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The obvious benefits derived from the increasing use of engineered nano-, new, and advanced materials and associated products have to be weighed out by a governance process against their possible risks. Differences in risk perception (beliefs about potential harm) among stakeholders, in particular nonscientists, and low transparency of the underlying decision processes can lead to a lack of support and acceptance of nano-, new, and other advanced material enabled products. To integrate scientific outcomes with stakeholders needs, this work develops a new approach comprising a nine-level, stepwise categorization and guidance system entitled "Knowledge, Information, and Data Readiness Levels" (KaRLs), analogous to the NASA Technology Readiness Levels. The KaRL system assesses the type, extent, and usability of the available data, information, and knowledge and integrates the participation of relevant and interested stakeholders in a cocreation/codesign process to improve current risk assessment, communication, and governance. The novelty of the new system is to communicate and share all available and relevant elements on material related risks in a user/stakeholder-friendly, transparent, flexible, and holistic way and so stimulate reflection, awareness, communication, and a deeper understanding that ultimately enables the discursive process that is needed for the sustainable risk governance of new materials., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Global Challenges published by Wiley‐VCH GmbH.)

Objective: To assess the safety and feasibility of aquablation in a first-in-man study. Aquablation is a novel minimally invasive water ablation therapy combining image guidance and robotics (AquaBeam(®) ) for the targeted and heat-free removal of prostatic tissue in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH)., Patients and Methods: A prospective, non-randomised, single-centre trial in men aged 50-80 years with moderate-to-severe LUTS was conducted. Under real-time image-based ultrasonic guidance, AquaBeam technology enables surgical planning and mapping, and leads to a controlled heat-free resection of the prostate using a high-velocity saline stream. Patients were evaluated at 1, 3, and 6 months after aquablation., Results: In all, 15 patients were treated with aquablation under general anaesthesia. The mean (range) age was 73 (59-86) years and prostate size was 54 (27-85) mL. A substantial median lobe was present in six of the 15 patients. The mean International Prostate Symptom Score (IPSS) was 23 and the maximum urinary flow rate (Qmax ) was 8.4 mL/s at baseline. The mean procedural time was 48 min with a mean aquablation treatment time of 8 min. All procedures were technically successful with no serious or unexpected adverse events (AEs). All but one patient had removal of catheter on day 1, and most of the patients were discharged on the first postoperative day. No patient required a blood transfusion, and postoperative sodium changes were negligible. There were no serious 30-day AEs. One patient underwent a second aquablation treatment within 90 days of the first procedure. The mean IPSS score statistically improved from 23.1 at baseline to 8.6 at 6 months (P < 0.001) and the Qmax increased from 8.6 mL/s at baseline to 18.6 mL/s at the 6-month follow-up (P < 0.001). At 6 months, the mean detrusor pressure at Qmax decreased to 45 cmH2 0 from 66 cmH2 0 at baseline (P < 0.05), and the mean prostate size was reduced to 36 mL, a 31% reduction in size vs baseline (P < 0.001). No cases of urinary incontinence or erectile dysfunction were reported., Conclusions: These preliminary results from this initial study show aquablation of the prostate is technically feasible with a safety profile comparable to other BPH technologies. The combination of surgical mapping by the operating surgeon and the high-velocity saline provides a promising technique delivering a conformal, quantifiable, and standardised heat-free ablation of the prostate. Advantages of this technique include reduction in resection time compared with other endoscopic methods, as well as the potential to preserve sexual function., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

In 2010, the EU FP NanoSustain project (247989) has been successfully launched with the objective to develop innovative solutions for the sustainable use, recycling and final treatment of engineered nanomaterials (ENMs). The same year, NanoValid (263147), a large-scale integrating EU FP7 project has been initiated and contract negotiations with the European Commission commenced, to develop new reference methods and materials applicable to the unique properties of ENMs. The paper presented will give an overview on the main objectives of these 2 new European research initiatives, on main tasks to achieve objectives, and on the impact on current standardization efforts and technical innovations.

Objective: To evaluate the efficacy and safety of the ProACT (Uromedica, Inc., MN, USA) balloon device, an alternative for the surgical management of incontinence after prostatectomy., Patients and Methods: The initial patients who received this device at our institution were evaluated, using urodynamics at baseline and at 6 months. Perioperative variables were recorded and pad usage, volume adjustments, an estimate of Incontinence Quality of Life (I-QoL) and adverse events were recorded at baseline, and 1, 3, 6, 12 and 24 months after surgery., Results: In all, 37 patients were treated on this protocol between November 2001 and March 2005. Of these, 30 had had radical prostatectomy and seven holmium laser enucleation of the prostate. The mean (range) pad usage decreased from 2.81 (1-12) at baseline to 0.7 (0-4) pads at 24 months, and the I-QOL increased from 49.7 (4.5-77) to 81.3 (13.6-100) over the same period. At 24 months, 62% of 34 men were pad-free and 81% required one pad or less. Bilateral explantation was required in three patients (11%) for infection (one) and balloon migration (two). All other adverse events were mild and transient., Conclusions: The ProACT balloon device is an acceptable therapy for the surgical management of incontinence after prostatectomy.

Ferritins are a class of iron storage protein spheres found mainly in the liver and spleen, which have attracted many research interests due to their unique structural features and biological properties. Recently, ferritin and apoferritin (ferritin devoid of the iron core), have been employed as chemically addressable nanoscale building blocks for functional materials development. However, the reactive residues of apoferritin or ferritin have never been specified and it is still unclear about the chemoselectivity of apoferritin towards different kinds of bioconjugation reagents. In this work, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry combined with enzymatic digestion analysis was used to identify the reactive lysine residues of horse spleen apoferritin when conjugated with N-hydroxysuccinimide reagents. The result demonstrated that among all the lysine residues, K97, K83, K104, K67 and K143 are the reactive ones that can be addressed.

Viruses and virus-like particles (VLPs) have been demonstrated to be robust scaffolds for the construction of nanomaterials. In order to develop new nanoprobes for time-resolved fluoroimmuno assays as well as to investigate the two-dimensional self-assembly of viruses and VLPs, the icosahedral turnip yellow mosaic virus (TYMV) was investigated as a potential building block in our study. TYMV is an icosahedral plant virus with an average diameter of 28 nm that can be isolated inexpensively in gram quantities from turnips or Chinese cabbage. There are 180 coat protein subunits per TYMV capsid. The conventional N-hydroxysuccinimide-mediated amidation reaction was employed for the chemical modification of the viral capsid. Tryptic digestion with sequential MALDI-TOF MS analysis identified that the amino groups of K32 of the flexible N-terminus made the major contribution for the reactivity of TYMV toward N-hydroxysuccinimide ester (NHS) reagents. The reactivity was also monitored with UV-vis absorbance and fluorescence, which revealed that approximately 60 lysines per particle could be addressed. We hypothesized that the flexible A chain contains the reactive lysine because the crystal structure of TYMV has shown that chain A is much more flexible compared to B and C, especially at the N-terminal region where the Lys-32 located. In addition, about 90 to 120 carboxyl groups, located in the most exposed sequence, could be modified with amines catalyzed with 1-(3-dimethylaminopropyl-3-ethylcarbodiimide) hydrochloride (EDC) and sulfo-NHS. TYMV was stable to a wide range of reaction conditions and maintained its integrity after the chemical conjugations. Therefore, it can potentially be employed as a reactive scaffold for the display of a variety of materials for applications in many areas of nanoscience.

Nucleolar dominance describes the silencing of one parental set of ribosomal RNA (rRNA) genes in a genetic hybrid, an epigenetic phenomenon that occurs on a scale second only to X-chromosome inactivation in mammals. An RNA interference (RNAi) knockdown screen revealed that the predicted Arabidopsis histone deacetylase, HDA6, is required for rRNA gene silencing in nucleolar dominance. In vivo, derepression of silenced rRNA genes upon knockdown of HDA6 is accompanied by nucleolus organizer region (NOR) decondensation, loss of promoter cytosine methylation, and replacement of histone H3 Lys 9 (H3K9) dimethylation with H3K4 trimethylation, H3K9 acetylation, H3K14 acetylation, and histone H4 tetra-acetylation. Consistent with these in vivo results, purified HDA6 deacetylates lysines modified by histone acetyltransferases whose substrates include H3K14, H4K5, and H4K12. HDA6 localizes, in part, to the nucleolus, supporting a model whereby HDA6 erases histone acetylation as a key step in an epigenetic switch mechanism that silences rRNA genes through concerted histone and DNA modifications.

The degree and distribution of mercury (Hg) accumulation in sediment and fish from a tributary affected by alluvial small-scale gold mining in the Madeira River/Amazon is studied, in relation to a reference site. The results obtained so far agree well with previous studies and confirm that a tremendous contamination of main food web compartments occurs in these highly exposed, but vulnerable tropical waters. An essential part of the released metallic Hg may still exist as macroscopic liquid Hg drops in the sediment. Both global (0.4 mg/kg of Hg) and local (0.1 mg/kg of Hg) background sediment values as well as safety levels for fish (0.5 mg/kg of Hg) are considerably exceeded by a factor of up to 25, 100, and 4, respectively, and give rise to serious concern, not least with regard to the formation of the very toxic monomethyl-Hg. It is further discussed that atmospheric transport and deposition of Hg in water reservoirs built for hydroelectric power generation may act as critical pathways for longterm Hg accumulation, even in unexposed riverine systems.

This is a report on two male patients aged 22 and 43 years, respectively, who developed a fatal progressive demential syndrome that lead to the death of one after 16 months and of the other patient after 25 months and that presented with the typical clinical pattern of "subcortical dementia". In both the cases, the hospital had suspected Creutzfeldt-Jacob's disease but this was not confirmed by microscopy of the tissue; the typical form of manifestation was absent. Instead, microscopy of the brain revealed a marked symmetric degeneration of the thalamus with special preference given to the anterior and media nuclear groups. Predilection for the neothalamic against the palaeothalamic and archithalamic structures produced a very strong impression of a system-related thalamic degeneration process of the type occasionally discussed on the basis of similar observations. Parallel to the atrophic process there were also degenerative changes that were less pronounced, in the rubro-olivo-cerebellar system and in one case a moderately pronounced involvement of the second motor neuron. Both observations of a "thalamic dementia" are discussed against the background of relevant literature published so far on the subject.

In a randomised double-blind longterm study the value of acetylsalicylic acid in prophylaxis against relapse was investigated against placebo in 58 patients with transitory ischemic attacks of prolonged reversible insults. During the 24 months of observation, significantly fewer relapses of cerebral ischemia occurred in patients with carotid transient ischemia attacks under acetylsalicyclic acid than in the control group. The recurrences usually took the form of transitory ischemic attacks. Of the 5 cerebral infarcts, 4 occurred in the control group, 3 patients died. Patients with vertebrobasilar insufficiency showed no response. On account of the relatively small number of patients the result of the study is to be regarded rather as a confirmation of the results of a larger series of investigations in the USA and Canada than solely a proof of the efficacy of acetylsalicylic acid.

A female is reported, which showed motor and sensory disturbances following severe hypokalemia induced by abuse of diuretics. Elevated CSF-protein and abnormal neurographic findings with restitution after substitution with potassium led to the diagnosis of a neurogenic involvement like a Guillain-Barré syndrome. In the literature similar cases are described. So it seems, that beside of myopathic changes neurogenic disturbances can appear as a neurological symptom of hypokalemia.

Tinnitus and vertigo, two common neurological complaints, often challenge the physician's ability with respect to possible etiology. Objective tinnitus can result from an abnormally patent eustachian tube, from tetanic contractions of the muscles of the soft palate, or from vascular abnormalities within the head or neck. Subjective tinnitus refers to lesions involving the external ear canal, tympanic membrane, ossicles, cochlea, auditory nerve, brainstem, and cortex. As many as 50% of patients with tinnitus do not exhibit associated hearing loss; in these patients, the cause of the tinnitus is rarely identified. An illusion of movement is specific for vestibular system disease--a peripheral or central location depending upon associated audiologic and neurologic symptoms, respectively. However, a presyncopal, light-headed sensation is most commonly associated with diffuse cerebral ischemia: in the young patient, this may be caused by a hyperventilation syndrome; in the aged individual, this can result from diffuse atherosclerotic cerebrovascular disease and decreased cardiac output. Postural and gait imbalance associated with acute vertigo indicates a unilateral peripheral vestibular or a central vestibular lesion; if vertigo is absent, either a cerebellar, proprioceptive, or bilateral peripheral vestibular lesion is likely. Transient oscillopsia suggests unilateral peripheral vestibular lesions. Permanent oscillopsia indicates a bilateral peripheral vestibular lesion or--in the absence of severe vertigo--brainstem or cerebellar damage.

In six patients with ischemic lesions of the visual pathways above the lateral geniculate body, the pupil light reflex was investigated under perimetric conditions. The size of the lesions--in four cases caused by lateralized cerebral infarction, in two cases by complicated migraine attacks--was certified by neurological examination and by angiography or computerized tomography respectively. The recordings were done with a portable pupillograph measuring the infrared light reflected from the iris. A Tübinger perimeter served as stimulator. All patients except one, whose visual fields recovered quickly and completely, showed parallel tracings concerning the sensory and the pupillographic profiles, in the older lesions as well as in the recent ones.

The process of lysolecithin-mediated hemolysis has been investigated by use of various ether-deoxy lysolecithin analogs (1-alkyl-propanediol-3-phosphorylcholine) with alkyl residues of 10-22 carbon atoms. Hemolytic activities were defined either as molar amounts to be added for 50% lysis (L50) or as cell-bound amounts at 50% lysis (A50). It was found, that in contrast to L50, A50 values are independent of experimental conditions. Moreover, L50 values primarily reflect the binding affinities, while A50 values give more accurate information on the actual membrane-disturbing potential. The strongest hemolytic C16-lysolecithin analog required 2 - 10(7) or 5 - 10(7) molecules bound per cell for 50% lysis at 0 or 37degrees C, respectively, corresponding to about 10 or 25% of the total membrane phospholipids. Evidence is presented, indicating that (a) lysophosphatides bind to cells below their critical micelle concentration, (b) micelles themselves are not generally necessary for cell lysis. Red cells of different species (man and cattle) as well as at varying temperatures exhibit significantly different sensitivities in terms of L50 and A50 values. These differences, however, depend on the degree of hydrophobicity of the lysolecithins and disappear in the case of lysolipids having C10 or C12 aliphatic residues. The data are in agreement with our hypothesis that cellular sensitivity to lysolecithin lysis may be determined by the degree of segregation of lysolecithin-rich areas within the membrane lipid phase.

Pathological nystagmus may be spontaneous, positional, or gaze-evoked. Peripheral vestibular nystagmus is usually rotatory, the horizontal component being most prominent. It is - in contrast to a central vestibular nystagmus - strongly inhibited by fixation. Spontaneous congenital nystagmus is also prominent with fixation, but it can usually be distinguished from acquired fixation nystagmus based on its long duration, atypical waveforms and high frequency. Two general types of positional nystagmus can be identified on the basis of nystagmus regularity: static and paroxysmal. The most common variety of positional nystagmus is the so-called benign paroxysmal positional nystagmus, which in the majority of cases occurs as an isolated symptom of unknown cause. Gaze-evoked nystagmus, prominent with fixation, includes dissociated, rebound and gaze-paretic nystagmus forms. Symmetrical gaze-evoked nystagmus is most commonly produced by ingestion of certain drugs. Phenomena related to nystagmus include: amblyopic, voluntary, and convergence-retraction nystagmus, ocular dysmetria, ocular flutter, opsoclonus, ocular bobbing, and ocular myoclonus.

Three cases of post-traumatic thrombosis of the distal extracranial internal carotid artery and vertebral artery are reported. Control angiograms showed considerable recession of changes caused by injury. Discussed is the significance of these findings for differentiation between post-traumatic artery changes and fibromuscular dysplasia.

Stability, distribution and metabolic fate of alkyl analogs of lysophosphatidylcholine have been studied in mice. Analogs employed were 1-hexadecyl- and 1-dodecyl-propanediol-3-phosphorylcholine (2-deoxy-lysophosphatidylcholine) and rac-1-octadecyl-2-methyl-glycero-3-phosphorylcholine (2-methoxy-lysophosphatidylcholine). It is demonstrated that (1) the half-life of these compounds in the organism was increased to the order of days as compared to minutes or hours for natural lysophosphatidylcholine, (2) the analogs were slowly degraded in vivo with partial incorporation of the hydrophobic part into neutral lipids and phosphatidylcholine. Deoxy analogs were apparently degraded faster than methoxy derivatives, and (3) due to this metabolism, accumulation of these compounds, even after repeated injections, did not occur in mice. Intravenous and intraperitoneal injections led to rapid and complete distribution of the lysolipids with slight enrichment in liver, kidneys and intestine. Subcutaneous or oral application resulted in a similar distribution, however, remarkable depot effects at the sites of administration were observed. Experiments with tumor-bearing mice indicated a reduced metabolic turnover and thus a slight enrichment of ether-lysophosphatidylcholine analogs in tumor tissue.

Using covered thermoelements, the authors determined in 26 non-dermopathic volunteers the changes in skin temperature produced by the application of Unguentum emulsificans aquosum SR, Unguentum emulsificans cum 50% aqua, Linimentum aquosum SR, Lotio Zinci oxydati SR, Lotio Zinci oxydati aethanolica SR and water. Lotio Zinci oxydati aethanolica SR had the strongest cooling effect, followed by Lotio Zinci oxydati SR and, with some reservations, Unguentum emulsificans aquosum SR. The two other external remedies are unsuitable as cold creams.

In order to prove that platelet scintigraphy (PSC) is able to detect carotid thrombi formations, we performed PSC in 15 patients directly before or immediately after a percutaneous carotid angiography. PSC was successful in demonstrating iatrogenic fresh carotid thrombi in 13 out of 15 cases. Out of 53 patients with cerebrovascular disease and carotid stenosis a pathologic platelet accumulation was seen in 39 carotid arteries, 31 on the symptomatic side; more often in slight- and middle-sized stenoses than in high degree stenoses. We assume that in these cases PSC detected carotid thrombi which caused arterio-arterial emboli.

Four cases with isolated cerebral infarction near the occipital pole resulting in homonymous hemianopic paracentral scotoma showed loss of pupillomotor sensitivity within the scotomatous defects. This supports previous similar findings in patients with homonymous hemianopia due to larger infarctions in the posterior cerebral artery territory.

Three patients with ischemic cerebrovascular disease suffered attacks of transient dyskinesias, consistent with hemiballism. Angiographically all of them showed occlusive disease of the cerebral arteries. Two patients had lesions in different cerebral arteries, but showed signs and symptoms of insufficiency of the carotid artery contralateral to the dyskinesias, which was occluded in one patient and severely stenosed in the other. The third patient had frank occlusion of the basilar artery. The blood supply of the nucleus subthalamicus receiving contributions from the carotid and vertebral arterial system as well would explain transient hemiballism as a symptom of the insufficiency of both arterial systems and would further be one of the possible explanations for the low frequency of this symptom. On the other hand the appearance of transient hemiballism should be regarded as indicative of significant occlusive disease of the cerebral arteries.

Four cases of homonymous hemianopia due to cerebral infarction in the posterior cerebral artery territory showed loss of pupillomotor sensitivity within the hemianopic defects, using small threshold-stimuli under perimetric conditions. Sensory and pupillographic profiles paralleled each other. The recordings were done with a portable pupillograph measuring the infrared light reflected from the iris. A Tübinger perimeter served as stimulator.