G protein-coupled receptor 40 expression in human melanoma - correlation with tumour thickness, AJCC stage and survival.

BACKGROUND: In melanoma, preclinical data suggest a possible role of polyunsaturated fatty acids inhibiting cell growth. A new target molecule for free fatty acids, the G protein-coupled receptor GPR40, was identified in melanoma cells. OBJECTIVES: The aim of this study was to investigate GPR40 expression in human melanocytic tissues and to evaluate its potential as a prognostic marker. METHODS AND RESULTS: A total of 114 tissue sections of naevi, primary melanoma and melanoma metastasis were immunohistochemically stained with anti-GPR40. The staining was evaluated, using the immunoreactivity scoring system. Compared to naevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR40 (P < 0.05). In primary melanoma, GPR40 expression positively correlated with tumour thickness (P = 0.044) and AJCC level (P = 0.017) and in melanoma metastasis with AJCC level (P = 0.035). Primary melanoma patients with high levels of GPR40 had a significantly poorer overall survival (P = 0.004) and shorter disease-free survival (0.040). CONCLUSION: The present study identified GPR40 as a novel target molecule in melanoma. First evidence for a potential role of the receptor in tumour progression and metastases was found, and it could be demonstrated that GPR40 expression is negatively correlated with patient's survival.

[Marginal protection of retinal cells by bisperoxovanadium : Appropriate therapy in the model of retinal ischemia?] / Marginale Protektion retinaler Zellen durch Bisperoxovanadium : Geeignete Therapie im Modell der retinalen Ischämie?

BACKGROUND: Ischemic processes usually lead to the destruction of retinal cells and therefore play a key role in a multitude of eye diseases. OBJECTIVE: The aim of this study was to investigate whether bisperoxovanadium has a potential neuroprotective effect in an ischemia/reperfusion animal model. MATERIAL AND METHODS: Initially, ischemia was induced in one eye of an ischemia/reperfusion model and 3 days later, a 14-day medication-based treatment was initiated. Bisperoxovanadium was administered intraperitoneally every 3 days. Subsequently, the number of ganglion cells, the rate of apoptosis, amacrine cells, macroglia, microglia, and their activation state, as well as photoreceptors were determined by histological and immunohistochemical analyses. RESULTS: In comparison to the control group, a significant retinal ganglion cell loss, a significant reduction of the inner layers as well as a decrease in photoreceptor and amacrine cell numbers could be determined in the ischemic eyes. In addition, there was an increase in the number of microglia in these animals. The rats treated with bisperoxovanadium did not exhibit a significant neuroprotective effect regarding the number of ganglion cells, the rate of apoptosis, macroglia, amacrine cells, or photoreceptors; however, a low structural degeneration of photoreceptors could be observed as an effect of the treatment. Additionally, fewer microglia and activated microglia were observed after bisperoxovanadium treatment. CONCLUSION: Bisperoxovanadium seems to have only a marginal neuroprotective effect on ischemic retinae. It needs to be examined whether earlier therapy onset, higher dose or different route of administration would significantly improve the results or whether this therapeutic approach is unsuitable.

Formation of n- and p-type regions in individual Si/SiO2 core/shell nanowires by ion beam doping.

A method for cross-sectional doping of individual Si/SiO2 core/shell nanowires (NWs) is presented. P and B atoms are laterally implanted at different depths in the Si core. The healing of the implantation-related damage together with the electrical activation of the dopants takes place via solid phase epitaxy driven by millisecond-range flash lamp annealing. Electrical measurements through a bevel formed along the NW enabled us to demonstrate the concurrent formation of n- and p-type regions in individual Si/SiO2 core/shell NWs. These results might pave the way for ion beam doping of nanostructured semiconductors produced by using either top-down or bottom-up approaches.

Spontaneous liquid crystal and ferromagnetic ordering of colloidal magnetic nanoplates.

Ferrofluids are familiar as colloidal suspensions of ferromagnetic nanoparticles in aqueous or organic solvents. The dispersed particles are randomly oriented but their moments become aligned if a magnetic field is applied, producing a variety of exotic and useful magnetomechanical effects. A longstanding interest and challenge has been to make such suspensions macroscopically ferromagnetic, that is having uniform magnetic alignment in the absence of a field. Here we report a fluid suspension of magnetic nanoplates that spontaneously aligns into an equilibrium nematic liquid crystal phase that is also macroscopically ferromagnetic. Its zero-field magnetization produces distinctive magnetic self-interaction effects, including liquid crystal textures of fluid block domains arranged in closed flux loops, and makes this phase highly sensitive, with it dramatically changing shape even in the Earth's magnetic field.

Nested case-control study of selected systemic autoimmune diseases in World Trade Center rescue/recovery workers.

OBJECTIVE: To test the a priori hypothesis that acute and chronic work exposures to the World Trade Center (WTC) site on or after September 11, 2001 were associated with risk of new-onset systemic autoimmune diseases. METHODS: A nested case-control study was performed in WTC rescue/recovery workers who had received a rheumatologist-confirmed systemic autoimmune disease diagnosis between September 12, 2001 and September 11, 2013 (n = 59), each of whom was individually matched to 4 randomly selected controls (n = 236) on the basis of year of hire (±1 year), sex, race, and work assignment (firefighter or emergency medical service). Acute exposure was defined according to the earliest time of arrival (morning of 9/11 versus later) at the WTC site, and chronic exposure was defined as duration (number of months) of WTC site-related work. Rheumatologists were blinded with regard to each subject's exposure status. The conditional odds ratios (CORs) with 95% confidence intervals (95% CIs) for incident autoimmune disease were derived from exact conditional logistic regression models. RESULTS: Rheumatoid arthritis was the most common autoimmune diagnosis (37% of subjects), followed by spondyloarthritis (22%), inflammatory myositis (14%), systemic lupus erythematosus (12%), systemic sclerosis (5%), Sjögren's syndrome (5%), antiphospholipid syndrome (3%), and granulomatosis with polyangiitis (Wegener's) (2%). The COR for incident autoimmune disease increased by 13% (COR 1.13, 95% CI 1.02-1.26) for each additional month worked at the WTC site. These odds were independent of the association between high acute exposure (working during the morning of 9/11) and disease outcome, which conveyed an elevated, but not statistically significant, risk (COR 1.85, 95% CI 0.86-3.89). CONCLUSION: Prolonged work at the WTC site, independent of acute exposure, was an important predictor of post-9/11 systemic autoimmune diseases. The WTC Health Program should expand surveillance efforts for those with extended exposures, as early detection can facilitate early treatment, which has been shown to minimize organ damage and improve quality of life.

Commensurate germanium light emitters in silicon-on-insulator photonic crystal slabs.

We report on the fabrication and characterization of silicon-on-insulator (SOI) photonic crystal slabs (PCS) with commensurately embedded germanium quantum dot (QD) emitters for near-infrared light emission. Substrate pre-patterning defines preferential nucleation sites for the self-assembly of Ge QDs during epitaxial growth. Aligned two-dimensional photonic crystal slabs are then etched into the SOI layer. QD ordering enhances the photoluminescence output as compared to PCSs with randomly embedded QDs. Rigorously coupled wave analysis shows that coupling of the QD emitters to leaky modes of the PCS can be tuned via their location within the unit cell of the PCS.

Role of surface-segregation-driven intermixing on the thermal transport through planar Si/Ge superlattices.

It has been highly debated whether the thermal conductivity κ of a disordered SiGe alloy can be lowered by redistributing its constituent species so as to form an ordered superlattice. By ab initio calculations backed by systematic experiments, we show that Ge segregation occurring during epitaxial growth can lead to κ values not only lower than the alloy's, but also lower than the perfect superlattice values. Thus we theoretically demonstrate that κ does not monotonically decrease as the Si- and Ge-rich regions become more sharply defined. Instead, an intermediate concentration profile is able to lower κ below both the alloy limit (total intermixing) and also the abrupt interface limit (zero intermixing). This unexpected result is attributed to the peculiar behavior of the phonon mean free path in realistic Si/Ge superlattices, which shows a crossover from abrupt-interface- to alloylike values at intermediate phonon frequencies of ∼3 THz. Our calculated κ's quantitatively agree with the measurements when the realistic, partially intermixed profiles produced by segregation are considered.

Three different brain tumours evolving from a common origin.

Despite an improved understanding of the molecular aberrations that occur in glioblastoma, the use of molecularly targeted therapies have so far been disappointing. We present a patient with three different brain tumours: astrocytoma, glioblastoma and gliosarcoma. Genetic analysis showed that the three different brain tumours were derived from a common origin but had each developed unique genetic aberrations. Included in these, the glioblastoma had PDGFRA amplification, whereas the gliosarcoma had MYC amplification. We propose that genetic heterogeneity contributes to treatment failure and requires comprehensive assessment in the era of personalised medicine.

Athermal photofluidization of glasses.

Azobenzene and its derivatives are among the most important organic photonic materials, with their photo-induced trans-cis isomerization leading to applications ranging from holographic data storage and photoalignment to photoactuation and nanorobotics. A key element and enduring mystery in the photophysics of azobenzenes, central to all such applications, is athermal photofluidization: illumination that produces only a sub-Kelvin increase in average temperature can reduce, by many orders of magnitude, the viscosity of an organic glassy host at temperatures more than 100 K below its thermal glass transition. Here we analyse the relaxation dynamics of a dense monolayer glass of azobenzene-based molecules to obtain a measurement of the transient local effective temperature at which a photo-isomerizing molecule attacks its orientationally confining barriers. This high temperature (T(loc)~800 K) leads directly to photofluidization, as each absorbed photon generates an event in which a local glass transition temperature is exceeded, enabling collective confining barriers to be attacked with near 100% quantum efficiency.

ALD grown bilayer junction of ZnO:Al and tunnel oxide barrier for SIS solar cell.

Various metal oxides are probed as extrinsic thin tunnel barriers in Semiconductor Insulator Semiconductor solar cells. Namely Al2O3, ZrO2, Y2O3, and La2O3 thin films are in between n-type ZnO:Al (AZO) and p-type Si substrates by means of Atomic Layer Deposition. Low reverse dark current-density as low as 3×10-7 A/cm2, a fill factor up to 71.3%, and open-circuit voltage as high as 527 mV are obtained, achieving conversion efficiency of 8% for the rare earth oxide La2O3. ZrO2 and notably Al2O3 show drawbacks in performance suggesting an adverse reactivity with AZO as also indicated by X-ray Photoelectron Spectroscopy.

Detecting artery occlusion and critical flow diminution in the case of an acute ischemic stroke--methodological pitfalls of common vascular diagnostic methods.

PURPOSE: None of the vascular emergency diagnostic methods commonly used in the case of acute ischemic stroke, i. e. CTA, color-coded duplex sonography (CCDS), MRA, and DSA, is free of restrictions due to physical and physiological characteristics. As a result, misleading results initiating an inappropriate acute therapeutic intervention or hampering a promising one cannot be excluded. We aimed to assess the type and frequency of methodological pitfalls occurring in this situation. MATERIALS AND METHODS: We retrospectively analyzed data of 269 consecutive patients admitted to our stroke unit with a clinical syndrome of an acute stroke. All patients underwent one or more vascular emergency diagnostic methods on a routine basis. RESULTS: 37 patients were excluded because of a final diagnosis other than ischemic stroke. 76 of 232 ischemic stroke patients underwent emergency diagnostic methods with two or more vascular examination techniques. Controversial results occurred in 20 patients and related to the detection and localization of large artery occlusion and its differentiation from a low/slow flow situation and the identification of critical cerebral flow diminution distal to large artery occlusion/severe stenosis. Methodological pitfalls were able to be most reliably resolved by CCDS. Within the whole cohort of ischemic stroke patients, vascular constellations susceptible to misinterpretation were diagnosed in 40 (17.2 %) patients. CONCLUSION: We recommend providing several techniques including CCDS in an emergency stroke setting and applying techniques with respect to diagnostic findings.

Two-dimensional microrheology of freely suspended liquid crystal films.

Smectic liquid crystals form freely-suspended, fluid films of highly uniform structure and thickness, making them ideal systems for studies of hydrodynamics in two dimensions. We have measured particle mobility and shear viscosity by direct observation of the gravitational drift of silica spheres and smectic islands included in these fluid membranes. In thick films, we observe a hydrodynamic regime dominated by lateral confinement effects, with the mobility of the inclusion determined predominantly by coupling of the fluid flow to the fixed boundaries of the film. In thin films, the mobility of inclusions is governed primarily by coupling of the fluid to the surrounding air, as predicted by Saffman-Delbrück theory.

Chiral isotropic liquids from achiral molecules.

A variety of simple bent-core molecules exhibit smectic liquid crystal phases of planar fluid layers that are spontaneously both polar and chiral in the absence of crystalline order. We found that because of intralayer structural mismatch, such layers are also only marginally stable against spontaneous saddle splay deformation, which is incompatible with long-range order. This results in macroscopically isotropic fluids that possess only short-range orientational and positional order, in which the only macroscopically broken symmetry is chirality--even though the phases are formed from achiral molecules. Their conglomerate domains exhibit optical rotatory powers comparable to the highest ever found for isotropic fluids of chiral molecules.

Helical nanofilament phases.

In the formation of chiral crystals, the tendency for twist in the orientation of neighboring molecules is incompatible with ordering into a lattice: Twist is expelled from planar layers at the expense of local strain. We report the ordered state of a neat material in which a local chiral structure is expressed as twisted layers, a state made possible by spatial limitation of layering to a periodic array of nanoscale filaments. Although made of achiral molecules, the layers in these filaments are twisted and rigorously homochiral--a broken symmetry. The precise structural definition achieved in filament self-assembly enables collective organization into arrays in which an additional broken symmetry--the appearance of macroscopic coherence of the filament twist--produces a liquid crystal phase of helically precessing layers.

[Life-threatening respiratory depression after pain therapy]. / Lebensbedrohliche Atemdepression nach Schmerztherapie.

The case is reported of a female patient with attack-like neuropathic pain following lower arm injury with repeated respiratory depression and unconsciousness even after several administrations of sufficiently dosed analgetics for suppression of the attacks. Readers are encouraged to make their own diagnosis on the basis of the clinical findings and to discuss the case online (http://www.blogs.springer.com/DerSchmerz). The discussion and the solution will be published in the next issue.

Vestibular paroxysmia: diagnostic features and medical treatment.

BACKGROUND: Vestibular paroxysmia (VP), which is attributed to neurovascular cross-compression (NVCC), leads to vertiginous spells. Although VP was described more than 30 years ago by Jannetta and colleagues, we still need more reliable data on its diagnostic features and the efficacy of medical treatment. METHODS: A follow-up study of 32 patients with recurrent short spells of vertigo and with diagnosis of VP by published criteria was performed using medical records and patient consultation (mean follow-up time 31.3 months). RESULTS: In 28% of patients the attacks occurred exclusively when at rest, whereas in 22% they were regularly precipitated by a certain action, most frequently a head turn (60%). The most common accompanying symptom was unsteadiness of stance or gait (75%). Constructive interference in steady state magnetic resonance imaging (n = 23) demonstrated at least one site of NVCC in all but one patient. Caloric testing disclosed a mild increase in vestibular deficit over time, and a hyperventilation-induced nystagmus was found in 70% of the tested patients (n = 23). The majority of patients were treated with carbamazepine (mean dose 568 mg/d) or oxcarbazepine (mean dose 870 mg/d). Treatment led to a significant reduction in the attack frequency to 10% of baseline (95% CI 6.69-14.96%), in attack intensity to 15% (95% CI 11.57-19.63%), and a reduction in attack duration to 11% (95% CI 6.72-17.40), after adjusting for time effects. CONCLUSION: This follow-up proves the usefulness of the diagnostic criteria, especially constructive interference in steady state magnetic resonance imaging, and the therapeutic efficacy of medical treatment.

Unilateral INO is associated with ocular tilt reaction in pontomesencephalic lesions: INO plus.

OBJECTIVE: Correlation of internuclear ophthalmoplegia (INO) with components of the ocular tilt reaction (OTR) in order to localize graviceptive (specifically otolithic) pathways in the brainstem. METHODS: We retrospectively analyzed data of 120 patients with INO (87 unilateral [9 of whom had one-and-a-half syndrome], 33 bilateral) for OTR (subjective visual vertical [SVV], ocular torsion, skew deviation) to localize causative brainstem lesions in MRI. RESULTS: Unilateral INO was accompanied by at least one component of OTR: SVV tilt in 96%, ocular torsion in 79%, and skew deviation in 50%. All components were directed to the contralesional side. Contralateral OTR occurred in 89% of patients with one-and-a-half syndrome. Only 9% of patients with bilateral INO exhibited OTR. MRI showed distinct lesions in 68%, which almost exclusively projected onto the pontomesencephalic medial longitudinal fascicle (96%). Follow-up measurements revealed SVV and ocular torsion normalized faster than the adduction deficit in INO. CONCLUSIONS: First, unilateral internuclear ophthalmoplegia (INO) is regularly associated with contraversive ocular tilt reaction (OTR): INO plus. Thus, graviceptive pathways join the medial longitudinal fascicle after crossing between the vestibular and abducens nuclei. Second, the different time course and degree of recovery of OTR components and INO signs can be explained by the hypothesis that vestibular tone imbalance is compensated by central vestibular adaptation mechanisms (probably driven mainly by cerebellar-vestibular projections), whereas impaired adduction is less susceptible to compensation according to Hering's law and can only be overcome by lesion repair. Third, bilateral INO is seldom associated with OTR, confirming that bilateral impairment of graviceptive pathways does not cause imbalance in roll plane.

Downbeat nystagmus: aetiology and comorbidity in 117 patients.

OBJECTIVES: Downbeat nystagmus (DBN) is the most common form of acquired involuntary ocular oscillation overriding fixation. According to previous studies, the cause of DBN is unsolved in up to 44% of cases. We reviewed 117 patients to establish whether analysis of a large collective and improved diagnostic means would reduce the number of cases with "idiopathic DBN" and thus change the aetiological spectrum. METHODS: The medical records of all patients diagnosed with DBN in our Neurological Dizziness Unit between 1992 and 2006 were reviewed. In the final analysis, only those with documented cranial MRI were included. Their workup comprised a detailed history, standardised neurological, neuro-otological and neuro-ophthalmological examination, and further laboratory tests. RESULTS: In 62% (n = 72) of patients the aetiology was identified ("secondary DBN"), the most frequent causes being cerebellar degeneration (n = 23) and cerebellar ischaemia (n = 10). In 38% (n = 45), no cause was found ("idiopathic DBN"). A major finding was the high comorbidity of both idiopathic and secondary DBN with bilateral vestibulopathy (36%) and the association with polyneuropathy and cerebellar ataxia even without cerebellar pathology on MRI. CONCLUSIONS: Idiopathic DBN remains common despite improved diagnostic techniques. Our findings allow the classification of "idiopathic DBN" into three subgroups: "pure" DBN (n = 17); "cerebellar" DBN (ie, DBN plus further cerebellar signs in the absence of cerebellar pathology on MRI; n = 6); and a "syndromatic" form of DBN associated with at least two of the following: bilateral vestibulopathy, cerebellar signs and peripheral neuropathy (n = 16). The latter may be caused by multisystem neurodegeneration.

Low recurrence rate of vestibular neuritis: a long-term follow-up.

We examined 103 patients with vestibular neuritis (VN) in a follow-up study (5.7 to 20.5 years, mean 9.8 years). Two patients (1.9%) had developed a second occurrence of VN 29 to 39 months after the first. VN affected the contralateral ear in both and caused less severe distressing vertigo and postural imbalance. Unlike Bell's palsy and sudden hearing loss, a relapse in the same ear did not occur.