Corticospinal mirror neurons

Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons’ discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited ‘classical’ mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation (‘suppression mirror-neurons’). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.     

Some Are More Equal - A Comparative Study on Swab Uptake and Release of Bacterial Suspensions

Objectives

Swabs are widely used to collect samples for microbiological analyses from various clinical settings. They vary by material, size, and structure of the tip. This study investigates the uptake and release capacities for liquid and bacteria.

Methods

Five swabs were analyzed for their uptake and release capacities of Staphylococcus aureus and Staphylococcus epidermidis suspensions. Two approaches were investigated providing volume-restricted and unrestricted amounts of bacterial suspensions to mimic various clinical situations. Volume and bacterial uptake and release were measured in milligrams and by counting colony forming units (CFU), respectively.

Results

Volume uptake and release in the unrestricted setting varied highly significant between 239.6 mg and 88.7 mg (p<0.001) and between 65.2 mg and 2.2 mg (p<0.001), respectively. In the volume-restricted setting the complete volume was absorbed by all swabs, volume release could only be detected for flocked swabs (2.7 mg; p<0.001). Highest amount of CFU release was detected for the MWE Dryswab in the unrestricted setting for both S. aureus and S. epidermidis with 1544 CFU and 553 CFU, respectively, lowest release for the Sarstedt neutral swab with 32 CFU and 17 CFU, respectively (p<0.001). In the volume-restricted setting MWE Σ-Swab released the highest bacterial amount with 135 CFU S. aureus and 55 CFU S. epidermidis, respectively, the lowest amount was released by Mast Mastaswab with 2 CFU S. aureus and 1 CFU S. epidermidis, respectively (p<0.001). Within the range of the utilized bacterial concentrations, uptake/release ratios were identical for the particular swab types and independent of the bacterial species.

Conclusions

The influence of the swab type on subsequent diagnostic results is often underestimated. Uptake and release of the investigated bacteria vary significantly between different swab types and sampling conditions. For best diagnostic outcome swabs should be chosen according to the examined situation and the swab performance profile.     

Biliary Endoprosthesis: A Prospective Analysis of Bacterial Colonization and Risk Factors for Sludge Formation

Bacterial colonization of biliary stents is one of the driving forces behind sludge formation which may result in stent occlusion. Major focus of the study was to analyze the spectrum and number of microorganisms in relation to the indwelling time of stents and the risk factors for sludge formation. 343 stents were sonicated to optimize the bacterial release from the biofilm and identified by matrix-associated laser desorption/ionization-time of flight mass spectrometer (MALDI-TOF). 2283 bacteria were analyzed in total. The most prevalent microorganisms were Enterococcus species (spp.) (504;22%), followed by Klebsiella spp. (218;10%) and Candida spp. (188;8%). Colonization of the stents mainly began with aerobic gram-positive bacteria (43/49;88%) and Candida spp. (25/49;51%), whereas stents with an indwelling time>60 days(d) showed an almost equal colonization rate by aerobic gram-negative (176/184;96%) and aerobic gram-positive bacteria (183/184;99%) and a high proportion of anaerobes (127/184;69%). Compared to stents without sludge, more Clostridium spp. [(P = 0.02; Odds Ratio (OR): 2.4; 95% confidence interval (95%CI): (1.1–4.9)]) and Staphylococcus spp. [(P = 0.03; OR (95%CI): 4.3 (1.1–16.5)] were cultured from stents with sludge. Multivariate analysis revealed a significant relationship between the number of microorganisms [P<0.01; OR (95%CI): 1.3(1.1–1.5)], the indwelling time [P<0.01; 1–15 d vs. 20–59 d: OR (95%CI): 5.6(1.4–22), 1–15 d vs. 60–3087 d: OR (95% CI): 9.5(2.5–35.7)], the presence of sideholes [P<0.01; OR (95%CI): 3.5(1.6–7.9)] and the occurrence of sludge. Stent occlusion was found in 70/343(20%) stents. In 35% of cases, stent occlusion resulted in a cholangitis or cholestasis. In conclusion, microbial colonization of the stents changed with the indwelling time. Sludge was associated with an altered spectrum and an increasing number of microorganisms, a long indwelling time and the presence of sideholes. Interestingly, stent occlusion did not necessarily lead to a symptomatic biliary obstruction.     

Higher Adenoma Detection Rates with Endocuff-Assisted Colonoscopy – A Randomized Controlled Multicenter Trial

Objectives

The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).

Methods

This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).

Results

The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates.

Conclusions

EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02034929","term_id":"NCT02034929"}}NCT02034929.     

Small Dense Low Density Lipoprotein Particles Are Associated with Poor Outcome after Angioplasty in Peripheral Artery Disease

Purpose

In patients suffering from symptomatic peripheral artery disease (PAD), percutaneous revascularization is the treatment of choice. However, restenosis may occur in 10 to 60% in the first year depending on a variety of factors. Small dense low density lipoprotein (sdLDL) particles are associated with an increased risk for cardiovascular events, but their role in the process of restenosis is not known. We conducted a prospective study to analyze the association of sdLDL particles with the outcome of balloon angioplasty in PAD. The composite primary endpoint was defined as improved walking distance and absence of restenosis.

Methods

Patients with angiographically documented PAD of the lower extremities who were scheduled for lower limb revascularization were consecutively recruited for the study. At baseline and at three month follow-up triglyceride, total cholesterol, LDL size and subclasses and HDL cholesterol and ankle-brachial index (ABI) were measured. Three months after the intervention duplex sonography was performed to detect restenosis.

Results

Sixty-four patients (53% male) with a mean age of 68.6±9.9 years were included. The proportion of small- dense LDL particles (class III and IV) was significantly lower (33.1±11.0% vs. 39.4±12.1%, p = 0.038) in patients who reached the primary end-point compared with those who did not. Patients with improved walking distance and without restenosis had a significantly higher LDL size at baseline (26.6±1.1 nm vs. 26.1±1.1 nm, p = 0.046) and at follow-up (26.7±1.1 nm vs. 26.2±0.9 nm, p = 0.044) than patients without improvement.

Conclusions

Small-dense LDL particles are associated with worse early outcome in patients undergoing percutaneous revascularization for symptomatic PAD.     

Quantification of Tumor Vessels in Glioblastoma Patients Using Time-of-Flight Angiography at 7 Tesla: A Feasibility Study

Purpose

To analyze if tumor vessels can be visualized, segmented and quantified in glioblastoma patients with time of flight (ToF) angiography at 7 Tesla and multiscale vessel enhancement filtering.

Materials and Methods

Twelve patients with newly diagnosed glioblastoma were examined with ToF angiography (TR = 15 ms, TE = 4.8 ms, flip angle = 15°, FOV = 160×210 mm², voxel size: 0.31×0.31×0.40 mm³) on a whole-body 7 T MR system. A volume of interest (VOI) was placed within the border of the contrast enhancing part on T1-weighted images of the glioblastoma and a reference VOI was placed in the non-affected contralateral white matter. Automated segmentation and quantification of vessels within the two VOIs was achieved using multiscale vessel enhancement filtering in ImageJ.

Results

Tumor vessels were clearly visible in all patients. When comparing tumor and the reference VOI, total vessel surface (45.3±13.9 mm² vs. 29.0±21.0 mm² (p<0.035)) and number of branches (3.5±1.8 vs. 1.0±0.6 (p<0.001) per cubic centimeter were significantly higher, while mean vessel branch length was significantly lower (3.8±1.5 mm vs 7.2±2.8 mm (p<0.001)) in the tumor.

Discussion

ToF angiography at 7-Tesla MRI enables characterization and quantification of the internal vascular morphology of glioblastoma and may be used for the evaluation of therapy response within future studies.     

MiRNA-1/133a Clusters Regulate Adrenergic Control of Cardiac Repolarization

The electrical properties of the heart are primarily determined by the activity of ion channels and the activity of these molecules is permanently modulated and adjusted to the physiological needs by adrenergic signaling. miRNAs are known to control the expression of many proteins and to fulfill distinct functions in the mammalian heart, though the in vivo effects of miRNAs on the electrical activity of the heart are poorly characterized. The miRNAs miR-1 and miR-133a are the most abundant miRNAs of the heart and are expressed from two miR-1/133a genomic clusters. Genetic modulation of miR-1/133a cluster expression without concomitant severe disturbance of general cardiomyocyte physiology revealed that these miRNA clusters govern cardiac muscle repolarization. Reduction of miR-1/133a dosage induced a longQT phenotype in mice especially at low heart rates. Longer action potentials in cardiomyocytes are caused by modulation of the impact of β-adrenergic signaling on the activity of the depolarizing L-type calcium channel. Pharmacological intervention to attenuate β-adrenergic signaling or L-type calcium channel activity in vivo abrogated the longQT phenotype that is caused by modulation of miR-1/133a activity. Thus, we identify the miR-1/133a miRNA clusters to be important to prevent a longQT-phenotype in the mammalian heart.     

Stable Composition of the Nano- and Picoplankton Community during the Ocean Iron Fertilization Experiment LOHAFEX

The iron fertilization experiment LOHAFEX was conducted in a cold-core eddy in the Southern Atlantic Ocean during austral summer. Within a few days after fertilization, a phytoplankton bloom developed dominated by nano- and picoplankton groups. Unlike previously reported for other iron fertilization experiments, a diatom bloom was prevented by iron and silicate co-limitation. We used 18S rRNA gene tag pyrosequencing to investigate the diversity of these morphologically similar cell types within the nano- and picoplankton and microscopically enumerated dominant clades after catalyzed reported deposition fluorescence in situ hybridization (CARD-FISH) with specific oligonucleotide probes. In addition to Phaeocystis, members of Syndiniales group II, clade 10–11, and the Micromonas clades ABC and E made up a major fraction of the tag sequences of the nano- and picoplankton community within the fertilized patch. However, the same clades were also dominant before the bloom and outside the fertilized patch. Furthermore, only little changes in diversity could be observed over the course of the experiment. These results were corroborated by CARD-FISH analysis which confirmed the presence of a stable nano- and picoplankton community dominated by Phaeocystis and Micromonas during the entire course of the experiment. Interestingly, although Syndiniales dominated the tag sequences, they could hardly be detected by CARD-FISH, possibly due to the intracellular parasitic life style of this clade. The remarkable stability of the nano- and picoplankton community points to a tight coupling of the different trophic levels within the microbial food web during LOHAFEX.     

Genome-Wide Association Study Reveals a Polymorphism in the Podocyte Receptor RANK for the Decline of Renal Function in Coronary Patients

Impaired kidney function is a significant health problem and a major concern in clinical routine and is routinely determined by decreased glomerular filtration rate (GFR). In contrast to single assessment of a patients'' kidney function providing only limited information on patients'' health, serial measurements of GFR clearly improves the validity of diagnosis. The decline of kidney function has recently been reported to be predictive for mortality and vascular events in coronary patients. However, it has not been investigated for genetic association in GWA studies. This study investigates for the first time the association of cardiometabolic polymorphisms with the decline of estimated GFR during a 4 year follow up in 583 coronary patients, using the Cardio-Metabo Chip. We revealed a suggestive association with 3 polymorphisms, surpassing genome-wide significance (p = 4.0 e-7). The top hit rs17069906 (p = 5.6 e-10) is located within the genomic region of RANK, recently demonstrated to be an important player in the adaptive recovery response in podocytes and suggested as a promising therapeutic target in glomerular diseases.     

Quantitative Stain-Free and Continuous Multimodal Monitoring of Wound Healing In Vitro with Digital Holographic Microscopy

Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure are commonly evaluated in in vitro wound assays. However, staining procedures and discontinuous monitoring are major drawbacks hampering accurate assessment of wound assays. We therefore investigated digital holographic microscopy (DHM) to appropriately monitor wound healing in vitro and secondly, to provide multimodal quantitative information on morphological and functional cell alterations as well as on motility changes upon cytokine stimulation. Wound closure as reflected by proliferation and migration of Caco-2 cells in wound healing assays was studied and assessed in time-lapse series for 40 h in the presence of stimulating epidermal growth factor (EGF) and inhibiting mitomycin c. Therefore, digital holograms were recorded continuously every thirty minutes. Morphological changes including cell thickness, dry mass and tissue density were analyzed by data from quantitative digital holographic phase microscopy. Stimulation of Caco-2 cells with EGF or mitomycin c resulted in significant morphological changes during wound healing compared to control cells. In conclusion, DHM allows accurate, stain-free and continuous multimodal quantitative monitoring of wound healing in vitro and could be a promising new technique for assessment of wound healing.