Indemnification of Corporate Officers and Directors

Doing business through the legal fiction\u27 of a corporate entity dates back to the Middle Ages

Adherence to medication in adults with Cystic Fibrosis: An investigation using objective adherence data and the Theoretical Domains Framework

Objectives Adherence to nebulizer treatment in adults with Cystic Fibrosis (CF) is poor, and interventions are needed. This research aimed to identify the factors affecting nebulizer adherence using the Theoretical Domains Framework (TDF) and to compare these for participants with different levels of adherence. Design Data‐prompted interviews using the TDF. Methods Eighteen semi‐structured interviews were conducted with adults with CF during which objectively measured adherence data were discussed. Framework analysis was used to code the data into TDF domains, and inductive qualitative content analysis was used to code different beliefs and experiences. Aspects of the TDF that differed between participants with different adherence levels were explored. Results Factors influencing adherence to treatment included all 14 domains of the TDF, 10 of which appeared to vary by adherence level: Skills; Memory and decision‐making; and Behavioural regulation; Environmental context and resources; Social influences; Beliefs about consequences; Beliefs about capability; Reinforcement; Social role and identify; Intentions; Optimism; and Emotions. Conclusions This study is the first to use objectively measured adherence data in a data‐prompted interview using the TDF framework to systematically assess the full range of factors potentially influencing adherence. The results highlighted that interventions need to consider issues of capability, opportunity, and motivation. Interventions that challenge dysfunctional beliefs about adherence and which support the development of routines or habits and problem‐solving may be particularly useful for adults with CF

Systemic chemotherapy decreases brain glucose metabolism

Objective: Cancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-based chemotherapy on glucose metabolism in the brain of cancer patients. Methods: Using sequential FDG-PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non-small-cell lung cancer. Results: Significant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network systems, including the corpus callosum, subcortical, and periventricular WM tracts. Interpretation Our data demonstrate a decrease in glucose metabolism in both gray and white matter structures associated with chemotherapy. Among the affected regions are those relevant to the maintenance of brain plasticity and global neurologic function. This study potentially offers novel insights into the spatial and temporal effects of systemic chemotherapy on brain metabolism in cancer patients

Scanning electrochemical microscopy as a local probe of oxygen permeability in cartilage

The use of scanning electrochemical microscopy, a high-resolution chemical imaging technique, to probe the distribution and mobility of solutes in articular cartilage is described. In this application, a mobile ultramicroelectrode is positioned close (not, vert, similar1 μm) to the cartilage sample surface, which has been equilibrated in a bathing solution containing the solute of interest. The solute is electrolyzed at a diffusion-limited rate, and the current response measured as the ultramicroelectrode is scanned across the sample surface. The topography of the samples was determined using Ru(CN)64−, a solute to which the cartilage matrix was impermeable. This revealed a number of pit-like depressions corresponding to the distribution of chondrocytes, which were also observed by atomic force and light microscopy. Subsequent imaging of the same area of the cartilage sample for the diffusion-limited reduction of oxygen indicated enhanced, but heterogeneous, permeability of oxygen across the cartilage surface. In particular, areas of high permeability were observed in the cellular and pericellular regions. This is the first time that inhomogeneities in the permeability of cartilage toward simple solutes, such as oxygen, have been observed on a micrometer scale

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN)

Background Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. Methods The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment. In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. Discussion This is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. Trial registration number This trial has been registered at clinicaltrials.gov , Identifier: NCT04318977. Data dissemination Results from the trial shall be published in peer-reviewed journals and presented at meetings and conferences

Enhanced Functional Recovery in MRL/MpJ Mice after Spinal Cord Dorsal Hemisection

Adult MRL/MpJ mice have been shown to possess unique regeneration capabilities. They are able to heal an ear-punched hole or an injured heart with normal tissue architecture and without scar formation. Here we present functional and histological evidence for enhanced recovery following spinal cord injury (SCI) in MRL/MpJ mice. A control group (C57BL/6 mice) and MRL/MpJ mice underwent a dorsal hemisection at T9 (thoracic vertebra 9). Our data show that MRL/MpJ mice recovered motor function significantly faster and more completely. We observed enhanced regeneration of the corticospinal tract (CST). Furthermore, we observed a reduced astrocytic response and fewer micro-cavities at the injury site, which appear to create a more growth-permissive environment for the injured axons. Our data suggest that the reduced astrocytic response is in part due to a lower lesion-induced increase of cell proliferation post-SCI, and a reduced astrocytic differentiation of the proliferating cells. Interestingly, we also found an increased number of proliferating microglia, which could be involved in the MRL/MpJ spinal cord repair mechanisms. Finally, to evaluate the molecular basis of faster spinal cord repair, we examined the difference in gene expression changes in MRL/MpJ and C57BL/6 mice after SCI. Our microarray data support our histological findings and reveal a transcriptional profile associated with a more efficient spinal cord repair in MRL/MpJ mice

SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Stromal cell-derived factor-1 (SDF1) and its major signaling receptor, CXCR4, were initially described in the immune system; however, they are also expressed in the nervous system, including the spinal cord. After spinal cord injury, the blood brain barrier is compromised, opening the way for chemokine signaling between these two systems. These experiments clarified prior contradictory findings on normal expression of SDF1 and CXCR4 as well as examined the resulting spinal cord responses resulting from this signaling.</p> <p>Methods</p> <p>These experiments examined the expression and function of SDF1 and CXCR4 in the normal and injured adult mouse spinal cord primarily using CXCR4-EGFP and SDF1-EGFP transgenic reporter mice.</p> <p>Results</p> <p>In the uninjured spinal cord, SDF1 was expressed in the dorsal corticospinal tract (dCST) as well as the meninges, whereas CXCR4 was found only in ependymal cells surrounding the central canal. After spinal cord injury (SCI), the pattern of SDF1 expression did not change rostral to the lesion but it disappeared from the degenerating dCST caudally. By contrast, CXCR4 expression changed dramatically after SCI. In addition to the CXCR4+ cells in the ependymal layer, numerous CXCR4+ cells appeared in the peripheral white matter and in the dorsal white matter localized between the dorsal corticospinal tract and the gray matter rostral to the lesion site. The non-ependymal CXCR4+ cells were found to be NG2+ and CD11b+ macrophages that presumably infiltrated through the broken blood-brain barrier. One population of macrophages appeared to be migrating towards the dCST that contains SDF1 rostral to the injury but not towards the caudal dCST in which SDF1 is no longer present. A second population of the CXCR4+ macrophages was present near the SDF1-expressing meningeal cells.</p> <p>Conclusions</p> <p>These observations suggest that attraction of CXCR4+ macrophages is part of a programmed response to injury and that modulation of the SDF1 signaling system may be important for regulating the inflammatory response after SCI.</p

Severe plastic deformation for producing superfunctional ultrafine-grained and heterostructured materials: An interdisciplinary review

Ultrafine-grained and heterostructured materials are currently of high interest due to their superior mechanical and functional properties. Severe plastic deformation (SPD) is one of the most effective methods to produce such materials with unique microstructure-property relationships. In this review paper, after summarizing the recent progress in developing various SPD methods for processing bulk, surface and powder of materials, the main structural and microstructural features of SPD-processed materials are explained including lattice defects, grain boundaries and phase transformations. The properties and potential applications of SPD-processed materials are then reviewed in detail including tensile properties, creep, superplasticity, hydrogen embrittlement resistance, electrical conductivity, magnetic properties, optical properties, solar energy harvesting, photocatalysis, electrocatalysis, hydrolysis, hydrogen storage, hydrogen production, CO2 conversion, corrosion resistance and biocompatibility. It is shown that achieving such properties is not limited to pure metals and conventional metallic alloys, and a wide range of materials are currently processed by SPD, including high-entropy alloys, glasses, semiconductors, ceramics and polymers. It is particularly emphasized that SPD has moved from a simple metal processing tool to a powerful means for the discovery and synthesis of new superfunctional metallic and nonmetallic materials. The article ends by declaring that the borders of SPD have been extended from materials science and it has become an interdisciplinary tool to address scientific questions such as the mechanisms of geological and astronomical phenomena and the origin of life

Seed production and germination in long\u27s bittercress (Cardamine longii) of Massachusetts

Cardamine longii (Brassicaceae), long\u27s bittercress, is an imperiled plant confined largely to freshwater tidal marshes of the eastern U.S. To better understand possible causes of rarity in the species, its reproductive output was studied in two southeastern Massachusetts populations. Plants were found to produce about 10 fruits per individual (five per inflorescence), with the majority of a population fruiting in July. About 78% of the flowers produced in the two populations set fruit, with each fruit yielding nine seeds on average. Seeds were viable as indicated by their ability to germinate in the laboratory. Without any prior cold treatment, germination levels reached 87% over a four-week period yet were markedly reduced when seeds were allowed to dry prior to incubation. We suggest that fruit and seed production and viability are not important factors in limiting C. longii\u27s population sizes and growth