Results Visualization in the XBrain XML Interface to a Relational Database

The University of Washington's XBrain application is used to dynamically export relational data over the web in XML format, as a prelude to data exchange. We describe additional tools to aid the human user in visualizing the dynamically generated XML results returned by the web application

Implications of a genetically determined nitric oxide deficit for endothelial cell-leukocyte interaction and cardiovascular disease

Blood flow-generated shear stress (FSS) is the major determinant of endothelial nitric oxide synthase (NOS-3) expression. In humans, a promoter variant of the NOS3 gene, the C-variant of the T-786C single nucleotide polymorphism, renders the gene insensitive to shear stress, resulting in a reduced endothelial cell (EC) capacity to generate nitric oxide (NO). Endothelial dysfunction, commonly associated with decreased NO bioavailability, may facilitate vascular inflammation. Consequently, individuals homozygous for the C-variant have an increased risk of developing cardiovascular (e.g., coronary heart disease (CHD)) and rheumatic diseases (e.g., rheumatoid arthritis (RA)). However, there are at least two mechanisms by which insuffcient NO production can be counterbalanced in CC-genotype endothelial cells (ECs), one of which involves a multicomponent pathway leading to the increased release of the anti-inflammatory prostanoid 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). Exposure of human ECs to physiological levels of FSS effectively reduced monocyte migration, not only through monolayers of TT- but most notably also of NO-deficient CC-genotype ECs. FSS up-regulated the expression of COX-2 and L-PGDS, the rate-limiting enzymes for 15d-PGJ2 synthesis, solely in CC-genotype ECs, and only these cells revealed an increased release of 15d-PGJ2 in response to FSS. Exogenously added 15d-PGJ2 significantly reduced the transmigration of monocytes through EC monolayers. In addition, pre-treatment with 15d-PGJ2 or exposure to FSS-pretreated CC-genotype ECs exerted a pronounced anti-inflammatory effect on the (transmigrated) monocytes, as demonstrated e.g. by an inhibitory effect on interleukin-1 beta (IL-1 beta) expression, a marker for monocyte pro-inflammatory activation. This inhibition occurs at the transcriptional level, as 15d-PGJ2 repressed tumor necrosis factor-alpha-induced IL-1 beta promoter activity in transiently transfected HEK293 cells. The anti-inflammatory activity of 15d-PGJ2 in monocytes involves the Nrf2-antioxidant response element (ARE) pathway. Similar to 15d-PGJ2, constitutive activation of Nrf2 reduced the expression of IL-1 beta. Bioinformatic analysis revealed three putative Nrf2-responsive elements (i.e., AREs) in the human IL-1B promoter, suggesting that Nrf2 may act through an as yet unknown mechanism to repress transcription of the IL-1B gene. Chromatin immunoprecipitation showed a 15d-PGJ2-induced binding of Nrf2 to the promoter of the IL-1B gene. Deletion of two of the identified ARE motifs attenuated the inhibitory potency of 15d-PGJ2 toward IL-1B promoter activity, thereby corroborating Nrf2 as a downstream effector of this prostanoid’s transcriptional effects. Given its powerful immunomodulatory properties, 15d-PGJ2 has been proposed to have anti-atherogenic potential. To evaluate its prognostic relevance, the relationship between plasma 15d-PGJ2 levels and disease severity and outcome in patients suffering from CHD, RA or both was investigated. The levels of 15d-PGJ2 were found to be significantly increased in the CHD group compared to age-matched controls, suggesting that 15d-PGJ2 may constitute a general defense mechanism to counteract the ongoing chronic inflammatory process in affected individuals. Moreover, pre-treatment with 15d-PGJ2 potently inhibited the in vitro transendothelial migration of interferon-gamma-producing human T helper type 1 cells, major players in atherosclerosis as well as various other chronic inflammatory disorders. Despite an inadequate capacity to form NO, CC-genotype ECs maintain a robust anti-inflammatory phenotype by enhancing the shear stress-dependent synthesis of 15d-PGJ2. Its anti-inflammatory activity on human monocytes may ascribe a novel role to Nrf2 as a direct repressor of pro-inflammatory gene expression

The role of inherited genetic variants in colorectal polyposis syndromes

Colorectal carcinoma (CRC) is the third most common cancer in men and the second most common cancer in women across the world. Most CRCs occur sporadically, but in 15–35% of cases, hereditary factors are important. Some patients with an inherited predisposition to CRC will be diagnosed with a “genetic polyposis syndrome” such as familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), polymerase proofreading associated polyposis (PPAP), NTHL1-associated polyposis, MSH3-associated polyposis or a hamartomatous polyposis syndrome. Individuals with ≥ 10 colorectal polyps have traditionally been referred for genetic diagnostic testing to identify APC and MUTYH mutations which cause FAP and MAP respectively. Mutations are found in most patients with > 100 adenomas but in only a minority of those with 10–100 adenomas. The reasons that diagnostic laboratories are not identifying pathogenic variants include mutations occurring outside of the open reading frames of genes, individuals exhibiting generalized mosaicism and the involvement of additional genes. It is important to identify patients with an inherited polyposis syndrome, and to define the mutations causing their polyposis, so that the individuals and their relatives can be managed appropriately

Rörelserädsla efter främre korsbandsskada: specifika situationer och rörelser : En semikvalitativ explorativ studie

Background: The anterior cruciate ligament (ACL) is the most commonly injured ligament in the human body. The injury often occurs in pivoting sports. A common consequence after ACL injury is kinesiophobia, which can contribute to prolonged rehabilitation and delayed return to sport. Increased understanding of psychological factors such as kinesiophobia could facilitate the rehabilitation process for ACL-patients. Objectives: To explore in which situations and movements ACL-injured individuals experience kinesiophobia, and which are most common. The associations between the number of fearful situations described and the scores in questionnaires regarding kinesiophobia were also evaluated.  Methods: Tampa Scale of Kinesiophobia (TSK), Anterior Cruciate Ligament - Return to Sports after Injury (ACL-RSI) and a custom made Kinesiophobia after ACL injury (KAAI) questionnaire were used. Data were analysed using Spearman’s Rho test. Answers to open-ended questions were categorized and provided qualitative input. Results: Common situations and movements considered fearful by ACL-injured persons were pivoting movements, situations with increased load on the injured knee, and walking on slippery/uneven ground. Significant correlations were seen between TSK and KAAI_TOTAL scores (rho = 0.728; p = 0.007), ACL-RSI and KAAI_TOTAL scores (rho = -0.755; p = 0.003), and ACL-RSI and TSK scores (rho= -0.828; p< 0.001).  Conclusion: This study shows that a higher number of situations and movements considered fearful might associate with higher levels of kinesiophobia in ACL-injured persons. Higher self-efficacy and readiness to return to sport might associate with fewer situations and movements considered fearful, e.g. pivoting movements and walking on slippery ground. Knowledge of this may improve rehabilitation in this field.Bakgrund: Främre korsbandet är det mest frekvent skadade ligamentet i människokroppen. Skadan sker ofta i sporter med pivoterande rörelser. En vanlig psykologisk konsekvens efter främre korsbandsskada är rörelserädsla, vilket kan orsaka förlängd rehabilitering och försenad återgång till idrott. Ökad kunskap om faktorer som rörelserädsla kan underlätta rehabiliteringsprocessen för personer med främre korsbandsskada. Syfte: Att undersöka i vilka situationer och rörelser som personer med främre korsbandsskada upplever rörelserädsla, samt vilka som är vanligast förekommande. Dessutom, att beräkna sambandet mellan poängen från enkäter angående rörelserädsla. Metod: Tampa Scale of Kinesiophobia (TSK), Anterior Cruciate Ligament - Return to Sports after Injury (ACL-RSI), och en specialutformad enkät (KAAI) skickades till deltagarna. Insamlad data analyserades med hjälp av korrelationstestet Spearman’s rho. Svar på öppna frågor kategoriserades och bidrog med ett kvalitativt perspektiv. Resultat: Pivoterande rörelser, situationer med ökad belastning på det skadade knäet och gång på halt/ojämnt underlag var de vanligast förekommande befarade situationer och rörelser hos deltagarna. Signifikanta korrelationer påvisades mellan TSK och KAAI_TOTAL poäng (rho = 0.728; p = 0.007), ACL-RSI och KAAI_TOTAL poäng(rho = -0.755; p = 0.003) samt ACL-RSI och TSK poäng (rho= -0.828; p< 0.001). Slutsats: Denna studie visar att ett större antal befarade situationer och rörelser kan associeras till högre nivåer av rörelserädsla hos personer med främre korsbandsskada. Högre tilltro till sin egen förmåga och större beredskap att återgå till idrott kan associeras med färre befarade situationer och rörelser. Exempel på dessa är pivoterande rörelser och gång på halt underlag. Kunskap om detta kan underlätta rehabilitering inom detta område

Rörelserädsla efter främre korsbandsskada: specifika situationer och rörelser : En semikvalitativ explorativ studie

Background: The anterior cruciate ligament (ACL) is the most commonly injured ligament in the human body. The injury often occurs in pivoting sports. A common consequence after ACL injury is kinesiophobia, which can contribute to prolonged rehabilitation and delayed return to sport. Increased understanding of psychological factors such as kinesiophobia could facilitate the rehabilitation process for ACL-patients. Objectives: To explore in which situations and movements ACL-injured individuals experience kinesiophobia, and which are most common. The associations between the number of fearful situations described and the scores in questionnaires regarding kinesiophobia were also evaluated.  Methods: Tampa Scale of Kinesiophobia (TSK), Anterior Cruciate Ligament - Return to Sports after Injury (ACL-RSI) and a custom made Kinesiophobia after ACL injury (KAAI) questionnaire were used. Data were analysed using Spearman’s Rho test. Answers to open-ended questions were categorized and provided qualitative input. Results: Common situations and movements considered fearful by ACL-injured persons were pivoting movements, situations with increased load on the injured knee, and walking on slippery/uneven ground. Significant correlations were seen between TSK and KAAI_TOTAL scores (rho = 0.728; p = 0.007), ACL-RSI and KAAI_TOTAL scores (rho = -0.755; p = 0.003), and ACL-RSI and TSK scores (rho= -0.828; p< 0.001).  Conclusion: This study shows that a higher number of situations and movements considered fearful might associate with higher levels of kinesiophobia in ACL-injured persons. Higher self-efficacy and readiness to return to sport might associate with fewer situations and movements considered fearful, e.g. pivoting movements and walking on slippery ground. Knowledge of this may improve rehabilitation in this field.Bakgrund: Främre korsbandet är det mest frekvent skadade ligamentet i människokroppen. Skadan sker ofta i sporter med pivoterande rörelser. En vanlig psykologisk konsekvens efter främre korsbandsskada är rörelserädsla, vilket kan orsaka förlängd rehabilitering och försenad återgång till idrott. Ökad kunskap om faktorer som rörelserädsla kan underlätta rehabiliteringsprocessen för personer med främre korsbandsskada. Syfte: Att undersöka i vilka situationer och rörelser som personer med främre korsbandsskada upplever rörelserädsla, samt vilka som är vanligast förekommande. Dessutom, att beräkna sambandet mellan poängen från enkäter angående rörelserädsla. Metod: Tampa Scale of Kinesiophobia (TSK), Anterior Cruciate Ligament - Return to Sports after Injury (ACL-RSI), och en specialutformad enkät (KAAI) skickades till deltagarna. Insamlad data analyserades med hjälp av korrelationstestet Spearman’s rho. Svar på öppna frågor kategoriserades och bidrog med ett kvalitativt perspektiv. Resultat: Pivoterande rörelser, situationer med ökad belastning på det skadade knäet och gång på halt/ojämnt underlag var de vanligast förekommande befarade situationer och rörelser hos deltagarna. Signifikanta korrelationer påvisades mellan TSK och KAAI_TOTAL poäng (rho = 0.728; p = 0.007), ACL-RSI och KAAI_TOTAL poäng(rho = -0.755; p = 0.003) samt ACL-RSI och TSK poäng (rho= -0.828; p< 0.001). Slutsats: Denna studie visar att ett större antal befarade situationer och rörelser kan associeras till högre nivåer av rörelserädsla hos personer med främre korsbandsskada. Högre tilltro till sin egen förmåga och större beredskap att återgå till idrott kan associeras med färre befarade situationer och rörelser. Exempel på dessa är pivoterande rörelser och gång på halt underlag. Kunskap om detta kan underlätta rehabilitering inom detta område

Rörelserädsla efter främre korsbandsskada: specifika situationer och rörelser : En semikvalitativ explorativ studie

Background: The anterior cruciate ligament (ACL) is the most commonly injured ligament in the human body. The injury often occurs in pivoting sports. A common consequence after ACL injury is kinesiophobia, which can contribute to prolonged rehabilitation and delayed return to sport. Increased understanding of psychological factors such as kinesiophobia could facilitate the rehabilitation process for ACL-patients. Objectives: To explore in which situations and movements ACL-injured individuals experience kinesiophobia, and which are most common. The associations between the number of fearful situations described and the scores in questionnaires regarding kinesiophobia were also evaluated.  Methods: Tampa Scale of Kinesiophobia (TSK), Anterior Cruciate Ligament - Return to Sports after Injury (ACL-RSI) and a custom made Kinesiophobia after ACL injury (KAAI) questionnaire were used. Data were analysed using Spearman’s Rho test. Answers to open-ended questions were categorized and provided qualitative input. Results: Common situations and movements considered fearful by ACL-injured persons were pivoting movements, situations with increased load on the injured knee, and walking on slippery/uneven ground. Significant correlations were seen between TSK and KAAI_TOTAL scores (rho = 0.728; p = 0.007), ACL-RSI and KAAI_TOTAL scores (rho = -0.755; p = 0.003), and ACL-RSI and TSK scores (rho= -0.828; p< 0.001).  Conclusion: This study shows that a higher number of situations and movements considered fearful might associate with higher levels of kinesiophobia in ACL-injured persons. Higher self-efficacy and readiness to return to sport might associate with fewer situations and movements considered fearful, e.g. pivoting movements and walking on slippery ground. Knowledge of this may improve rehabilitation in this field.Bakgrund: Främre korsbandet är det mest frekvent skadade ligamentet i människokroppen. Skadan sker ofta i sporter med pivoterande rörelser. En vanlig psykologisk konsekvens efter främre korsbandsskada är rörelserädsla, vilket kan orsaka förlängd rehabilitering och försenad återgång till idrott. Ökad kunskap om faktorer som rörelserädsla kan underlätta rehabiliteringsprocessen för personer med främre korsbandsskada. Syfte: Att undersöka i vilka situationer och rörelser som personer med främre korsbandsskada upplever rörelserädsla, samt vilka som är vanligast förekommande. Dessutom, att beräkna sambandet mellan poängen från enkäter angående rörelserädsla. Metod: Tampa Scale of Kinesiophobia (TSK), Anterior Cruciate Ligament - Return to Sports after Injury (ACL-RSI), och en specialutformad enkät (KAAI) skickades till deltagarna. Insamlad data analyserades med hjälp av korrelationstestet Spearman’s rho. Svar på öppna frågor kategoriserades och bidrog med ett kvalitativt perspektiv. Resultat: Pivoterande rörelser, situationer med ökad belastning på det skadade knäet och gång på halt/ojämnt underlag var de vanligast förekommande befarade situationer och rörelser hos deltagarna. Signifikanta korrelationer påvisades mellan TSK och KAAI_TOTAL poäng (rho = 0.728; p = 0.007), ACL-RSI och KAAI_TOTAL poäng(rho = -0.755; p = 0.003) samt ACL-RSI och TSK poäng (rho= -0.828; p< 0.001). Slutsats: Denna studie visar att ett större antal befarade situationer och rörelser kan associeras till högre nivåer av rörelserädsla hos personer med främre korsbandsskada. Högre tilltro till sin egen förmåga och större beredskap att återgå till idrott kan associeras med färre befarade situationer och rörelser. Exempel på dessa är pivoterande rörelser och gång på halt underlag. Kunskap om detta kan underlätta rehabilitering inom detta område