Vesicle solubilization by bile salts: comparison of macroscopic theory and simulation.

Lipid metabolism is accompanied by the solubilization of lipid bilayer membranes by bile salts. We use Brownian dynamics simulations to study the solubilization of model membranes and vesicles by sodium cholate. The solubilization pathways of small and large vesicles are found to be different. Both results for small and large vesicles can be compared with predictions of a macroscopic theoretical description. The line tension of bilayer edges is an important parameter in the solubilization process. We propose a simple method to determine the line tension by analyzing the shape fluctuations of planar membrane patches. Macroscopic mechanical models provide a reasonable explanation for processes observed when a spherical vesicle consisting of lipids and adsorbed bile salt molecules is transformed into mixed lipid-bile salt micelles.

The accuracy of 3D fluoroscopy-navigated screw insertion in the upper and subaxial cervical spine.

PURPOSE: Due to better primary stability and repositioning options, pedicle screws are increasingly used during posterior stabilization of the cervical spine. However, the serious risks generally associated with the insertion of screws in the cervical spine remain. The purpose of this study is to examine the accuracy of pedicle screw insertion with the use of 3D fluoroscopy navigation systems, also accounting for various spine levels. METHODS: Data of 64 patients were collected during and after screw implantation (axial and subaxial) in the cervical spine. 207 screws were implanted from C1 to C7 and analyzed for placement accuracy according to postoperative CT scans and following the modified Gertzbein and Robbins classification. RESULTS: The accuracy of most of the inserted screws was assessed as grade 2 according to the modified Gertzbein and Robbins classification. 93.9% of the screws implanted at C1 or C2, and 78.51% of the screws implanted at levels C3-C7 showed placement accuracy grade 2 or better, indicating pedicle wall perforation of <2 mm. Overall, seven complications were observed. In three cases, the vertebral artery was affected, leading to one fatality. Surgical revision was necessary once because of Magerl screw misplacement and three times due to impaired wound healing. No radicular symptoms resulted from screw malposition. CONCLUSION: Axial and subaxial screws can be inserted with a high grade of accuracy using 3D fluoroscopy-based navigation systems. Nevertheless, while this useful innovation helps to minimize the risks of misplacement, the surgery is still a challenge, as arising complications remain severe.

Factors contributing to severe early childhood caries in south-west Germany.

OBJECTIVES: The purpose of this study is to investigate the contribution of selected variables to the occurrence of severe early childhood caries (S-ECC) in 3- to 5-year-old kindergarten children. METHODS: A cross-sectional study was conducted in 2010 in 30 randomly selected kindergartens in the German Rhein-Neckar district. After informed consent, parents were asked to complete a questionnaire. The oral examinations took place in the selected kindergartens and the WHO methods as well as the criteria proposed by the American Academy of Pediatric Dentistry were followed. Logistic regression was applied to explore the main factors contributing to S-ECC in a multivariate model. RESULTS: In all, 1,007 children aged 3 to 5 years with an average age of 4.1 (SD = 0.8) years were examined. Five variables were associated significantly with the occurrence of S-ECC: breastfeeding for more than 12 months (OR = 3.27), use of the nursing bottle in bed (OR = 3.08), start of tooth brushing after the first anniversary (OR = 2.42), regular visits at the dentists (OR = 0.14) and mother with immigration background (OR = 4.05). Prevalence rate of S-ECC was 9.5 %. The mean d(3+4)mft values were 5.69 (S-ECC group) and 0.23 (non-S-ECC group). CONCLUSION: These results show that occurrence of S-ECC is a complex interaction between socioeconomic, psychological and behavioural factors of parents. New and specific ways to provide preventive dental care for toddlers and infants of caries risk groups have to be developed. CLINICAL RELEVANCE: Parents of newborn children have to receive information about timely start of tooth brushing and adequate use of nursing bottles.

Uniportal robotic assisted surgery for anatomical lung resection-First German experience.

BACKGROUND: Uniportal robotic-assisted thoracic surgery (uRATS) has emerged as a promising technique with potential advantages over multiportal approaches. This study aims to evaluate our initial outcomes of uRATS. MATERIAL AND METHODS: Five patients underwent anatomic lung resections with systematic nodal dissection through a uniportal robotic approach by one surgeon. The results were compared to the results of the first five uniportal video-assisted thoracic surgery (uVATS) anatomical resections performed by the same surgeon. RESULTS: No adverse events occurred during the uRATS-procedures. Comparable surgical outcomes were observed between uRATS and uVATS, including hospital stays, complication rates, and blood loss. The average procedural time was slightly but non-significantly longer in the uRATS-group. Average pain-scores were lower in the uRATS group. One patient in each group experienced major postoperative complications, with one case of in-hospital mortality in the uRATS-group. CONCLUSION: The outcomes of uRATS/uVATS were comparable, highlighting the potential and the feasibility of this technique. Prospective studies comparing the learning curves, complication rate and hospital-stay are required in order to justify the superiority of robotics over uVATS.

Treating menopausal symptoms with a complex remedy or placebo: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of a complex remedy compared with placebo to treat menopausal symptoms. METHODS: A total of 102 peri- and postmenopausal women requiring treatment for menopausal symptoms were randomized to receive a complex anthroposophic remedy prepared in the homeopathic manner (Apis regina tota GL D4, Argentum metallicum D5, Ovaria bovis GL D4), 3 × 10 globuli daily (2 × 12 weeks) and placebo (12 weeks) in different orders of remedy (R) and placebo (P) (1: R/R/P, 2: P/R/R, 3: R/P/R). The primary endpoint was change in climacteric symptoms assessed by the Menopause Rating Scale II (MRS II) after 12 weeks. Secondary endpoints were changes of symptoms and safety throughout the study. RESULTS: Reduction of symptoms after 12 weeks did not differ between remedy and placebo (total score MRS II: -1.4, 95% confidence interval (CI) -2.8 to 0 vs. -2.3, 95% CI -4.4 to -0.3, p = 0.441) and had no clinical relevance (defined as reduction in MRS II ≥ -3.5). Comparison of secondary outcomes at 12 weeks between remedy and placebo or between groups after the 2nd or 3rd period compared to previous periods did not differ. Treatment with remedy for 24 consecutive weeks did not reach clinical relevance either. However, total reduction of symptoms after three periods in Group 1 (R/R/P) (-5.0, 95% CI -7.5 to -2.5) and Group 2 (P/R/R) (-5.9, 95% CI -8.7 to -3.1) reached clinical relevance whereas almost no decrease of symptoms after three periods was seen in Group 3 (R/P/R) (-0.5, 95% CI -2.9 to 1.9). CONCLUSIONS: Treatment with the complex remedy for 12 or 24 weeks did not result in clinically significant improvement of menopausal symptoms.

Interactions between spheroidal colloidal particles.

Using Derjaguin's approximation, we have evaluated the interaction energy associated with van der Waals, electrostatic, depletion, and capillary forces between colloidal spheroids. If the interaction range between spheroids is distinctly smaller than the lengths of their principal axes, then simple pair potentials that depend on particle distance and orientation can be derived. Attractive interactions between adjacent spheroids favor their parallel alignment. Parallel spheroids can be arranged into a variety of densely packed configurations. All of these configurations turn out to have the same lattice energy. We discuss the implications of this degeneracy with respect to the stability of photonic crystals consisting of spheroids.

Depletion force between anisometric colloidal particles.

A simple mathematical model for the depletion force between two arbitrarily shaped large convex colloidal particles immersed in a suspension of small spherical particles is proposed. Using differential geometry, the interaction potential is expressed in terms of the mean and Gaussian curvature of the particle surfaces. The accuracy of theoretical results is tested by Monte Carlo simulations for parallel and nonparallel circular cylinders. The agreement between theoretical results and simulated data is very good if the density of the depletion agent is not too high.

Monte Carlo study of the self-assembly of achiral bolaform amphiphiles into helical nanofibers.

It is shown by coarse-grained off-lattice Monte Carlo simulations that a geometrically induced frustration of the parallel arrangement of rigid achiral bolaform amphiphiles can cause chirality in self-assembled nanostructures. The amphiphilic molecules are represented as rigid linear chains of 8 equally sized hydrophobic spheres (tail) and a hydrophilic sphere (head) at each end. The hydrophilic and hydrophobic spheres differ in size. A very simple interaction scheme consisting of only hard-core repulsion between all spheres and square-well attraction between hydrophobic spheres is sufficient for self-assembly into helical fibers for molecules with head/tail diameter ratios ranging from 1.3 to 1.8.

The role of the primate extrastriate area V4 in vision.

Area V4 is a part of the primate visual cortex. Its role in vision has been extensively debated. Inferences about the functions of this area have now been made by examination of a broad range of visual capacities after ablation of V4 in rhesus monkeys. The results obtained suggest that this area is involved in more complex aspects of visual information processing than had previously been suggested. Monkeys had particularly severe deficits in situations where the task was to select target stimuli that had a lower contrast, smaller size, or slower rate of motion than the array of comparison stimuli from which they had to be discriminated. Extensive training on each specific task resulted in improved performance. However, after V4 ablation, the monkeys could not generalize the specific task to new stimulus configurations and to new spatial locations.

Metacontrast: its relation to evoked potentials.

Electrophysiological correlates of metacontrast were studied by means of averaged evoked potentials recorded from the scalp in man. Under conditions in which the brightness of the first of two successive stimuli appears diminished there is no accompanying attenuation of the evoked potentials to that stimulus. The results suggest that the amplitude and latency of evoked potentials correlate with stimulus intensity but not with brightness.

Effects of frontal eye field and superior colliculus ablations on eye movements.

Two parallel neural pathways are primarily responsible for the control of saccadic eye movements--one mediated through the frontal eye fields and the other through the superior colliculus. When both pathways are disrupted, control of saccadic eye movements is lost. Disruption of either pathway alone produces only subtle deficits.

Perceptual deficits and the activity of the color-opponent and broad-band pathways at isoluminance.

The deficits in texture, motion, and depth perception incurred in monkeys at isoluminance were compared with the responses of neurons of the color-opponent and broad-band systems in the lateral geniculate nucleus. Texture perception, assumed to be carried by the color-opponent system, and motion and depth perception, ascribed to the broad-band pathway, were all found to be compromised but not abolished at isoluminance. Correspondingly, both the color-opponent and the broad-band systems were affected at isoluminance, but the activity of the neurons in neither system was abolished. These results suggest that impairment of visual capacities at isoluminance cannot be uniquely attributed to either of these systems and that isoluminant stimuli are inappropriate for the psychophysical isolation of these pathways.

Isolation, structure, and synthesis of a human seminal plasma peptide with inhibin-like activity.

A basic peptide isolated from pooled human seminal plasma exhibited inhibin-like activity by suppressing pituitary follicle-stimulating hormone secretion in vitro and in vivo. The peptide has been characterized and sequenced, and a 31-amino-acid synthetic replicate showed full biological activity in vitro.

An all D-amino acid opioid peptide with central analgesic activity from a combinatorial library.

A synthetic combinatorial library containing 52,128,400 D-amino acid hexapeptides was used to identify a ligand for the mu opioid receptor. The peptide, Ac-rfwink-NH2, bears no resemblance to any known opioid peptide. Simulations using molecular dynamics, however, showed that three amino acid moieties have the same spatial orientation as the corresponding pharmacophoric groups of the opioid peptide PLO17. Ac-rfwink-NH2 was shown to be a potent agonist at the mu receptor and induced long-lasting analgesia in mice. Analgesia produced by intraperitoneally administered Ac-rfwink-NH2 was blocked by intracerebroventricular administration of naloxone, demonstrating that this peptide may cross the blood-brain barrier.

Eye movements modulate visual receptive fields of V4 neurons.

The receptive field, defined as the spatiotemporal selectivity of neurons to sensory stimuli, is central to our understanding of the neuronal mechanisms of perception. However, despite the fact that eye movements are critical during normal vision, the influence of eye movements on the structure of receptive fields has never been characterized. Here, we map the receptive fields of macaque area V4 neurons during saccadic eye movements and find that receptive fields are remarkably dynamic. Specifically, before the initiation of a saccadic eye movement, receptive fields shrink and shift towards the saccade target. These spatiotemporal dynamics may enhance information processing of relevant stimuli during the scanning of a visual scene, thereby assisting the selection of saccade targets and accelerating the analysis of the visual scene during free viewing.

The effects of frontal eye field and dorsomedial frontal cortex lesions on visually guided eye movements.

In the frontal lobe of primates, two areas play a role in visually guided eye movements: the frontal eye fields (FEF) and the medial eye fields (MEF) in dorsomedial frontal cortex. Previously, FEF lesions have revealed only mild deficits in saccadic eye movements that recovered rapidly. Deficits in eye movements after MEF ablation have not been shown. We report the effects of ablating these areas singly or in combination, using tests in which animals were trained to make saccadic eye movements to paired or multiple targets presented at various temporal asynchronies. FEF lesions produced large and long-lasting deficits on both tasks. Sequences of eye movements made to successively presented targets were also impaired. Much smaller deficits were observed after MEF lesions. Our findings indicate a major, long-lasting loss in temporal ordering and processing speed for visually guided saccadic eye movement generation after FEF lesions and a significant but smaller and shorter-lasting loss after MEF lesions.

Organization of the Drosophila melanogaster hsp70 heat shock regulation unit.

Expression from the Drosophila melanogaster hsp70 promoter was controlled by a regulatory unit that was composed of two sequence elements that resembled the heat shock consensus sequence. The unit functioned in both orientations and at different distances from downstream promoter sequences. Each element of the unit alone was essentially inactive. Association of two elements resulted in a dramatic increase of transcription from the hsp70 promoter. This synergistic effect was independent of the relative orientation of the elements and, to a large extent, of the distance between them. Duplication of a region containing only one element also yielded a highly active, heat-regulated promoter. Genes with three to five elements were three to four times more active than those with a single regulatory unit.

The ON and OFF channels of the visual system.

In the vertebrate retina, all photoreceptors hyperpolarize in response to light. In the outer retina, at the bipolar cell level, a dual system is created from the cones forming the ON and OFF channels. In the rod system a similar arrangement is found, but the ON and OFF channels in many species are formed using an amacrine cell network in the inner retina. Physiological experiments in which the ON bipolar cells are pharmacologically blocked reveal that in the primate the two channels remain largely segregated in the geniculostriate system until they reach the cortex, where they converge upon single cells. Behavioral studies show that following ON channel block, notable deficits arise in the detection of light increments but not light decrements. These and related studies suggest that the ON and OFF channels optimize information transfer to the CNS by providing excitatory signals for both increases and decreases in light energy.

The color-opponent and broad-band channels of the primate visual system.

Physiological, anatomical and psychophysical studies have identified several parallel channels of information processing in the primate visual system. Two of these, the color-opponent and the broad-band channels, originate in the retina and remain in part segregated through several higher cortical stations. To improve understanding of their function, recent studies have examined the visual capacities of monkeys following selective disruption of these channels. Color vision, fine- but not coarse-form vision and stereopsis are severely impaired in the absence of the color-opponent channel, whereas motion and flicker perception are impaired at high but not low temporal frequencies in the absence of the broad-band channel. The results suggest that the color-opponent channel extends the range of vision in the spatial and wavelength domains, and that the broad-band channel extends it in the temporal domain. Lesion studies also indicate that these channels must reach higher cortical centers through extrastriate regions other than just area V4 and the middle temporal area, and that the analysis performed by these two regions cannot be uniquely identified with specific visual capacities.

Vitrectomy with or without encircling band for pseudophakic retinal detachment: a multi-centre, three-arm, randomised clinical trial. VIPER Study Report No. 1--design and enrolment.

PURPOSE: Scleral buckling is currently used in addition to vitrectomy for the treatment of pseudophakic retinal detachment (PRD) to better support the vitreous base and better visualisation of the periphery. AIMS: The aims of this study are to evaluate (1) whether the combination of 20 G vitrectomy and scleral buckling is superior to 20 G vitrectomy alone (control) (confirmatory), and (2) whether transconjunctival 23/25 G vitrectomy is non-inferior to 20 G vitrectomy (both without scleral buckling) regarding operation success (exploratory). METHODS: The VIPER (Vitrectomy Plus Encircling Band Vs. Vitrectomy Alone For The Treatment Of Pseudophakic Retinal Detachment) study is an unmasked, multi-centre, three-arm randomised trial. Patients with PRD were eligible, excluding complicated retinal detachment or otherwise severe ophthalmologic impairment. Patients were randomised to one of three interventions: 20 G vitrectomy alone (control C), combination of 20 G vitrectomy and circumferential scleral buckling (experimental treatment E1) or 23/25 G vitrectomy alone (experimental treatment E2). The primary endpoint is the absence of any indication for a retina re-attaching procedure during 6 months of follow-up. Secondary endpoints include best corrected visual acuity, retina re-attaching procedures, complications and adverse events. RESULTS: From June 2011 to August 2013, 257 patients were enrolled in the study. The internet randomisation service assigned 100 patients each to the treatment arms C and E1, and 57 patients to treatment E2. The imbalance is due to the fact that several retinal surgeons did not qualify for performing E2. The random assignment was stratified and balanced (ie, 1:1 or 1:1:1 ratio) by surgeon. CONCLUSIONS: The described study represents a methodologically rigorous protocol evaluating the benefits of three different vitrectomy approaches to PRD. The projected results will help to establish their overall efficacy and will permit conclusions regarding their relative value. TRIAL REGISTRATION NUMBER: DRKS00003158 (German Clinical Trials Register, DRKS).