Two-photon lithography for customized microstructured surfaces and their influence on wettability and bacterial load.

BACKGROUND: Device-related bacterial infections account for a large proportion of hospital-acquired infections. The ability of bacteria to form a biofilm as a protective shield usually makes treatment impossible without removal of the implant. Topographic surfaces have attracted considerable attention in studies seeking antibacterial properties without the need for additional antimicrobial substances. As there are still no valid rules for the design of antibacterial microstructured surfaces, a fast, reproducible production technique with good resolution is required to produce test surfaces and to examine their effectiveness with regard to their antibacterial properties. METHODS: In this work various surfaces, flat and with microcylinders in different dimensions (flat, 1, 3 and 9 µm) with a surface area of 7 × 7 mm were fabricated with a nanoprinter using two-photon lithography and evaluated for their antibiofilm effect. The microstructured surfaces were cultured for 24 h with different strains of Pseudomonas aeruginosa and Staphylococcus aureus to study bacterial attachment to the patterned surfaces. In addition, surface wettability was measured by a static contact angle measurement. RESULTS: Contact angles increased with cylinder size and thus hydrophobicity. Despite the difference in wettability, Staphylococcus aureus was not affected by the microstructures, while for Pseudomonas aeruginosa the bacterial load increased with the size of the cylinders, and compared to a flat surface, a reduction in bacteria was observed for one strain on the smallest cylinders. CONCLUSIONS: Two-photon lithography allowed rapid and flexible production of microcylinders of different sizes, which affected surface wettability and bacterial load, however, depending on bacterial type and strain.

Which parameters influence cognitive, psychiatric and long-term seizure outcome in mesial temporal lobe epilepsy after selective amygdalohippocampectomy?

BACKGROUND: We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. METHODS: Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. RESULTS: At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex-with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials-with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = - 2.341, p = 0.019). CONCLUSIONS: SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome.

Defects in microvillus crosslinking sensitize to colitis and inflammatory bowel disease.

Intestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links the microvilli and is required for proper brush border organization. Whether microvillus crosslinking is involved in the intestinal barrier function or colitis is currently unknown. We investigate the role of microvillus crosslinking in colitis in mice with deletion of the IMAC component CDHR5. Electron microscopy shows pronounced brush border defects in CDHR5-deficient mice. The defects result in severe mucosal damage after exposure to the colitis-inducing agent DSS. DSS increases the permeability of the mucus layer and brings bacteria in direct contact with the disorganized brush border of CDHR5-deficient mice. This correlates with bacterial invasion into the epithelial cell layer which precedes epithelial apoptosis and inflammation. Single-cell RNA sequencing data of patients with ulcerative colitis reveals downregulation of CDHR5 in enterocytes of diseased areas. Our results provide experimental evidence that a combination of microvillus crosslinking defects with increased permeability of the mucus layer sensitizes to inflammatory bowel disease.

Bright light therapy as a non-pharmacological treatment option for multiple sclerosis-related fatigue: A randomized sham-controlled trial.

Background: Fatigue is a common symptom in people with multiple sclerosis (pwMS) that significantly impairs quality of life. Bright light therapy may be a cheap treatment option with little to no adverse events. Objectives: To evaluate the effectiveness of bright light therapy as a treatment option for MS-related fatigue. Methods: This was randomized sham-controlled trial including 26 pwMS with a Fatigue Severity Scale (FSS) Score ≥36. Participants were assigned to receive either bright white light therapy (n = 13) or dim red light (sham-intervention; n = 13). Participants used the respective intervention for 30 min each morning for two weeks, followed by a two-week washout period. The primary endpoint was the difference in FSS scores following light treatment as calculated by analysis of covariance. Results: There was no significant difference in FSS (F(1,23) = 2.39, p = .136, partial ⴄ2 = .094). However, FSS scores generally improved over the course of the study in a clinically relevant manner. Conclusion: Bright light therapy decreased FSS scores over the course of this study. However, this effect was not significant in comparison to a sham intervention.

Antimicrobial materials with improved efficacy dedicated to large craniofacial bone defects after tumor resection.

The research was focused on alternative treatment techniques, separating immediate and long-term reconstruction stages. The work involved development of ceramic materials dedicated to reconstruction of the temporomandibular joint area. They were based on alumina (aluminum oxide) and characterized by varying porosities. A broad spectrum of studies was conducted to test the proposed material and determine its suitability for mandibular reconstruction. They compared the effects of substrate properties of ceramic materials in terms of biocompatibility, microbiology and systemic toxicity in in vivo studies. Finally it was concluded that Alumina LithaLox 350D is best suited for jawbone implants.

Imaging visuospatial memory in temporal lobe epilepsy-Results of an fMRI study.

PURPOSE: Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland's Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. METHODS: We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). RESULTS: Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. CONCLUSION: While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

Effects of metformin on human bone-derived mesenchymal stromal cell-breast cancer cell line interactions.

Metformin is used to treat patients with type 2 diabetes mellitus and was found to lower the incidence of cancer. Bone metastasis is a common impairment associated with advanced breast cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC)-breast cancer cell line interactions. BM-MSCs grown from box chisels were tested for growth-stimulating and migration-controlling activity on four breast cancer cell lines either untreated or after pretreatment with metformin. Growth stimulation was tested in MTT tests and migration in scratch assays. Furthermore, the expression of adipokines of BM-MSCs in response to metformin was assessed using Western blot arrays. Compared to breast cancer cell lines (3.6 ± 1.4% reduction of proliferation), 500 µM metformin significantly inhibited the proliferation of BM-MSC lines (mean 12.3 ± 2.2 reduction). Pretreatment of BM-MSCs with metformin showed variable effects of the resulting conditioned media (CM) on breast cancer cell lines depending on the specific BM-MSC-cancer line combination. Metformin significantly reduced the migration of breast cancer cell lines MDA-MB-231 and MDA-MB-436 in response to CM of drug-pretreated BM-MSCs. Assessment of metformin-induced alterations in the expression of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. In conclusion, the anticancer activities of metformin are the result of a range of direct and indirect mechanisms that lower tumor proliferation and progression. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the positive effects of the drug in selected breast cancer patients.

The effectiveness of surface disinfectants and a micellic H2O2 based water disinfectant on Candida auris.

BACKGROUND: As infection control faces new challenges from emerging, multidrug resistant strains of the yeast Candida auris, this study was conducted in order to examine the efficacy of hospital surface disinfectants and a new water disinfectant against C. auris biofilm forms. METHODS: We tested four reference strains of C. auris (NCPF8971, NCPF8977, NCPF8984, DSM21092) and one C. albicans strain (ATCC10231) against disinfectants based on ethanol (ETH), quaternary ammonium (QAC), a combination of glutaraldehyde, quaternary ammonium and surfactant (ALD) and potassium peroxymonosulfate (PP) as well as 3.4% H2O2 and 4.25% H2O2 alone. In addition, a micellic-based formulation containing 17% v/v hydrogene peroxide disinfectant (mH2O2) was tested. The efficacy of the disinfectants was measured in a 96-well plate using tetrazolium salt reduction (XTT) and the log10 reduction assay. RESULTS: ETH and QAC displayed in clinically recommended concentrations more than 5log10 reduction and more than 80% XTT activity reduction for all of the Candida biofilms and planktonic cells. Only biofilms of C. auris NCPF8984 were additionally sensitive to all remaining disinfectants. All tested C. auris biofilms were sensitive to PP disinfectant and showed more than 5log10 reduction. However, the XTT assay showed a reduction of less than 80% for the PP disinfectant, indicating the presence of active but non-culturable cells. The 25% mH2O2 (corresponding to 4.25% H2O2) killed Candida biofilms after 1 minute.

Mucosal Biofilms Are an Endoscopic Feature of Irritable Bowel Syndrome and Ulcerative Colitis.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socioeconomic impact. In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging. Here we analyzed the prevalence of endoscopically visible mucosal biofilms in gastrointestinal disease and associated changes in microbiome composition and metabolism. METHODS: The presence of mucosal biofilms was assessed in 1426 patients at 2 European university-based endoscopy centers. One-hundred and seventeen patients were selected for in-depth molecular and microscopic analysis using 16S ribosomal RNA gene amplicon-sequencing of colonic biopsies and fecal samples, confocal microscopy with deep learning-based image analysis, scanning electron microscopy, metabolomics, and in vitro biofilm formation assays. RESULTS: Biofilms were present in 57% of patients with IBS and 34% of patients with ulcerative colitis compared with 6% of controls (P < .001). These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing links the presence of biofilms to a dysbiotic gut microbiome, including overgrowth of Escherichia coli and Ruminococcus gnavus. R. gnavus isolates cultivated from patient biofilms also formed biofilms in vitro. Metabolomic analysis found an accumulation of bile acids within biofilms that correlated with fecal bile acid excretion, linking this phenotype with a mechanism of diarrhea. CONCLUSIONS: The presence of mucosal biofilms is an endoscopic feature in a subgroup of IBS and ulcerative colitis with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and ulcerative colitis, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease.

Language network reorganization before and after temporal lobe epilepsy surgery.

OBJECTIVE: Epilepsy surgery is the recommended treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). This method offers a good chance of seizure freedom but carries a considerable risk of postoperative language impairment. The extremely variable neurocognitive profiles in surgical epilepsy patients cannot be fully explained by extent of resection, fiber integrity, or current task-based functional MRI (fMRI). In this study, the authors aimed to investigate pathology- and surgery-triggered language organization in TLE by using fMRI activation and network analysis as well as considering structural and neuropsychological measures. METHODS: Twenty-eight patients with unilateral TLE (16 right, 12 left) underwent T1-weighted imaging, diffusion tensor imaging, and task-based language fMRI pre- and postoperatively (n = 15 anterior temporal lobectomy, n = 11 selective amygdalohippocampectomy, n = 2 focal resection). Twenty-two healthy subjects served as the control cohort. Functional connectivity, activation maps, and laterality indices for language dominance were analyzed from fMRI data. Postoperative fractional anisotropy values of 7 major tracts were calculated. Naming, semantic, and phonematic verbal fluency scores before and after surgery were correlated with imaging parameters. RESULTS: fMRI network analysis revealed widespread, bihemispheric alterations in language architecture that were not captured by activation analysis. These network changes were found preoperatively and proceeded after surgery with characteristic patterns in the left and right TLEs. Ipsilesional fronto-temporal connectivity decreased in both left and right TLE. In left TLE specifically, preoperative atypical language dominance predicted better postoperative verbal fluency and naming function. In right TLE, left frontal language dominance correlated with good semantic verbal fluency before and after surgery, and left fronto-temporal language laterality predicted good naming outcome. Ongoing seizures after surgery (Engel classes ID-IV) were associated with naming deterioration irrespective of seizure side. Functional findings were not explained by the extent of resection or integrity of major white matter tracts. CONCLUSIONS: Functional connectivity analysis contributes unique insight into bihemispheric remodeling processes of language networks after epilepsy surgery, with characteristic findings in left and right TLE. Presurgical contralateral language recruitment is associated with better postsurgical language outcome in left and right TLE.

A New Synthetic Conduit for the Treatment of Peripheral Nerve Injuries.

BACKGROUND: Peripheral nerve defects (PND) often cause lifelong physical disability, and the available treatment options are often not satisfactory. PND are usually bridged with an autologous nerve transplant or a nerve guidance conduit (NGC), when coaptation as preferred technique is not possible. The aim of this experimental study was to determine the effectiveness of a novel NGC for regeneration in the treatment of PND. MATERIALS AND METHODS: A conduit made of gelatin with an innovative interior structure was tested for the repair of a 6-mm gap versus direct microsurgical suture repair without gap. RESULTS: We found that bridging the defect with this conduit was as effective as direct microsurgical coaptation without a defect. CONCLUSIONS: This nerve conduit, effective in bridging neural defects, appears as an alternative to autologous nerve grafts, avoiding the problems related to nerve graft harvesting, host-donor differences in diameter, mismatches in number and pattern of fascicles, cross-sectional shape and area, and morbidity of the donor area.

Preparation and antibiofilm studies of curcumin loaded chitosan nanoparticles against polymicrobial biofilms of Candida albicans and Staphylococcus aureus.

Polymicrobial biofilms related infections are an important clinical problem with classical antibiotics being not sufficient in therapy. Here, curcumin (Cur) was loaded on positively charged chitosan nanoparticles (CSNP). The antibiofilm activities against mono- and polymicrobial biofilms of Candida albicans and Staphylococcus aureus were evaluated. The average diameter of CSNP-Cur was 134.37 ±â€¯1.99 nm and its surface charge was +18.10 ±â€¯0.82 mV. Cur released from NPs was slower at pH 7.4 than at pH 5.4. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to observe biofilm architecture and live/dead organisms within biofilm on medical silicone surface. CSNP-Cur exhibited excellent antibiofilm activity against planktonic bacteria or fungi, mono- and polymicrobial biofilm formations and preformed biofilms. SEM and CLSM showed that CSNP-Cur was able to reduce biofilm thickness as well as kill microbial cells embedded in biofilm on silicone surfaces.

Co-immobilization of cellobiose dehydrogenase and deoxyribonuclease I on chitosan nanoparticles against fungal/bacterial polymicrobial biofilms targeting both biofilm matrix and microorganisms.

Polymicrobial biofilm related infections have been a major threat in health care. In this study, the co-immobilization of cellobiose dehydrogenase (CDH) and deoxyribonuclease I (DNase) on positively charged chitosan nanoparticles (CSNPs) resulted in a bi-functional nanoparticle (CSNP-DNase-CDH) targeting both biofilm matrix and microorganisms. The in-vitro antibiofilm activities of CSNPs against monomicrobial and polymicrobial biofilms of Candida albicans and Staphylococcus aureus were evaluated. The results showed that CSNPs were able to penetrate across the matrix of biofilms and interfere with embedded microbial cells. CSNP-DNase-CDH exhibited a higher activity than CSNPs loaded with only DNase or CDH for inhibiting monomicrobial and polymicrobial biofilm formation as well as for disrupting pre-formed biofilms. Furthermore, CSNP-DNase-CDH could disrupt the biofilm formation through degradation of eDNA, reduce biofilm thickness, and kill microbial cells on silicone. The bi-functional CSNP is applicable for the protection of medical devices from polymicrobial biofilms or the treatment of device associated infections.

Procedural memory consolidation is associated with heart rate variability and sleep spindles.

Sleep and memory studies often focus on overnight rather than long-term memory changes, traditionally associating overnight memory change (OMC) with sleep architecture and sleep patterns such as spindles. In addition, (para-)sympathetic innervation has been associated with OMC after a daytime nap using heart rate variability (HRV). In this study we investigated overnight and long-term performance changes for procedural memory and evaluated associations with sleep architecture, spindle activity (SpA) and HRV measures (R-R interval [RRI], standard deviation of R-R intervals [SDNN], as well as spectral power for low [LF] and high frequencies [HF]). All participants (N = 20, Mage  = 23.40 ± 2.78 years) were trained on a mirror-tracing task and completed a control (normal vision) and learning (mirrored vision) condition. Performance was evaluated after training (R1), after a full-night sleep (R2) and 7 days thereafter (R3). Overnight changes (R2-R1) indicated significantly higher accuracy after sleep, whereas a significant long-term (R3-R2) improvement was only observed for tracing speed. Sleep architecture measures were not associated with OMC after correcting for multiple comparisons. However, individual SpA change from the control to the learning night indicated that only "SpA enhancers" exhibited overnight improvements for accuracy and long-term improvements for speed. HRV analyses revealed that lower SDNN and LF power was associated with better OMC for the procedural speed measure. Altogether, this study indicates that overnight improvement for procedural memory is specific for spindle enhancers, and is associated with HRV during sleep following procedural learning.

Tissue-regenerative potential of the secretome of γ-irradiated peripheral blood mononuclear cells is mediated via TNFRSF1B-induced necroptosis.

Peripheral blood mononuclear cells (PBMCs) have been shown to produce and release a plethora of pro-angiogenetic factors in response to γ-irradiation, partially accounting for their tissue-regenerative capacity. Here, we investigated whether a certain cell subtype of PBMCs is responsible for this effect, and whether the type of cell death affects the pro-angiogenic potential of bioactive molecules released by γ-irradiated PBMCs. PBMCs and PBMC subpopulations, including CD4+ and CD8+ T cells, B cells, monocytes, and natural killer cells, were isolated and subjected to high-dose γ-irradiation. Transcriptome analysis revealed subpopulation-specific responses to γ-irradiation with distinct activation of pro-angiogenic pathways, cytokine production, and death receptor signalling. Analysis of the proteins released showed that interactions of the subsets are important for the generation of a pro-angiogenic secretome. This result was confirmed at the functional level by the finding that the secretome of γ-irradiated PBMCs displayed higher pro-angiogenic activity in an aortic ring assay. Scanning electron microscopy and image stream analysis of γ-irradiated PBMCs revealed distinct morphological changes, indicative for apoptotic and necroptotic cell death. While inhibition of apoptosis had no effect on the pro-angiogenic activity of the secretome, inhibiting necroptosis in stressed PBMCs abolished blood vessel sprouting. Mechanistically, we identified tumor necrosis factor (TNF) receptor superfamily member 1B as the main driver of necroptosis in response to γ-irradiation in PBMCs, which was most likely mediated via membrane-bound TNF-α. In conclusion, our study demonstrates that the pro-angiogenic activity of the secretome of γ-irradiated PBMCs requires interplay of different PBMC subpopulations. Furthermore, we show that TNF-dependent necroptosis is an indispensable molecular process for conferring tissue-regenerative activity and for the pro-angiogenic potential of the PBMC secretome. These findings contribute to a better understanding of secretome-based therapies in regenerative medicine.

Growth Media for Mixed Multispecies Oropharyngeal Biofilm Compositions on Silicone.

AIMS: Microbial colonization of silicone voice prostheses by bacteria and Candida species limits the device lifetime of modern voice prostheses in laryngectomized patients. Thus, research focuses on biofilm inhibitive properties of novel materials, coatings, and surface enhancements. Goal of this in vitro study was the evaluation of seven commonly used growth media to simulate growth of mixed oropharyngeal species as mesoscale biofilms on prosthetic silicone for future research purposes. METHODS AND RESULTS: Yeast Peptone Dextrose medium (YPD), Yeast Nitrogen Base medium (YNB), M199 medium, Spider medium, RPMI 1640 medium, Tryptic Soy Broth (TSB), and Fetal Bovine Serum (FBS) were used to culture combined mixed Candida strains and mixed bacterial-fungal compositions on silicone over the period of 22 days. The biofilm surface spread and the microscopic growth showed variations from in vivo biofilms depending on the microbial composition and growth medium. CONCLUSION: YPD and FBS prove to support continuous in vitro growth of mixed bacterial-fungal oropharyngeal biofilms deposits over weeks as needed for longterm in vitro testing with oropharyngeal biofilm compositions. SIGNIFICANCE AND IMPACT OF STUDY: The study provides data on culture conditions for mixed multispecies biofilm compositions that can be used for future prosthesis designs.

Interaction of Adipose-Derived Stromal Cells with Breast Cancer Cell Lines.

BACKGROUND: Assisted lipotransfer for breast reconstruction involves the isolation and supplementation of adipose-derived stromal cells. This procedure has raised concerns regarding safety with respect to promotion of tumor growth and relapse. Several in vitro and animal experimental studies have indicated increased survival, growth, and invasive characteristics of breast cancer cells on interaction with adipose-derived stromal cells. These results seem to be in poor concordance with clinical observations of a low rate of cancer recurrences after assisted lipotransfer. METHODS: The authors investigated the effects of adipose-derived stromal cells and adipose-derived stromal cells differentiated into adipocytes and fibroblasts on five breast cancer cell lines (i.e., T47D, MCF-7, BT20, MDA-MB-231, and ZR-75-1) and MCF-10A, a nonmalignant counterpart. RESULTS: Conditioned media of adipose-derived stromal cells stimulated the proliferation of breast cancer cell lines depending on the individual adipose-derived stromal cell-breast cancer cell line combination. Conditioned media of adipose-derived stromal cells differentiated into adipocytes gave a lower response, and conditioned media of fibroblasts were also active. A putative cancer stem cell-like phenotype was not increased by adipose-derived stromal cell-conditioned media, no physical interaction of cancer cells with adipose-derived stromal cells was detectable on scanning electron microscopy, and cell migration was not enhanced. Adipogenic differentiation of adipose-derived stromal cells indicated that hepatocyte growth factor, insulin-like growth factor-binding protein-3, insulin-like growth factor-binding protein-6, interleukin-6, CCL2/MCP-1, and macrophage colony-stimulating factor are not linked to the proliferative activity of conditioned media. CONCLUSION: The results indicate that the adipose-derived stromal cells used for assisted lipotransfer are not expected to increase the risk of tumor recurrence to a major degree in correspondence with the clinical observation of the affected breast cancer patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries.

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

The effect of daytime napping and full-night sleep on the consolidation of declarative and procedural information.

Many studies investigating sleep and memory consolidation have evaluated full-night sleep rather than alternative sleep periods such as daytime naps. This multi-centre study followed up on, and was compared with, an earlier full-night study (Schabus et al., 2004) investigating the relevance of daytime naps for the consolidation of declarative and procedural memory. Seventy-six participants were randomly assigned to a nap or wake group, and performed a declarative word-pair association or procedural mirror-tracing task. Performance changes from before to after a 90-min retention interval filled with sleep or quiet wakefulness were evaluated between groups. Associations between performance changes, sleep architecture, spindles, and slow oscillations were investigated. For the declarative task we observed a trend towards stronger forgetting across a wake period compared with a nap period, and a trend towards memory increase over the full-night. For the procedural task, accuracy was significantly decreased following daytime wakefulness, showed a trend to increase with a daytime nap, and significantly increased across full-night sleep. For the nap protocol, neither sleep stages, spindles, nor slow oscillations predicted performance changes. A direct comparison of day and nighttime sleep revealed that daytime naps are characterized by significantly lower spindle density, but higher spindle activity and amplitude compared with full-night sleep. In summary, data indicate that daytime naps protect procedural memories from deterioration, whereas full-night sleep improves performance. Given behavioural and physiological differences between day and nighttime sleep, future studies should try to characterize potential differential effects of full-night and daytime sleep with regard to sleep-dependent memory consolidation.

Antibiofilm efficacy of curcumin in combination with 2-aminobenzimidazole against single- and mixed-species biofilms of Candida albicans and Staphylococcus aureus.

Mixed fungal and bacterial biofilm associated infections of implants have been a huge challenge in health care because of the increased resistance to antimicrobials and the critical biological differences between fungi and bacteria. In this study, we evaluated the 2-aminobenzimidazole (2ABI) and curcumin (CUR) alone to inhibit planktonic cell growth, adhesion as well as single and mixed species biofilms of Candida albicans and Staphylococcus aureus on silicone. The combined effects between 2ABI and CUR on mixed species biofilm formation and pre-formed biofilm were assessed. Our work showed that 2ABI or CUR alone was effective as a sole agent, inhibiting planktonic growth, adhesion and the biofilm formation of bacteria and fungi on the silicone surface. The combination of 2ABI and CUR exhibited the enhanced effect on mixed biofilm compared to mono-drug therapy. The biofilm architecture was investigated by scanning electron microscopy (SEM) and the distinction of living/dead organisms within biofilm was examined by confocal laser scanning microscopy (CLSM). The combination activity was most potent on mixed biofilm. These results suggest the potential applicability of 2ABI and CUR to treatment of biofilm related device infections.