1,174 research outputs found
On the regulation and effects of chronic inflammation in inflammatory bowel disease
No full textInflammatory bowel disease is thought to result from the inappropriate and ongoing activation of the mucosal immune system driven by the presence of normal luminal flora. In this process monocytes/macrophages contribute to and maintain chronic inflammation by being both regulatory and effector cells. This study aimed at exploring the effects and regulation of chronic inflammation in inflammatory bowel disease (IBD) at three different levels, (i) patient outcome by the analysis of the effects of inflammation on trombogenesis and dysplasia, (ii) cellular functions, by examination of inflammatory molecules in leukocytes derived from patients with IBD, and (iii) potential future treatment, by evaluation of the anti-inflammatory properties of statins on monocytes. By using age as a marker of thrombogenesis we show that patients with IBD had thrombosis earlier in life than patients not suffering from IBD, indicating an increased thrombotic risk. Increased disease activity probably contributes to the risk and a suggested mechanism in mediating thrombosis is involvement of pro-inflammatory cytokines, shifting the intravascular environment from haemodynamic stable to a procoagulative state. We observed no association between IBD and the most frequent hereditary prothrombotic conditions. In patients with ulcerative colitis, we detected an increased number of activated colonic eosinophils containing transforming growth factor-alpha (TGF-alpha). Eosinophils containing TGF-alpha may play both physiological and pathophysiological roles. Actions intended to enhance mucosal protection and facilitate repair during active inflammation could instead, during subclinical, chronic inflammation, lead to a transformation into dysplasia and the development of malignancy in long-standing ulcerative colitis. By assessment of circulating monocytes from patients with Crohn’s disease, we show that these monocytes are sensitized to chemotaxis prior to mucosal invasion. Furthermore, we show that it is possible to regulate the inflammatory response ex vivo in monocytes by statins. We demonstrate that pravastatin and atorvastatin not only lower cholesterol synthesis and lipid accumulation in human monocyte cultures, but also potently inhibit the generation of pro-inflammatory mediators and oxygen consumption in activated monocytes. Moreover, we found that atorvastatin transcriptionally activates peroxisome proliferator-activated receptor gamma in human monocytes, suggesting that statins may control inflammatory responses by the regulation of intracellular lipid homeostasis
On the regulation and effects of chronic inflammation in inflammatory bowel disease
No full textPopular Abstract in Swedish Den kroniska inflammation som ses hos personer med inflammatorisk tarmsjukdom är troligen en immunologisk reaktion riktad mot normala tarmbakterier. I denna process har monocyter/makrofager (särskild celltyp av vita blodkroppar) en central betydelse. Det är huvudsakligen makrofager i tarmslemhinnan som styr det immunsvar som utvecklas då tarmfloran kommer i kontakt med immunsystemet. Dessutom bidrar nyrekryterade monocyter från blodbanan till den kroniska inflammation som ses vid ulcerös kolit och Crohns sjukdom genom utsöndring av inflammatoriska molekyler. Dessa molekyler kan aktivera koagulationssystemet med ökad blodproppsbenägenhet som följd. Aktiverade inflammatoriska celler producerar även tillväxtfaktorer vilka kan bidraga till den ökade cancerrisk som ses vid inflammatorisk tarmsjukdom. Målet med denna avhandling var att studera reglering och konsekvenser av kronisk inflammation vid inflammatorisk tarmsjukdom på tre olika nivåer; effekter av kronisk inflammation avseende: (i) blodproppsbildning och cancerutveckling (ii) inflammationsmekanismer (iii) effekten på cellnivå av inflammationsdämpande läkemedel (statiner). Vi fann att venös blodpropp uppträder tidigare i livet hos patienter med inflammatorisk tarmsjukdom. Ökad sjukdomsaktivitet bidrar troligen till den ökade risken och en möjlig förklaring kan vara ökad halt av inflammationsbefrämjande cytokiner (små molekyler som utsöndras från celler) vilka ökar blodets benägenhet att levra sig i kärlen. Hittills kända medfödda koagulations sjukdomar är inte vanligare bland patienter med inflammatorisk tarmsjukdom. Vi fann att patienter med ulcerös kolit har ökat antal aktiverade eosinofiler (särskild celltyp av vita blodkroppar) i kolonslemhinnan innehållande tillväxtfaktorn TGF-alfa. TGF-alfa har sannolikt betydelse både för läkning av slemhinnan vid aktiv inflammation, men kan troligen också bidra till cellförändring och utveckling av cancer vid långvarig kronisk inflammation. I blod taget från patienter med aktiv Crohns sjukdom fann vi ökad halt av de inflammatoriska cytokinerna TNF-alfa och MCP-1, samt ökad halt av fettpartikeln oxiderat LDL. Monocyter tagna från patienter med Crohns sjukdom visade sig ha ökad utsöndring av MCP-1 och minskad utsöndring av cytokinet MIF. Då vi undersökte hur produktionen av inflammatoriska cytokiner regleras i blodburna monocyter (via aktivering av transkriptionsfaktorn NF-kappaB) såg vi ingen skillnad jämfört mot friska kontroller. Dessa resultat tyder på att perifert cirkulerande monocyter vid aktiv Crohns sjukdom har en benägenhet att ansamlas i inflammatoriska härdar, där den inflammatoriska aktiveringen sker. Statiner är hämmare av enzymet HMG-CoA reduktas och är potenta läkemedel som påverkar fettomsättningen och sannolikt även har effekter på immunsystemet. HMG-CoA reduktas hämmar bildandet av mevalonsyra, som förutom att bilda kolesterol, även är förstadium till ett flertal andra substanser som har betydelse för normal cellaktivitet. Då vi behandlade monocyter tagna från patienter med aktiv Crohns sjukdom i cellodlingsförsök med statinen atorvastatin minskade utsöndringen av MCP-1 och TNF-alfa. Vidare fann vi att då fettomsättning i monocyter nedreglerades med statinerna pravastatin eller atorvastatin minskade utsöndringen av inflammatoriska molekyler, så som MCP-1, TNF-alfa, MMP-9. Dessutom minskade syrgaskonsumtion i dessa celler tydande på minskat bildande av skadliga fria syrgasradikaler. Slutligen fann vi att atorvastatin genom att reglera intracellulär fettomsättning aktiverar transkriptionsfaktorn PPAR-gamma i monocyter. Påverkan på den intracellulära fettomsättningen är en möjlig förklaringsmekanism till statiners inflammationsdämpande egenskaper. Trots att man måste vara försiktig att överföra våra resultat till den kliniska verkligheten, tyder de på en möjlig terapeutisk inflammationsdämpande effekt av statiner. De indikerar att statiner kan ha verkan vid ett flertal inflammatoriska tillstånd där aktiverade monocyter har en central betydelse, som t. ex. vid inflammatoriska tarmsjukdomar. Så länge vi saknar botande behandling är studier av specifika ämnen som hämmar bildningen och utsöndringen av cytokiner viktiga för att förbättra behandlingen av patienter med Crohns sjukdom och ulcerös kolit. Både steroider, azatioprin och metotrexat som idag är den etablerade behandlingen vid Crohns sjukdom har bred immundämpande verkan med ett flertal oönskade effekter. Av stort kliniskt värde är att få fram potenta inflammationsdämpande läkemedel som saknar sidoeffekter vid den kroniska behandlingen. Vår förhoppning är att en ökad kunskap om de molekylära mekanismerna kan ge ett nytt perspektiv på inflammationens uppkomst och bidra till utveckling av individuell och riktad terapi med ett minimum av biverkningar.Inflammatory bowel disease is thought to result from the inappropriate and ongoing activation of the mucosal immune system driven by the presence of normal luminal flora. In this process monocytes/macrophages contribute to and maintain chronic inflammation by being both regulatory and effector cells. This study aimed at exploring the effects and regulation of chronic inflammation in inflammatory bowel disease (IBD) at three different levels, (i) patient outcome by the analysis of the effects of inflammation on trombogenesis and dysplasia, (ii) cellular functions, by examination of inflammatory molecules in leukocytes derived from patients with IBD, and (iii) potential future treatment, by evaluation of the anti-inflammatory properties of statins on monocytes. By using age as a marker of thrombogenesis we show that patients with IBD had thrombosis earlier in life than patients not suffering from IBD, indicating an increased thrombotic risk. Increased disease activity probably contributes to the risk and a suggested mechanism in mediating thrombosis is involvement of pro-inflammatory cytokines, shifting the intravascular environment from haemodynamic stable to a procoagulative state. We observed no association between IBD and the most frequent hereditary prothrombotic conditions. In patients with ulcerative colitis, we detected an increased number of activated colonic eosinophils containing transforming growth factor-alpha (TGF-alpha). Eosinophils containing TGF-alpha may play both physiological and pathophysiological roles. Actions intended to enhance mucosal protection and facilitate repair during active inflammation could instead, during subclinical, chronic inflammation, lead to a transformation into dysplasia and the development of malignancy in long-standing ulcerative colitis. By assessment of circulating monocytes from patients with Crohn’s disease, we show that these monocytes are sensitized to chemotaxis prior to mucosal invasion. Furthermore, we show that it is possible to regulate the inflammatory response ex vivo in monocytes by statins. We demonstrate that pravastatin and atorvastatin not only lower cholesterol synthesis and lipid accumulation in human monocyte cultures, but also potently inhibit the generation of pro-inflammatory mediators and oxygen consumption in activated monocytes. Moreover, we found that atorvastatin transcriptionally activates peroxisome proliferator-activated receptor gamma in human monocytes, suggesting that statins may control inflammatory responses by the regulation of intracellular lipid homeostasis
Generating Secure and Gentle Grip on Soft Substrates
No full textGeneration of grip on soft tissue in the surgical field is most commonly done with forceps that generate friction grip, that is, the translation of normal (pinch) forces into shear forces. Errors made with these surgical grippers are often force-related: applying too low pinch forces results in slipping of the tissue out of the gripper, and too high pinch forces may lead to tissue damage. One possible solution for generating tissue grip that is secure yet gentle is the adhesive grip. In this case, contact between tissue and gripper is maintained by attracting gripper-tissue interactions, and gripping strength does not depend on the applied pinch forces. Inspiration for the design of such a gripper can be derived from the tree frog, an animal that uses adhesive grip to grip on a range of substrates in its habitat. The main aim of this thesis is to translate grip-generating principles used by tree frogs into designs of artificial adhesives that can generate firm yet gentle grip on soft substrates. The designs of the artificial adhesives in this thesis are inspired by two important characteristics of the tree frog’s attachment apparatus: the hierarchical surface pattern on the tree-frog toe-pad and reinforcing fibrillar structures located inside the pad. Specifically, the aim of this thesis is to mimic function rather than form, and focuses on mechanisms underlying the tree-frog attachment apparatus to satisfy two main requirements for strong grip: (1) contact formation and (2) preservation of the formed contact.Medical Instruments & Bio-Inspired Technolog
Improving the Meta-Grip: Redesigning for unsupervised use
No full textThe Meta-Grip is a tool for climbers to measure hand and finger strength. A climber uses the Meta-Grip by hanging on either a sloper or crimp. The Meta-Grip measures the force through a load cell and transfers the data to a computer where the data can be viewed and analyzed. The current Meta-Grip is built for research. Because of this, the current Meta-Grip cannot be used unsupervised, the embodiment needs improvements and the price of 2520 euros for the costs is too high for the intended market. The current Meta- Grip can only do measurements, an addition to its functionalities would be the ability to also train on the Meta-Grip. This let to the following goal for redesigning the Meta-Grip: “Redesign the Meta-Grip in such a way that it becomes an affordable and recognizable tool that measures finger and hand strength and provides immediate and understandable feedback to the climber, that can be used unsupervised by climbers and is an addition to the currently available training tools.“. To redesign the Meta-Grip, the design process is structured in four phases: analysis, ideation, concept design and final validation. The following methods were used: literature research, online market research, online surveys, sketching, prototyping, user testing, hosting creative sessions and expert interviews. The redesigned Meta-Grip is a product-service system. The Meta-Grip, made for fanatic climbers, has a range in holds that differ in type and difficulty. Holds are available in alder wood for skin friendliness or polyurethane coated with quartz sand for high friction, to the user’s discretion. With two load cells and a Bluetooth module , a connection can be established to the mobile phone application of the Meta-Grip. This application, the service, is used to execute measurements, follow exercises and training plans and determine climbing goals. A button on the Meta-Grip allows users to turn the Meta-Grip on and connect the Meta-Grip via Bluetooth to the application on their phone. To instruct the user on how to use the Meta-Grip before the Bluetooth connection is available, instructions are placed on the left side of the Meta-Grip. The system is powered by a 9V battery. The installation of the Meta-Grip is made such that it will fit any normal climbing gym with two M10 bolts. This research has shown the potential of a redesigned Meta-Grip. Through the application, the Meta-Grip can be used unsupervised and changing the design has made the Meta-Grip more versatile and recognizable for climbers. The cost price is estimate at 120 euros, making it a large price reduction. The next step is to further elaborate the concept and all parts of the product-service system to make it ready for launching the Meta-Grip to the market. <br/
Gelders Rivierdijkenplan: Hoofdlijnennotitie
No full textIn januari 1993 besloten Gedeputeerde Staten dat er een beleidsplan voor de rivierdijken moest komen: het Gelders Rivierdijkenplan (GRIP). Het voorliggende document, de hoofdlijnennotitie GRIP, is een eerste stap op weg naar dat plan. Zij is bedoeld om in een vroeg stadium de hoofdpunten van het toekomstig beleid te bespreken met betrokkenen en belanghebbenden. Het resultaat van die discussie, de vastgestelde hoofdlijnennotitie, dient vervolgens als vertrekpunt voor de opstelling van het rivierdijkenplan. De hoofdlijnennotitie bevat vijf hoofdstukken. Het eerste hoofdstuk omschrijft doel en opzet van de notitie en de procedure die moet leiden tot het Gelders Rivierdijkenplan. Het tweede hoofdstuk schetst achtergronden en (voor)geschiedenis van de dijkverbetering. Het derde hoofdstuk bevat een probleemanalyse met daarin opmerkingen over de verschillende dijkfuncties en -waarden, de afstemming van dijkverbeteringsplannen op andere plannen, de besluitvormingsprocedure bij dijkverbetering, en het dijkbeheer en - onderhoud. Hoofdstuk vier behandelt status en doelstellingen van het plan. De hoofdlijnen van het toekomstig waterkeringsbeleid worden uiteengezet in hoofdstuk vijf. Ten slotte zijn vijf bijlagen en een overzichtskaart van de stand van de rivierdijkverbeteringswerken toegevoegd. In de notitie zijn de dijken langs de randmeren buiten beschouwing gelaten omdat deze buiten het rivierengebied vallen
Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis
No full text<p><b>Background:</b> Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.</p>
<p><b>Methods and Findings:</b> Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.</p>
<p><b>Conclusions:</b> Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.</p>
The impact of grip strength recovery on grip force accuracy in chronic stroke
No full text2020 Summer.Includes bibliographical references.Decreased grip force accuracy and grip strength are two well-documented grip impairments that impede upper extremity function after stroke. Grip force accuracy is essential to perform precise motor actions in everyday life. Further, grip strength represents the ability to produce maximal grip force in a short duration of time and constitutes as a hallmark of upper extremity recovery in chronic stroke. Adequate grip strength and grip force accuracy are both important for regaining motor function after stroke. Despite this, no study has investigated whether the recovery of grip strength influences improvements in force accuracy. Purpose: Therefore, the purpose of the study was to investigate the impact of grip strength recovery on grip force accuracy in chronic stroke patients. Methods: We recruited two distinct stroke groups with low (less than 60%) and high (60% or more) grip strength recovery. The grip strength recovery was computed as the percent of paretic grip strength relative to nonparetic grip. A total of thirty-three participants, eleven in low strength recovery group (age 64 ±14.8 years; 6 females and 5 males), eleven in high strength recovery group (age 65.9 ± 9.9 years, 7 females and 4 males) and eleven age matched controls (age 69.6 ± 9.8 years, 4 females and 7 males) participated in the study. To examine the impact of grip strength recovery on grip force accuracy, all participants performed two tasks; 1) maximum voluntary contraction (MVC) and 2) dynamic force tracking task, using each hand. We quantified grip strength as the maximum force produced in the MVC task. Further, we assessed force accuracy by measuring root mean square error relative to the absolute target force. Result: The grip strength recovery in low strength recovery stroke group (27.1 ± 17.7)% was lower compared to the high strength recovery group (92.4 ± 24.9)% and controls (94.9 ±18.9)%. A significant main effect of Group [F (2, 30) = 34.53, p 0.05). A significant interaction between Group×Hand, [F (2, 30) = 7.21, p < 0.05, partial ղ2 = 0.33] demonstrated that the relative RMSE of paretic hand was significantly increased in low strength recovery stroke group compared to the high strength recovery (p < 0.05). Importantly, the relative RMSE of paretic hand in high strength recovery group was significantly greater than the control group's non-dominant hand (p < 0.05). Overall, a significant negative relationship between grip strength recovery and paretic relative RMSE (r = -0.598, p = 0.003) was found when investigating correlations in both groups together. In low strength recovery group, we found a negative association between the grip strength recovery and paretic relative RMSE, (r = -0.552, p = 0.078). However, in high strength recovery group, we found no association between the grip strength recovery (r = 0.308, p = 0.357). Conclusion: Grip strength recovery and force accuracy follow differential patterns of improvement for low and high strength recovery stroke groups. In chronic stroke survivors with strength recovery less than 60%, grip strength recovery is associated with grip force accuracy. However, in chronic stroke survivors with strength recovery more than 60%, the grip force accuracy may still be impaired despite near-normal grip strength recovery. After substantial gain in grip strength recovery, interventions that enhance grip force accuracy may be needed to improve the upper-extremity function. Our study results suggest, after improvement in strength, patients need additional interventions such as exergaming that will train force accuracy, to help them use this regained strength more meaningfully
Supplementary_Tables – Supplemental material for Switching from originator infliximab to the biosimilar CT-P13 in 313 patients with inflammatory bowel disease
No full textSupplemental material, Supplementary_Tables for Switching from originator infliximab to the biosimilar CT-P13 in 313 patients with inflammatory bowel disease by Viktoria Bergqvist, Mohammad Kadivar, Daniel Molin, Leif Angelison, Per Hammarlund, Marie Olin, Jörgen Torp, Olof Grip, Stefan Nilson, Erik Hertervig, Jan Lillienau and Jan Marsal in Therapeutic Advances in Gastroenterology</p
Explaining Myanmar's Regime Transition: The Periphery is Central
No full textIn 2010, Myanmar (Burma) held its first elections after 22 years of direct military rule. Few compelling explanations for this regime transition have emerged. This article critiques popular accounts and potential explanations generated by theories of authoritarian ‘regime breakdown’ and ‘regime maintenance’. It returns instead to the classical literature on military intervention and withdrawal. Military regimes, when not terminated by internal factionalism or external unrest, typically liberalise once they feel they have sufficiently addressed the crises that prompted their seizure of power. This was the case in Myanmar. The military intervened for fear that political unrest and ethnic-minority separatist insurgencies would destroy Myanmar’s always-fragile territorial integrity and sovereignty. Far from suddenly liberalising in 2010, the regime sought to create a ‘disciplined democracy’ to safeguard its preferred social and political order twice before, but was thwarted by societal opposition. Its success in 2010 stemmed from a strategy of coercive state-building and economic incorporation via ‘ceasefire capitalism’, which weakened and co-opted much of the opposition. Having altered the balance of forces in its favour, the regime felt sufficiently confident to impose its preferred settlement. However, the transition neither reflected total ‘victory’ for the military nor secured a genuine or lasting peace
The SF-36: a simple, effective measure of mobility disability for epidemiological studies
No full textBackgroundMobility disability is a major problem in older people. Numerous scales exist for the measurement of disability but often these do not permit comparisons between study groups. The physical functioning (PF) domain of the established and widely used Short Form-36 (SF-36) questionnaire asks about limitations on ten mobility activities.ObjectivesTo describe prevalence of mobility disability in an elderly population, investigate the validity of the SF-36 PF score as a measure of mobility disability, and to establish age and sex specific norms for the PF score.MethodsWe explored relationships between the SF-36 PF score and objectively measured physical performance variables among 349 men and 280 women, 59-72 years of age, who participated in the Hertfordshire Cohort Study (HCS). Normative data were derived from the Health Survey for England (HSE) 1996.Results32% of men and 46% of women had at least some limitation in PF scale items. Poor SF-36 PF scores (lowest fifth of the gender-specific distribution) were related to: lower grip strength; longer timed-up-and-go, 3m walk, and chair rises test times in men and women; and lower quadriceps peak torque in women but not men. HSE normative data showed that median PF scores declined with increasing age in men and women.ConclusionOur results are consistent with the SF-36 PF score being a valid measure of mobility disability in epidemiological studies. This approach might be a first step towards enabling simple comparisons of prevalence of mobility disability between different studies of older people. The SF-36 PF score could usefully complement existing detailed schemes for classification of disability and it now requires validation against them
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