Whooping Cough in Adults: A Series of Severe Cases.

Bordetella pertussis is a gram-negative aerobic coccobacillus causing contagious respiratory tract disease called whooping cough. The virulence factors consist of pertussis toxin, filamentous hemagglutinin, fimbriae, lipooligosaccharide, and adenylate cyclase toxin. The disease causes a worldwide threat to public health despite a high vaccination coverage. The course of whooping cough in adults is frequently atypical, causing difficulty in diagnosis. In this report we present five patients hospitalized with Bordetella pertussis infection manifesting atypical and severe symptoms. The diagnosis was based on serological tests: serum concentration of specific antibodies against pertussis toxin and sputum cultures. We observed a wide spectrum of symptoms, from benign (sinus pain - 80 %, headaches - 20 %), through moderate (hemoptysis - 40 %; chest pain 60 %) to severe symptoms (cardiac arrhythmia - 40 %; syncope - 60 %). Bordetella pertussis infection can cause life-threatening complications and exacerbation of concomitant chronic diseases. Most vaccination programs cover only the first few months of life. Booster doses should be considered in adults, especially those immunocompromised or with pulmonary complications, but also in healthcare workers who are exposed to the contagion and also may spread the infection.

Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

Antibiotic Treatment of Hospitalized Patients with Pneumonia Complicated by Clostridium Difficile Infection.

Clostridium difficile infection (CDI) is one of the most common gastrointestinal complication after antimicrobial treatment. It is estimated that CDI after pneumonia treatment is connected with a higher mortality than other causes of hospitalization. The aim of the study was to assess the relationship between the kind of antibiotic used for pneumonia treatment and mortality from post-pneumonia CDI. We addressed the issue by examining retrospectively the records of 217 patients who met the diagnostic criteria of CDI. Ninety four of those patients (43.3 %) came down with CDI infection after pneumonia treatment. Fifty of the 94 patients went through severe or severe and complicated CDI. The distribution of antecedent antibiotic treatment of pneumonia in these 50 patients was as follows: ceftriaxone in 14 (28 %) cases, amoxicillin with clavulanate in 9 (18 %), ciprofloxacin in 8 (16.0 %), clarithromycin in 7 (14 %), and cefuroxime and imipenem in 6 (12 %) each. The findings revealed a borderline enhancement in the proportion of deaths due to CDI in the ceftriaxone group compared with the ciprofloxacin, cefuroxime, and imipenem groups. The corollary is that ceftriaxone should be shunned in pneumonia treatment. The study demonstrates an association between the use of a specific antibiotic for pneumonia treatment and post-pneumonia mortality in patients who developed CDI.

Antibiotic Treatment of Hospitalized Patients with Pneumonia Complicated by Clostridium Difficile Infection.

Clostridium difficile infection (CDI) is one of the most common gastrointestinal complication after antimicrobial treatment. It is estimated that CDI after pneumonia treatment is connected with a higher mortality than other causes of hospitalization. The aim of the study was to assess the relationship between the kind of antibiotic used for pneumonia treatment and mortality from post-pneumonia CDI. We addressed the issue by examining retrospectively the records of 217 patients who met the diagnostic criteria of CDI. Ninety four of those patients (43.3 %) came down with CDI infection after pneumonia treatment. Fifty of the 94 patients went through severe or severe and complicated CDI. The distribution of antecedent antibiotic treatment of pneumonia in these 50 patients was as follows: ceftriaxone in 14 (28 %) cases, amoxicillin with clavulanate in 9 (18 %), ciprofloxacin in 8 (16.0 %), clarithromycin in 7 (14 %), and cefuroxime and imipenem in 6 (12 %) each. The findings revealed a borderline enhancement in the proportion of deaths due to CDI in the ceftriaxone group compared with the ciprofloxacin, cefuroxime, and imipenem groups. The corollary is that ceftriaxone should be shunned in pneumonia treatment. The study demonstrates an association between the use of a specific antibiotic for pneumonia treatment and post-pneumonia mortality in patients who developed CDI.

Lund-Mackay System for Computed Tomography Evaluation of Paranasal Sinuses in Patients with Granulomatosis and Polyangiitis.

Granulomatosis with polyangiitis (GPA), a disease capable of affecting any organ, most often acts upon the upper respiratory tract. Diagnostic imaging is primarily represented by computed tomography (CT) of paranasal sinuses. The aim of this study was to define the characteristic changes in paranasal CT in patients with GPA and to evaluate diagnostic usefulness of the Lund-Mackey scoring system (L-M System). The study encompassed 43 patients with GPA of the mean age of 47.7 ± 12.8 years who were treated topically with mupirocin. We found that inflammation occurred mainly in the maxillary sinuses (72%). The mean L-M score was 5.8 ± 6.1. The right maxillary sinus had the highest percentage (12.6%) of score hits of 1, i.e., partial opacification and the left ostiomeatal complex had the highest percentage (7.6%) of score of 2, i.e., complete opacification or obstruction. The following changes were the most characteristic for GPA: sinus mucosal thickening, widespread bone damage, and osteogenesis. We conclude that the long-term topical mupirocin treatment of GPA may inhibit nasal bone damage, but also may led to permanent rhinological changes of the rhinosinusitis type. The Lund-Mackey staging system is a useful diagnostic imaging option in GPA patients.

Prevalence of Olfactory Impairment in Granulomatosis with Polyangiitis.

Granulomatosis with Polyangiitis (GPA) is a rare disease of unknown origin. It may damage all organs and systems, even olfactory and taste sense. The aim of the study was to determine the sense of smell in patients with GPA and to identify factors related to disease course, activity, and duration, which may be associated with olfactory dysfunction. The comparison of olfactory function screening scores with Sniffin' Sticks standardized norms showed that 74% of the investigated patients had olfactory dysfunction. The olfactory performance was diminished in all parts of Sniffin' Sticks test: threshold scores 4.4 vs. 7.1 (p = 0.007); odor discrimination 9.0 vs. 11.9 (p = 0.008); and olfactory identification 9.8 vs. 12.2 (p = 0.011) in the GPA patients vs. control subjects, respectively. Scores acquired during all three parts of the test were combined to assess the TDI-score. The median TDI-score in the GPA group (27.5) was significantly lower than that in the control group (32.0) (p = 0.002). Active nasal and paranasal sinus inflammation in GPA leads to olfactory dysfunction, the patients are often unaware of. The dysfunction is permanent and does not abates along with decreasing intensity of the inflammatory process. GPA therapy should include recommendations on nutrition, personal hygiene, and food poisoning prevention.

Protein threading by learning.

By using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems.

Motion of grains, droplets, and bubbles in fluid-filled nanopores.

Molecular dynamics studies of nanometer-sized rigid grains, droplets and bubbles in nanometer-sized pores indicate that the drag force may have a hydrodynamic form if the moving object is dense and small compared to the pore diameter. Otherwise, the behavior is nonhydrodynamic. The terminal speed is insensitive to whether the falling droplet is made of liquid or a solid. The velocity profiles within droplets and bubbles that move in the pore are usually nonparabolic and distinct from those corresponding to individual fluids. The density profiles indicate motional shape distortion of the moving objects.

Kinetic nonoptimality and vibrational stability of proteins.

Scaling of folding times in Go models of proteins and of decoy structures with the Lennard-Jones potentials in the native contacts reveal power law trends when studied under optimal folding conditions. The power law exponent depends on the type of native geometry. Its value indicates lack of kinetic optimality in the model proteins. In proteins, mechanical and thermodynamic stabilities are correlated.

Boundary conditions at a fluid-solid interface.

We study the boundary conditions at a fluid-solid interface using molecular dynamics simulations covering a broad range of fluid-solid interactions and fluid densities and both simple and chain-molecule fluids. The slip length is shown to be independent of the type of flow, but rather is related to the fluid organization near the solid, as governed by the fluid-solid molecular interactions.

Dynamic modeling of gene expression data.

We describe the time evolution of gene expression levels by using a time translational matrix to predict future expression levels of genes based on their expression levels at some initial time. We deduce the time translational matrix for previously published DNA microarray gene expression data sets by modeling them within a linear framework by using the characteristic modes obtained by singular value decomposition. The resulting time translation matrix provides a measure of the relationships among the modes and governs their time evolution. We show that a truncated matrix linking just a few modes is a good approximation of the full time translation matrix. This finding suggests that the number of essential connections among the genes is small.

Dynamical chaos and power spectra in toy models of heteropolymers and proteins.

The dynamical chaos in Lennard-Jones toy models of heteropolymers is studied by molecular dynamics simulations. It is shown that two nearby trajectories quickly diverge from each other if the heteropolymer corresponds to a random sequence. For good folders, on the other hand, two nearby trajectories may initially move apart but eventually they come together. Thus good folders are intrinsically nonchaotic. A choice of a distance of the initial conformation from the native state affects the way in which a separation between the twin trajectories behaves in time. This observation allows one to determine the size of a folding funnel in good folders. We study the energy landscapes of the toy models by determining the power spectra and fractal characteristics of the dependence of the potential energy on time. For good folders, folding and unfolding trajectories have distinctly different correlated behaviors at low frequencies.

Fundamental patterns underlying gene expression profiles: simplicity from complexity.

Analysis of previously published sets of DNA microarray gene expression data by singular value decomposition has uncovered underlying patterns or "characteristic modes" in their temporal profiles. These patterns contribute unequally to the structure of the expression profiles. Moreover, the essential features of a given set of expression profiles are captured using just a small number of characteristic modes. This leads to the striking conclusion that the transcriptional response of a genome is orchestrated in a few fundamental patterns of gene expression change. These patterns are both simple and robust, dominating the alterations in expression of genes throughout the genome. Moreover, the characteristic modes of gene expression change in response to environmental perturbations are similar in such distant organisms as yeast and human cells. This analysis reveals simple regularities in the seemingly complex transcriptional transitions of diverse cells to new states, and these provide insights into the operation of the underlying genetic networks.

Scaling of folding properties in go models of proteins.

Insights about scaling of folding properties of proteins are obtained bystudying folding in heteropolymers described by Go-like Hamiltonians. Bothlattice and continuum space models are considered. In the latter case, themonomer-monomer interactions correspond to the Lennard-Jones potential.Several statistical ensembles of the two- and three-dimensional targetnative conformations are considered. Among them are maximally compactconformations which are confined to a lattice and those which are obtainedeither through quenching or annealing of homopolymers to their compactlocal energy minima. Characteristic folding times are found to grow aspower laws with the system size. The corresponding exponents are notuniversal. The size related deterioration of foldability is found to beconsistent with the scaling behavior of the characteristic temperatures:asymptotically, the folding temperature becomes much lower than thetemperature at which glassy kinetics become important. The helicalconformations are found to have the lowest overall scaling exponent andthe best foldability among the classes of conformations studied. Thescaling properties of the Go-like models of the protein conformationsstored in the Protein Data Bank suggest that proteins are not optimizedkinetically.

Statistical mechanics of protein-like heteropolymers.

A strategy is outlined for obtaining the free energy of a typical designed heteropolymer. The design procedure considers the probability that the target conformation is occupied in comparison with all the other conformations that could house the given sequence. Numerical calculations on lattice heteropolymer models are presented to illustrate the key physical principles.

Energy landscapes, supergraphs, and "folding funnels" in spin systems.

Dynamical connectivity graphs, which describe dynamical transition rates between local energy minima of a system, can be displayed against the background of a disconnectivity graph which represents the energy landscape of the system. The resulting supergraph describes both dynamics and statics of the system in a unified coarse-grained sense. We give examples of the supergraphs for several two-dimensional spin and protein-related systems. We demonstrate that disordered ferromagnets have supergraphs akin to those of model proteins whereas spin glasses behave like random sequences of amino acids that fold badly.

Structure-based design of model proteins.

A structure-based, sequence-design procedure is proposed in which one considers a set of decoy structures that compete significantly with the target structure in being low energy conformations. The decoy structures are chosen to have strong overlaps in contacts with the putative native state. The procedure allows the design of sequences with large and small stability gaps in a random-bond heteropolymer model in both two and three dimensions by an appropriate assignment of the contact energies to both the native and nonnative contacts. The design procedure is also successfully applied to the two-dimensional HP model.

Cell dynamics of folding in two-dimensional model proteins.

BACKGROUND: Functionally useful proteins are sequences of amino acids that fold rapidly under appropriate conditions into their native states. It is believed that rapid folders are sequences for which the folding dynamics entail the exploration of restricted conformations-the phase space can be thought of as a folding funnel. While there are many experimentally accessible predictions pertaining to the existence of such funnels and a coherent picture of the kinetics of folding has begun to emerge, there have been relatively few simple studies in the controlled setting of well-characterized lattice models. RESULTS: We design rapidly folding sequences by assigning the strongest couplings to the contacts present in a target native state in a two-dimensional model of heteropolymers. Such sequences have large folding transition temperatures and low glass transition temperatures. The dependence of median folding times on temperature is investigated. The pathways to folding and their dependence on the temperature are illustrated via a study of the cell dynamics-a mapping of the dynamics into motion within the space of the maximally compact cells. CONCLUSIONS: Folding funnels can be defined operationally in a coarse-grained sense by mapping the states of the system into maximally compact conformations and then by identifying significant connectivities between them.