitted to the ICU over a 10-month period. Interventions: None. Main variables of interest: Hourly data were manually gathered on alterations or "events" in systolic blood pressure, heart rate and oxygen saturation throughout ICU stay to construct an events index and mortality prediction models. Results: The mean first-day events index was 6.37±10.47 points, and was significantly associated to mortality (p: <0.001), with a discrimination capacity for hospital mortality of 0.666 (area under the ROC curve). A second index included this first-day events index, age, pre-admission location, and the Glasgow coma score. A model constructed with this second index plus diagnosis upon admission was validated by using the Jackknife method (Hosmer-Lemeshow,H: =13.8554, insignificant); the area under ROC curve was 0.818. Conclusions: A prognostic index with performance very similar to that of habitual systems can be constructed from routine ICU data with only a few patient characteristics. These results may serve as a guide for the possible automated construction of ICU prognostic indexes (AU)

Objetivo: Comprobar si el grado y duración de las alteraciones en las variables fisiológicas recogidas en la monitorización rutinaria en UCI durante el primer día de estancia, junto con pocos datos adicionales, proporcionan información similar a la obtenida con los sistemas tradicionales de predicción de mortalidad. Diseño: Estudio observacional, prospectivo y multicéntrico (EURICUS-II). Ámbito: 55 UCIs de Europa. Pacientes: 17.598 pacientes consecutivos, ingresados durante 10 meses. Intervenciones: ninguna. Variables de interés principales: se recogieron manualmente datos horarios sobre alteraciones o "eventos" en la presión arterial sistólica, frecuencia cardiaca y saturación de oxígeno, para construir un índice basado en estos eventos y un modelo de predicción de mortalidad. Resultados: El índice de eventos el primer día fue 6,37±10,47 puntos y se asoció significativamente con la mortalidad (p<0,001), con una capacidad de discriminación (área bajo la curva ROC) para la mortalidad de 0.666. Se construyó un segundo índice que incluye este índice de eventos en el primer día, la edad, procedencia del ingreso y puntuación de la Escala de Coma de Glasgow. Un modelo construido con este segundo índice más el diagnóstico fue validado mediante el método jackknife (Hosmer-Lemeshow, H=13.8554, no significativo), con un área bajo la curva ROC de 0,818. Conclusiones: Se puede construir un índice pronóstico con rendimiento similar al de los sistemas habituales a partir de los datos de monitorización de los pacientes en la UCI junto a escasas características del paciente. Nuestros resultados pueden servir de guía para la posible construcción automatizada de índices pronósticos (AU)

Relationship between mortality and first-day events index from routinely gathered physiological variables in ICU patients.

OBJECTIVE: To test the hypothesis that the degree and duration of alterations in physiological variables routinely gathered by intensive care unit (ICU) monitoring systems during the first day of admission to the ICU, together with a few additional routinely recorded data, yield information similar to that obtained by traditional mortality prediction systems. DESIGN: A prospective observational multicenter study (EURICUS II) was carried out. SETTING: Fifty-five European ICUs. PATIENTS: A total of 17,598 consecutive patients admitted to the ICU over a 10-month period. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Hourly data were manually gathered on alterations or "events" in systolic blood pressure, heart rate and oxygen saturation throughout ICU stay to construct an events index and mortality prediction models. RESULTS: The mean first-day events index was 6.37±10.47 points, and was significantly associated to mortality (p<0.001), with a discrimination capacity for hospital mortality of 0.666 (area under the ROC curve). A second index included this first-day events index, age, pre-admission location, and the Glasgow coma score. A model constructed with this second index plus diagnosis upon admission was validated by using the Jackknife method (Hosmer-Lemeshow, H=13.8554, insignificant); the area under ROC curve was 0.818. CONCLUSIONS: A prognostic index with performance very similar to that of habitual systems can be constructed from routine ICU data with only a few patient characteristics. These results may serve as a guide for the possible automated construction of ICU prognostic indexes.

The role of hydrogen bonding in tethered polymer layers.

A molecular theory to study the properties of end-tethered polymer layers, in which the polymers have the ability to form hydrogen bonds with water, is presented. The approach combines the ideas of the single-chain mean-field theory to treat tethered layers with the approach of Dormidontova (Macromolecules, 2002, 35, 987.) to include hydrogen bonds. The generalization includes the consideration of position-dependent polymer-water and water-water hydrogen bonds. The theory is applied to model poly(ethylene oxide) (PEO), and the predictions are compared with equivalent polymer layers that do not form hydrogen bonds. It is found that increasing the temperature lowers the solubility of the PEO and results in a collapse of the layer at high enough temperatures. The properties of the layer and their temperature dependence are shown to be the result of the coupling between the conformational entropy of the chains, the ability of the polymer to form hydrogen bonds, and the intermolecular interactions. The structural and thermodynamic properties of the PEO layers, such as the lateral pressure-area isotherms and polymer chemical potentials, are studied as a function of temperature and type of tethering surface. The possibility of phase separation of the PEO layer at high enough temperature is predicted due to the reduced solubility induced by breaking of polymer-water hydrogen bonds. A discussion of the advantages and limitations of the theory, together with how to apply the approach to different hydrogen-bonding polymers, is presented.

Critical care medicine in the hospital: lessons from the EURICUS-studies.

We have performed a retrospective analysis of the EURICUS-studies using their database at the Foundation for Research on Intensive Care in Europe (FRICE) and other related documents, among which the various reports produced to the European Union which granted the studies, with the following purposes: a) to select and describe the most relevant observational and experimental results of the EURICUS studies; b) to inventory the main obstacles to the appropriate organization of intensive care medicine in the Hospital and c) to highlight amid the acquired knowledge those subjects which could have a direct and primary impact for improving the organization and management of intensive care units (ICUs). The EURICUS-studies have shown a rather non-systematic variation on the variables of the organization and management, resulting in a significant waste of resources and in a generally perceived insufficient performance of ICUs in Europe. Three major roadblocks were found: a) the lack of a clear concept of Critical Care Medicine; b) the lack of defined objectives both regarding the planning of the facilities and the activities to be developed in the ICU and c) the lack of a purposeful organization and management of work in the ICU. The further development and integration of each ICU in the Hospital should consider the following: a) the system approach to the analysis and standardization of processes of care; b) the redefinition of all jobs in each ICU; c) the definition of patient/nurse ratios in each ICU and sibling departments and d) to professionalize the organization and management of the ICU.

[Long-term follow-up is indicated after surgery for a phaeochromocytoma]. / Langdurige controle aangewezen na chirurgische behandeling wegens een feochromocytoom.

Two patients presented with symptoms that suggested a recurrence of phaeochromocytoma, 17 and 14 years after a first manifestation of this disease for which they had undergone successful surgery. The first patient, a 57-year-old man, had typical symptoms of phaeochromocytoma and had recently experienced deterioration of the glycaemic control of his diabetes mellitus type 2. After initial evaluation and treatment with alpha-adrenergic blockade and propranolol, he again underwent surgery. In addition to peritoneal metastases confirmed to be caused by malignant phaeochromocytoma he also had a carcinoma of the caecum. The second patient, a 32-year-old woman, complained of headache and palpitations and had liver-enzyme disorders. Ultrasound examination revealed a tumour in the right upper abdomen and a recurrence of phaeochromocytoma was diagnosed; an intact pregnancy was also found. After a healthy son had been born by caesarian section, she underwent debulking of the large intra-abdominal lymph nodes and of two metastases in the lung. At the last follow-up she was under treatment with radioactive 123I-meta-iodobenzylguanidine (123-MIBG) because of residual metastases. Studies report recurrence ofphaeochromocytoma in 8-20% of cases, and such a recurrence may be either benign or malignant. Factors predictive for recurrence are older age, a malignant primary tumour, tumour weight above 60 g, extra-adrenal origin of the tumour and peroperative tumour spill. Long-term follow-up of patients is indicated, even after successful initial surgery.

Adolescent melanoma: risk factors and long term survival.

AIMS: To report the adolescent melanomas with focus on differences in clinical characteristics, prognostic factors, disease free (DFS) and overall survival (OS) in comparison with adults. METHODS: A single institution retrospective study in which 49 adolescent patients were compared to an adult group of 972 patients. The 10-year DFS, 10-year OS and prognostic factors were calculated for both groups. RESULTS: The median age for the adolescent patients was 17 (range 12-19) years and 49 (range 20-93) years for the adult patients. Median follow-up time was 92 (range 4-366) months. Adolescent patients presented more often with locally advanced melanoma (p<0.01). The median Breslow thickness was 1.6 vs 2.0mm for the adults (p=0.075). Increasing age, ulceration, Breslow thickness, tumour location, male gender and stage at diagnosis were calculated to be negative prognostic factors for the adult group. In the adolescent group, only the stage at diagnosis was a significant negative predictor. The 10-year DFS and OS for the adolescent patients and adult group were not significantly different regarding AJCC stages I-III. CONCLUSION: Although adolescent patients presented more often with locally advanced disease, there are no significant differences in the 10-year DFS and OS between adolescent and adult patients. In our series, we could not confirm the prognostic factors found in the adult group for the adolescent patients, except for the stage at diagnosis.

Surgical treatment of recurrent pleomorphic adenoma of the parotid gland: a clinical analysis of 52 patients.

BACKGROUND: Surgical management of recurrent pleomorphic adenoma of the parotid gland has a considerable risk of facial nerve injury and a high re-recurrence rate. To obtain more insight into this issue we evaluated our experiences. METHODS: Medical records and histologic material of all these patients (31 women and 21 men), who had been treated from 1976-1995 were reviewed. Median interval between initial treatment and commencement of recurrences was 3 (0.8-18) years. Last surgery consisted of parotidectomy in 48 patients (92%), including 19 (40%) total procedures and wide local excision with involved skin in four patients. RESULTS: At a median follow-up of 9 years, eight patients (8/52; 15%) had re-recurrences develop, including 4 of 21 patients (19%) after a previous parotidectomy (group I) and 4 of 31 patients (13%) without prior parotidectomy (group II). The chance of re-recurrence in a group of patients with a minimal follow-up of 10 years after salvage surgery was 17% (4 of 24). The risk of a new relapse was, respectively, 4% and 8% at 1 and 5 years after treatment of recurrent disease. Acceptable N.VII function was preserved in 45 of the 49 (92%) nerves at risk. The risk of N.VII injuy was higher and more serious in group I (29% vs 10% in group II). The function of four of the five (80%) reconstructed zygomaticotemporal branches of the N.VII was adequate. CONCLUSION: Surgical treatment of recurrent pleomorphic adenoma of the parotid gland, usually consisting of a parotidectomy with wide extent and eventually facial nerve reconstruction, demonstrates favorable results with acceptable morbidity. The risk of new relapse and N.VII injury was higher after previous parotidectomy.

Long-term follow-up of avascular necrosis of the femoral head in the dog.

In a clinical study of 35 dogs with avascular necrosis of the femoral head, 60 per cent were Yorkshire terriers; the mean age of 33 of the dogs at onset of clinical signs was seven months. The dogs had the following signs: muscle atrophy (n = 25), shortening of the affected leg (n = 14), pain on passive movement of the hip joint (n = 28), and crepitation of the hip joint (n = 8). Radiographic findings were irregular density and flattening of the femoral head in combination with degenerative joint disease. Conservative treatment consisted of exercise therapy, and surgical treatment of a standard femoral head and neck excision. In 17 of the dogs the results of therapy were evaluated with the help of a questionnaire. It is concluded that femoral head and neck excision is indicated when conservative treatment fails to lead to clinical improvement within four weeks. Femoral head and neck excision has a good long term prognosis; however, slight intermittent lameness may remain.

[Mandibular and maxillary fractures in dogs and cats]. / Fracturen van de mandibula en maxilla bij hond en kat.

Fractures of the mandible and maxilla are often caused by car accidents or by falling from a height. Frequently the fractures are open, especially when the fracture is located rostrally. During diagnostic work-up, special attention should be given to concomitant injury of the brain, and to cervical and thoracic injuries. The principles of treatment for jaw fractures are identical to those for complicated long bone fractures. Adaptations of techniques are necessary because of the need for undisturbed food intake, the presence of dental elements in the fragments, the poor soft tissue coverage especially in the rostral part of the mandible, and the typical mechanical load of the bones. The dental roots should be avoided when possible. Pharyngostomy prior to fracture treatment allows optimal assessment of the occlusion during surgery. In general, the treatment should permit non-supported food intake by the patient after surgery.