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Abstract Inhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties. NR8383 rat lung AM were treated with ultrafine (uf), fine (f) TiO2 or fine crystalline silica (DQ12 quartz). Physico-chemical particle properties were investigated by transmission electron microscopy, elemental analysis and thermogravimetry. Aggregation and agglomeration tendency of the particles were determined in assay-specific suspensions by means of dynamic light scattering. All three particle types were rapidly taken up by AM. DQ12 and ufTiO2 , but not fTiO2 , caused increased extracellular reactive oxygen species (ROS), heme oxygenase 1 (HO-1) mRNA expression and tumor necrosis factor (TNF)-α release. Inducible nitric oxide synthase (iNOS) mRNA expression was increased most strongly by ufTiO2 , while DQ12 exclusively triggered interleukin (IL) 1β release. However, oscillations of intracellular calcium concentration and increased intracellular ROS were observed with all three samples. Uptake inhibition experiments with cytochalasin D, chlorpromazine and a Fcγ receptor II (FcγRII) antibody revealed that the endocytosis of fTiO2 by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO2 was dominated by FcγIIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO2 , ufTiO2 and DQ12 relate to differences in the involvement of specific uptake mechanisms.

Abstract In the initiation and progression of pulmonary inflammation, macrophages have classically been considered as a crucial cell type. However, evidence for the role of epithelial type II cells in pulmonary inflammation has been accumulating. In the current study, a combined in vivo and in vitro approach has been employed to investigate the mechanisms of quartz-induced proinflammatory activation of lung epithelial cells. In vivo, enhanced expression of the inflammation- and oxidative stress-related genes HO-1 and iNOS was found on the mRNA level in rat lungs after instillation with DQ12 respirable quartz. Activation of the classical NF-κB pathway in macrophages and type II pneumocytes was indicated by enhanced immunostaining of phospho-IκBα in these specific lung cell types. In vitro, the direct, particle-mediated effect on proinflammatory signalling in a rat lung epithelial (RLE) cell line was compared to the indirect, macrophage product-mediated effect. Treatment with quartz particles induced HO-1 and COX-2 mRNA expression in RLE cells in an NF-κB independent manner. Supernatant from quartz-treated macrophages rapidly activated the NF-κB signalling pathway in RLE cells and markedly induced iNOS mRNA expression up to 2000-fold compared to non-treated control cells. Neutralisation of TNFα and IL-1β in macrophage supernatant did not reduce its ability to elicit NF-κB activation of RLE cells. In addition the effect was not modified by depletion or supplementation of intracellular glutathione. The results from the current work suggest that although both oxidative stress and NF-κB are likely involved in the inflammatory effects of toxic respirable particles, these phenomena can operate independently on the cellular level. This might have consequences for in vitro particle hazard testing, since by focusing on NF-κB signalling one might neglect alternative inflammatory pathways.

Abstract Persistent inflammation and associated excessive oxidative stress have been crucially implicated in quartz-induced pulmonary diseases, including fibrosis and cancer. We have investigated the significance of the particle surface reactivity of respirable quartz dust in relation to the in vivo generation of reactive oxygen and nitrogen species (ROS/RNS) and the associated induction of oxidative stress responses in the lung. Therefore, rats were intratracheally instilled with 2 mg quartz (DQ12) or quartz whose surface was modified by either polyvinylpyridine-N-oxide (PVNO) or aluminium lactate (AL). Seven days after instillation, the bronchoalveolar lavage fluid (BALF) was analysed for markers of inflammation (total/differential cell counts), levels of pulmonary oxidants (H2O2, nitrite), antioxidant status (trolox equivalent antioxidant capacity), as well as for markers of lung tissue damage, e.g. total protein, lactate dehydrogenase and alkaline phosphatase. Lung homogenates as well as sections were investigated regarding the induction of the oxidative DNA-lesion/oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) using HPLC/ECD analysis and immunohistochemistry, respectively. Homogenates and sections were also investigated for the expression of the bifunctional apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) by Western blotting and immunohistochemistry. Significantly increased levels of H2O2 and nitrite were observed in rats treated with non-coated quartz, when compared to rats that were treated with either saline or the surface-modified quartz preparations. In the BALF, there was a strong correlation between the number of macrophages and ROS, as well as total cells and RNS. Although enhanced oxidant generation in non-coated DQ12-treated rats was paralleled with an increased total antioxidant capacity in the BALF, these animals also showed significantly enhanced lung tissue damage. Remarkably however, elevated ROS levels were not associated with an increase in 8-OHdG, whereas the lung tissue expression of APE/Ref-1 protein was clearly up-regulated. The present data provide further in vivo evidence for the crucial role of particle surface properties in quartz dust-induced ROS/RNS generation by recruited inflammatory phagocytes. Our results also demonstrate that quartz dust can fail to show steady-state enhanced oxidative DNA damage in the respiratory tract, in conditions were it elicits a marked and persistent inflammation with associated generation of ROS/RNS, and indicate that this may relate to compensatory induction of APE/Ref-1 mediated base excision repair.

Abstract Background It has become increasingly evident that dietary Se plays a significant role in reducing the incidence of lung, colorectal and prostate cancer in humans. Different forms of Se vary in their chemopreventative efficacy, with Se-methylselenocysteine being one of the most potent. Interestingly, the Se accumulating plant Astragalus bisulcatus (Two-grooved poison vetch) contains up to 0.6% of its shoot dry weight as Se-methylselenocysteine. The ability of this Se accumulator to biosynthesize Se-methylselenocysteine provides a critical metabolic shunt that prevents selenocysteine and selenomethionine from entering the protein biosynthetic machinery. Such a metabolic shunt has been proposed to be vital for Se tolerance in A. bisulcatus. Utilization of this mechanism in other plants may provide a possible avenue for the genetic engineering of Se tolerance in plants ideally suited for the phytoremediation of Se contaminated land. Here, we describe the overexpression of a selenocysteine methyltransferase from A. bisulcatus to engineer Se-methylselenocysteine metabolism in the Se non-accumulator Arabidopsis thaliana (Thale cress). Results By over producing the A. bisulcatus enzyme selenocysteine methyltransferase in A. thaliana, we have introduced a novel biosynthetic ability that allows the non-accumulator to accumulate Se-methylselenocysteine and γ-glutamylmethylselenocysteine in shoots. The biosynthesis of Se-methylselenocysteine in A. thaliana also confers significantly increased selenite tolerance and foliar Se accumulation. Conclusion These results demonstrate the feasibility of developing transgenic plant-based production of Se-methylselenocysteine, as well as bioengineering selenite resistance in plants. Selenite resistance is the first step in engineering plants that are resistant to selenate, the predominant form of Se in the environment.

Competing Interests: Disclosures J. Jordan has served as a consultant for Novartis, Boehringer-Ingelheim, and Novo-Nordisk and is cofounder of Eternygen GmbH (Modest relationship). J. Tank received funding from Boston-Scientific, Boehringer-Ingelheim, and Novo-Nordisk. The other authors report no conflicts.

Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and over 13 billion COVID-19 vaccine doses have been administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to an acute disease, i.e. COVID-19, but also to a post-acute COVID-19 syndrome (PACS, "long COVID"). Currently, the side effects of COVID-19 vaccines are increasingly being noted and studied. Here, we summarise the currently available indications and discuss our conclusions that (i) these side effects have specific similarities and differences to acute COVID-19 and PACS, that (ii) a new term should be used to refer to these side effects (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), and that (iii) there is a need to distinguish between acute COVID-19 vaccination syndrome (ACVS) and post-acute COVID-19 vaccination syndrome (PACVS) - in analogy to acute COVID-19 and PACS ("long COVID"). Moreover, we address mixed forms of disease caused by natural SARS-CoV-2 infection and COVID-19 vaccination. We explain why it is important for medical diagnosis, care and research to use the new terms (PCVS, ACVS and PACVS) in order to avoid confusion and misinterpretation of the underlying causes of disease and to enable optimal medical therapy. We do not recommend to use the term "Post-Vac-Syndrome" as it is imprecise. The article also serves to address the current problem of "medical gaslighting" in relation to PACS and PCVS by raising awareness among the medical professionals and supplying appropriate terminology for disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Polymethylmethacrylate (PMMA) removal during septic total joint arthroplasty revision is associated with a high fracture and perforation risk. Ultrasonic cement removal is considered a bone-preserving technique. Currently, there is still a lack of sound data on efficacy as it is difficult to detect smaller residues with reasonable technical effort. However, incomplete removal is associated with the risk of biofilm coverage of the residue. Therefore, the study aimed to investigate the efficiency of ultrasonic-based PMMA removal in a human cadaver model. The femoral components of a total hip and a total knee prosthesis were implanted in two cadaver femoral canals by 3rd generation cement fixation technique. Implants were then removed. Cement mantle extraction was performed with the OSCAR-3-System ultrasonic system (Orthofix®). Quantitative analysis of cement residues was carried out with dual-energy and microcomputer tomography. With a 20 µm resolution, in vitro microcomputer tomography visualized tiniest PMMA residues. For clinical use, dual-energy computer tomography tissue decomposition with 0.75 mm resolution is suitable. With ultrasound, more than 99% of PMMA was removed. Seven hundred thirty-four residues with a mean volume of 0.40 ± 4.95 mm 3 were identified with only 4 exceeding 1 cm in length in at least one axis. Ultrasonic cement removal of PMMA was almost complete and can therefore be considered a highly effective technique. For the first time, PMMA residues in the sub-millimetre range were detected by computer tomography. Clinical implications of the small remaining PMMA fraction on the eradication rate of periprosthetic joint infection warrants further investigations., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Purpose: Two strategies of initial patient care exist in endovascular thrombectomy (ET) depending on the site of initial admission: the mothership (MS) and drip-and-ship (DnS) principles. This study compares both strategies in regard to patient outcome in a local network of specialized hospitals., Methods: Two-hundred-and-two patients undergoing ET in anterior circulation ischemic stroke between June 2016 and May 2018 were enrolled. Ninety two patients were directly admitted to our local facility (MS), One-hundred-and-ten were secondarily referred to our facility. Group comparisons between admission strategies in three-months modified Rankin Scale (mRS), Maas Score and Alberta-Stroke-Program-Early-computed-tomography-score (ASPECTS), National-Institutes-of-Health-Stroke-Scale (NIHSS), age and onset-to-recanalization-time were performed. Correlation between admission strategy and mRS was calculated. A binary logistic regression model was computed including mRS as dependent variable., Results: There were neither significant group differences in three-months mRS between MS and DnS nor significant correlations. Patients tended to achieve a better outcome with DnS. Collateralization status differed between MS and DnS (p = 0.003) with better collateralization in DnS. There were no significant group differences in NIHSS or ASPECTS but in onset-to-recanalization-time (p < 0.001) between MS and DnS. Binary logistic regression showed a high explanation of variance of mRS but no significant results for admission strategy., Conclusions: Functional outcome in patients treated with ET is comparable between the MS and DnS principles. Tendentially better outcome in the DnS subgroup may be explained by selection bias due to a higher willingness to apply ET in patients with worse baseline conditions (e.g. worse collateralization), if patients undergoing MS are already on site.

Purpose: Despite improved techniques and sophisticated postinterventional care, symptomatic intracranial hemorrhage (sICH) remains the most feared complication of mechanical thrombectomy (MT). Based on peri-interventional parameters, we aimed to discover which patients have a higher risk of sICH., Methods: From March 2017 until March 2020 consecutive patients with acute ischemic stroke (AIS) and confirmed large-vessel occlusion who underwent MT were analyzed retrospectively. Demographic, clinical, and radiological variables and parameters specific to thrombectomy were reviewed. A univariate analysis was performed and statistically significant variables were included in a logistic regression model to identify independent factors predictive of sICH., Results: A total of 236 patients with confirmed large-vessel occlusion were included and 22 (9.3%) had sICH. Univariate predictors of sICH included diabetes mellitus, glucose > 11.1 mmol/L, creatinine clearance (CrCl) ≤ 30 ml/min/1.73, ASPECTS indicating pretreatment infarct size, acute internal carotid artery (ICA) occlusion, stent implantation, tirofiban use, time from symptom onset to groin puncture > 4.5 h and high contrast medium consumption. In the adjusted analysis, ASPECTS < 6 (OR 3.673, p = 0.041), and amount of contrast injected ≥ 140 ml (OR 5.412, p = 0.003) were independent predictors of sICH, but not any more baseline glucose > 11.1 mmol/L (OR 1.467, p = 0.584), CrCl ≤ 30 ml/min/1.73 (OR 4.177, p = 0.069), acute ICA occlusion (OR 2.079, p = 0.181), stent implantation (OR 0.465, p = 0.512), tirofiban use (OR 5.164, p = 0.167), and time from onset-to-groin puncture (OR 1.453, p = 0.514)., Conclusion: The amount of contrast medium used is a modifiable factor associated with sICH. This association is novel and may be related to the neurotoxicity of the contrast medium disrupting the blood-brain barrier., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Having suffered a syncope or dizziness are frequent reasons for admissions to an emergency ward. Carefully taken anamnesis and clinical examination are mostly leading to a correct diagnosis. Red flags like new ECG changes, syncope during physical activity or others should lead to further diagnostic steps. Orthostatic intolerance is one of the most common reasons for dizziness and/or syncope. Autonomic testing including tilt table testing has to be done carefully and judged in an overall view together with anamnesis and clinical presentation. We present a clinical approach to the wide field of orthostatic intolerance with hints for the need of further autonomic testing., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht-Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The morphology of the more superficial tissue of the human tongue was investigated and discussed with the clinical appearance of fissures. Three regions could be distinguished according to the presence and shape of the aponeurosis linguae: the central region showed a thick aponeurotic plate with myotendinous muscle fibre insertions. The lateral region showed still an aponeurosis linguae but of reduced thickness and without muscle insertions. The edge-wise and lower region showed no aponeurosis linguae but a fatty subcutis and myocutaneous muscle fibre insertions lacking specific molecules of myotendinous junctions. This system of partially developed exoskeleton seems to underlie but not to be involved in tongue fissures, which are more superficial within the epidermis and dermis., (© 2022 The Author. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The platysma of the rhesus monkey consists of two parts: a platysma myoides located similar to the human platysma, and a platysma cervicale passing the dorsal cervical region and being in contact with the cheek pouch. Our investigation showed that the muscle fiber morphology was comparable in both parts. Muscle spindles were only present in regions connected to the cheek pouch and contained only nuclear chain fibers. It is tempting to speculate that they sense the filling of the cheek pouch rather than mimic activities., (© 2021 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Due to its clinical importance and due to a suggestion regarding the afferent innervation, the microscopic appearance of the frontalis muscle was investigated., Methods: From seven human cadavers, serial sections of the frontalis muscle were studied using light microscopy. Immunhistochemistry was performed using antibodies against collagen XXII and neurofilament., Results: The macroscopic appearance of the muscle was in accordance with the literature. At both insertion sides, the muscle fiber endings expressed collagen XXII, a marker for myotendinous junctions, although no tendons were present at the origin side. Neuromuscular junctions were seen in the middle part of the muscle belly (insertion of the nerve fibers of the facialis nerve) and in the cranial part toward the galea aponeurotica (possible afferent fibers?)., Conclusions: This study summarizes the microscopic appearance of the frontalis muscle. It is a first example that collagen XXII can be expressed even without tendon formation. It confirms the absence of corpuscular afferent neuronal structures within the muscle., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Within the panniculus carnosus-associated skeletal muscles in the human, the palmaris brevis and the platysma showed myotendinous/myofascial junctions with clear distance to the corium and the specific connection collagen type XXII. The orbicularis oris muscle, in contrast, contained bundles of striated muscle fibers reaching the corium at two distinct levels: the predominant inner ending was connected to the elastic network of the inner corium and the outer ending was within the more superficial collagen network. At both locations, the striated muscle fibers showed brush-like cytoplasmic protrusions connecting a network which was not oriented toward the muscle fibers. Collagen type XXII was not present., (© 2021 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Background: The risk of stroke after carotid sinus massage is greater if there is preexisting carotid stenosis or carotid plaques. We present the case of a patient with underlying 40% carotid stenosis, who developed a watershed stroke after a self-neck massage in our stroke unit. We show a well-documented case with magnetic resonance images before and after the neck massage. We report a case of a watershed brain infarct after a self-massage of the carotid sinus, with preexisting carotid artery stenosis. Neck massage continues to be a significant cause of stroke and should therefore not be performed by patients. Clinicians must be aware of the implications of a carotid sinus massage in both the outpatient and inpatient settings., Case Presentation: We admitted a 58-year-old white male patient, with no relevant medical history, to our department with a brain stem infarct. During his stay at our stroke unit, the patient performed a self-neck massage with consecutive bradycardia and asystole, resulting in left-side hemiparesis. The underlying cause of the hemodynamic stroke is believed to be secondary to this intensive neck massage performed by the patient. The patient also suffered from unknown right internal carotid artery stenosis., Conclusion: Clinicians and patients must be aware that neck massage can lead to ischemic stroke. We postulate that repetitive impaired cardiac output can lead to a hemodynamic (watershed-type) stroke.

Background: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth., Aims: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage., Methods: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used., Results: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n  = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay., Conclusion: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Variations in the hypothenar muscles influence the susceptibility of Guyon's canal and surgical procedures in this region. The hypothenar regions of both hands of 38 human donors were dissected and the single muscles identified. A semiquantitative evaluation included 19 donors. The opponens digiti minimi and the abductor digiti minimi were constantly present. The flexor digiti minimi showed various appearances: in 58% it formed one belly, in 21% two bellies, and in 21% it was missing. Rare unilateral supernumerary muscles (2.5% in this study) were associated to the abductor digiti minimi. The variation of the flexor digiti minimi and the possible appearance of additional muscles should be recognized for hypothenar region pathologies. Clin. Anat., 33:643-645, 2020. © 2019 Wiley Periodicals, Inc., (© 2019 The Author. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.)

The original version of this article unfortunately contained a mistake.

Objective: To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions., Methods: Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters., Results: Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6-46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention., Conclusions: This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

The palmaris brevis muscle contains numerous muscle spindles to control changes of the muscle length but is devoid of tendon-associated neuronal elements (e.g. Golgi tendon organs or Ruffini-like corpuscles) controlling changes in muscle strength. Pacinian bodies, frequently seen in the palm of the hand, show no direct association to the muscle bundles. The observed innervation pattern of the palmaris brevis muscle points to a specific type of neuronal regulation, present in skeletal muscles with no skeletal connection., (© 2019 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The horizontal raphe (HR) as a demarcation line dividing the retina and choroid into separate vascular hemispheres is well established, but its development has never been discussed in the context of new findings of the last decades. Although factors for axon guidance are established (e.g., slit-robo pathway, ephrin-protein-receptor pathway) they do not explain HR formation. Early morphological organization, too, fails to establish a HR. The development of the HR is most likely induced by the long posterior ciliary arteries which form a horizontal line prior to retinal organization. The maintenance might then be supported by several biochemical factors. The circulation separate superior and inferior vascular hemispheres communicates across the HR only through their anastomosing capillary beds resulting in watershed zones on either side of the HR. Visual field changes along the HR could clearly be demonstrated in vascular occlusive diseases affecting the optic nerve head, the retina or the choroid. The watershed zone of the HR is ideally protective for central visual acuity in vascular occlusive diseases but can lead to distinct pathological features.

The diffusion rate for proper nutrition of the inner retina depends mainly on four factors which are discussed in this review: 1. The diffusion distance between blood and retinal ganglion cells shows morphological variants in different mammalian species, namely a choroidal nutrition type, a retinal nutrition type, and a mixture of both types. 2. Low oxygen concentration levels in the inner retina force the diffusion of oxygen especially in the choroidal nutrition type. Other nutrients might be supplied by surrounding cells, mainly Müller cells. 3. Diffusion in the eye is influenced by the intraocular pressure, which is vital for the retinal ganglion cells but might also influence their proper function. Again, the nutrition types established might explain the differences in normal intraocular pressure levels among different species. 4. Temperature is a critical feature in the eye which has to be buffered to avoid neuronal damage. The most effective buffer system is the increased blood turnover in the choroid which has to be established in all species., Competing Interests: The author declares no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Purpose: This study compares computed tomography angiography-based collateral scoring systems in regard to their inter-rater reliability and potential to predict functional outcome after endovascular thrombectomy, and relates them to parenchymal perfusion as measured by computed tomography perfusion., Methods: Eighty-four patients undergoing endovascular thrombectomy in anterior circulation ischaemic stroke were enrolled. Modified Tan Score, Miteff Score, Maas Score and Opercular Index Score ratio were assessed in pre-interventional computed tomography angiographies independently by two readers. Collateral scores were tested for inter-rater reliability by weighted-kappa, for correlations with three-months modified Rankin Scale, and their potential to differentiate between patients with favourable (modified Rankin Scale ≤2) and poor outcome (modified Rankin Scale ≥3). Correlations with relative cerebral blood volume and relative cerebral blood flow were tested in patients with available computed tomography perfusion., Results: Very good inter-rater reliability was found for Modified Tan, Miteff and Opercular Index Score ratio, and substantial reliability for Maas. There were no significant correlations between collateral scores and three-months modified Rankin Scale, but significant group differences between patients with favourable and poor outcome for Maas, Miteff and Opercular Index Score ratio. Miteff and Maas were significant predictors of favourable outcome in binary logistic regression analysis. Miteff best differentiated between both outcome groups in receiver-operating characteristics, and Maas reached highest sensitivity for favourable outcome prediction of 96%. All collateral scores significantly correlated with mean relative cerebral blood volume and relative cerebral blood flow., Conclusions: Computed tomography angiography scores are valuable in estimating functional outcome after mechanical thrombectomy and reliable across readers. The more complex scores, Maas and Miteff, show the best performances in predicting favourable outcome.

Die S1-Leitlinie "Diagnostik und Therapie der erektilen Dysfunktion" (AWMF-Registernummer 030 / 112) steht in einer vollständig überarbeiteten Neufassung zur Verfügung. Erektile Dysfunktion ist definiert als die fortwährende Unfähigkeit, eine penile Erektion, die für einen befriedigenden Geschlechtsverkehr ausreicht, zu erreichen oder aufrechtzuerhalten. Betroffen sind Millionen Bundesbürger: Bei Männern mit regelmäßiger sexueller Aktivität nimmt die erektile Dysfunktion von 2,3 Prozent in der dritten Lebensdekade auf 53,4 Prozent in der siebten Lebensdekade zu. Die Leitlinie gibt dezidierte Empfehlungen zur adäquaten Diagnose und zur Therapie der erektilen Dysfunktion, die seit der Einführung der Phosphodiesterase-5-(PDE-5-)Hemmer häufig unkritisch erfolgt., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

The mimic muscles are usually described as containing no muscle spindles. In the present publication the human platysma was reinvestigated concerning its content of corpuscular sensors. Serial sections through the platysma of seven donors revealed numerous muscle spindles but no Pacini corpuscules. The muscle spindles were located in the cranial two-thirds of the platysma, and were evenly distributed with a tendency to have more spindles in the lateral part of the muscle. Immunohistochemical staining with S46 antibodies revealed a predominance of nuclear bag fibers. The results point to an extended function of the platysma as an afferent center of the lower face mimic muscles., (© 2017 Anatomical Society.)

The pathogenesis of glaucoma is complex which has led to numerous hypothesizes concerning the important factors creating this specific type of inner retinal degeneration namely apoptosis of retinal ganglion cells. We favor a primary vascular etiology and provide evidence that the pathogenesis of glaucoma should not be confined to changes exclusively at the optic nerve head but must include changes occurring in the peripheral retina with particular emphasis on the watershed zones of both the retina and choroid. This focus may help to sharpen ones awareness for early glaucoma treatment particularly in patients with minimal findings suggestive of glaucoma., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: To define age-related changes in the visual field by comparing 'standard' central and unique peripheral visual field measurements in healthy volunteers., Methods: In a single center, retrospective, Cross-sectional, observational study, 20 volunteers with no retinal diseases or risk factors, ranging in age between 30 and 94 years (four age groups: 30's, 50's, 70's, 90's) were measured in one eye (preferentially the right one) using a Humphrey visual field 24-2 and 60-4., Results: While the central visual field remained relatively well preserved during aging showing only a mild reduction in sensitivity, a profound loss of the peripheral visual field was observed beginning in the fifth decade of life and decreasing continuously up to the 90ies., Conclusions: The peripheral visual field declined substantially from the 4th decade onward while the central visual field remained quite stable.

Purpose: To review the roles of the different vascular beds nourishing the inner retina [retinal ganglion cells (RGCs)] during normal development of the human eye, using our own tissue specimens to support our conclusions., Methods: An extensive search of the appropriate literature included PubMed, Google scholar, and numerous available textbooks. In addition, choroidal and retinal NADPH-diaphorase stained whole mount preparations were investigated., Results: The first critical interaction between vascular bed and RGC formation occurs in the sixth to eighth month of gestation leading to a massive reduction of RGCs mainly in the peripheral retina. The first 3 years of age are characterized by an intense growth of the eyeball to near adult size. In the adult eye, the influence of the choroid on inner retinal nutrition was determined by examining the peripheral retinal watershed zones in more detail., Conclusion: This delicately balanced situation of RGC nutrition is described in the different regions of the eye, and a new graphic presentation is introduced to combine morphological measurements and clinical visual field data.

The vestibular system has more connections with and influence on higher cortical centers than previously thought. These interactions with higher cortical centers and the phenomena that they elicit require a structural intact cerebral cortex. To date, little is known about the role and influence of the vestibular system on one's body experience. In this study we show that caloric vestibular stimulation (CVS) in healthy participants has an effect on the perceptive component of one's body experience. After CVS all participants showed a statistically significant difference of thigh width estimation. In contrast to previous studies, which demonstrated an influence of CVS on higher cortical centers with an intact cerebral cortex both the cognitive and affective component of body experience were not effected by the CVS. Our results demonstrate the influence of the vestibular system on body perception and emphasize its role in modulating different perceptive-qualities which contributes to our body experience. We found that CVS has a limited influence on one's conscious state, thought process and higher cortical functions.

A dual C-H/N-H dehydrogenative coupling of quinoline-type N-oxides with sulfoximines that leads to N-(hetero)arylsulfoximines in high yields has been realized by using a catalytic amount of CuBr in air. The method does not require any additional ligand, base, reactivity modifier or oxidant and provides a practical route towards a series of sulfoximidoyl-functionalized quinolines and derivatives., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Muscle spindles are crucial for neuronal regulation of striated muscles, but their presence and involvement in the superficial perineal muscles is not known., Methods: Bulbospongiosus and ischiocavernosus muscle specimens were obtained from 31 human cadavers. Serial sections were stained with hematoxylin and eosin, Sirius red, antibodies against Podocalyxin, myosin heavy chain isoforms (MyHC-slow tonic, S46; MyHC-2a/2x, A4.74), and neurofilament for the purpose of muscle spindle screening, counting, and characterization., Results: A low but consistent number of spindles were detected in both muscles. The muscles contained few intrafusal fibers, but otherwise showed normal spindle morphology. The extrafusal fibers of both muscles were small in diameter., Conclusions: The presence of muscle spindles in bulbospongiosus and ischiocavernosus muscles supports physiological models of pelvic floor regulation and may provide a basis for further clinical observations regarding sexual function and micturition. The small number of muscle spindles points to a minor level of proprioceptive regulation., (© 2014 Wiley Periodicals, Inc.)

Purpose: The bulbospongiosus muscle is part of the superficial muscular layer of the perineum and pelvic floor. Its morphology remains controversial in the literature. Therefore, we reinvestigated the fascial arrangement and fiber courses of the bulbospongiosus muscle and its topographical relation to the external anal sphincter., Materials and Methods: The perineum was dissected in 9 male cadavers (mean ± SD age 78.3 ± 10.7 years). Select samples were obtained for histology and immunohistochemistry. In 43 patients (mean age 60.7 ± 12 years) the topographical relation between the bulbospongiosus muscle and the external anal sphincter was determined by magnetic resonance imaging., Results: The perineum contains several fascial layers consisting of elastic and collagen fibers as well as bundles of smooth muscle cells. The bulbospongiosus muscle was subdivided into a ventral and dorsal portion, which developed in 4 variants. The ventral insertion formed a morphological unity with the ischiocavernous muscle while the dorsal origin had a variable relation to the external anal sphincter (5 variants). A muscle-like or connective tissue-like connection was frequently present between the muscles. However, in some cases the muscles were completely separated., Conclusions: We suggest a concept of variations of bulbospongiosus muscle morphology that unifies the conflicting literature. Its ventral fiber group and the ischiocavernosus muscle form a functional and morphological unity. While the bulbospongiosus muscle and the external anal sphincter remain independent muscles, their frequent connection might have clinical implications for perineal surgery and anogenital disorders., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe 'densified regions' in human postlaminar optic nerves of donors with the clinical diagnosis of primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG)., Methods: Optic nerves of 25 eyes with POAG and of 19 eyes with PEXG were investigated. Clinical data and axon counts of Epon-embedded semi-thin sections were used to determine the stage of the disease. Ultrathin sections were performed of selected areas and studied with an electron microscope. Immunofluorescence staining of paraffin sections was performed including antibodies against glial fibrillary acidic protein (GFAP), neural cellular adhesion molecule, vimentin and laminin., Results: Early changes in both types of glaucoma showed increased numbers of areas with a densified appearance. The lack of GFAP staining and of ultrastructurally light nuclei within these areas indicated loss of astroglia., Conclusion: For the first time, a special type of neurodegeneration in optic nerves with mild glaucomatous changes is described.

Introduction: Postural tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterized by excessive tachycardia of unknown etiology. Our objective in this study was to evaluate the correlation between C-fiber involvement as shown by skin biopsy and adrenergic cardiac metaiodobenzylguanadine (MIBG) uptake in POTS patients., Methods: Skin biopsies of 84 patients with POTS were examined by Protein Gene Product 9.5 (PGP9.5) immunohistochemistry and were compared with MIBG myocardial scintigraphy imaging data., Results: Mean intraepidermal nerve fiber (IENF) density was in the lower normal age-adjusted range, 7.2 ± 2.9/mm (normal ≥ 7/mm), and was slightly below the normal range in 45% of POTS patients. MIBG uptake was reduced in 21% of patients. Low IENF density correlated with reduced cardiac MIBG uptake (r = 0.39, P = 0.001)., Conclusions: A subset of neuropathic POTS patients may harbor mild small fiber neuropathy with abnormalities of unmyelinated nerve fibers in the skin associated with reduced myocardial postganglionic sympathetic innervation., (© 2014 Wiley Periodicals, Inc.)

Many patients with postural tachycardia syndrome (PoTS) suffer from fatigue, daytime sleepiness, and sleeping disturbances. The objective of this study was to compare subjective and objective sleep quality of PoTS patients with a group of healthy controls. All patients completed a Pittsburgh Sleep Quality Index questionnaire and the Epworth Sleepiness Scale. The patients sleep architecture, heart rate, and heart rate variability (HRV) measurements were taken during one night at the sleep laboratorium. All data was collected at the Sleep Unit, at Helios Klinikum Wuppertal. Thirty-eight patients diagnosed with PoTS were compared to 31 healthy controls, matched in age and gender. Patients with PoTS reached significantly higher scores in sleep questionnaires, which means that they were more sleepy and had a lower sleep quality. Polysomnography showed a significantly higher proportion of stage 2 sleep. The results of HRV analysis in different sleep stages confirmed changes in autonomic activity in both groups. PoTS patients, however, showed a diminished variability of the low-frequency (LF) band, high-frequency (HF) band, and LF/HF ratio in different sleep stages. It can therefore be gathered that PoTS could be considered as potential differential diagnosis for sleep disturbances since PoTS patients had a subjective diminished sleep quality, reached higher levels of daytime sleepiness, and showed a higher proportion of stage 2 sleep. PoTS patients showed furthermore a reduction of LF/HF ratio variability in different sleep stages.

The aim of the present study was to demonstrate the location of the different members of the caveolin (cav) family in human muscle spindles. Twenty spindles of three human muscles (vastus medialis, ischiocavernosus, bulbospongiosus) from 12 cadavers were immunohistochemically stained for cav-1, cav-2, and cav-3, and the equatorial and polar regions evaluated. All layers of the outer and inner spindle capsule and all blood vessels within the spindle stained for cav-1 and cav-2. In the muscle spindle, intrafusal muscle fibres stained selectively for cav-3, but with a patchy appearance. Caveolinopathies may therefore also include changes in muscle spindle function., (© 2014 Anatomical Society.)

Several aspects of chronologic and biologic aging in the human choroid are reviewed from the literature. They often reveal methodological problems for age-dependent changes of the following parameters: choroidal thickness, choroidal pigmentation, choroidal vasculature and blood flow, and choroidal innervation. On reinterpreting some data of studies concerning Bruch's membrane, changes observed at different age points seem more likely to be nonlinear. Concluding from the data presented so far, chronologic aging should not be used as a factor for physiological changes in the human choroid. Longitudinal study designs are necessary to further establish the impact of age. Meanwhile, a more biologic oriented model of aging processes in the choroid should be established, including specified conditions (e.g., light exposure and refractory state). This would help to define more individual strategies for prevention and early stages of a certain defined disease.

Bone marrow derived cells (BMDCs) can be found in almost every tissue showing a distinct turnover and density. Since caveolin-1 regulates junction-associated proteins in endothelial and epithelial cells, its role for BMDC was investigated in the eyes of caveolin-1 knock-out mice transplanted with GFP-marked BMDC. Distribution and turnover of BMDC in connective tissues (cornea, iris, ciliary body and choroid) was not altered. The absence of caveolin-1, however, caused a significant decrease of BMDC turnover in cornea epithelium, ciliary epithelium, and in the retina. This finding emphasizes an important, hitherto unknown role of caveolin-1 in neuronal and epithelial tissues., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the association between mortality of breast cancer women and the social-demographic and clinical characteristics. During the mortality study of 1,086 women diagnosed with breast cancer and treated from 2000 to 2005 at a cancer hospital in the city of Vitória, Espírito Santo, medical records and tumor registration cards were controlled. The Mortality Information System and the Reclink program were used to identify 280 deaths. Patients were classified under death and non-death, and variables percentages were calculated. For variables that showed statistical significance, considering the level of 0.10, the crude and adjusted odds ratio (OR) were calculated by logistic regression model. There was a correlation between mortality and the following variables: women coming from the Unified Health System (p = 0.014; OR = 2.38), negative c-erb B-2 tumor marker (p = 0.027; OR = 2.03), advanced (III and IV) staging (p = 0.001; OR = 6.89 and OR = 17.13, respectively), presence of metastasis (p = 0.001; OR = 18.23) and recurrence (p = 0.010; OR = 3.53). Mortality associated with staging underlines the necessity of warning the population about the benefits of early diagnosis of the disease of cancer.

This population-based study was designed to detect the prevalence of anemia in a healthy population of children (18 months to 7 years) and women (14 to 30 years) tested in 2006-2007 in the state of Rio Grande do Sul, Brazil as part of an effort to tackle this massive problem that still affects so many people in the XXI century. Anemia was defined according to the WHO. Capillary blood was measured and socioeconomic status was determined according to the Brazilian Association of Market Research Agencies. The median prevalence of anemia in 2198 children was 45.4% and in 1999 women 36.4%. Anemia decreased with age during childhood; although significantly more prevalent in lower classes individuals, it was also high in the upper classes. There are indirect evidences that the lack of iron supplementation and/or iron fortified food may play a role in it. Professionals and society wise measures of education have to be implemented in order to address possible biologic factors involved in childhood psychosocial development in southern Brazil.

Non-motor symptoms are now commonly recognized in Parkinson's disease (PD) and can include dysautonomia. Impairment of cardiovascular autonomic function can occur at any stage of PD but is typically prevalent in advanced stages or related to (anti-Parkinsonian) drugs and can result in atypical blood pressure (BP) readings and related symptoms such as orthostatic hypotension (OH) and supine hypertension. OH is usually diagnosed with a head-up-tilt test (HUT) or an (active) standing test (also known as Schellong test) in the laboratory, but 24 h ambulatory blood pressure monitoring (ABPM) in a home setting may have several advantages, such as providing an overview of symptoms in daily life alongside pathophysiology as well as assessment of treatment interventions. This, however, is only possible if ABPM is administrated correctly and an autonomic protocol (including a diary) is followed which will be discussed in this review. A 24-h ABPM does not only allow the detection of OH, if it is present, but also the assessment of cardiovascular autonomic dysfunction during and after various daily stimuli, such as postprandial and alcohol dependent hypotension, as well as exercise and drug induced hypotension. Furthermore, information about the circadian rhythm of BP and heart rate (HR) can be obtained and establish whether or not a patient has a fall of BP at night (i.e., "dipper" vs. non-"dipper"). The information about nocturnal BP may also allow the investigation or detection of disorders such as sleep dysfunction, nocturnal movement disorders, and obstructive sleep apnea, which are common in PD. Additionally, a 24-h ABPM should be conducted to examine the effectiveness of OH therapy. This review will outline the methodology of 24 h ABPM in PD, summarize findings of such studies in PD, and briefly consider common daily stimuli that might affect 24 h ABPM.

Purpose: Indocyanine green (ICG) has been widely used as a vital dye for macular surgery. However, ICG can be toxic to retinal cells. Here we evaluate whether tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a free radical scavenger, can protect against ICG-induced retinal damage in rats., Methods: Brown Norway rats received intravitreal injections of ICG 0.5 % or BSS as controls. Tempol (20 mg/kg BW) or PBS as a control was administered intraperitoneally 24 h and 30 min before ICG and once daily for 7 consecutive days. Tempol was detected in the retina using electron paramagnetic resonance (EPR) spectroscopy. One week after ICG injections, the effects of tempol on retinal toxicity were assessed by retinal ganglion cell (RGC) back-labeling and by light microscopy. Electroretinography (ERG) was performed after 1 and 2 weeks., Results: ICG administration reduced RGC numbers by 17 % (1,943 ± 45 vs. 2,342 ± 31 RGCs/mm(2)). Tempol treatment rescued RGCs in a significant manner (2,258 ± 36, p < 0.01) and diminished morphological changes detected by light microscopy. ICG-injected eyes showed a significant reduction of ERG potentials only in PBS-treated animals (V(max) 530 ± 145 µV vs. 779 ± 179 µV, p = 0.0052), but not in the tempol-treated group., Conclusions: Tempol significantly attenuates ICG-induced toxicity in rat retinas and may therefore be considered for further evaluation as accompanying treatment in ICG-assisted chromovitrectomy.

Distribution and lack of nidogen-1, part of numerous basement membranes, were studied in the mouse eye. For that purpose, eyes of C57BL/6 and nidogen-1 knockout mice were stained immunohistochemically for nidogen-1, and intraocular pressure measurements and light- and electron microscopy were used to study the nidogen-1 knockout animals. In normal mice, nidogen-1 was present in many basement membranes, but showed irregularities underneath the corneal epithelium, in Bruch's membrane and in the iris. Homozygous knockout of nidogen-1 in the mouse showed only mild pathological changes. In the anterior eye segment, small interruptions were noted in the nonpigmented ciliary epithelium without further consequences. In the posterior eye segment, interruptions of the inner limiting membrane led to small retinal ectopias and subsequent changes in the optic nerve. In summary, the knockout of nidogen-1 showed mild but significant morphological changes pointing to the importance of this protein which can in part, but not completely; be replaced by nidogen-2.

The current terrestrial risk assessment of insecticides regarding nontarget arthropods considers exclusively beneficial organisms, whereas herbivorous insects, such as grasshoppers, are ignored. However, grasshoppers living in field margins or meadows adjacent to crops may potentially be exposed to insecticides due to contact with or ingestion of contaminated food. Therefore, the present study assessed effects of five active ingredients of insecticides (dimethoate, pirimicarb, imidacloprid, lambda-cyhalothrin, and deltamethrin) on the survival of Chorthippus sp. grasshopper nymphs by considering two routes of exposure (contact and oral). The experiments were accompanied by monitoring field margins that neighbored cereals, vineyards, and orchards. Grasslands were used as reference sites. The laboratory toxicity tests revealed a sensitivity of grasshoppers with regard to the insecticides tested in the present study similar to that of the standard test species used in arthropod risk assessments. In the field monitoring program, increasing grasshopper densities were detected with increasing field margin width next to cereals and vineyards, but densities remained low over the whole range of field margins from 0.5 to 20 m next to orchards. Grasshopper densities equivalent to those of grassland sites were only observed in field margins exceeding 9 m in width, except for field margins next to orchards. These results may indicate that current insecticide risk assessments are insufficiently protective for grasshoppers in field margins., (Copyright © 2012 SETAC.)