74 Ge( n , γ ) cross section below 70 keV measured at n_TOF CERN.

Neutron capture reaction cross sections on 74 Ge are of importance to determine 74 Ge production during the astrophysical slow neutron capture process. We present new resonance data on 74 Ge( n , γ ) reactions below 70 keV neutron energy. We calculate Maxwellian averaged cross sections, combining our data below 70 keV with evaluated cross sections at higher neutron energies. Our stellar cross sections are in agreement with a previous activation measurement performed at Forschungszentrum Karlsruhe by Marganiec et al., once their data has been re-normalised to account for an update in the reference cross section used in that experiment.

Approaching the Gamow Window with Stored Ions: Direct Measurement of

We report the first measurement of low-energy proton-capture cross sections of ^{124}Xe in a heavy-ion storage ring. ^{124}Xe^{54+} ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The ^{125}Cs reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis.

BACKGROUND: Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo-associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the 'comedo switch'. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG-associated skin disorders. RESULTS: In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin-like growth factor 1 receptors; peroxisome proliferator-activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis. CONCLUSIONS: Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne.

Quasifree (p, 2p) Reactions on Oxygen Isotopes: Observation of Isospin Independence of the Reduced Single-Particle Strength.

Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R^{3}B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type ^{A}O(p,2p)^{A-1}N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.

Strong Neutron Pairing in core+4n Nuclei.

The emission of neutron pairs from the neutron-rich N=12 isotones ^{18}C and ^{20}O has been studied by high-energy nucleon knockout from ^{19}N and ^{21}O secondary beams, populating unbound states of the two isotones up to 15 MeV above their two-neutron emission thresholds. The analysis of triple fragment-n-n correlations shows that the decay ^{19}N(-1p)^{18}C^{*}→^{16}C+n+n is clearly dominated by direct pair emission. The two-neutron correlation strength, the largest ever observed, suggests the predominance of a ^{14}C core surrounded by four valence neutrons arranged in strongly correlated pairs. On the other hand, a significant competition of a sequential branch is found in the decay ^{21}O(-1n)^{20}O^{*}→^{18}O+n+n, attributed to its formation through the knockout of a deeply bound neutron that breaks the ^{16}O core and reduces the number of pairs.

[Coagulation factors and multiple sclerosis : Key factors in the pathogenesis?] / Gerinnungsfaktoren und Multiple Sklerose : Schlüsselfaktoren in der Pathogenese?

Environmental factors and genetic predisposition influence the individual risk to develop multiple sclerosis (MS). Preclinical results in animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), prove a significant contribution of the corpuscular and plasmatic coagulation system for the severity of MS. It was recently shown that key molecules of the coagulation cascade, such as fibrinogen, thrombin and factor XII can influence neuroinflammatory disorders such as MS. The inhibition of both fibrinogen and factor XII led to a significantly improved disease course in animal models. Furthermore, in patients suffering from MS a dysregulation of diverse coagulation factors was demonstrated. The precise role of these changes for the pathogenesis of MS remains to be clarified. Nonetheless, the identification of molecular mechanisms between inflammation and the coagulation cascade might provide completely new perspectives for the therapy of MS; however, as most of the currently available data were obtained from animal models, this knowledge must be interpreted with an adequate degree of caution.

Subthreshold Ξ

Results on the production of the double strange cascade hyperon Ξ^{-} are reported for collisions of p(3.5 GeV)+Nb, studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18 at GSI Helmholtzzentrum for Heavy-Ion Research, Darmstadt. For the first time, subthreshold Ξ^{-} production is observed in proton-nucleus interactions. Assuming a Ξ^{-} phase-space distribution similar to that of Λ hyperons, the production probability amounts to P_{Ξ^{-}}=[2.0±0.4(stat)±0.3(norm)±0.6(syst)]×10^{-4} resulting in a Ξ^{-}/(Λ+Σ^{0}) ratio of P_{Ξ^{-}}/P_{Λ+Σ^{0}}=[1.2±0.3(stat)±0.4(syst)]×10^{-2}. Available model predictions are significantly lower than the measured Ξ^{-} yield.

Phased-array of microcoils allows MR microscopy of ex vivo human skin samples at 9.4 T.

PURPOSE: The aim of this study was to demonstrate the feasibility of a custom-made phased-array microcoil within a 400 MHz animal system for the morphological characterization of human skin tissue in correlation with histopathology. MATERIALS AND METHODS: A dedicated 7-channel microcoil-based MR detector arranged in a phased-array geometry was developed to combine the advantages of both a large field of view and a high signal-to-noise ratio. Standard gradient echo sequences were adapted for the characterization of skin morphology ex vivo. RESULTS: In this study, the feasibility of using this type of microdetector, combined with specially manufactured sample holders, to achieve high-resolution MR images of fresh and formalin-fixed, normal and hidradenitis suppurativa diseased skin was successfully demonstrated. The setup presented in this work allows reliable acquisitions of high-resolution images with in-plane resolution up to 25 × 25 µm², and 100 µm in the orthogonal direction, thereby allowing the differentiation of typical layers of the skin, sebaceous glands and hair follicle. CONCLUSION: This study demonstrates that MR microscopy on skin biopsies can be applied at low cost on a standard animal MR imaging system. The successful imaging of different skin structures ex vivo is a prerequisite for non-invasive, in vivo application of skin MR microscopy for accurate complementary disease diagnosis in dermatology.

[Neurological disorders and glaucoma - an overview]. / Neurologische Erkrankungen und Glaukom - ein Überblick.

Due to the anatomic location of the N. opticus to the brain and its embryological development as a "bulging part of the brain", a close connection between the opticoneuropathy and certain neurological diseases exists. Glaucoma is a chronic neurodegenerative disorder and many cellular and molecular mechanisms of the chronic neurodegenerative diseases are common in the brain. For example, elevated levels of multiple biomarkers of Alzheimer's disease were found in the aqueous humor of patients with primary open-angle glaucoma. Also a decreased cerebrospinal fluid pressure (CSFP) has been demonstrated in patients with glaucoma and Alzheimer's disease. The resulting translaminar pressure difference is seen as one of the pathogenic mechanisms of the formation of the optic neuropathy in both diseases. Other hypotheses, such as the influence of oxidative stress, excitotoxicity, mitochondrial dysfunction, genetic factors and vascular factors play additional roles in the pathogenesis of the different diseases. Experimental studies have shown that dopaminergic amacrine cells are present in the retina. The dopamine in the retina is necessary for the light adaptation and the signal processing in the rods and cones. Parkinson's disease is characterised by a loss of dopaminergic neurons in the basal ganglia-substantia nigra pars compacta of the midbrain. These decreased levels of dopamine also have an effect on the eye and the afferent signal processing. So there are reductions in visual acuity, disturbances in colour vision and contrast sensitivity and reduction of the retinal nerve fiber layer in patients affected with Parkinson's disease. With the examples of Alzheimer's disease, Parkinson's disease and the chronic inflammatory disease multiple sclerosis, we demonstrate the association between the neurological diseases and the opticoneuropathy in primary open-angle glaucoma.

[Pregabalin and gabapentin in multiple sclerosis: clinical experiences and therapeutic implications]. / Ionenkanalmodulatoren bei Multipler Sklerose : Bestandsaufnahme der Anwendung in der Praxis.

BACKGROUND: Due to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ion channel modulators (e. g. pregabalin, gabapentin, carbamazepine). The aim of this study was to investigate the use of these drugs in clinical practice in a larger patient cohort. PATIENTS: Data from 533 MS patients [439 without and 94 patients with add-on therapy (treatment group)] were evaluated retrospectively. All patients received a detailed neurological examination including evaluation of EDSS scores. RESULTS: Pregabalin and gabapentin are used most commonly. Abnormal sensations are the most frequent reason for therapy initiation. Patients with higher EDSS values and/or under mitoxantrone treatment most frequently receive additional therapy. CONCLUSION: So far, it is not known whether the investigated agents exert a beneficial influence on the disease course of MS itself beyond a mere symptomatic treatment. Further research efforts and clinical studies are necessary to address this question.

[Physiology of aqueous humor formation, diurnal fluctuation of intraocular pressure and its significance for glaucoma]. / Physiologie der Kammerwasserproduktion sowie der Tagesdruckschwankungen und deren Bedeutung für das Glaukom.

In the human eye there is a balance between production of aqueous humor as well as its drainage. The intraocular pressure is held through different mechanisms in a stable balance. The aqueous humor is secreted by the ciliary epithelium lining the ciliary processes. Three physiological processes contribute to the formation and chemical composition of the aqueous humor: diffusion (5 %), ultrafiltration (15 %) and active secretion (80 %). The normal intraocular pressure amounts to 15 ± 3 mmHg, the normal diurnal fluctuation 5 mmHg. Aqueous humor leaves the eye by passive bulk flow via two pathways: the trabecular route and the uveoscleral route. In glaucoma patients this balance is disturbed resulting in individual high intraocular pressure or, respectively, high diurnal fluctuations. This leads to loss of retinal ganglion cells and visual field loss. As a recommendation for glaucoma patients it is useful to construct diurnal intraocular pressure curves to evaluate the "type of pressure" and to determine the diurnal fluctuations or, respectively, the time of the pressure maxima. With this knowledge, treatment of glaucoma patients can be managed in a more individualised manner and it seems to slow down the progress of the disease better than by merely reducing the intraocular pressure.

Early effective treatment may protect from cognitive decline in paediatric multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is a critical feature for patients with childhood or juvenile multiple sclerosis (MS). OBJECTIVE: To promote the understanding of CI and to address the impact of different pharmacological treatment strategies on cognitive performance in this patient group. METHODS: A cohort of 19 patients with therapy-naïve or ß-Interferon-treated juvenile MS completed a comprehensive neuropsychological assessment at initial presentation (baseline) and on average 2.5 years later (follow-up). The assessments were complemented with a neuropaediatric examination and conventional cerebral magnetic resonance imaging (MRI). RESULTS: 9 patients (47%) were impaired in at least one test at baseline (z-score <-1.645 compared with age-adjusted normative data), with the highest impairment frequency in the domains processing speed and attention & executive functions. At follow-up a higher impairment frequency was prominent in those patients whose therapy had not been escalated (N = 13, 69% impaired in at least one test), while cognition was preserved or ameliorated in patients whose treatment had been escalated to highly effective drugs (N = 6, 0% impaired) during the observational period. These group differences at follow-up were not attributable to differences regarding demographics, MRI metrics or cognitive performance at baseline. CONCLUSION: Our findings confirm that paediatric MS is associated with considerable CI already in early disease stages. Early administration of highly effective treatment may protect from cognitive decline or alleviate CI in juvenile MS, but larger controlled trials are warranted to confirm these preliminary results.

[Comparison of frequency doubling technology perimetry and achromatic standard automated perimetry in patients with migraine without aura and controls]. / Auffälligkeiten in der achromatischen Perimetrie bei Patienten mit Migräne ohne Aura im Vergleich zu den Ergebnissen in der Frequenzverdopplungsperimetrie.

BACKGROUND: The frequency doubling technology perimetry predominantly tests the magnocellular visual pathway (M-cells) whereas the achromatic standard automated perimetry examines magno- and parvocellular ganglion cells. The aim of this study was to investigate whether patients with migraine without aura are conspicuous in these perimeters. MATERIALS AND METHODS: Thirty-two patients with migraine without aura (f:m = 2:30, mean age 40.4 +/- 11.34 years) were compared with nineteen controls (f:m = 1:18, mean age 40.15 +/- 12.5 years). Subjects with systemic health problems or ocular diseases were excluded from the study. Beside the ophthalmological examinations (visual acuity, refraction, intraocular pressure, slit lamp and fundus examination) quantitative analysis of visual field by Octopus 1 - 2 - 3 perimeter and Humphrey frequency doubling technology perimeter (FDT) were performed. Different parameters (mean deviation [MD] and pattern standard deviation [PSD]) were statistically compared using non-parametric tests. RESULTS: The clinical ophthalmological examinations were inconspicuous in all migraine sufferers and controls. Statistical analysis showed no significant difference of MD and PSD between the patients with migraine and controls in the frequency doubling perimetry. However, there was a significant difference of MD using the achromatic standard perimetry in migraine sufferers in comparison to the controls (migraine - right eye MD 0.4 +/- 1.33 dB, migraine - left eye MD 0.2 +/- 1.47 dB, controls-right eye MD -1.4 +/- 0.76, controls - left eye -1.4 +/- 0.84; Mann-Whitney U test: p < 0.001 with Bonferoni-Holms-correction). CONCLUSION: In migraine sufferers without aura we found a reduction of contrast sensitivity in the achromatic standard perimetry but not in the frequency doubling technology perimetry. This can be indicative of a stronger involvement of the parvocellular pathway in migraine without aura patients. These results should be take into consideration in further perimetric examinations.

[Structural and morphological changes in the eyes of arterial hypertensive patients with and without anti-CCP-positive rheumatoid arthritis]. / Strukturelle und morphologische Veränderungen am Auge bei Patienten mit arterieller Hypertonie mit und ohne Anti-CCP-positiver rheumatoider Arthritis.

INTRODUCTION: To investigate the additive systemic inflammatory process of rheumatoid arthritis (RA) in arterial hypertension patients, structural and morphological changes of the retina and optic nerve head were assessed by modern topographic technologies. Similarities of underlying vascular mechanisms between RA and arterial hypertension are interesting and have not been researched in depth. The aim of this study is to evaluate changes of RA and arterial hypertension with the optic coherence topography (OCT) and Heidelberg retina tomography (HRT III), to validate RA changes in comparison to arterial hypertension only patients and, finally, if these methods are useful to detect the chronic inflammatory influence of the RA on the eye. METHODS: In this prospective study design, data of 18 patients with RA and arterial hypertension (55.3 ± 4.31 years old), positive for antibodies against cyclic citrullinated peptides, 21 patients with arterial hypertension (54.2 ± 4.18 years old) and 19 healthy subjects (53.1 ± 3.25 years old) were included. Intensive ophthalmologic and internistic screening tests were carried out in all subjects. All participants were investigated for the retinal nerve fiber layer (RNFL) and macula thickness with the OCT (Carl Zeiss AG Germany) and for stereometric parameters of the optic nerve head with the Heidelberg Retina Tomograph III (Heidelberg Engineering Germany). The pachymetry was conducted by the Orbscan II system (Bausch & Lomb). Statistical data were assessed by SPSS, v20.0. RESULTS: No significant differences were found in visual function, diastolic and systolic blood pressure. RNFL, and macular thickness (Stratus-OCT) were almost consistent between the groups and even the main stereometric parameters measured with HRT III showed no significant differences. CONCLUSION: Contrary to our study hypothesis no structural and morphological changes could be detected in patients with arterial hypertension without RA compared to healthy subjects. Furthermore, no RA-specific effects could be shown in comparison with the hypertension group. Thus, the used examination techniques are not suitable to prove the systemic inflammatory influence of RA on the eye.

Platelets and vascular inflammation of the brain.

UNLABELLED: There is emerging evidence that platelets have an important role in inflammation beyond their involvement in hemostasis. Platelets can contribute to inflammatory reactions via crosstalk both with immune cells and endothelial cells. Inflamed vessels are characterized by the presence of activated endothelial cells. These activated endothelial cells upregulate receptors necessary for leukocyte recruitment, but also for the adhesion of platelets. Subsequently, immune cells can bind to platelets through adhesion receptors presented on the platelet surface, thus supporting leukocyte recruitment to the vessel wall. There are several neurological diseases associated with vascular inflammation including multiple sclerosis (MS) and stroke. Increased markers of platelet activation could be demonstrated in patients suffering from MS compared to healthy individuals. Reports from murine models indicate that platelets may be of importance for disease progression and severity by mediating leukocyte recruitment as one potential underlying mechanism. Blocking platelet function disease severity was considerably ameliorated. Moreover, processes of tissue remodelling may be influenced by platelet derived mediators. Whether a role of platelets for vascular inflammation can be extrapolated to further neurological diseases will have to be investigated in further in depth experimental and clinical trials. CONCLUSION: Platelets and platelet associated mechanisms may offer novel starting points to understand neurovascular diseases from a different point of view and to develop novel approaches to access the disease.

Long-term effects of dalfampridine in patients with multiple sclerosis.

BACKGROUND/OBJECTIVE: Dalfampridine is the extended-release formulation of 4-aminopyridine and is approved for the symptomatic treatment of impaired mobility in patients with multiple sclerosis. Our aim was to examine the short- and long-term effects of treatment with dalfampridine on motoric and cognitive assessment parameters of multiple sclerosis (MS) patients over 9-12 months. METHODS: Fifty-two patients with MS with an EDSS between 4.0 and 7.0 and impaired mobility were evaluated for parameters of walking ability, MSFC, cognitive and motor fatigue and evoked potentials at treatment initiation with dalfampridine as well as 2 weeks and after 9-12 months later. RESULTS: Thirty out of fifty-two patients (~60%) were still on treatment after 9-12 months. Two weeks after treatment initiation, significant ameliorations could be found for T25FW, maximum walking distance as well as motoric and cognitive fatigue which still persisted after 9-12 months. In contrast significant effects for velocity were observed only after 2 weeks, for improvement in PASAT only after 9-12 months. A tendency for improvement of somatosensory evoked potentials was found in a subset of patients. CONCLUSION: Dalfampridine shows positive short- and long-term effects on motoric and cognitive assessment parameters in an open-label observational study in a cohort of patients with MS.

[Importance of perimetric differential diagnostics in patients with primary open-angle glaucoma]. / Stellenwert einer perimetrischen Differenzialdiagnostik beim primären Offenwinkelglaukom.

Functional deficits in glaucomatous optic neuropathy are, apart from other disturbances in the visual field, typically detected with achromatic perimetry as a well accepted gold standard. With the development of new perimetric devices and strategies (e.g. short wave perimetry, frequency doubling perimetry and flicker perimetry) individually different patterns of scotomas in the different perimetric devices could be recognized. The reasons for this could be a different sensitivity reaction of the ganglion cell subpopulations to an increased intraocular pressure as well as an influence of the underlying systemic diseases. To obtain a differentiated detection of the functional loss in the visual field in glaucoma, the use of different perimetric methods seems to be reasonable and helpful.

[Sensitivity and specificity of flicker perimetry with Pulsar. Comparison with achromatic (white-on-white) perimetry in glaucoma patients]. / Sensitivität und Spezifität der Flimmerperimetrie mit dem Pulsar. Vergleich zur achromatischen (Weiß-Weiß-)Perimetrie bei Glaukompatienten.

The early detection of functional glaucoma damage plays an increasingly more central role in the diagnosis and treatment of glaucoma disease. Using selective perimetry detection of early glaucomatous defects is more likely and one of these methods is flicker perimetry with Pulsar. Flicker perimetry is used to analyze the temporal visual function in combination with spatial resolution and contrast sensitivity as opposed to standard automated perimetry which measures the differential light sensitivity with a non-specific stimulus. This study showed a higher sensitivity and specificity of Pulsar perimetry in comparison to achromatic perimetry in glaucoma patients.

[Importance of flicker contrast tests in functional glaucoma diagnostics]. / Bedeutung der Flimmer-Kontrasttests in der funktionellen Glaukomdiagnostik.

One of the many unsolved problems concerning glaucoma is early detection and many different methodologies have been developed. This article concentrates on methodologies belonging to the class of flicker contrast tests which present dynamic stimuli (with temporal frequencies generally above 10 Hz) and assess the perceptual thresholds for contrast, be it global or locally resolved. The tests include global flicker sensitivity, flicker perimetry (current embodiment: Pulsar), Rauschfeld campimetry, frequency doubling perimetry and flicker-defined edge perimetry. These different approaches are placed into historical perspective and are critically assessed.

CD8+ T-cell immunity in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculopathy (CIDP) is a common, but often misdiagnosed disease of the peripheral nervous system with assumed autoimmune pathogenesis. While current concepts of CIDP postulate a pathogenetic role of B cells and (auto)antibodies, the relevance of CD8 T cells present in the biopsies is still elusive. Thus, we asked whether nervous tissue infiltrating and blood-derived lymphocytes in CIDP are clonally expanded to evaluate the involvement of T cells in the pathogenesis of the disease. METHODS: We characterized the clonal composition of the T-cell receptor repertoire in sural nerve biopsies (n = 25) and matching peripheral blood (n = 12) of patients with CIDP using PCR-based CDR3 spectratyping and subsequent DNA sequencing. As controls we used inflammatory myopathies (dermatomyositis, inclusion body myositis) and nonpathologic control biopsies. Immunohistochemistry was employed to visualize expanded CD8+ T-cell populations in sural nerve biopsies. RESULTS: In contrast to controls, T cells in CIDP biopsies showed strong monoclonal and oligoclonal restrictions in their T-cell receptor repertoire. Strikingly, clonal expansions found in the biopsies were reflected in the CD8+ T-cell pool of patients' peripheral blood. Clones overlapping between blood and biopsy could be confirmed by CDR3 sequencing. Finally, the predominance of expanded nerve-infiltrating CD8+ T-cell clones was visualized by immunohistochemistry. CONCLUSIONS: Together, these data provide strong evidence for an antigen-driven, major histocompatibility complex class I restricted, CD8+ T-cell-mediated attack against peripheral nerve tissue components contributing to the pathogenesis of CIDP.