Chemical characterization and reactivity of iron chelator-treated amphibole asbestos.

Iron in amphibole asbestos is implicated in the pathogenicity of inhaled fibers. Evidence includes the observation that iron chelators can suppress fiber-induced tissue damage. This is believed to occur via the diminished production of fiber-associated reactive oxygen species. The purpose of this study was to explore possible mechanisms for the reduction of fiber toxicity by iron chelator treatments. We studied changes in the amount and the oxidation states of bulk and surface iron in crocidolite and amosite asbestos that were treated with iron-chelating desferrioxamine, ferrozine, sodium ascorbate, and phosphate buffer solutions. The results have been compared with the ability of the fibers to produce free radicals and decompose hydrogen peroxide in a cell-free system in vitro. We found that chelators can affect the amount of iron at the surface of the asbestos fibers and its valence, and that they can modify the chemical reactivity of these surfaces. However, we found no obvious or direct correlations between fiber reactivity and the amount of iron removed, the amount of iron at the fiber surface, or the oxidation state of surface iron. Our results suggest that surface Fe3+ ions may play a role in fiber-related carboxylate radical formation, and that desferrioxamine and phosphate groups detected at treated fiber surfaces may play a role in diminishing and enhancing, respectively, fiber redox activity. It is proposed that iron mobility in the silicate structure may play a larger role in the chemical reactivity of asbestos than previously assumed

Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage

Objectives: Patients with severe subarachnoid haemorrhage (SAH) often suffer from complications with delayed cerebral ischaemia (DCI) due to vasospasm that is difficult to identify by clinical examination. The purpose of this study was to monitor seizures and to measure cerebrospinal fluid (CSF) concentrations of neurofilament light (NFL) and tau, and to see whether they could be used for predicting preclinical DCI. Methods: We prospectively studied 19 patients with aneurysmal SAH who underwent treatment with endovascular coiling. The patients were monitored with continuous EEG (cEEG) and received external ventricular drainage (EVD). CSF samples of neurofilament light (NLF) and total tau (T‐tau) protein were collected at day 4 and day 10. Cox regression analysis was applied to evaluate whether seizures and protein biomarkers were associated with DCI and poor outcome. Results: Seven patients developed DCI (37%), and 4 patients (21%) died within the first 2 months. Six patients (32%) had clinical seizures, and electrographic seizures were noted in one additional patient (4.5%). Increased tau ratio (proportion tau10/tau4) was significantly associated with DCI and hazard ratio [HR=1.33, 95% confidence interval (CI) 1.055‐1.680. P = .016]. Conclusion: Acute symptomatic seizures are common in SAH, but their presence is not predictive of DCI. High values of the tau ratio in the CSF may be associated with development of DCI

Nuclear expression of PG-21, SRC-1, and pCREB in regions of the lumbosacral spinal cord involved in pelvic innervation in young adult and aged rats

In rats, ageing results in dysfunctional patterns of micturition and diminished sexual reflexes that may reflect degenerative changes within spinal circuitry. In both sexes the dorsal lateral nucleus and the spinal nucleus of the bulbospongiosus, which lie in the L5-S1 spinal segments, contain motor neurons that innervate perineal muscles, and the external anal and urethral sphincters. Neurons in the sacral parasympathetic nucleus of these segments provide autonomic control of the bladder, cervix and penis and other lower urinary tract structures. Interneurons in the dorsal gray commissure and dorsal horn have also been implicated in lower urinary tract function. This study investigates the cellular localisation of PG-21 androgen receptors, steroid receptor co-activator one (SRC-1) and the phosphorylated form of c-AMP response element binding protein (pCREB) within these spinal nuclei. These are components of signalling pathways that mediate cellular responses to steroid hormones and neurotrophins. Nuclear expression of PG-21 androgen receptors, SRC-1 and pCREB in young and aged rats was quantified using immunohistochemistry. There was a reduction in the number of spinal neurons expressing these molecules in the aged males while in aged females, SRC-1 and pCREB expression was largely unchanged. This suggests that the observed age-related changes may be linked to declining testosterone levels. Acute testosterone therapy restored expression of PG-21 androgen receptor in aged and orchidectomised male rats, however levels of re-expression varied within different nuclei suggesting a more prolonged period of hormone replacement may be required for full restoratio

The perception of sound in a city environment : Could it affect the understanding of instructions?

Detta arbete handlar om ifall perceptionen av ljud i stadsmiljöer kan påverka uppfattningen av instruktioner och minne. I den litterära bakgrunden presenteras vad ett ljud är, vad skillnaden är mellan Hi-fi och Lo-fi ljudlandskap samt en generell överblick om vad noise är och hur människans minne fungerar. Frågeställningen som undersöktes var om perceptionen av olika ljud i en stadsmiljö kan påverka uppfattningen av instruktioner. För att kunna svara på frågeställningen skapades tre olika ljudsekvenser, där två av sekvenserna innehåller ljuden som kan påverka instruktionerna och en är kontrollsekvensen för att se om instruktionerna är lätta att följa. Den urvalsgrupp som deltog fick lyssna och utföra olika instruktioner samt svara på kvalitativa frågor. Detta användes sedan för nå en slutsats. Vid ett framtida arbete och fördjupning av undersökningen kan det leda till att information och ljud i spel inte går förlorade i mängden av andra ljud, perspektivet av dem finns kvar

Estrogen Receptor Expression in Relation to Pain Modulation and Transmission: Experimental Studies in Rats

Estrogens have a remarkably wide range of actions in the mammalian brain. They not only play a pivotal role in reproductive behavior and sexual differentiation, but also contribute to e.g. thermoregulation, feeding, memory, neuronal survival and the perception of somatosensory stimuli. A multitude of studies on both animals and human subjects has demonstrated potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and therefore need to be evaluated specifically in relation to the localization and intrinsic characteristics of the neurons engaged. The overall aim of this thesis is to gain specific knowledge of the possible cellular mechanisms by which estrogens may influence the transmission of nociceptive stimuli at the level of the spinal cord. The estrogen receptors, by which estrogens regulate non-genomic as well as genomic mechanisms, are crucial to estrogen signaling in general and essential to the estrogen-induced effects in the brain. In Paper I, we use immunohistochemistry to label neurons containing estrogen receptor-! (ERα) in the medullary and spinal dorsal horn of female rats. Large numbers of ER!-expressing neurons were found in lamina I and lamina II, i.e. in the areas involved in the processing of primary afferent nociceptive information. This distribution in part overlaps that of enkephalin, a potent pain-inhibiting endogenous opioid. The effects of gonadal hormones on pain modulation may, to a great extent, be blocked by the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in the prosecution of hormonal pain regulation. By combining immunohistochemical labeling of ERα with in situ hybridization of preproenkephalin mRNA (Paper II), we demonstrate that the majority of enkephalinergic neurons in the superficial laminae of the spinal and medullary dorsal horn express ER!. This co-localization and the fact that the preproenkephalin gene contains a sequence that binds ERs, suggest that estrogens may potentially regulate enkephalin expression in these cells. This is further supported by the findings in Paper III in which we show that a single subcutaneous injection of estradiol induces a significant increase (on average 68%) in preproenkephalin mRNA content in the spinal cord after 4 hours. The expression of the enkephalin gene in the spinal cord is thus sensitive to fluctuating estradiol levels. In Paper IV, a noxious injection of formalin is used to induce activation of a neuronal population involved in nociceptive transmission from the face. By using a dual-labeling immunohistochemistry protocol, we were able to identify ER!-expressing cells within this neuronal population suggesting that nociceptive-responsive neurons in the medullary dorsal horn express ER!. In all, our findings provide morphological as well as biochemical evidence in support for an estrogen-dependent modulation of nociceptive processing at the level of the dorsal horn

Comparison between adaptive and fixed stimulus paired-pulsetranscranial magnetic stimulation (ppTMS) in normal subjects

Objectives Paired-pulse TMS (ppTMS) examines cortical excitability but may require lengthy test procedures and fine tuning of stimulus parameters due to the inherent variability of the elicited motor evoked potentials (MEPs) and their tendency to exhibit a ‘ceiling/floor effects’ in inhibition trials. Aiming to overcome some of these limitations, we implemented an ‘adaptive’ ppTMS protocol and compared the obtained excitability indices with those from ‘conventional’ fixed-stimulus ppTMS. Methods Short- and long interval intracortical inhibition (SICI and LICI) as well as intracortical facilitation (ICF) were examined in 20 healthy subjects by adaptive ppTMS and fixed-stimulus ppTMS. The test stimulus intensity was either adapted to produce 500 μV MEPs (by a maximum likelihood strategy in combination with parameter estimation by sequential testing) or fixed to 120% of resting motor threshold (rMT). The conditioning stimulus was 80% rMT for SICI and ICF and 120% MT for LICI in both tests. Results There were significant (p < 0.05) intraindividual correlations between the two methods for all excitability measures. There was a clustering of SICI and LICI indices near maximal inhibition (‘ceiling effect’) in fixed-stimulus ppTMS which was not observed for adaptive SICI and LICI. Conclusions Adaptive ppTMS excitability data correlates to those acquired from fixed-stimulus ppTMS. Significance Adaptive ppTMS is easy to implement and may serve as a more sensitive method to detect changes in cortical inhibition than fixed stimulus ppTMS. Whether equally confident data are produced by less stimuli with our adaptive approach (as already confirmed for motor threshold estimation) remains to be explored

Molntjänster i kommuner

Studien syftar till att utreda frågeställningen “Vilka hinder har Stockholms läns kommuner vid implementering av externa molntjänster?”. Målet är att skapa en grund för att kunna adressera dessa problem och skapa förbättrade förutsättningar. Problemet bottnar i en eftersläpande digital utveckling inom Sveriges offentliga sektor och kommuner, vilken inte är i linje med Sveriges digitaliseringsvision. Forskningsfrågan undersöks genom en kvalitativ fallstudie där data genereras från intervjuer med sju av kommunerna i Stockholms län. Genom en tematisk analys har fem olika teman identifierats. Resultaten visade att kommunerna upplever hindrande faktorer såsom begränsade lagar, ekonomiska aspekter, brist på kompetens, motivation och ledarskap, samt hur det kommunala självstyret hindrar samarbete och gemensamma lösningar kring molntjänster.The study aims to investigate the question “What obstacles do the municipalities in Stockholm County face when implementing external cloud services?”. The problem is based on insufficient digital development in Sweden's public sector and municipalities that is not aligned with Sweden's digitalization vision. The research question is explored through a qualitative case study, with data generated from interviews conducted with seven municipalities in Stockholm County, where five different themes have been identified through thematic analysis. The results showed that municipalities face hindering factors such as conflicting laws, economic aspects, lack of competence, motivation and leadership, as well as how municipal self-governance hinders collaboration and shared solutions regarding cloud services

Property development of culture protected building

I Gävle kommuns översiktsplan, Gävle stad 2025, finns en vision om att öka invånarantalet. För att detta ska vara möjligt krävs det ett stort tillskott av nya bostäder. Ett alternativ till att skapa nya bostäder är genom en funktionsändring av befintliga byggnader, vilket är ett alternativ som Gävle kommun ser positivt på. En fastighet som står inför en funktionsändring i syfte att exploatera Gävle är Norr 9:7. Fastigheten har ny ägare vars vision är att bygga om fastigheten till ett modernt och attraktivt bostadsområde. Fastigheten ligger centralt och används idag av Gefle Dagblad som kontorslokaler och tidningstryckeri. Den här rapporten redovisar fastighetsutvecklingen av den kulturmärkta byggnaden som finns inom fastigheten. Utifrån byggnadens förutsättningar, efterfrågan på bostadsmarknaden och de önskemål som ställts av den nya fastighetsägaren och kommunen har förslagshandlingar tagits fram. Förslagshandlingarna redovisar planlösningar för verksamhetslokaler och bostäder. Bostäderna är utformade att uppfylla tillgänglighetskraven som BBR ställer vid ombyggnad och funktionsändring. Rapporten redovisar också en ekonomisk analys som ger ett förslag på en rimlig hyresnivå för bostäderna. Då många avgränsnin