Miracle-dz/UniFAR-FTUs huggingface dataset:
Certolizumab pegol attenuates the pro-inflammatory state in endothelial cells in a manner that is atheroprotective.

OBJECTIVES Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and premature cardiovascular death. Anti-TNF therapy is thought to reduce clinical cardiovascular disease risk and improve vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to explore the effects of certolizumab pegol (CZP) on TNF-activated human aortic endothelial cells (HAoECs). METHODS HAoECs were cultured in vitro and exposed to i) TNF alone, ii) TNF plus CZP, or iii) neither agent. Microarray analysis and quantitative polymerase chain reaction were used to analyse gene expression. Activation of NF-κB was investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was performed to detect microparticle release from HAoECs. RESULTS TNF alone had strong effects on endothelial gene expression, while TNF and CZP together produced a global gene expression pattern similar to untreated controls. In particular, genes for E-selectin, VCAM-1 and ICAM-1 were significantly up-regulated by TNF treatment. Notably, the TNF/CZP cocktail prevented the up-regulation of these genes. TNF-induced nuclear translocation of NF-κB was abolished by treatment with CZP. In addition the increased production of endothelial microparticles in TNF-activated HAoECs was prevented by treatment with CZP. CONCLUSIONS We have found at cellular level, that a clinically available TNF inhibitor, CZP i) reduces adhesion molecule expression; ii) prevents TNF-induced activation of the NF-κB pathway and iii) prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions.
Prospective Comparative Study of the Scarf and Ludloff Osteotomies in the Treatment of Hallux Valgus

Background: This study compares two diaphyseal osteotomies (scarf and Ludloff) which correct moderate to severe metatarsus primus varus. This is a single surgeon, prospective cohort study with clinical and radiological follow up at 12 months. Materials and Methods: There were 57 patients in each group. Both groups were similar in terms of age, gender and preoperative deformity. Clinical assessment included visual analogue scale questionnaires for subjective assessment and functional activities and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Standardized weight bearing radiographs were analyzed. Results: There was no statistically significant difference between the two groups at 6 and 12 months in subjective satisfaction, AOFAS score, improvement in functional activities and range of movements. The improvement in pain (at best) and transfer lesions at 12 months was significantly better in the scarf group (p < 0.05). The radiological results at 6 and 12 months including intermetatrsal angle (p < 0.001), hallux valgus angle (p < 0.01), distal metatarsal articular angle and seasmoid position (p < 0.05) were significantly better in the scarf osteotomy group. There were three cases (5%) of delayed union in the Ludloff group. Two of these healed with dorsiflexion malunion. One patient in the Ludloff osteotomy group developed a complex regional pain syndrome. There were two wound complications in the scarf group. Conclusion: Overall the patients who had a scarf osteotomy had a superior outcome at 6 and 12 months. Level of Evidence: II, Prospective Comparative Study
The Effects of Alcohol Dependence on the Quality of Life and Sex Life of Women

Background: Alcohol dependence is a multi-dimensional and chronic disorder which affects the physical, psychological, social, sexual health and thus the quality of life of the individual. Objectives: This research was designed in order to determine the effect of alcohol dependence on the quality of life and sexual life of women. Methods: The research was a cross-sectional and comparative relation study, consisting of a case study group constituted of women who consulted Prof. Dr. Mazhar Osman Mental Health and Disorders Training and Research Hospital's Alcohol and Substance Research, Treatment, Education Center between July 2009 and July 2010 and who were diagnosed as alcohol addicted and a healthy group, constituted of women who consulted the Gynecology Clinic of the same hospital (alcohol dependent group = 71, healthy group = 183). The data were collected using ‘World Health Organization Quality of Life Scale Brief Form’ (WHOQOL-BREF TR), Female Sexual Function Index (FSFI), Beck Depression Inventory (BDI). Data were analyzed by percentage, mean, chi-square, student's t-test, and multivariate analysis by use of SPSS 13.0 program. Results: It was determined that the alcohol-dependent women presented lower WHOQOL-BREF-TR sub-dimensions and lower FSFI total scores and sub-dimensions but higher scores in BDI scale in comparison to the healthy group. Conclusions: The alcohol dependence negatively affects the quality of life and sexual life in women.
Stimulation of “Stress-regulated” Mitogen-activated Protein Kinases (Stress-activated Protein Kinases/c-Jun N-terminal Kinases and p38-Mitogen-activated Protein Kinases) in Perfused Rat Hearts by Oxidative and Other Stresses*

“Stress-regulated” mitogen-activated protein kinases (SR-MAPKs) comprise the stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) and the p38-MAPKs. In the perfused heart, ischemia/reperfusion activates SR-MAPKs. Although the agent(s) directly responsible is unclear, reactive oxygen species are generated during ischemia/reperfusion. We have assessed the ability of oxidative stress (as exemplified by H2O2) to activate SR-MAPKs in the perfused heart and compared it with the effect of ischemia/reperfusion. H2O2 activated both SAPKs/JNKs and p38-MAPK. Maximal activation by H2O2 in both cases was observed at 0.5 mm. Whereas activation of p38-MAPK by H2O2 was comparable to that of ischemia and ischemia/reperfusion, activation of the SAPKs/JNKs was less than that of ischemia/reperfusion. As with ischemia/reperfusion, there was minimal activation of the ERK MAPK subfamily by H2O2. MAPK-activated protein kinase 2 (MAPKAPK2), a downstream substrate of p38-MAPKs, was activated by H2O2 to a similar extent as with ischemia or ischemia/reperfusion. In all instances, activation of MAPKAPK2 in perfused hearts was inhibited by SB203580, an inhibitor of p38-MAPKs. Perfusion of hearts at high aortic pressure (20 kilopascals) also activated the SR-MAPKs and MAPKAPK2. Free radical trapping agents (dimethyl sulfoxide and N-t-butyl-α-phenyl nitrone) inhibited the activation of SR-MAPKs and MAPKAPK2 by ischemia/reperfusion. These data are consistent with a role for reactive oxygen species in the activation of SR-MAPKs during ischemia/reperfusion.
Les cténophores : de leur position dans l'arbre des métazoaires (approche phylogénomique) à leur diversité taxonomique (phylogénie moléculaire et anatomie comparée)

Les ctenophores representent l’un des quatre embranchements animaux exterieurs aux Bilateria. La majoritedes especes sont planctoniques et gelatineuses, et sont reconnaissables a leurs huit rangees de peignes dont lebattement permet la nage. Leur systematique est encore de nos jours mal comprise. L'anatomie desctenophores offre peu de caracteres aussi bien pour placer la lignee dans l’arbre des metazoaires, que pouretablir les relations de parente au sein de l’embranchement et delimiter les especes, et jusqu’a present lesdonnees moleculaires n’ont pas permis de resoudre ces problemes de maniere satisfaisante. L’objectif de cetravail de these est de contribuer a ameliorer notre comprehension de l'evolution des ctenophores adifferentes echelles taxonomiques. A l’echelle des metazoaires, la position phylogenetique des ctenophores aete abordee par une approche phylogenomique. Un effort significatif a ete realise pour ameliorerl’echantillonnage taxonomique a travers le sequencage et l’assemblage des transcriptomes de 22 especes denon-Bilateria (ctenophores, cnidaires, spongiaires). Deux jeux de donnees independants ont ete analyses, lepremier representant une mise a jour d’une supermatrice existante de 128 genes ; le second (4235 genes)ayant ete entierement construit de novo via un protocole original comportant la mise au point de nouvellesmethodes pour traiter de maniere semi-automatisee les principales sources potentielles d’artefact(contaminations, paralogies, donnees manquantes). Les resultats contredisent certaines etudes recentes enmontrant que les spongiaires et non les ctenophores representent le groupe-frere des autres metazoaires. Laposition exacte de ces derniers reste a ce stade incertaine (trois options se presentant suivant les analyses). Al’echelle intra-phyletique, l'analyse d'un jeu de donnees comprenant les marqueurs ADNr 18S et InternalTranscribed Spacers (ITS), associee a des analyses de genes dupliques chez les ctenophores et aux analysesphylogenomiques precedentes, a permis de resoudre une grande partie des relations phylogenetiques entre lesordres et les familles de ctenophores, tout en permettant de preciser la position de la racine. Enfin, a uneechelle taxonomique plus fine, une comparaison approfondie entre deux especes du genre Pleurobrachia aumoyen de marquages immunohistochimiques montre le potentiel de ces techniques comme source denouveaux caracteres structuraux « micro-anatomiques » a valeur diagnostique pour la delimitation etl’identification des especes de ctenophores. En conclusion, ce travail se veut une contribution au progres dela systematique d’un embranchement encore meconnu et d’une grande importance pour la comprehensiondes evenements anciens de l’evolution animale.
Determinants of Menopausal Symptoms among Ghanaian Women

The onset of menopause is unique to every woman with varying symptoms which have implications on health and well-being. This study evaluated the perception, knowledge and beliefs about menopause and the prevalence of climacteric symptoms. The study was a cross-sectional survey of 280 menopausal women aged 45 years and older in the Accra Metropolis of the Greater Accra Region of Ghana. Data on socio-demographic characteristics, knowledge, beliefs and experience of menopausal symptoms were collected using a semi-structured questionnaire. Anthropometric data on weight, height, % body fat and MUAC were also taken. All data were analyzed using SPSS version 16.0 and presented as means and frequencies. Predictors of menopausal symptoms were determined by logistic regression. The mean age of onset of menopause was (48±2.9) years with 98.2% having some knowledge of the signs and symptoms of menopause. The most frequently reported menopausal symptoms by the women were: night sweats (83.2%), hot flashes (76.4%), mood swings (72.5%) and vaginal dryness (71.4%). The significant predictors for the occurrence of the most common symptoms reported were: age at onset of menstruation, age of start of menopause, body weight and % body fat. There was a decreased risk of experiencing symptoms such as night sweats, mood swings and vaginal dryness as age at menopause increased. Menopausal transition was determined by both vasomotor and urogenital symptoms. Counseling and support are needed to enable women manage the symptoms better. Most women have heard of and know what menopause is.
Yeast nuclear pore complex assembly defects determined by nuclear envelope reconstruction.

Assembly of nuclear pore complexes (NPCs) is a critical yet poorly understood cellular function. One approach to studying NPC assembly is to identify yeast mutants defective in this process. This requires robust assays for NPC assembly that can be used for phenotypic analysis. We have previously reconstructed yeast nuclei from electron micrographs of serially sectioned cells to precisely determine the number of NPCs (Winey et al., 1997). Here we report the analysis of strains mutant in either of two nucleoporin-encoding genes, NIC96 (Zabel et al., 1996) and NUP192 (Kosova et al., 1999). Using conditional alleles of either gene, we have found that the NPC number falls significantly following shift to the restrictive temperature. We conclude that the drop in NPC number results from the failure to assemble new NPCs during cell divisions, leading to the dilution of NPCs that existed when the cells were shifted to the restrictive temperature. We are also able to document a subtle defect in NPC numbers in nup192-15 cells at their permissive temperature. The data presented here quantitatively demonstrate that NPC numbers fall in nic96-1 and nup192-15 strains upon shifting to the restrictive temperature, indicating that these gene products are required for NPC assembly.
Side-to-Side Isoperistaltic Strictureplasty in Extensive Crohn’s Disease: A Prospective Longitudinal Study

ObjectiveTo report on the results of a prospective longitudinal study of a new bowel-sparing procedure (side-to-side isoperistaltic strictureplasty [SSIS]) in patients with extensive Crohn’s disease. MethodsBetween January 1992 and April 1999, the authors operated on 469 consecutive patients for Crohn’s disease of the small bowel. Seventy-one patients (15.1%) underwent at least one strictureplasty; of these, 21 (4.5%; 12 men, 9 women; mean age 39) underwent an SSIS. The long-term changes occurring in the SSIS were studied radiographically, endoscopically, and histopathologically. ResultsThe indication for surgical intervention was symptomatic partial intestinal obstruction in each of the 21 patients. Fourteen SSISs were constructed in the jejunum, four in the ileum, and three with ileum overlapping colon. The average length of the SSIS was 24 cm. Performance of an SSIS instead of a resection resulted in preservation of an average of 17% of small bowel length. One patient suffered a postoperative gastrointestinal hemorrhage. All patients were discharged on oral feedings after a mean of 8 days. In all cases, SSIS resulted in resolution of the preoperative symptoms. With follow-up extending to 7.5 years in 20 patients (one patient died of unrelated causes), radiographic, endoscopic, and histopathologic examination of the SSIS suggests regression of previously active Crohn’s disease. ConclusionsSSIS is a safe and effective procedure in patients with extensive Crohn’s disease. The authors’ results provide radiographic, endoscopic, and histopathologic evidence that active Crohn’s disease regresses at the site of the SSIS.
“Waiting for the Other Shoe to Drop:” Distress and Coping During and After Treatment for Breast Cancer

This study explored distress and coping strategies during and after breast cancer treatment. Open ended interview questions were used to explore stress and coping across the illness trajectory and during continuing care. With permission, 49 of the 50 interviews were audiotaped. Interviews also involved the use of the Impact of Events Scale-Revised (IES-R), the Ways of Coping (WAYS) and the Lubben Social Support Network Scale (LSNS-6). Data analysis involved a sequential quantitative (dominant)-qualitative (non-dominant) design. A mean-split procedure was used to compare lower and higher distress. The overall IES-R score as well as the Avoidance, Intrusions, and Hyperarousal subscales were all statistically significant between the higher-lower distress groups. Fourteen of the 22 individual IES-R items were significantly different between groups. WAYS subscale scores were not significantly different but 21% of the individual items were. Stress involves (1) physical stressors and (2) psychosocial stressors: (fear of recurrence and family-focused concerns). Coping involves (1) activity-based strategies, (2) cognitive strategies, and (3) spiritual strategies. Breast cancer survivors experience persistent concern about recurrence and uncertainty about the future. Understanding the nature of distress and how women cope during and after treatment are key to improved care for women who have breast cancer.
Routine, self-administered, touch-screen, computer-based suicidal ideation assessment linked to automated response team notification in an HIV primary care setting.

BACKGROUND Human immunodeficiency virus (HIV) and AIDS continue to be associated with an underrecognized risk for suicidal ideation, attempted suicide, and completed suicide. Suicidal ideation represents an important predictor for subsequent attempted and completed suicide. We sought to implement routine screening of suicidal ideation and associated conditions using computerized patient-reported outcome (PRO) assessments. METHODS Two geographically distinct academic HIV primary care clinics enrolled patients who attended scheduled visits from December 2005 through February 2009. Touch-screen, computer-based PRO assessments were implemented into routine clinical care. Substance abuse, alcohol consumption, depression, and anxiety were assessed. The 9-item Patient Health Questionnaire assesses the frequency of suicidal ideation in the preceding 2 weeks. A response of "nearly every day" triggered an automated page to predetermined clinic personnel, who completed more detailed self-harm assessments. RESULTS Overall, 1216 patients (740 from the University of Alabama at Birmingham and 476 from the University of Washington) completed the initial PRO assessment during the study period. Patients were predominantly white (646 [53%]) and male (959 [79%]), with a mean age (+/- standard deviation) of 44 +/- 10 years. Among surveyed patients, 170 (14%) endorsed some level of suicidal ideation, whereas 33 (3%) admitted suicidal ideation nearly every day. In multivariable analysis, suicidal ideation risk was lower with advancing age (odds ratio [OR], 0.74 per 10 years; 95% confidence interval [CI], 0.58-0.96) and was increased with current substance abuse (OR, 1.88; 95% CI, 1.03-3.44) and more-severe depression (OR, 3.91 for moderate depression [95% CI, 2.12-7.22] and 25.55 for severe depression [95% CI, 12.73-51.30]). DISCUSSION Suicidal ideation was associated with current substance abuse and depression. The use of novel technologies to incorporate routine self-reported screening for suicidal ideation and other health domains allows for timely detection and intervention for this life-threatening condition.
Subthreshold depressive disorder in adolescents: predictors of escalation to full-syndrome depressive disorders.

OBJECTIVES Subthreshold depressive disorder is one of the best established risk factors for the onset of full-syndrome depressive disorders. However, many youths with subthreshold depressive disorder do not develop full-syndrome depression. We examined predictors of escalation to full-syndrome depressive disorders in a community sample of 225 adolescents with subthreshold depressive disorder. METHOD Criteria for subthreshold depressive disorder were an episode of depressed mood or loss of interest or pleasure lasting at least 1 week and at least two of the seven other DSM-IV-associated symptoms for major depression. Participants were assessed four times from mid-adolescence to age 30 years using semistructured diagnostic interviews. RESULTS The estimated risk for escalation to full-syndrome depressive disorders was 67%. Five variables accounted for unique variance in predicting escalation: severity of depressive symptoms, medical conditions/symptoms, history of suicidal ideation, history of anxiety disorder, and familial loading for depression. Adolescents with three or more risk factors had an estimated 90% chance of escalating to full-syndrome depressive disorder, compared with 47% of adolescents with fewer than three risk factors. CONCLUSIONS These data may be useful in identifying a subgroup of youths with subthreshold depressive disorder who are at especially high risk for escalating to full-syndrome depressive disorders.
The Effect of Acculturation on Progesterone/Estriol Ratios and Preterm Birth in Hispanics

OBJECTIVE: To examine the Hispanic acculturation paradox by identifying the effect of acculturation on serum progesterone and estriol levels, the progesterone/estriol ratio, and preterm birth. METHODS: We used an observational, prospective design with 468 self-identified, low-income, pregnant Hispanic women. We used the Language Proficiency Subscale (from the Bidimensional Acculturation Scale for Hispanics) to measure acculturation. We measured progesterone and estriol in maternal serum at 22–24 weeks of pregnancy. We defined preterm birth as birth before 37 weeks of gestation. Statistical analysis was by Wilcox-Mann-Whitney and Kruskal-Wallis tests, analysis of variance, t tests, logistic regression, and structural equation modeling. RESULTS: English proficiency had an adjusted odds ratio of 4.03 (95% confidence interval 1.44–11.25), P<. 001, and the lowest quartile of the progesterone/estriol ratio had an adjusted odds ratio of 2.93 (95% confidence interval 1.25–6.89), P<. 001, to predict preterm birth. English proficiency was associated with a decrease in progesterone/estriol ratio and an increase in preterm birth. In structural equation modeling, the progesterone/estriol ratio mediated the relationship between acculturation and preterm birth. CONCLUSION: Hispanic woman have four times the risk of a preterm birth if they are more acculturated (ie, proficient in English). These findings demonstrate another possible aspect of obstetric risk, that of acculturation. Further refinement of the risk of acculturation is essential to clarify how we can adjust our clinical care to prevent increasing preterm birth with the increasing Hispanic population. LEVEL OF EVIDENCE: III
The Role of Focal Adhesion Kinase-Phosphatidylinositol 3-Kinase-Akt Signaling in Hepatic Stellate Cell Proliferation and Type I Collagen Expression*

Following a fibrogenic stimulus, the hepatic stellate cell (HSC) undergoes a complex activation process associated with increased cell proliferation and excess deposition of type I collagen. The focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is activated by platelet-derived growth factor (PDGF) in several cell types. We investigated the role of the FAK-PI3K-Akt pathway in HSC activation. Inhibition of FAK activity blocked HSC migration, cell attachment, and PDGF-induced PI3K and Akt activation. Both serum- and PDGF-induced Akt phosphorylation was inhibited by LY294002, an inhibitor of PI3K. A constitutively active form of Akt stimulated HSC proliferation in serum-starved HSCs, whereas LY294002 and dominant-negative forms of Akt and FAK inhibited PDGF-induced proliferation. Transforming growth factor-β, an inhibitor of HSC proliferation, did not block PDGF-induced Akt phosphorylation, suggesting that transforming growth factor-β mediates its antiproliferative effect downstream of Akt. Expression of type I collagen protein and α1(I) collagen mRNA was increased by Akt activation and inhibited when PI3K activity was blocked. Therefore, FAK is important for HSC migration, cell attachment, and PDGF-induced cell proliferation. PI3K is positioned downstream of FAK. Signals for HSC proliferation are transduced through FAK, PI3K, and Akt. Finally, expression of type I collagen is regulated by the PI3K-Akt signaling pathway.