Early Detection of Infection Chains & Outbreaks: Use Case Infection Control.

Within the HiGHmed Project there are three medical use cases. The use cases include the scopes cardiology, oncology and infection. They serve to specify the requirements for the development and implementation of a local and federated platform, with the result that data from medical care and research should be retrievable, reusable and interchangeable. The Use Case Infection Control aims to establish an early detection of transmission events as well as clusters and outbreaks of various pathogens. Therefore the use case wants to establish the smart infection control system (SmICS).

Background noise exerts diverse effects on the cortical encoding of foreground sounds.

In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions.NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may contribute to robust signal representation and discrimination in acoustic environments with prominent background noise.

Identifying structural flow defects in disordered solids using machine-learning methods.

We use machine-learning methods on local structure to identify flow defects-or particles susceptible to rearrangement-in jammed and glassy systems. We apply this method successfully to two very different systems: a two-dimensional experimental realization of a granular pillar under compression and a Lennard-Jones glass in both two and three dimensions above and below its glass transition temperature. We also identify characteristics of flow defects that differentiate them from the rest of the sample. Our results show it is possible to discern subtle structural features responsible for heterogeneous dynamics observed across a broad range of disordered materials.

Salmonella appendicitis in renal transplantation.

While appendicitis remains one of the commonest surgical diseases, there are relatively few reports following renal transplantation. A 33-year-old man was admitted with diarrhea, fever, and epigastric pain 7 years following a cadaveric renal transplant. CT scanning confirmed a diagnosis of appendicitis which was removed within 24 hours of admission. Histology and blood cultures following surgery confirmed Salmonella type b appendicitis. Patient was safely discharged home 5 days following hospital admission.

Metronidazole single versus multiple daily dosing in serious intraabdominal/pelvic and diabetic foot infections.

The purpose of the study was to compare the clinical efficacy of once-daily versus multiple dose regimens of metronidazole in inpatients with serious/systemic Bacteroides fragilis infections, i.e., intraabdominal/pelvic and diabetic foot infections. A retrospective chart review was performed on 145 adult inpatients who received combination therapy with metronidazole for B. fragilis abdominal/pelvic infection or diabetic (deep) foot infections/osteomyelitis. Exclusion criteria included metronidazole given for indications other than those mentioned, patients who received only one dose of metronidazole, and patients who received oral metronidazole only. The 145 patients were in two groups: 66 patients in the metronidazole 1 g (i.v.) q24h (Group A) and 79 patients who received metronidazole 500 mg (i.v./p.o.) q6-8h dosing (Group B). Patient demographics included age, gender, indications of metronidazole, concomitant, antibiotics, and co-morbidities. Data collection also included length of stay (LOS), antibiotic days, and clinical outcomes. The 145 patients in our study had a mean age of 66 years, 61% were female and 39% male. Most patients were being treated for definitive intraabdominal/pelvic infections (82%), or probable intraabdominal/pelvic infections (22%). Only 6% had deep diabetic foot infections of osteomyelitis (percentages exceed 100% since a patient can have more than one indication) and were included since B. fragilis is also and important pathogen in diabetic osteomyelitis. Group A patients had more concomitant antibiotics and co-morbidities (p < 0.0001 and p < 0.05 respectively, chi-square test for trend) than Group B patients. There were no statistically significant differences between groups A and B for LOS and antibiotic days (p = 0.42 and p = 0.92 respectively, by rank-sum test), but after adjusting for concomitant antibiotics and co-morbidities Group A patients had clinically shorter LOS and fewer antibiotic days. Unadjusted mortality and failure rates were non-significantly higher in group A (relative ratios of 12.1%/6.3% = 6.3% = 1.91 and 18.2%/ 10.1% = 1.80 respectively), but after adjusting for concomitant antibiotics and co-morbidities with stratification analysis, groups A and B were virtually the same (risk differences of

Effects of auditory stimulus context on the representation of frequency in the gerbil inferior colliculus.

Prior studies of dynamic conditioning have focused on modulation of binaural localization cues, revealing that the responses of inferior colliculus (IC) neurons to particular values of interaural phase and level disparities depend critically on the context in which they occur. Here we show that monaural frequency transitions, which do not simulate azimuthal motion, also condition the responses of IC neurons. We characterized single-unit responses to two frequency transition stimuli: a glide stimulus comprising two tones linked by a linear frequency sweep (origin-sweep-target) and a step stimulus consisting of one tone followed immediately by another (origin-target). Using sets of glide and step stimuli converging on a common target, we constructed conditioned response functions (RFs) depicting the variability in the response to an identical stimulus as a function of the preceding origin frequency. For nearly all cells, the response to the target depended on the origin frequency, even for origins outside the excitatory frequency response area of the cell. Results from conditioned RFs based on long (2-4 s) and short (200 ms) duration step stimuli indicate that conditioning effects can be induced in the absence of the dynamic sweep, and by stimuli of relatively short duration. Because IC neurons are tuned to frequency, changes in the origin frequency often change the "effective" stimulus duty cycle. In many cases, the enhancement of the target response appeared related to the decrease in the "effective" stimulus duty cycle rather than to the prior presentation of a particular origin frequency. Although this implies that nonselective adaptive mechanisms are responsible for conditioned responses, slightly more than half of IC neurons in each paradigm responded significantly differently to targets following origins that elicited statistically indistinguishable responses. The prevailing influence of stimulus context when discharge history is controlled demonstrates that not all the mechanisms governing conditioning depend on the discharge history of the recorded neuron. Selective adaptation among the neuron's variously tuned afferents may help engender stimulus-specific conditioning. The demonstration that conditioning effects reflect sensitivity to spectral as well as spatial stimulus contrast has broad implications for the processing of a wide range of dynamic acoustic signals and sound sequences.

Differential regulation of three catalytic activities of platelet-activating factor (PAF)-dependent transacetylase.

We have previously established that PAF-dependent transacetylase (TA) purified to apparent homogeneity from rat kidney membranes and cytosol contains three separate catalytic activities, namely PAF lysophospholipid transacetylase (TAL), PAF sphingosine transacetylase (TAS), and PAF acetylhydrolase (AH). In the present investigation, we studied the biochemical factors and mechanism(s) that differentially regulate these three TA activities of the purified enzymes. We found that only the TAS activity of the TA purified from the membranes was stimulated by phosphatidyl-serine (PS) with optimal concentration of activation occurring at 25 microM. Other acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylinositol 4-phosphate (PIP), are partially effective, while diacylglycerol and free fatty acids had no effect on the TAS activity. PS exerted its effect on the TAS activity through the increases of both Km and Vmax. In addition, N-ethylmalimide (NEM) and dithiobis-(2-nitro-5-thiobenzoic acid) (DTNB) strongly inhibited the TAS activity and partially decreased the TAL and AH activities of the purified membrane enzyme in a dose-dependent manner. The addition of PS, but not by its substrate, sphingosine, could prevented the inhibition by NEM on the basal level of TAS. On the other hand, the inhibition of TAL by NEM and DTNB were partially protected by the substrate, lysoplasmalogens. Furthermore, PAF fully protects the inhibition of AH, partially protects the inhibition of TAL, and does not protect the inhibition of TAS by NEM. These results suggested that the three individual catalytic activities of TA have different dependencies on the thiol-containing residue(s) of the enzyme, i.e., cysteine. Furthermore, the nonresponsiveness of the purified cytosolic TAS to PS activation is consistent with our previous notions that membrane and cytosolic TA are posttranslationally distinct.

Fas-mediated apoptosis eliminates B cells that acquire self-reactivity during the germinal center response to NP.

C57Bl/6 mice with the lpr mutation of Fas (CD95) were tested for deviation from the genetically restricted antibody response to the hapten 4-hydroxy-3-nitrophenyl acetyl (NP). lambda1+ germinal centers (GC) with the canonical v186.2 V(H) gene element develop in lpr/lpr mice with the same time course as in wild-type (+/+) mice. In contrast to +/+ mice, however, lambda1+ GC persist in the spleens of lpr/lpr mice 25 days after immunization. Virtually all of the lambda1+ GC are reactive with NP 10 days after immunization. Sixteen days after immunization, however, many of the lambda1+ GC are not reactive with NP, and few of the lambda1+ GC are reactive with NP 25 days after immunization. The V(H) gene elements of three lambda1+NP- GC 25 days after immunization are derived by somatic mutation of v186.2, but have lost reactivity with NP. The mutated VDJs from these GC react with cells in spleen sections from +/+ and lpr/lpr mice, indicating that they represented secondary antibody responses induced by self antigens that are available as presented antigen. These data indicate that Fas-mediated apoptosis serves to eliminate a (limited) population of B cells that acquire reactivity to "self antigens" by somatic mutation of VDJs in the GC.

Platelet-activating factor (PAF)-dependent transacetylase and its relationship with PAF acetylhydrolases.

Platelet-activating factor (PAF)-dependent transacetylase (TA) is an enzyme that transfers an acetyl group from PAF to acceptor lipids such as lysophospholipids and sphingosine. This enzyme is distributed in membrane and cytosol of the cells. We previously revealed that TA purified from rat kidney membrane showed an amino acid sequence similarity to that of bovine PAF-acetylhydrolase (AH) (II). In the present study, we purified TA from the rat kidney cytosol and analyzed its amino acid sequence. The amino acid sequence of the cytosolic TA is similar to that of bovine PAF-AH (II) and membrane TA. To clarify the relationship between TA and PAF-AH (II), we isolated cDNA of rat PAF-AH (II). The predicted amino acid sequence of rat PAF-AH (II) from isolated cDNA included all the sequences found in TAs purified from the membrane and cytosolic TAs. In addition, monoclonal antibody to recombinant PAF-AH (II) cross-reacted with both cytosolic and membrane TAs. Consistent with sequence identity, recombinant PAF-AH (II) showed TA activity, whereas recombinant PAF-AH Ib, which is a different subtype of intracellular PAF-AHs, did not possess TA activity. Analysis of a series of site-directed mutant PAF-AH (II) proteins showed that TA activity was decreased, whereas PAF-AH activity was not affected in C120S and G2A mutant proteins. Thus, Cys(120) and Gly(2) are implicated in the catalysis of TA reaction in this enzyme. Furthermore, the transfer of acetate from PAF to endogenous acceptor lipids was significantly increased in a time-dependent manner in CHO-K1 cells transfected with PAF-AH (II) gene. These results demonstrate that PAF-AH (II) can function, as a TA in intact cells, and PAF-AH (II) and TA are the same enzyme.

Promoting physical activity in rural communities: walking trail access, use, and effects.

INTRODUCTION: Environmental and policy approaches to promote physical activity, such as walking trail construction and promotion, are being widely recommended, yet sparse data exist on their effectiveness. In conjunction with ongoing community-intervention projects in Missouri, walking trails are being built, promoted, and evaluated. Objectives include determining: (1) patterns and correlates of walking, (2) the availability of places to walk and perform other forms of physical activity, (3) the extent of walking trail use and possible effects on rates of physical activity, and (4) attitudes toward the trails and their uses. METHODS: In 12 rural counties in Missouri we used a cross-s ectional telephone survey to ask a population-based sample of residents aged >18 years (n=1269) some standard and specially developed questions about walking behaviors, knowledge, and attitudes. RESULTS: Only 19.5% of respondents were classified as regular walkers. About one third of respondents (36.5%) reported having access to walking trails in their area, and 50.3% reported having access to indoor facilities for exercise. Among persons with access to walking trails, 38.8% had used the trails. Groups who were more likely to have used the walking trails included women, persons with more education, those making $35,000 or more per year, and regular walkers. Among persons who had used the trails, 55.2% reported they had increased their amount of walking since they began using the trail. Women and persons with a high school education or less were more than twice as likely to have increased the amount of walking since they began using the walking trails. CONCLUSIONS: Walking trails may be beneficial in promoting physical activity among segments of the population at highest risk for inactivity, in particular women and persons in lower socioeconomic groups.