Intrinsic network activity reflects the fluctuating experience of tonic pain.

Although we know sensation is continuous, research on long-lasting and continuously changing stimuli is scarce and the dynamic nature of ongoing cortical processing is largely neglected. In a longitudinal study, 38 participants across four sessions were asked to continuously rate the intensity of an applied tonic heat pain for 20 min. Using group-independent component analysis and dual regression, we extracted the subjects' time courses of intrinsic network activity. The relationship between the dynamic fluctuation of network activity with the varying time courses of three pain processing entities was computed: pain intensity, the direction of pain intensity changes, and temperature. We were able to dissociate the spatio-temporal patterns of objective (temperature) and subjective (pain intensity/changes of pain intensity) aspects of pain processing in the human brain. We found two somatosensory networks with distinct functions: one network that encodes the small fluctuations in temperature and consists mainly of bilateral primary somatosensory cortex (SI), and a second right-lateralized network that encodes the intensity of the subjective experience of pain consisting of SI, secondary somatosensory cortex, the posterior cingulate cortex, and the thalamus. We revealed the somatosensory dynamics that build up toward a current subjective percept of pain. The timing suggests a cascade of subsequent processing steps toward the current pain percept.

Patients with chronic pain exhibit individually unique cortical signatures of pain encoding.

Chronic pain is characterised by an ongoing and fluctuating intensity over time. Here, we investigated how the trajectory of the patients' endogenous pain is encoded in the brain. In repeated functional MRI (fMRI) sessions, 20 patients with chronic back pain and 20 patients with chronic migraine were asked to continuously rate the intensity of their endogenous pain. Linear mixed effects models were used to disentangle cortical processes related to pain intensity and to pain intensity changes. At group level, we found that the intensity of pain in patients with chronic back pain is encoded in the anterior insular cortex, the frontal operculum, and the pons; the change of pain in chronic back pain and chronic migraine patients is mainly encoded in the anterior insular cortex. At the individual level, we identified a more complex picture where each patient exhibited their own signature of endogenous pain encoding. The diversity of the individual cortical signatures of chronic pain encoding results bridge between clinical observations and neuroimaging; they add to the understanding of chronic pain as a complex and multifaceted disease.

A nationwide passive surveillance on fungal infections shows a low burden of azole resistance in molds and yeasts in Tyrol, Austria.

PURPOSE: To determine the burden of antifungal resistance in fungi over the last 10 years. METHODS: Performance of a semi-nationwide surveillance on antifungal resistance. RESULTS: We observed a low frequency of azole resistance in Aspergillus fumigatus, a moderate increase of echinocandin resistance in yeasts, and a stable amphotericin B activity in yeasts and molds. Posaconazole resistance in Aspergillus terreus occurred in a few isolates. CONCLUSION: The burden of resistance in fungi seems to be low in Tyrol, Austria.

The extent of environmental and body contamination through aerosols by hydro-surgical debridement in the lumbar spine.

INTRODUCTION: Surgical site infections occur in 1-6% of spinal surgeries. Effective treatment includes early diagnosis, parenteral antibiotics and early surgical debridement of the wound surface. MATERIALS AND METHODS: On a human cadaver, we executed a complete hydro-surgery debridement including a full surgical setup such as draping. The irrigation fluid was artificially contaminated with Staphylococcus aureus (ATCC 6538). Surveillance cultures were used to detect environmental and body contamination of the surgical team. RESULTS: For both test setups, environmental contamination was observed in an area of 6 × 8 m. Both test setups caused contamination of all personnel present during the procedure and of the whole operating theatre. However, the concentration of contamination for the surgical staff and the environment was lower when an additional disposable draping device was used. CONCLUSIONS: The study showed that during hydro-surgery debridement, contaminated aerosols spread over the whole surgical room and contaminate the theatre and all personnel.

Pain and the emotional brain: pain-related cortical processes are better reflected by affective evaluation than by cognitive evaluation.

The experience of pain has been dissociated into two interwoven aspects: a sensory-discriminative aspect and an affective-motivational aspect. We aimed to explore which of the pain descriptors is more deeply rooted in the human brain. Participants were asked to evaluate applied cold pain. The majority of the trials showed distinct ratings: some were rated higher for unpleasantness and others for intensity. We compared the relationship between functional data recorded from 7 T MRI with unpleasantness and intensity ratings and revealed a stronger relationship between cortical data and unpleasantness ratings. The present study underlines the importance of the emotional-affective aspects of pain-related cortical processes in the brain. The findings corroborate previous studies showing a higher sensitivity to pain unpleasantness compared to ratings of pain intensity. For the processing of pain in healthy subjects, this effect may reflect the more direct and intuitive evaluation of emotional aspects of the pain system, which is to prevent harm and to preserve the physical integrity of the body.

Imperfect cross-linking of xanthan for pH-responsive bio-based composite moist wound dressings by stencil printing.

The work addresses the use of bio-based and -degradable materials for the production of a moist, adaptive and anti-microbial wound dressing. The dressing is targeted to exhibit a pH-dependent active agent release. Xanthan hydrogel structures are coated on cellulose fabrics via stencil printing and subsequently cross-linked using glyoxal. By alteration of the cross-linker content from 1 to 6% by mass, the hydrogel elasticity can be tuned within a range of 2-16 kPa storage modulus. Increasing initial glyoxal concentrations also result in higher amounts of glyoxal release. Glyoxal, an anti-microbial agent with approval in veterinary medicine, is mostly released upon wound application supporting infection management. As wound simulation, normal saline, as pH 5 and pH 8 buffer solutions, were used. The release profile and magnitude of approx. 65%-90% glyoxal is pH-dependent. Increased release rates of glyoxal are present in pH 8 fluids, which mostly base on faster hydrogel swelling. Higher total glyoxal release is present in pH 5 fluid and normal saline after 3 days. Accordingly, a pH-dependent release profile was encountered. As glyoxal attacks any cell unselectively, it is expected to be effective against antibiotic resistant bacteria. By stencil printing the dressing size can be adjusted to minimize healthy glyoxal tissue exposure.

Caspofungin: when and how? The microbiologist's view.

The echinocandins are antifungal agents, which act by inhibiting the synthesis of ß-(1,3)-D-glucan, an integral component of fungal cell walls. Caspofungin, the first approved echinocandin, demonstrates good in vitro and in vivo activity against a range of Candida species and is an alternative therapy for Aspergillus infections. Caspofungin provides an excellent safety profile and is therefore favoured in patients with moderately severe to severe illness, recent azole exposure and in those who are at high risk of infections due to Candida glabrata or Candida krusei. In vivo/in vitro resistance to caspofungin and breakthrough infections in patients receiving this agent have been reported for Candida and Aspergillus species. The types of pathogens and the frequency causing breakthrough mycoses are not well delineated. Caspofungin resistance resulting in clinical failure has been linked to mutations in the Fksp subunit of glucan synthase complex. European Committee for Antimicrobial Susceptibility Testing and Clinical and Laboratory Standards Institute need to improve the in vitro susceptibility testing methods to detect fks hot spot mutants. Caspofungin represents a significant advance in the care of patients with serious fungal infections.

Investigation on how dynamic effective connectivity patterns encode the fluctuating pain intensity in chronic migraine.

Chronic migraine is characterised by persistent headaches for >15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 min). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients. The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.

Individually unique dynamics of cortical connectivity reflect the ongoing intensity of chronic pain.

ABSTRACT: Chronic pain diseases are characterised by an ongoing and fluctuating endogenous pain, yet it remains to be elucidated how this is reflected by the dynamics of ongoing functional cortical connections. In this study, we investigated the cortical encoding of 20 patients with chronic back pain and 20 chronic migraineurs in 4 repeated fMRI sessions. A brain parcellation approach subdivided the whole brain into 408 regions. Linear mixed-effects models were fitted for each pair of brain regions to explore the relationship between the dynamic cortical connectivity and the observed trajectory of the patients' ratings of fluctuating endogenous pain. Overall, we found that periods of high and increasing pain were predominantly related to low cortical connectivity. The change of pain intensity in chronic back pain was subserved by connections in left parietal opercular regions, right insular regions, as well as large parts of the parietal, cingular, and motor cortices. The change of pain intensity direction in chronic migraine was reflected by decreasing connectivity between the anterior insular cortex and orbitofrontal areas, as well as between the PCC and frontal and anterior cingulate cortex regions. Of interest, the group results were not mirrored by the individual patterns of pain-related connectivity, which rejects the idea of a common neuronal core problem for chronic pain diseases. The diversity of the individual cortical signatures of chronic pain encoding results adds to the understanding of chronic pain as a complex and multifaceted disease. The present findings support recent developments for more personalised medicine.

Intrinsic network activity reflects the ongoing experience of chronic pain.

Analyses of intrinsic network activity have been instrumental in revealing cortical processes that are altered in chronic pain patients. In a novel approach, we aimed to elucidate how intrinsic functional networks evolve in regard to the fluctuating intensity of the experience of chronic pain. In a longitudinal study with 156 fMRI sessions, 20 chronic back pain patients and 20 chronic migraine patients were asked to continuously rate the intensity of their endogenous pain. We investigated the relationship between the fluctuation of intrinsic network activity with the time course of subjective pain ratings. For chronic back pain, we found increased cortical network activity for the salience network and a local pontine network, as well as decreased network activity in the anterior and posterior default mode network for higher pain intensities. Higher pain intensities in chronic migraine were accompanied with lower activity in a prefrontal cortical network. By taking the perspective of the individual, we focused on the variability of the subjective perception of pain, which include phases of relatively low pain and phases of relatively high pain. The present design of the assessment of ongoing endogenous pain can be a powerful and promising tool to assess the signature of a patient's endogenous pain encoding.

In vitro susceptibility testing in fungi: a global perspective on a variety of methods.

Candida and Aspergillus species are the most common causes of invasive fungal infections in immunocompromised patients. The introduction of new antifungal agents and recent reports of resistance emerging during treatment have highlighted the need for in vitro susceptibility testing. For some drugs, there is a supporting in vitro-in vivo correlation available from studies of clinical efficacy. Both intrinsic and emergent antifungal drug resistance are encountered. Various testing procedures have been proposed, including macrodilution and microdilution, agar diffusion, disk diffusion and Etest. Early recognition of infections caused by pathogens that are resistant to one or more antifungals is highly warranted to optimise treatment and patient outcome.

High percentage of microbial colonization of osteosynthesis material in clinically unremarkable patients.

Stabilization of fractures with internal fixation devices is a common procedure and implant-associated infections are a dreaded complication. The exact pathomechanism is not completely understood; however, microbial colonization of osteosynthesis material is considered a trigger for infection. This study aimed to determine the colonization rate of osteosynthesis implants in patients with no clinical or laboratory signs of infection, using two methods, conventional culture and polymerase chain reaction (PCR) of sonication fluid. Fifty-seven patients aged between 18 and 79 years without signs of infection who underwent routine removal of osteosynthesis devices between March 2015 and May 2017 were included in this study. Osteosynthesis material was investigated by sonication followed by cultivation of the sonication fluid in blood culture bottles and PCR analysis, simultaneously. Additionally, electron scanning microscopy was performed in nine representative implants to evaluate biofilm production. Thirty-two (56.1%) implants showed a positive result either by culture or PCR with coagulase-negative staphylococci being the most commonly identified microorganism (68.1%). Furthermore, the detection rate of the culture (50.9%) was significantly higher compared to PCR (21.1%). The scanning electron microscopy imaging demonstrated biofilm-like structures in four of six culture and/or PCR-positive samples. This study is the first, to the best of our knowledge, to demonstrate bacterial colonization of osteosynthesis implants in healthy patients with no clinical or laboratory signs of infection. Colonization rate was unexpectedly high and conventional culture was superior to PCR in microbial detection. The common understanding that colonization is a trigger for infection underlines the need for strategies to prevent colonization of implant material like antibiotic-loaded coating or intraoperative gel application.

Activities of antifungal agents against yeasts and filamentous fungi: assessment according to the methodology of the European Committee on Antimicrobial Susceptibility Testing.

We compared the activities of antifungal agents against a wide range of yeasts and filamentous fungi. The methodology of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for yeasts and spore-forming molds was applied; and a total of 349 clinical isolates of Candida spp., other yeast species, Aspergillus spp., and nondermatophyte non-Aspergillus spp. were investigated. The average geometric mean (GM) of the MICs of the various drugs for Candida spp. were as follows: amphotericin B (AMB), 0.55 microg/ml; liposomal amphotericin B (l-AMB); 0.35 microg/ml; itraconazole (ITC), 0.56 microg/ml; voriconazole (VRC), 0.45 microg/ml; posaconazole (POS), 0.44 microg/ml; and caspofungin (CPF), 0.45 microg/ml. The data indicated that the majority of Candida spp. were susceptible to the traditional and new antifungal drugs. For Aspergillus spp., the average GM MICs of AMB, l-AMB, ITC, VRC, POS, and CPF were 1.49 microg/ml, 1.44 microg/ml, 0.65 microg/ml, 0.34 microg/ml, 0.25 microg/ml, and 0.32 microg/ml, respectively. For the various zygomycetes, the average GM MICs of AMB, l-AMB, ITC, and POS were 1.36 microg/ml, 1.42 microg/ml, 4.37 microg/ml, and 1.65 microg/ml, respectively. Other yeastlike fungi and molds displayed various patterns of susceptibility. In general, the minimal fungicidal concentrations were 1 to 3 dilutions higher than the corresponding MICs. POS, AMB, and l-AMB showed activities against a broader range of fungi than ITC, VRC, and CPF did. Emerging pathogens such as Saccharomyces cerevisiae and Fusarium solani were not killed by any drug. In summary, the EUCAST data showed that the in vitro susceptibilities of yeasts and filamentous fungi are variable, that susceptibility occurs among and within various genera and species, and that susceptibility depends on the antifungal drug tested. AMB, l-AMB, and POS were active against the majority of pathogens, including species that cause rare and difficult-to-treat infections.

Long-sleeved medical workers' coats and their microbiota.

In this study we aimed to assess the contamination rate of long-sleeved medical workers' coats (N = 100) in a point-prevalence study. Ninety-one percent of the coats were contaminated with normal human flora, but only the minority (9%) showed presence of pathogenic non-multiresistant bacteria. The data of this study may implicate that long-sleeved coats harbor low risk for the treated patients to be contaminated with pathogenic bacteria during medical consultation.

Outbreak report: a nosocomial outbreak of vancomycin resistant enterococci in a solid organ transplant unit.

Background: Vancomycin resistant enterococci (VRE) are an emerging problem in health care settings. The purpose of the investigation was to assess the extent of the outbreak including environmental contamination and to limit further transmission. Methods: We used retrospective patient and laboratory data including pulse field gel electrophoresis (PFGE) typing and virulence and resistance gene analysis. For comparison of medians the Mann-Whitney and for comparison of proportions the Fisher exact tests were used. Results: PFGE typing of VRE strains of an outbreak of 15 VRE cases in a solid transplant unit revealed that nine of the cases belonged to one identical pattern (A), which was only found twice in the environment. Eleven further positive environmental samples showed a different, but identical PFGE pattern E. Only one patient was infected with this environmental strain.Two of nine (22.2%) PFGE A, but nine of eleven (81.2%) PFGE E samples were positive for gelatinase E (p = 0.01), which is described as enhancing biofilm production, suggesting a survival benefit for this strain on inanimate surfaces. Conclusion: Routine disinfection was not able to stop the cluster, but after repeated enforcement of the infection prevention and control (IPC) bundle such as training, strict adherence to hand hygiene and surface disinfection no further cases were observed. We conclude that certain VRE strains predominate in the environment whereas others predominate in humans. Enforcement of the IPC bundle is essential for controlling VRE outbreaks and reducing further transmission.

The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients.

We assessed Calcofluor white staining, Aspergillus polymerase chain reaction, and a galactomannan enzyme immunoassay for diagnosis of fungal infection with use of computed tomography-guided percutaneous lung biopsy specimens obtained from 61 patients. The sensitivity and specificity of computerized tomography, Aspergillus polymerase chain reaction, and galactomannan enzyme immunoassay were 100% and 50%, 100% and 86%, and 88% and 94%, respectively.

Nosocomial outbreak of extensively drug-resistant Pseudomonas aeruginosa associated with aromatherapy.

An increase of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) in various clinical specimens among intensive care unit patients (n = 7) initiated an outbreak investigation consisting of patient data analyses, control of adherence to infection control guidelines, microbiologic surveys, and molecular-based studies. XDR-PA was detected in a jointly used aroma-oil nursing bottle for aromatherapy. We implemented the restriction of oil sharing among patients. Hence, the outbreak was controlled successfully.

A point prevalence survey on hand hygiene, with a special focus on Candida species.

BACKGROUND: A 1-day point prevalence study evaluated hand hygiene compliance, yeast colonization, and contamination, focusing on the hands of health care workers (HCWs) and patient-oriented surfaces. METHODS: Hand hygiene compliance was evaluated by applying the direct observation technique and the World Health Organization's compliance program, "My Five Moments for Hand Hygiene." A total of 128 samples from HCWs working in intensive care (n = 11) and intermediate care (n = 2) units and 65 environmental samples from Innsbruck Medical University Hospital were investigated. RESULTS: Hand hygiene compliance was superior for nurses (83.5%) and moderate for medical doctors (45.2%). In general, fungal growth was unique; only 9 of 128 HCW samples and only 4 of 65 environmental samples yielded positive results. The genetic relatedness of yeasts from the same species was investigated by random amplified polymorphic DNA (RAPD) typing. RAPD profiles exhibited the potential for cross-transmission of yeasts. CONCLUSION: In general, the fungal colonization and contamination rate was low, but a high level of hand hygiene compliance was lacking.

Tolerability of N-chlorotaurine in chronic rhinosinusitis applied via yamik catheter.

OBJECTIVES: A rational approach in the treatment of chronic rhinosinusitis (CRS) is the intranasal application of antiseptic agents, due to the pathogenetic role of bacteria and fungi. N-Chlorotaurine (NCT), a mild endogenous oxidant with broad-spectrum antimicrobial activity, has been tested for the first time in CRS. METHODS: This one-arm phase IIa clinical study is the first step in the clinical development of this promising substance for local therapy of CRS. The nasal and paranasal cavities of 12 patients were rinsed with 10-20 ml of 1% aqueous NCT solution, applied via a novel catheter system (YAMIK). Treatment consisted of three lavages per week for 4 weeks. RESULTS: NCT caused neither alterations of the mucosa nor burning pain during application. Nevertheless, the insertion of the catheter, the insufflation of the posterior cuff and the overpressure inside the sinuses after infiltration led to moderate pain in some patients. Mucosal swelling decreased in all subjects, nasal breathing could be improved in nine patients and impaired olfaction in seven. Polyps did not disappear within the 1-month period of the study. CONCLUSIONS: The good tolerability and possible beneficial effects of NCT encourage its further investigation in CRS. Despite some limitations the YAMIK catheter proved to be a convenient and safe device for rinsing the nasal and paranasal sinuses.

Diagnosing and monitoring of invasive aspergillosis during antifungal therapy by polymerase chain reaction: an experimental study in mice.

This study evaluated the value of polymerase chain reaction (PCR) for diagnosing and monitoring of invasive aspergillosis during amphotericin B therapy. PCR, microscopy and culture of tissues samples (n = 126) and blood samples (n = 78) of experimentally infected mice (n = 42) were performed. The PCR results of treated were compared to those of untreated animals; Aspergillus fumigatus and A. terreus were used in this study. In the amphotericin B treated group the sensitivities of PCR, microscopic examination and culture of the various tissues were 69, 58, and 53%, respectively; the specificities of all examinations were 100%. In the untreated group the sensitivities of PCR, microscopic examination, and culture were 72, 64, and 57%, respectively; the specificities of all examinations were 100%. The 78 blood samples taken from mice under therapy were tested by PCR over a period of 8 days following Aspergillus infection. The test sensitivity was 77%, the specificity 46%, the positive predictive value 59%, and the negative predictive value 67%. In the untreated group the sensitivity was 92%, the specificity 46%, the positive predictive value 63%, and the negative predictive value 86%. The results suggest that this PCR method has possible clinical value for improving the diagnosis of invasive Aspergillus infection. Monitoring of blood under antifungal therapy is not recommended.