Miracle-dz/UniFAR-FTUs huggingface dataset:
Photopheresis in the treatment of cutaneous T-cell lymphoma: current status

Cutaneous T-cell lymphoma is the overall name for a group of malignancies in which malignant T-lymphocytes localize at the skin. Of the current 20 recognized subtypes of the disease, the most common are mycosis fungoides and Sézary syndrome. Extracorporeal photopheresis (ECP), an immunomodulating procedure that treats pheresed blood with a photoactive agent, received US Food and Drug Administration approval in 1988 as a medical device for the treatment of CTCL patients, one of many treatment options for such patients. This was followed in 2003 by guidelines in the United Kingdom that recommended ECP for patients with advanced CTCL, particularly after skin-directed treatment options have failed. ECP is now under investigation for use in patients with earlier stages of CTCL. This article reviews the evolution of the ECP technique – for example, the most recent generation of the device requires a lower extracorporeal volume of blood than the previous version did, thus making it possible for more patients to be candidates for the procedure. In addition, there has been progress in understanding how ECP works at the cellular level.
Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lidocaine, bupivacaine, and ropivacaine.

BACKGROUND Several mechanisms have been proposed to explain toxicity of local anesthetics to chondrocytes, including the blockade of potassium channels and mitochondrial injury. The purposes of this investigation were to study the effects of lidocaine, bupivacaine, and ropivacaine on human chondrocyte viability and mitochondrial function in vitro and to characterize the type of cell death elicited following exposure. METHODS Primary chondrocyte cultures from patients with osteoarthritis undergoing knee replacement were treated with saline solution and the following concentrations of local anesthetics: 2%, 1%, and 0.5% lidocaine, 0.5% and 0.25% bupivacaine, and 0.5% and 0.2% ropivacaine for one hour. Cell viability and apoptosis were measured by flow cytometry at twenty-four hours and 120 hours after treatment. Nuclear staining and caspase 3 and 9 cleavage assays (Western blot) were used to further establish the induction of apoptosis. Mitochondrial dysfunction was evaluated by the accumulation of mitochondrial DNA damage (quantitative Southern blot), changes in adenosine triphosphate production (bioluminescence kit), and mitochondrial protein levels (Western blot analysis). RESULTS Exposure of primary human chondrocytes to a 2% concentration of lidocaine caused massive necrosis of chondrocytes after twenty-four hours, 1% lidocaine and 0.5% bupivacaine caused a detectable, but not significant, decrease in viability after twenty-four hours, while 0.5% lidocaine, 0.25% bupivacaine, and both concentrations of ropivacaine (0.5% and 0.2%) did not affect chondrocyte viability. Flow cytometry analysis of chondrocytes 120 hours after drug treatment revealed a significant decrease in viability (p < 0.05) with a concomitant increase in the number of apoptotic cells at all concentrations of lidocaine, bupivacaine, and ropivacaine analyzed, except 0.2% ropivacaine. Apoptosis was verified by observation of condensed and fragmented nuclei and a decrease in procaspase 3 and 9 levels. Local anesthetics induced mitochondrial DNA damage and a decrease in adenosine triphosphate and mitochondrial protein levels. CONCLUSIONS Lidocaine, bupivacaine, and ropivacaine cause delayed mitochondrial dysfunction and apoptosis in cultured human chondrocytes.
Effect of Venlafaxine versus Fluoxetine on Metabolism of Dextromethorphan, a CYP2D6 Probe

Two antidepressants, venlafaxine and fluoxetine, were evaluated in vivo for their effect on cytochrome P450 2D6 (CYP2D6) activity, measured by the ratio of dextromethorphan, a sensitive CYP2D6 marker, to its metabolite dextrorphan (i.e., DM:DT) excreted in urine after DM coadministration. Twenty‐eight healthy extensive metabolizers of CYP2D6 received either venlafaxine (37.5 mg bid for 7 days, then 75 mg bid until Day 28) or fluoxetine (20 mg daily for 28 days); 26 completed the study. Plasma concentrations of both drugs and their active metabolites were determined. DM:DTs were evaluated at baseline (Day0), on Days 7 and 28 of dosing, and 2 weeks after drug discontinuation (Day 42). Steady‐state drug and metabolite levels were achieved in both groups by Day 28. Mean DM:DTs for venlafaxine and fluoxetine differed statistically significantly (p < 0.001) on Days 7,28, and 42. Comparisons of DM:DT as a percentage of baseline values showed that DM:DT increased 1.2‐fold for venlafaxine and 9.1‐fold for fluoxetine on Day 7 (p < 0.001) and increased 2.1‐fold for venlafaxine and 17.1‐fold for fluoxetine on Day 28 (p < 0.001). Inhibition of CYP2D6 metabolism persisted for 2 weeks after discontinuation of fluoxetine, unlike the case with venlafaxine. These in vivo results confirm in vitro data demonstrating significantly weaker inhibition of CYP2D6 with venlafaxine than with fluoxetine. This suggests that clinically significant interactions involving CYP2D6 inhibition could occur between fluoxetine and drugs metabolized by CYP2D6 but may be less likely to occur with venlafaxine.
Actinobacillus actinomycetemcomitans in human periodontal disease.

Recent evidence implicates Actinobacillus actinomycetemcomitans in the etiology of localized juvenile periodontitis. This paper reviews the morphological, biochemical and serological charcteristics of A. actinomycetemcomitans, evidence incriminating it as a periodontopathogen, its importance in human nonoral infections, and virulence factors which may be involved in the pathogenesis of A. actinomycetemcomitans infections. A. actinomycetemcomitans is a non-motile, gram-negative, capnophilic, fermentative coccobacillus which closely resembles several Haemophilus species but which does not require X or V growth factors. The organism has been categorized into 10 biotypes based on the variable fermentation of dextrin, maltose, mannitol, and xylose and into 3 serotypes on the basis of heat stable, cell surface antigens. A. actinomycetemcomitans' primary human ecologic niche is the oral cavity. It is found in dental plaque, in periodontal pockets, and buccal mucosa in up to 36% of the normal population. The organism can apparently seed from these sites to cause severe infections throughout the human body such as brain abscesses and endocarditis. There is a large body of evidence which implicates A. actinomycetemcomitans as an important micro-organism in the etiology of localized juvenile periodontitis including: (1) an increased prevalence of the organism in almost all localized juvenile periodontitis patients and their families compared to other patient groups; (2) the observation that localized juvenile periodontitis patients exhibit elevated antibody levels to A. actinomycetemcomitans in serum, saliva and gingival crevicular fluid; (3) the finding that localized juvenile periodontitis can be successfully treated by eliminating A. actinomycetemcomitans from periodontal pockets; (4) histopathologic investigations showing that A. actinomycetemcomitans invades the gingival connective tissue in localized juvenile periodontitis lesions; (5) the demonstration of several pathogenic products from A. actinomycetemcomitans including factors which may: (a) facilitate its adherence to mucosal surfaces such as capsular polysaccharides; (b) inhibit host defense mechanisms including leukotoxin, a polymorphonuclear leukocyte chemotaxis inhibiting factor, and a lymphocyte suppressing factor (c) cause tissue destruction such as lipopolysaccharide endotoxin, a bone resorption-inducing toxin, acid and alkaline phosphatases, collagenase, a fibroblast inhibiting factor and an epitheliotoxin. (ABSTRACT TRUNCATED AT 400 WORDS)
Developmental expression and activities of specific fos and jun proteins are functionally related to osteoblast maturation: role of Fra-2 and Jun D during differentiation.

Developmental studies of oncogene expression implicate the Fos and Jun family of transcription factors in the regulation of bone growth and differentiation. Promoters of many developmentally regulated genes, including osteocalcin, a marker of osteoblast differentiation, contain AP-1 sites that bind Fos/Jun dimers. Here, we demonstrate that the selective expression of fos- and jun-related genes is functionally related to the stage of osteoblast growth and differentiation in vitro. During osteoblast proliferation, nuclear protein levels of all seven activating protein-1 (AP-1) members are maximal. Subsequently, during the period of extracellular matrix maturation, levels decline. In fully differentiated osteoblasts, Fra-2 and (to a lesser extent) Jun D are the principal AP-1 members detectable by Western blot analysis. AP-1 complex composition and binding activity also exhibit developmental changes. All Fos and Jun family members are involved in AP-1 complex formation in proliferating cells, whereas Fra-2 and Jun D predominate in AP-1 complexes in differentiated osteoblasts. Overexpression of Fos and Jun family members in ROS 17/2.8 cells markedly affects the expression of an osteocalcin promoter-chloramphenicol acetyltransferase construct. Coexpression of only one AP-1 pair, Fra-2 and Jun D, stimulated reporter expression, whereas coexpression of other AP-1 pairs down-regulated expression (i.e. c-jun and any Fos family member) or had no effect (i.e. Fra-1 and Jun B). Promoter deletion analyses indicate that these effects are site specific. Consequential effects of Fra-2 on osteoblast differentiation are further demonstrated by antisense studies in which osteoblast differentiation and the development of a bone tissue-like organization were suppressed. Consistent with recent findings suggesting that AP-1 complex composition can selectively regulate gene transcription, our findings demonstrate that differential expression of Fos and Jun family members could play a role in the developmental regulation of bone-specific gene expression and, as a result, may be functionally significant for osteoblast differentiation.
Animal Cytogenetics and Comparative Mapping

ABC Fax + 41 61 306 12 34 E-mail karger@karger.ch www.karger. com © 2001 S. Karger AG, Basel 0301–0171/01/0942–0043$17.50/0 Accessible online at: www.karger. com/journals/ccg Abstract. Forty autosomal type I loci earlier mapped in goat were comparatively FISH mapped on river buffalo (BBU) and sheep (OAR) chromosomes, noticeably extending the physical map in these two economically important bovids. All loci map on homoeologous chromosomes and chromosome bands, with the exception of COL9A1 mapping on BBU10 (homoeologous to cattle/goat chromosome 9) and OAR9 (homoeologous to cattle/goat chromosome 14). A FISH mapping control with COL9A1 on both cattle and goat chromosomes gave the same results as those obtained in river buffalo and sheep, respectively. Direct Gand R-banding comparisons between Bovinae (cattle and river buffalo) and Caprinae (sheep and goat) chromosomes 9 and 14 confirmed that a simple translocation of a small pericentromeric region occurred between the two chromosomes. Comparisons between physical maps obtained in river buffalo and sheep with those reported in sixteen human chromosomes revealed complex chromosome rearrangements (mainly translocations and inversions) differentiating bovids (Artiodactyls) from humans (Primates).
Stress and coping in spouses of persons with spinal cord injuries

Objective: To examine the sources of stress and the patterns of coping of spouses of persons with spinal cord injuries (SCI) among Hong Kong Chinese. Design: A cross-sectional correlation design. A set of structured questionnaires and semi-structured interviews were administered. Subjects: Forty spouses of persons with SCI were recruited and interviewed. Outcome measures: These included coping strategies, depression, care-giving burden, life satisfaction and marital adjustment. Results: The most stressful situations reported by the participants concerned health issues of their injured partners, the family and marital interactions, and the care-giving burden imposed on them. Cluster analysis indicated a potential at-risk group, characterized by high scores in external locus of control, inadequate coping modes and limited social support. They were noted to manifest high levels of depression, care-giving burden, low levels of life satisfaction and marital adjustment. Conclusion: The identification of the potential at-risk group indicates that spouses of persons with SCI suffer levels of stress comparable to those of their injured partners. Rehabilitation plans should include this potential at-risk group to help them release the stress and to prevent them from developing clinically significant mental disorders.
Different roles of CheY1 and CheY2 in the chemotaxis of Rhizobium meliloti

Cells of Rhizobium meliloti swim by the unidirectional, clockwise rotation of their right‐handed helical flagella and respond to tactic stimuli by modulating the flagellar rotary speed. We have shown that wild‐type cells respond to the addition of proline, a strong chemoattractant, by a sustained increase in free‐swimming speed (chemokinesis). We have examined the role of two response regulators, CheY1 and CheY2, and of CheA autokinase in the chemotaxis and chemokinesis of R. meliloti by comparing wild‐type and mutant strains that carry deletions in the corresponding genes. Swarm tests, capillary assays, and computerized motion analysis revealed that (i) CheY2 alone mediates 60 to 70% of wild‐type taxis, whereas CheY1 alone mediates no taxis, but is needed for the full tactic response; (ii) CheY2 is the main response regulator directing chemokinesis and smooth swimming in response to attractant, whereas CheY1 contributes little to chemokinesis, but interferes with smooth swimming; (iii) in a CheY2‐overproducing strain, flagellar rotary speed increases upon addition and decreases upon removal of attractant; (iv) both CheY2 and CheY1 require phosphorylation by CheA for activity. We conclude that addition of attractant causes inhibition of CheA kinase and removal causes activation, and that consequent production of CheY1‐P and CheY2‐P acts to slow the flagellar motor. The action of the chief regulator, CheY2‐P, on flagellar rotation is modulated by CheY1, probably by competition for phosphate from CheA.
Gr upSM The Mechanisms of Vascular Thrombosis in Behcet ’ s Disease

Behcet’s disease is a systemic vasculitis of every kinds and sizes of vessels. The prevalence of vascular involvement in BD has been reported as up to % 51.5. Vascular involvement includes superficial thrombophlebitis, deep venous thrombosis, arterial thrombosis, aneurysms and pseudoaneurysms. The inflammation induced endothelial injury seems to be the main mechanism underlying vascular thrombosis in BD. However, because of higher prevalence of thrombosis in BD in comparison to other vasculitic disease, some other possible trombotic mechanisms have been suspected to take role in the pathogenesis of vascular thrombosis in Behcet’s disease; for this reason the roles of coagulant and anticoagulant factors, fibrin and fibrinolytic pathway, and of thrombocytes have been studied for many years. In recent years, there are some studies confirming an existence of protrombotic state due to alterations in platelet activity and changes in coagulation mechanisms like increased hypofibrinolysis, altered fibrinogen structure and impaired fibrinogen function. The possible roles of thrombophilic factors like the mutations in factor V, prothrombin and MTHFR genes seem to be not confirmed by recent studies. The studies performed on homocysteine, Lipoprotein (a) and antiphospholipid antibodies have been evaluated with a careful approach. Emel Koseoglu* Department of Neurology, Faculty of Medicine, University of Erciyes, Kayseri-Turkey *Corresponding author: Emel Koseoglu, Department of Neurology, Faculty of Medicine, University of Erciyes, Kayseri-Turkey, Email: emelk@erciyes.edu. tr Published Date: September 30, 2016
Effects of aprotinin on plasma coagulation kinetics determined by thrombelastography: role of Factor XI

Background: Aprotinin is commonly administered in settings involving cardiopulmonary bypass and liver transplantation to decrease peri‐operative bleeding. Thrombelastography has been utilized to monitor coagulation in these settings, and aprotinin delays clot initiation, presumably by inhibiting kallikrein; however, aprotinin also inhibits Factor XI (FXI), a contact system protein. Thus, it was hypothesized that celite‐activated thrombelastography coagulation kin‐etics would be decreased via aprotinin‐mediated FXI inhibition.
Measuring colour rivalry suppression in amblyopia

AIMS To determine if the colour rivalry suppression is an index of the visual impairment in amblyopia and if the stereopsis and fusion evaluator (SAFE) instrument is a reliable indicator of the difference in visual input from the two eyes. METHODS To test the accuracy of the SAFE instrument for measuring the visual input from the two eyes, colour rivalry suppression was measured in six normal subjects. A test neutral density filter (NDF) was placed before one eye to induce a temporary relative afferent defect and the subject selected the NDF before the fellow eye to neutralise the test NDF. In a non-paediatric private practice, 24 consecutive patients diagnosed with unilateral amblyopia were tested with the SAFE. Of the 24 amblyopes, 14 qualified for the study because they were able to fuse images and had no comorbid disease. The relation between depth of colour rivalry suppression, stereoacuity, and interocular difference in logMAR acuity was analysed. RESULTS In normal subjects, the SAFE instrument reversed temporary defects of 0.3 to 1.8 log units to within 0.6 log units. In amblyopes, the NDF to reverse colour rivalry suppression was positively related to interocular difference in logMAR acuity (β=1.21, p<0.0001), and negatively related to stereoacuity (β=−0.16, p=0.019). The interocular difference in logMAR acuity was negatively related to stereoacuity (β=−0.13, p=0.009). CONCLUSIONS Colour rivalry suppression as measured with the SAFE was found to agree closely with the degree of visual acuity impairment in non-paediatric patients with amblyopia.
Factors contributing to nursing leadership: A systematic review

Objectives: Leadership practices of health care managers can positively or negatively influence outcomes for organizations, providers and, ultimately, patients. Understanding the factors that contribute to nursing leadership is fundamental to ensuring a future supply of nursing leaders who can positively influence outcomes for health care providers and patients. The purpose of this study was to systematically review the multidisciplinary literature to examine the factors that contribute to nursing leadership and the effectiveness of educational interventions in developing leadership behaviours among nurses. Methods: The search strategy began with 10 electronic databases (e.g. CINAHL, Medline). Published quantitative studies were included that examined the factors that contribute to leadership or the development of leadership behaviours in nurse leaders. Quality assessments, data extraction and analysis were completed on all included studies. Results: A total of 27,717 titles/abstracts were screened resulting in 26 included manuscripts reporting on 24 studies. Twenty leadership factors were examined and categorized into four groups - behaviours and practices of individual leaders, traits and characteristics of individual leaders, influences of context and practice settings, and leader participation in educational activities. Specific behaviours and practices of individual leaders, such as taking on or practising leadership styles, skills and roles, were reported as significantly influencing leadership in eight studies. Traits and characteristics of individual leaders were examined in six studies with previous leadership experience (three studies) and education levels (two of three studies) having positive effects on observed leadership. Context and practice settings had a moderate influence on leadership effectiveness (three of five studies). Nine studies that examined participation in leadership development programs all reported significant positive influences on observed leadership. Conclusion: These findings suggest that leadership can be developed through specific educational activities, and by modelling and practising leadership competencies. However, the relatively weak study designs provide limited evidence for specific factors that could increase the effectiveness of current nursing leadership or guide the identification of future nurse leaders. Robust theory and research on interventions to develop and promote viable nursing leadership for the future are needed to achieve the goal of developing healthy work environments for health care providers and optimizing care for patients.
Molecular genetics of aortic valve disease

Purpose of review Bicuspid aortic valve is the most common type of cardiac malformation and predisposes to aortic valve calcification, which is the third leading cause of heart disease in adults. These seemingly temporally disparate diseases have been described as having genetic influences but limited data exist on the precise genetic causes in humans. Several advances in the molecular genetics of aortic valve formation and calcification have recently been identified and are described here. Recent findings A large family with autosomal-dominant aortic valve disease consisting of bicuspid aortic valve and aortic valve calcification was studied using genome-wide linkage analysis. This led to the identification of a nonsense mutation in NOTCH1 in affected individuals. This finding was supported by the discovery of a NOTCH1 frameshift mutation in an unrelated family with similar aortic valve disease, suggesting that NOTCH1 haploinsufficiency was a genetic cause of aortic valve malformations and calcification. The NOTCH signaling pathway was linked to a molecular pathway for aortic valve calcification, as NOTCH1 was found to repress activation of Runx2 – a transcription factor critical for osteoblast cell fate that is up-regulated in calcified human aortic valves. Summary The recent genetic and biochemical findings provide novel insights into the molecular and genetic basis for aortic valve dysmorphogenesis and calcification. Future studies focusing on the identification of additional disease-causing and susceptibility genes will aid in the development of prevention strategies. Ultimately, it will be the careful dissection of these molecular pathways that will hopefully lead to novel therapeutic options.