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.

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.

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.

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.

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.

Dispersal of single and mixed non-albicans Candida species biofilms by ß-1,3-glucanase in vitro.

ß-1,3-glucan plays a role in non-albicans Candida species biofilm formation and survival of biofilm Candida to stresses. In this study, we evaluated the antibiofilm activity of ß-1,3-glucanase, which can degrade poly-ß(1 â†’ 3)-glucose of non-albicans Candida species biofilms, on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis and Candida krusei. Biofilm by all tested species in microplate were dispersed more than 60%. ß-1,3-glucanase also detached mixed species biofilm in microplate and on medical material surface. ß-1,3-glucanase had no effect on Candida planktonic growth as well as adhesion. However, further biofilm formation was inhibited with ß-1,3-glucanase added at 24 h after biofilm initiation. ß-1,3-glucanase markedly enhanced the antifungal susceptibility of amphotericin B. The examination using confocal laser scanning microscopy and scanning electron microscope confirmed the antibiofilm activity of ß-1,3-glucanase. Our findings demonstrate that ß-1,3-glucanase may be useful as an antibiofilm agent.

Inhibition activity of Lactobacilli supernatant against fungal-bacterial multispecies biofilms on silicone.

Fungal-bacterial multispecies biofilms play a major role in failure of medical silicone devices, such as voice prostheses in laryngectomiy. In this study, we determined the effect of Lactobacilli supernatant (cell free) on mixed biofilm formation of fungi and bacteria on silicone in vitro. Lactobacilli supernatant inhibited the adhesion (90 min) of mixed fungi and bacteria species with an efficiency of >90%. Mixed biofilm formation and the metabolic activity of the biofilms were inhibited by 72.23% and 58.36% by Lactobacilli supernatant. The examination using confocal laser scanning microscopy and scanning electron microscopy confirmed that Lactobacilli supernatant inhibited the growth of mixed biofilm and damaged the cells. Moreover, Lactobacilli supernatant also inhibited Candida yeast-to-hyphal transition. Therefore, Lactobacilli supernatant may serve as a possible antibiofilm agent to limit biofilm formation on voice prostheses.

Does Extracellular DNA Production Vary in Staphylococcal Biofilms Isolated From Infected Implants versus Controls?

BACKGROUND: Prosthetic implant infections caused by Staphylococcus aureus and epidermidis are major challenges for early diagnosis and treatment owing to biofilm formation on the implant surface. Extracellular DNA (eDNA) is actively excreted from bacterial cells in biofilms, contributing to biofilm stability, and may offer promise in the detection or treatment of such infections. QUESTIONS/PURPOSES: (1) Does DNA structure change during biofilm formation? (2) Are there time-dependent differences in eDNA production during biofilm formation? (3) Is there differential eDNA production between clinical and control Staphylococcal isolates? (4) Is eDNA production correlated to biofilm thickness? METHODS: We investigated eDNA presence during biofilm formation in 60 clinical and 30 control isolates of S aureus and S epidermidis. The clinical isolates were isolated from patients with infections of orthopaedic prostheses and implants: 30 from infected hip prostheses and 30 from infected knee prostheses. The control isolates were taken from healthy volunteers who had not been exposed to antibiotics and a hospital environment during the previous 3 and 12 months, respectively. Control S epidermidis was isolated from the skin of the antecubital fossa, and control S aureus was isolated from the nares. For the biofilm experiments the following methods were used to detect eDNA: (1) fluorescent staining with 4',6-diamidino-2-phenylindole (DAPI), (2) eDNA extraction using a commercial kit, and (3) confocal laser scanning microscopy for 24-hour biofilm observation using propidium iodide and concanavalin-A staining; TOTO®-1 and SYTO® 60 staining were used for observation and quantification of eDNA after 6 and 24 hours of biofilm formation. Additionally antibiotic resistance was described. RESULTS: eDNA production as observed by confocal laser scanning microscopy was greater in clinical isolates than controls (clinical isolates mean ± SD: 1.84% ± 1.31%; control mean ± SD: 1.17% ± 1.37%; p < 0.005) after 6 hours of biofilm formation. After 24 hours, the amount of eDNA was greater in biofilms of S epidermidis than in biofilms of S aureus (S aureus mean ± SD: 1.35% ± 2.0%; S epidermidis mean ± SD: 6.42% ± 10.6%; p < 0.05). Clinical isolates of S aureus and S epidermidis produced more eDNA than control isolates at 6 hours of biofilm formation. The extraction method also showed that clinical isolates produced substantially greater amounts of eDNA than controls. CONCLUSIONS: S aureus and S epidermidis exhibit a differential production of DNA with time. Clinical isolates associated with implant infections produce greater amounts of eDNA than controls. Future research might focus on the diagnostic value of eDNA as a surrogate laboratory marker for biofilm formation in implant infections. CLINICAL RELEVANCE: eDNA should be considered as a potential future diagnostic tool or even a possible target to modify biofilms for successful treatment of biofilm-associated infections.

Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions via MKK6 activation.

During inflammation, neutrophils are rapidly mobilized from the bone marrow storage pool into peripheral blood (PB) to enter lesional sites, where most rapidly undergo apoptosis. Monocytes constitute a second wave of inflammatory immigrates, giving rise to long-lived macrophages and dendritic cell subsets. According to descriptive immunophenotypic and cell culture studies, neutrophils may directly "transdifferentiate" into monocytes/macrophages. We provide mechanistic data in human and murine models supporting the existence of this cellular pathway. First, the inflammatory signal-induced MKK6-p38MAPK cascade activates a monocyte differentiation program in human granulocyte colony-stimulating factor-dependent neutrophils. Second, adoptively transferred neutrophils isolated from G-CSF-pretreated mice rapidly acquired monocyte characteristics in response to inflammatory signals in vivo. Consistently, inflammatory signals led to the recruitment of osteoclast progenitor cell potential from ex vivo-isolated G-CSF-mobilized human blood neutrophils. Monocytic cell differentiation potential was retained in left-shifted band-stage neutrophils but lost in neutrophils from steady-state PB. MKK6-p38MAPK signaling in HL60 model cells led to diminishment of the transcription factor C/EBPα, which enabled the induction of a monocytic cell differentiation program. Gene profiling confirmed lineage conversion from band-stage neutrophils to monocytic cells. Therefore, inflammatory signals relayed by the MKK6-p38MAPK cascade induce monocytic cell differentiation from band-stage neutrophils.

Depressive symptoms predict the quality of sleep in patients with partial epilepsy--A combined retrospective and prospective study.

INTRODUCTION: Epilepsy is one of the most common neurological diseases and has many detrimental effects on the patients' well-being as well as sleep quality. The aim of this study was to assess the subjective quality of sleep and influencing factors on subjective sleep quality in patients with partial epilepsy using a combined retrospective and prospective study design. METHODS: We conducted a combined retrospective and prospective study in patients with partial epilepsy and analyzed subjective ratings of sleep quality in 32 patients (17 female, 15 male; mean age: 40.41 ± 12.67 years, range: 20-64) with partial epilepsy (mean duration of epilepsy diagnosis: 18.31 ± 13.26 years) and 32 healthy gender-matched and age-matched controls. All patients filled out a seizure diary for 90 days, which included the number, duration, and type (partial vs. secondary generalized) of epileptic seizures and intake of antiepileptic and sleep medications. At baseline, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Beck's Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Poor sleepers were defined by a PSQI score of ≥ 5. RESULTS: Twenty-three patients (72%) reported 15.17 ± 25.54 seizures in the previous three months, and nine (28%) patients reported being seizure-free. During the 90-day diary period, twenty-two patients (69%) documented a total of 319 epileptic seizures, while ten patients (31%) reported that they were seizure-free. The mean PSQI score of all patients was 4.88 ± 2.92 (range: 1-14) and the mean ESS score was 5.25 ± 2.98 (range: 0-10). The mean PSQI score of the control group was 3.25 ± 1.57 (range: 1-6), and their mean ESS score was 6.72 ± 3.48 (range: 0-14). The comparison of the two groups showed a significantly higher PSQI score in the patient group (t = 2.778, p = 0.008), but no statistically significant difference regarding their ESS score (t = -1.811, p = 0.075). Sixteen (50%) patients were poor sleepers. Good sleepers showed a significantly lower PSQI (2.69 ± 1.08 vs. 7.06 ± 2.49; p < 0.001) and BDI scores (2.38 ± 2.50 vs. 9.63 ± 7.63; p < 0.002) than poor sleepers. Linear regression analysis showed that the BDI score was the significant predictor for the PSQI score (estimate: 0.2019; p = 0.00819) and for the ESS score (estimate: 0.2251; p = 0.0321). CONCLUSION: In patients with partial epilepsy, a higher depression score was the best predictor for a poor subjective sleep quality and increased daytime sleepiness.

Awareness of memory deficits in subjective cognitive decline, mild cognitive impairment, Alzheimer's disease and Parkinson's disease.

BACKGROUND: Impaired awareness of memory deficits has been recognized as a common phenomenon in Alzheimer's disease (AD) and research is now increasingly focusing on awareness in groups at risk for future dementia. This study aimed to determine whether levels of awareness differ among healthy elderly people and patients with subjective cognitive decline (SCD), amnestic and non-amnestic subtypes of mild cognitive impairment (aMCI, naMCI), Alzheimer's disease (AD) and Parkinson's disease (PD), to explore correlates of awareness and to establish frequencies of memory over- and underestimation within each diagnostic group. METHODS: 756 consecutive outpatients of a memory clinic and 211 healthy controls underwent thorough neuropsychological testing. Impairment of awareness was measured as the difference between subjective memory appraisals (16-item questionnaire on current memory-related problems in everyday life) and objective memory performance (15-item delayed recall task). Subgroups of over- and underestimators were classified using percentile ranks of controls. RESULTS: At group level, awareness significantly decreased along the naMCI→aMCI→AD continuum, with naMCI patients showing a tendency towards overestimation of memory dysfunction. PD patients showed accurate self-appraisals as long as memory function was largely unaffected. However, there was a considerable between-group overlap in awareness scores. Furthermore, different correlates of awareness were observed depending on the diagnostic group. In general, unawareness seems to be associated with decreased cognitive performance in various domains (especially memory), higher age and lower levels of depression and self-reported functional impairment. CONCLUSION: Impaired awareness is an important symptom in aMCI. Yet, given the considerable variability in awareness scores, longitudinal studies are required to evaluate their predictive power.

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.

Archaea influence composition of endoscopically visible ileocolonic biofilms.

The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.

Prevalence of mild cognitive impairment subtypes in patients attending a memory outpatient clinic--comparison of two modes of mild cognitive impairment classification. Results of the Vienna Conversion to Dementia Study.

BACKGROUND: Early detection of dementia is becoming more and more important owing to the advent of pharmacologic treatment. OBJECTIVE: The goals of this study were to establish prevalence of mild cognitive impairment (MCI) subtypes in an outpatient memory clinic cohort using two different modes of MCI determination. DESIGN: Consecutive patients complaining of cognitive problems who came to the memory outpatient clinic for assessment of a possible cognitive disorder were included in the study. SETTING: Academic medical center. PARTICIPANTS: Six hundred eighty consecutive patients complaining about cognitive problems who came to the memory outpatient clinic for assessment of a possible cognitive disorder and fulfilled the inclusion criteria were included in the study. For 676 patients, sufficient data for MCI classification were available. RESULTS: Categorizing MCI patients into MCI subtypes according to the minimum mode of MCI classification revealed the following results: 106 patients (15.7%) were categorized as cognitively healthy, whereas 570 patients (84.3%) met the criteria for MCI. MCI patients were subtyped as amnestic mild cognitive impairment (aMCI) single domain (31 patients; 4.6%), aMCI multiple domain (226 patients; 33.4%), non-aMCI single domain (125 patients; 18.5%), and non-aMCI multiple domain (188 patients; 27.8%). Categorizing MCI patients into MCI subtypes according to the mean mode of MCI classification revealed the following results: 409 patients (60.5%) were categorized as cognitively healthy, whereas 267 patients (39.5%) met the criteria for MCI. MCI patients were subtyped as aMCI single domain (47 patients; 6.9%), aMCI multiple domain (57 patients; 8.5%), non-aMCI single domain (97 patients; 14.3%), and non-aMCI multiple domain (66 patients; 9.8%). CONCLUSION: MCI diagnosis frequencies are substantially affected by the criteria used for estimation of MCI. The effect of modifying the presence of impairment on a single cognitive measure versus the presence of impairment on a mean composite score of a certain domain differed considerably, ranging from 39.5% to 84.3%, indicating the importance of the development of guidelines for operationalizing MCI.

New synthetic prosthesis for peripheral nerve injuries: an experimental pilot study.

INTRODUCTION: Even the most modern technology has failed to induce satisfactory functional regeneration of traumatically severed peripheral nerves. Delayed neural regeneration and in consequence, slower neural conduction seriously limit muscle function in the area supplied by the injured nerve. This study aimed to compare a new nerve coaptation system involving an innovative prosthesis with the classical clinical method of sutured nerve coaptation. Besides the time and degree of nerve regeneration, the influence of electrostimulation was also tested. METHODS: The sciatic nerve was severed in 14 female Göttingen minipigs with an average weight of 40.4 kg. The animals were randomized into 2 groups: One group received the new prosthesis and the other underwent microsurgical coaptation. In each group, according to the randomization a part of the animals received postoperative electrostimulation. Postoperative monitoring and the stimulation schedule covered a period of 9 months, during which axonal budding was evaluated monthly. RESULTS: The data from the pilot study indicate that results with the nerve prosthesis were comparable with those of conventional coaptation. CONCLUSION: The results indicate that implantation of the nerve prosthesis allows for good and effective neural regeneration. This new and simple treatment option for peripheral nerve injuries can be performed in any hospital with surgical facilities as it does not involve the demanding microsurgical suture technique that can only be performed in specialized centers.

Application of platelet-rich plasma for enhanced bone regeneration in grafted sinus.

PURPOSE: The present study was conducted to evaluate the effect of platelet-rich plasma (PRP) on new bone formation and remodeling after grafting of the maxillary sinus with an algae-derived hydroxyapatite AlgOss/C Graft/Algipore. MATERIALS AND METHODS: Fourteen consecutive patients with severely atrophic maxillae underwent uni- or bilateral grafting of the maxillary sinus with a mixture of collected bone, algae-derived hydroxyapatite AlgOss/C Graft/Algipore (ratio 1:10), and a combined addition of PRP and thrombin (Tissucol Kit; Baxter, Vienna, Austria) to allow for fast clotting. After an average healing period of 7.1 months bone samples were retrieved. Patients from a former consecutive series treated without PRP served as control group. Statistical analysis was done by Welch 2-sample t test and mixed linear model testing. RESULTS: In the coronal specimen portions, mean values for newly formed bone area, biomaterial area and marrow space of 32.2% ± 10.4%, 20.1% ± 13.0%, and 47.7% ± 8.5% were found with PRP, respectively. In the control group the corresponding values were 27.6% ± 13.4%, 20.3% ± 12.9%, and 52.1% ± 9.3%. In the apical specimen portions in the PRP group, the newly formed bone area, biomaterial area, and marrow space was 25.7% ± 15.0%, 23.4% ± 14.9%, and 50.9% ± 12.5%, respectively. The corresponding values in the control group were 17.0% ± 8.6%, 34.5% ± 11.2%, and 48.5% ± 8.5%. CONCLUSIONS: Statistical evaluation of the samples proved significantly better overall resorption of algae-derived hydroxyapatite AlgOss/C Graft/Algipore and increased new bone formation when PRP was used, especially in the apical region.

Diagnosis of contact injuries in a mediaeval skeleton analysed by µCT and histology.

During an archaeological excavation in Altenberg/Linz (Upper Austria), the well-preserved skeletal remains of a mature male dated the 13th century AD were recovered. Several elements of the skeleton yielded alterations caused by trauma: beside a malunion of the left ulna which was accompanied by shortening of the diaphysis, a luxation and deformation of the left radial head was observed (Monteggia-type lesion, Bado-type I). Moreover, at the anterior aspect of the corresponding humerus, a chalice-shaped, newly built bone structure that framed the displaced capitulum radii was visible. This structure formed a sort of "alternative joint" that functionally even allowed some movements, although considerably restricted in regard to flexion/extension and even more in pronation/supination.To verify the assumption of a "single event", we not only investigated the concerned skeletal portions by gross-anatomical examination, but also by non-invasive conventional radiological, micro-computed tomographical, and histological techniques. Particular morphological features, injuries at the calvarium, and fractures of other postcranial elements imply the scenario of a close combat; although survived, the traumata obviously resulted in partial invalidity.

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.

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.