Inefficient Magnetic-Field Amplification in Supersonic Laser-Plasma Turbulence.

We report a laser-plasma experiment that was carried out at the LMJ-PETAL facility and realized the first magnetized, turbulent, supersonic (Ma_{turb}≈2.5) plasma with a large magnetic Reynolds number (Rm≈45) in the laboratory. Initial seed magnetic fields were amplified, but only moderately so, and did not become dynamically significant. A notable absence of magnetic energy at scales smaller than the outer scale of the turbulent cascade was also observed. Our results support the notion that moderately supersonic, low-magnetic-Prandtl-number plasma turbulence is inefficient at amplifying magnetic fields compared to its subsonic, incompressible counterpart.

Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness.

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals.

Computational Synaptic Modeling of Pitch and Duration Mismatch Negativity in First-Episode Psychosis Reveals Selective Dysfunction of the N-Methyl-D-Aspartate Receptor.

Mismatch negativity (MMN) to pitch (pMMN) and to duration (dMMN) deviant stimuli is significantly more attenuated in long-term psychotic illness compared to first-episode psychosis (FEP). It was recently shown that source-modeling of magnetically recorded MMN increases the detection of left auditory cortex MMN deficits in FEP, and that computational circuit modeling of electrically recorded MMN also reveals left-hemisphere auditory cortex abnormalities. Computational modeling using dynamic causal modeling (DCM) can also be used to infer synaptic activity from EEG-based scalp recordings. We measured pMMN and dMMN with EEG from 26 FEP and 26 matched healthy controls (HCs) and used a DCM conductance-based neural mass model including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, N-methyl-D-Aspartate (NMDA), and Gamma-aminobutyric acid receptors to identify any changes in effective connectivity and receptor rate constants in FEP. We modeled MMN sources in bilateral A1, superior temporal gyrus, and inferior frontal gyrus (IFG). No model parameters distinguished groups for pMMN. For dMMN, reduced NMDA receptor activity in right IFG in FEP was detected. This finding is in line with literature of prefrontal NMDA receptor hypofunction in chronic schizophrenia and suggests impaired NMDA-induced synaptic plasticity may be present at psychosis onset where scalp dMMN is only moderately reduced. To the best of our knowledge, this is the first report of impaired NMDA receptor activity in FEP found through computational modeling of dMMN and shows the potential of DCM to non-invasively reveal synaptic-level abnormalities that underly subtle functional auditory processing deficits in early psychosis.

Primary anastomosis with a defunctioning stoma versus Hartmann's procedure for perforated diverticulitis--a comparison of stoma reversal rates.

PURPOSE: The ideal treatment of patients with perforated diverticulitis is still controversial. Hartmann's procedure has been the treatment of choice for decades, but primary anastomosis with a defunctioning stoma has become an accepted alternative. The aim of this study was to evaluate the stoma reversal rates after these two surgical strategies. METHODS: A retrospective review of the data from patients with perforated sigmoid diverticulitis between 2002 and 2011 undergoing a Hartmann's procedure (HP) versus a primary anastomosis with a defunctioning stoma (PA) was performed. Additionally, patients were contacted by mail or telephone in March 2012 using a standardized questionnaire. RESULTS: A total of 98 patients were identified: 72 undergoing HP and 26 patients receiving PA. The median follow-up time was 63 months (range 4-118). Whilst 85 % of patients with PA have had their stoma reversed, only 58 % of patients with an HP had a stoma reversal (p = 0.046). The median period until stoma reversal was significantly longer for HP (19 weeks) than for PA (12 weeks; p = 0.03). The 30-day mortality for PA was 12 % as opposed to 25 % for HP (p = 0.167). According to the Clavien-Dindo classification, surgical complications occurred significantly less frequently in patients with PA (p = 0.014). CONCLUSION: The stoma reversal rates for PA are significantly higher than for HP. Thus, depending on the overall clinical situation, primary resection and anastomosis with a proximal defunctioning stoma might be the optimal procedure for selected patients with perforated diverticular disease.

Impact of pressure and gas type on adhesion formation and biomaterial integration in laparoscopy.

BACKGROUND: Laparoscopic mesh repair of inguinal and incisional hernias has been widely adopted. Nevertheless, knowledge about the impact of pneumoperitoneum on mesh integration is rare. The present study investigates pressure and gas-dependent effects of pneumoperitoneum on adhesion formation and biomaterial integration in a standardized animal model. METHODS: Laparoscopic intraperitoneal onlay mesh implantation (IPOM) was performed in 32 female chinchilla rabbits using CO(2) or helium for pneumoperitoneum. Intra-abdominal pressures were 3 or 6 mmHg. Animals were killed after 21 days, and the abdominal wall was explanted for subsequent histopathological examinations. Adhesions were assessed qualitatively with a scoring system, and the adhesion surface was analyzed semiquantitatively by planimetry. Infiltration of macrophages (CD68), expression of matrix metalloproteinase 13 (MMP-13), and cell proliferation (Ki67) were analyzed at the mesh to host interface by immunohistochemistry. The collagen type I/III ratio was analyzed by cross-polarization microscopy to determine the quality of mesh integration. RESULTS: After 21 days, perifilamental infiltration with macrophages (CD68) and percentage of proliferating cells (Ki67) were highest after 6 mmHg of CO(2) pneumoperitoneum. The extent of adhesions, as well as the expression of MMP-13 and the collagen type I/III ratio, were similar between groups. CONCLUSIONS: Our experiments showed no pressure or gas-dependent alterations of adhesion formation and only minor effects on biomaterial integration. Altogether, there is no evidence for a clinically negative effect of CO(2) pneumoperitoneum.

Imaging epilepsy in larval zebrafish.

Our understanding of the genetic aetiology of paediatric epilepsies has grown substantially over the last decade. However, in order to translate improved diagnostics to personalised treatments, there is an urgent need to link molecular pathophysiology in epilepsy to whole-brain dynamics in seizures. Zebrafish have emerged as a promising new animal model for epileptic seizure disorders, with particular relevance for genetic and developmental epilepsies. As a novel model organism for epilepsy research they combine key advantages: the small size of larval zebrafish allows high throughput in vivo experiments; the availability of advanced genetic tools allows targeted modification to model specific human genetic disorders (including genetic epilepsies) in a vertebrate system; and optical access to the entire central nervous system has provided the basis for advanced microscopy technologies to image structure and function in the intact larval zebrafish brain. There is a growing body of literature describing and characterising features of epileptic seizures and epilepsy in larval zebrafish. Recently genetically encoded calcium indicators have been used to investigate the neurobiological basis of these seizures with light microscopy. This approach offers a unique window into the multiscale dynamics of epileptic seizures, capturing both whole-brain dynamics and single-cell behaviour concurrently. At the same time, linking observations made using calcium imaging in the larval zebrafish brain back to an understanding of epileptic seizures largely derived from cortical electrophysiological recordings in human patients and mammalian animal models is non-trivial. In this review we briefly illustrate the state of the art of epilepsy research in zebrafish with particular focus on calcium imaging of epileptic seizures in the larval zebrafish. We illustrate the utility of a dynamic systems perspective on the epileptic brain for providing a principled approach to linking observations across species and identifying those features of brain dynamics that are most relevant to epilepsy. In the following section we survey the literature for imaging features associated with epilepsy and epileptic seizures and link these to observations made from humans and other more traditional animal models. We conclude by identifying the key challenges still facing epilepsy research in the larval zebrafish and indicate strategies for future research to address these and integrate more directly with the themes and questions that emerge from investigating epilepsy in other model systems and human patients.

Gas-related impact of pneumoperitoneum on systemic wound healing.

INTRODUCTION: The aim of the present study was to investigate the gas-dependent effects of pneumoperitoneum on wound healing distant from the abdomen. MATERIALS AND METHODS: Dorsal skin incisions were performed in 54 male Sprague-Dawley rats. A CO(2) or a helium pneumoperitoneum of 3 mmHg was maintained before, with an overall duration of 30 min (each n = 18). Rats in the control group received laparotomy only (n = 18). Animals were killed after 5 and 10 days. The infiltration of macrophages (CD 68), expression of matrix metalloproteinase 13 (MMP-13) and collagen I/III ratios were analysed in the dorsal skin wounds. RESULTS: Both after 5 and 10 days, infiltration of macrophages and expression of MMP-13 were greatest after helium pneumoperitoneum. After 5 days, collagen I/III ratio was significantly increased in the helium group. After 10 days, collagen I/III ratio was lowest in the CO(2) group. CONCLUSION: Our results suggest beneficial effects on systemic wound healing for helium pneumoperitoneum as compared to CO(2).

Analysis of c-myc, PAI-1 and uPAR in patients with incisional hernias.

BACKGROUND: Disturbed wound healing leading to alterations in collagen composition has been thought to play a key role in the pathogenesis of incisional hernia formation. The aim of the present study was to further characterise the scarring process in such patients. METHODS: Mature skin scars from patients with either primary or recurrent incisional hernias were compared to mature abdominal skin scars from patients without hernias. The distribution of collagen types I and III was analysed using crosspolarisation microscopy. Expression of c-myc--a parameter for cell differentiation and proliferation--and of PAI-1 and uPAR--parameters of the proteolytic cascade in wound healing--were determined by immunohistochemistry. RESULTS: In agreement with previous studies, decreased collagen I/III ratios were found in patients with incisional hernias. In these patients, c-myc levels were significantly elevated whereas plasminogen activator inhibitor-1 (PAI-1) and urokinase-plasminogen activator receptor (uPAR) levels were only slightly increased. In contrast to controls, a significant correlation between c-myc, PAI-1 and uPAR expression and collagen I/III ratios was found in patients with incisional hernias. CONCLUSION: The differential correlation of collagen types and expression of c-myc, PAI-1 and uPAR within the scar tissue might represent a causal factor in incisional hernia formation.

[Medicine between humanitarianism and competition: the patients' point of view]. / Medizin zwischen Humanität und Wettbewerb: Ein aktuelles Patientenmeinungsbild.

BACKGROUND: An open medical market is supposed to be a promising tool for preserving the meagre resources of the German public health care system. The competition between humane and economic practice induces conflicts which burden physicians as well as patients. To analyse this problem by scientific means, inpatients were interviewed with the help of a standardised protocol. PATIENTS AND METHODS: During 10 weeks 524 inpatients were interviewed. The structured questionnaire consisted of nine closed-ended questions with multiple-choice answers. Question 3 included a free amendment. The gender ratio was balanced, and the age pattern represented the typical patient collective of our clinic. RESULTS AND CONCLUSION: The majority of patients expect negative changes in their medical service and the social attitude towards patients and physicians due to promoted medical competition. Besides an increasing financial load, losses in trust, self-determination, and therapeutic freedom are expected. Instead a responsible transparency will not be achieved. Patients still judge the economically dominated reforms on the German health care market with scepticism or even hostility. In their point of view future discussions must aim at a more modern attitude towards health economics in order to bridge the schism they perceive between medical competition and humanitarianism. The understanding of strong financial management as a prime condition for stable social security is the basis of synergies to deal with upcoming reforms.

Mesh migration into the esophageal wall after mesh hiatoplasty: comparison of two alloplastic materials.

BACKGROUND: Hiatal mesh implantation in the operative treatment of gastroesophageal reflux disease has become an increasing therapy option. Besides clinical results little is known about histological changes in the esophageal wall. METHODS: Two different meshes [polypropylene (PP), Prolene; polypropylene-polyglecaprone 25 composite (PP-PG), Ultrapro] were placed on the diaphragm circular the esophagus of 20 female rabbits. After three months a swallow with iodine water-soluble contrast medium for functional analysis was performed. After the animals were sacrificed, histopathological evaluation of the foreign-body reaction, the localization of the mesh relating to the esophageal wall was analyzed. RESULTS: Sixteen rabbits survived the complete observation period of three months. After three months distinctive mesh shrinkage was observed in all animals and meshes had lost up to 50% of their original size before implantation. We found a delayed passage of the fluid into the stomach in all operated animals. There was a significant increased diameter of the outer ring of granulomas in the PP group (76.5 +/- 8.0) compared to the PP-PG group (64 +/- 8.5; p = 0.002). However, we found a mesh migration into the esophageal wall in six out of seven animals (PP) and five out of nine animals (PP-PG), respectively. CONCLUSION: Experimental data suggest that more knowledge is necessary to assess the optimal size, structure, and position of prosthetic materials for mesh hiatoplasty. The indication for mesh implantation in the hiatal region should be carried out very carefully.

X-ray imaging with grazing-incidence microscopes developed for the LIL program.

This article describes x-ray imaging with grazing-incidence microscopes, developed for the experimental program carried out on the Ligne d'Integration Laser (LIL) facility [J. P. Le Breton et al., Inertial Fusion Sciences and Applications 2001 (Elsevier, Paris, 2002), pp. 856-862] (24 kJ, UV-0.35 nm). The design includes a large target-to-microscope (400-700 mm) distance required by the x-ray ablation issues anticipated on the Laser MégaJoule facility [P. A. Holstein et al., Laser Part. Beams 17, 403 (1999)] (1.8 MJ) which is under construction. Two eight-image Kirkpatrick-Baez microscopes [P. Kirkpatrick and A. V. Baez J. Opt. Soc. Am. 38, 766 (1948)] with different spectral wavelength ranges and with a 400 mm source-to-mirror distance image the target on a custom-built framing camera (time resolution of approximately 80 ps). The soft x-ray version microscope is sensitive below 1 keV and its spatial resolution is better than 30 microm over a 2-mm-diam region. The hard x-ray version microscope has a 10 microm resolution over an 800-microm-diam region and is sensitive in the 1-5 keV energy range. Two other x-ray microscopes based on an association of toroidal/spherical surfaces (T/S microscopes) produce an image on a streak camera with a spatial resolution better than 30 microm over a 3 mm field of view in the direction of the camera slit. Both microscopes have been designed to have, respectively, a maximum sensitivity in the 0.1-1 and 1-5 keV energy range. We present the original design of these four microscopes and their test on a dc x-ray tube in the laboratory. The diagnostics were successfully used on LIL first experiments early in 2005. Results of soft x-ray imaging of a radiative jet during conical shaped laser interaction are shown.

Improved abdominal wall wound healing by helium pneumoperitoneum.

BACKGROUND: Despite widespread use of the endoscopic technique in the treatment of inguinal and incisional hernias, knowledge about its impact on abdominal wall wound healing is rare. Questions remain regarding the risk of port-site hernias and hernia recurrence. The current study investigated the gas-dependent effects of pneumoperitoneum on laparotomy wound healing. METHODS: Laparotomy was performed in 54 male Sprague-Dawley rats. A carbon dioxide (n = 18) or helium (n = 18) pneumoperitoneum of 3 mmHg was maintained before and after laparotomy, with an overall duration of 30 min. The rats in the control group (n = 18) received no pneumoperitoneum. The animals were killed after 5 and 10 days, and the abdominal wall was explanted for subsequent histopathologic examinations of the laparotomy wound. The granuloma formation in hematoxylin and eosin-stained sections was analyzed. Infiltration of macrophages (CD68) and expression of matrix metalloproteinases (MMP-8 and MMP-13) were examined by immunohistochemistry. The collagen type 1 to type 3 ratio was investigated by cross-polarization microscopy after Sirius Red staining. RESULTS: After 5 and 10 days, the percentages of CD68-positive cells, granuloma formation, and expression of MMP-8 did not differ between the groups. In contrast, after both 5 and 10 days, the expression of MMP-13 and the collagen 1 to 3 ratio were significantly higher after helium pneumoperitoneum than in the control animals. CONCLUSION: The results suggest that helium pneumoperitoneum may ameliorate wound healing within the abdominal wall and could therefore represent a beneficial gas for endoscopic hernia repair.

Laparoscopy and collagen metabolism.

The collagens represent a vital component within the wound healing process and physiological scar formation. Therefore, analysing the influence of new operative procedures on collagen metabolism is of great surgical interest. As the endoscopic technique has, nowadays, become routinely applied for diverse abdominal diseases worldwide, we present a review of literature facing its impact on collagen biology.

Incisional intercostal hernia after a nephrectomy.

The aim of the present case report is to present the diagnostic and therapeutic challenge of intercostal incisional hernia. We report on a female patient with leftsided intercostal incisional hernia between the eleventh and twelfth rib due to preceding lumbar incision for tumor nephrectomy. Because of its infrequence, diagnosis was established late although simple clinical examination and ultrasound investigation displayed the hernia. At laparotomy, a 5x5 cm(2) fascial defect with a colonic sliding hernia was found. Hernia repair using permanent mesh reinforcement in the retromuscular position is described. Abdominal incisional hernia in the intercostal region is rare and therefore easily overlooked. As with other incisional hernias, the hernia repair using mesh implantation in the retromuscular region is technically feasible and represents the treatment of choice.

Modification of collagen formation using supplemented mesh materials.

BACKGROUND: Formation of recurrent inguinal and incisional hernia shows an underlying defect in the wound healing process. Even following mesh repair an altered collagen formation and insufficient mesh integration has been found as main reason for recurrences. Therefore the development of bioactive mesh materials to achieve a local modification of the scar formation to improve patients outcome is advisable. METHODS: Thirty-six male Wistar rats were used within this study. A Mersilene (R) mesh sample was implanted after midline skin incision and subcutaneous preparation. Before implantation mesh samples were incubated for 30 minutes with either one of the following agents: doxycycline, TGF-beta 3, zinc-hydrogeneaspartate, ascorbic acid, hyaluronic acid. Incubation with a physiologic 0.9 % NaCl solution served as control. Seven and 90 days after mesh implantation 3 animals from each group (n = 6) were sacrificed for morphological observations. Collagen quantity and quality was analyzed measuring the collagen/protein as well as the collagen type I/III ratio. RESULTS: Following an implantation interval of 90 days supplementation with doxycycline (39.3 +/- 7.0 microg/mg) and hyaluronic acid (34.4 +/- 5.8 microg/mg) were found to have a significantly increased collagen/protein ratio compared to implantation of the pure Mersilene (R) mesh samples (28.3 +/- 1.9 microg/mg). Furthermore, an overall increase of the collagen type I/III ratio was found in all groups indicating scar maturation over time. However, no significant differences were found after 7 and 90 days of implantation comparing collagen type I/III ratio of supplemented mesh samples and control group. CONCLUSIONS: In summary, we found an influence of supplemented mesh materials on collagen deposition. However, the investigated bioactive agents with reported influence on wound healing were not associated with an improved quality in scar formation.

Risk factors related to recurrence in inguinal hernia repair: a retrospective analysis.

The aim of this study was to analyze and evaluate the long-term recurrence rate and risk factors for inguinal hernia recurrence in patients treated by the Shouldice suture repair. A total of 293 hernias treated by Shouldice suture technique in 1992 were studied retrospectively. After a 10-year follow-up, 15 potential risk factors for recurrence were assessed in 142 patients undergoing 171 Shouldice repairs. Recurrent hernias showed a significantly higher (22.0%) recurrence rate than primary inguinal hernias (7.7%). Furthermore, an age of more than 50 years, smoking, and the presence of two or more similarly affected relatives were found to be independent risk factors for recurrence. The present study underlines the importance of patient-related risk factors for the development of a recurrent inguinal hernia. Patients at risk should preoperatively be identified in order to improve treatment by, for example, the application of mesh techniques.

Biomaterial-dependent MMP-2 expression in fibroblasts from patients with recurrent incisional hernias.

With regard to the pathogenesis of recurrent incisional hernia, an impaired connective tissue quality leading to an aberrant scarring process has been proposed. For the matrix metalloproteinase (MMP-2) a pathogenetic involvement in direct inguinal hernia development is reported. With mesh implantation as the gold standard treatment for incisional hernias, the aim of the present study was to investigate the MMP-2 expression in patients with recurrent incisional hernias with and without mesh-materials. In primary fibroblast cultures obtained from skin scars in patients with and without recurrent incisional hernias, MMP-2 synthesis and gene expression were investigated. Furthermore, MMP-2 synthesis and gene expression of fibroblasts were compared after incubation with two different mesh materials: polypropylene and absorbable polyglactin filaments. MMP-2 enzyme activity was determined by semiquantitative zymography and mRNA synthesis by quantitative RT-PCR. Both MMP-2 enzyme activity and mRNA expression were similar in hernia and control fibroblasts in vitro. In control fibroblasts mesh incubation did not significantly affect MMP-2 expression, whereas polypropylene mesh contact of fibroblasts from patients with recurrent incisional hernias led to a major decrease of MMP-2 activity and of mRNA expression. In the absence of biomaterials fibroblasts from recurrent incisional hernia, patients have no alterations of their MMP-2 synthesis compared to control fibroblasts, whereas a specific response was found after biomaterial contact hereby indicating differences in fibroblast phenotype.

[Abdominal compartment syndrome]. / Abdominelles Kompartmentsyndrom.

Abdominal compartment syndrome (ACS) is characterized by a persistent pathologic increase in intra-abdominal pressure (IAP) exceeding 20 mmHg with consecutive dysfunction of multiple organ systems. The main causes of ACS are abdominal trauma, obstruction, infection, and sepsis, but it may also be initiated by extra-abdominal diseases. The gold standard for diagnosis is repeated assessment of the IAP measurements of bladder pressure. The incidence of ACS is up to 15% in operative ICUs and the therapy of choice for it is decompressive laparotomy. Nevertheless, mortality is high, up to 60%.

Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures.

Dravet syndrome is the prototype of SCN1A-mutation associated epilepsies. It is characterised by prolonged seizures, typically provoked by fever. We describe the evaluation of an SCN1A mutation in a child with early-onset temperature-sensitive seizures. The patient carries a heterozygous missense variant (c3818C > T; pAla1273Val) in the NaV1.1 brain sodium channel. We compared the functional effects of the variant vs. wild type NaV1.1 using patch clamp recordings from channels expressed in Chinese Hamster Ovary Cells at different temperatures (32, 37, and 40 °C). The variant channels produced a temperature-dependent destabilization of activation and fast inactivation. Implementing these empirical abnormalities in a computational model predicts a higher threshold for depolarization block in the variant, particularly at 40 °C, suggesting a failure to autoregulate at high-input states. These results reveal direct effects of abnormalities in NaV1.1 biophysical properties on neuronal dynamics. They illustrate the value of combining cellular measurements with computational models to integrate different observational scales (gene/channel to patient).