Miracle-dz/UniFAR-FTUs huggingface dataset:
Atrial fibrillation is associated with high levels of monocyte-platelet-aggregates and increased CD11b expression in patients with aortic stenosis

Summary A growing body of evidence suggests a pivotal role of inflammatory processes in AF in a bidirectional manner. Infiltrating leukocytes seem to promote both structural and electrical remodelling processes in patients with AF. Monocyte-platelets-aggregates (MPAs) are sensitive markers of both platelets and monocyte activation. So far it is not clear whether the content of MPAs is affected by AF. The present study examined the content of MPAs and the activation of monocytes in elderly patients with an aortic stenosis in dependence of AF. These patients are known to have a high prevalence of AF. Flow-cytometric quantification analysis demonstrated that patients with AF have an increased content of MPAs (207 ± 13 cells/μl vs 307 ± 21 cells/μl, p<0.001), and enhanced expression of CD11b on monocytes (p<0.001), compared to patients in stable sinus rhythm (SR). The number of CD14+/CD16+ monocytes were only slightly elevated in patients with AF. These findings were seen in patients with permanent AF. But also patients with paroxysmal AF, even when presenting in SR, the MPAs were increased by 50 % (p<0.05) as well as the CD11b expression, which was twice as high (p<0.05) compared to stable SR. These results demonstrate for the first time a dependency of MPAs and CD11b expression on monocytes in the presence of AF and support the notion of a close relationship between AF, thrombogenesis and inflammation. The content of MPAs and the extent of activation on monocytes appear promising as biomarkers for paroxysmal AF and as possible future targets for developing novel pharmacological therapeutic strategies. Supplementary Material to this article is available online at www.thrombosis-online.com.
Characterisation of the host inflammatory response to Staphylococcus epidermidis in neonatal whole blood

Background: Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late-onset sepsis, and gestational age is the most important risk factor for these infections. Objective: To characterise innate immune responses to S epidermidis by assessment of whole blood in vitro cytokine production in a large group of preterm and term infants. Results: The S epidermidis-induced in vitro production of proinflammatory cytokines such as intracytoplasmic interleukin (IL) 6 and tumour necrosis factor α in cord blood samples was found to be dependent on gestational age (R = 0.279, 95% CI 0.10 to 0.44, p = 0.002; R = 0.251, 95% CI 0.07 to 0.41, p = 0.005, respectively; n = 121). In contrast, the production of anti-inflammatory cytokines such as IL10 and transforming growth factor β was not associated with gestational age. When different stimulation strategies were compared, a strong correlation was noted for cytokine responses after lipopolysaccharide and S epidermidis exposure—that is, IL6 (R = 0.431, 95% CI 0.29 to 0.55, p<0.001, n = 161) and IL10 (R = 0.332, 95% CI 0.18 to 0.47, p<0.001, n = 161). In addition, a lower IL6 production was found in supernatants of whole blood cultures infected with a clinically isolated IcaABD-positive (biofilm production) strain compared with a control IcaABD-negative ATCC strain (p = 0.009). Conclusions: These in vitro data suggest that proinflammatory responses to S epidermidis are dependent on gestational age in preterm infants, whereas the counteracting anti-inflammatory response to S epidermidis may not be directly related to gestational age. Individual host factors may have a role as well as bacterial determinants, such as biofilm production. Further studies are encouraged to investigate the different aspects of innate immune responses to CoNS in vivo.
Role of sensory nerves in the rapid cutaneous vasodilator response to local heating in young and older endurance‐trained and untrained men

The ability to increase skin blood flow (SkBF) rapidly in response to local heating is diminished with advanced age; however, the mechanisms are unclear. The primary aim of this study was to investigate the role of sensory nerves in this age‐related change. A secondary aim was to investigate the effect of aerobic fitness on sensory nerve‐mediated vasodilatation in young and aged skin. We measured SkBF (using laser Doppler flowmetry) in young and older endurance‐trained and untrained men (n = 7 in each group) at baseline and during 35 min of local skin heating to 42°C at two sites on the ventral forearm. One site was pretreated with topical anaesthetic cream to block local sensory nerve function. Cutaneous vascular conductance (CVC) was calculated as SkBF divided by mean arterial pressure and normalized to maximal values (CVCmax) achieved during local heating to 44°C. At the untreated site, the rapid vasodilatation during the first ∼5 min of local heating (initial peak) was lower in the older untrained group (68 ± 3%CVCmax) compared with all other groups (young trained, 76 ± 4%CVCmax; young untrained, 75 ± 5%CVCmax; and older trained, 81 ± 3%CVCmax; P < 0.05). Sensory nerve blockade abolished these differences among the groups (P > 0.05). The contribution of sensory nerve‐mediated vasodilatation was lower in the older untrained group compared with all other groups (P< 0.05). Our results suggest that the age‐related decline in the rapid vasodilator response to local heating in human skin is explained by diminished sensory nerve‐mediated vasodilatation. These findings also indicate that this age‐related change can be prevented through participation in regular aerobic exercise.
Safety and Effectiveness of Varenicline in a Veteran Population with a High Prevalence of Mental Illness

Background Varenicline is a selective nicotinic receptor partial agonist used to aid in the process of smoking cessation. Research on varenicline's approval for marketing demonstrated that after 12 weeks of treatment, at least 44% of patients successfully quit smoking and, on average, 13% of individuals discontinued therapy due to an adverse drug event (ADE). Growing postmarketing data linked varenicline to an increase in neuropsychiatric symptoms. Objective To evaluate the safety profile, specifically psychiatric symptoms, and effectiveness of varenicline in a veteran population and to determine whether there is an association among specific baseline demographics and success rate. Methods The study was a retrospective review of a prospective performance measure involving veterans initiated on varenicline. Patients were contacted via telephone throughout treatment and at week 12 for effectiveness follow-up. Smoking history was obtained and medication counseling was provided. The primary endpoint was tobacco cessation between weeks 9 and 12 of therapy. Varenicline's safety profile and discontinuation rates due to ADEs were also analyzed. Results Of the 50 patients included in the study, 30% (n = 15) successfully quit smoking and 70% (n = 35) failed therapy (lack of effectiveness, n = 22; intolerability, n = 13). Prevalence of underlying mental illness in the success group (4/15; 27%) versus failure group (20/35; 57%) was statistically significant (p< 0.001). All patients who discontinued therapy due to an increase in mood and behavioral changes (n = 4) had an underlying psychiatric illness. The study results demonstrate a lower success rate and a higher incidence of discontinuation due to an ADE in our veteran population compared with premarketing data. An inverse association was shown between psychiatric disorders and success. Conclusions Cautious treatment initiation and close monitoring of veterans initiated on varenicline are warranted. Furthermore, the results from this study demonstrate the need for prospective effectiveness trials to determine the clinical significance of the results.
Value of serologic markers for clinical diagnosis and population studies of coeliac disease.

BACKGROUND There is a need for serologic markers in selecting patients with symptoms compatible with coeliac disease for intestinal biopsy and for population screening. Few comparative studies have been done. METHODS Sera from 55 patients with coeliac disease and 65 referents, aged between 8 months and 79 years, were investigated. Anti-gliadin, anti-reticulin, anti-endomysium, and anti-jejunal antibodies were measured. The sensitivities, specificities, and positive predictive values for different disease prevalence levels were calculated. Confidence intervals, rarely used in this type of study, were calculated. RESULTS AND CONCLUSIONS In most tests the antibody levels were age-correlated. The highest sensitivities in combination with high specificities were found for IgA anti-gliadin antibodies in children less than 5 years of age and IgA anti-endomysium antibodies in older children and adults. These tests were most useful for testing a population with a high disease prevalence, such as patients with gastrointestinal symptoms, although the results for many tests had overlapping confidence intervals. For screening unselected populations with a low disease prevalence, in which a test with maximum specificity is desired, only anti-endomysium antibodies had sufficiently high predictive value to be of practical use.
Synthesis and Pharmacological Evaluation of Novel Pleuromutilin Derivatives with Substituted Benzimidazole Moieties

A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives was evaluated in vitro for their antibacterial activity against Escherichia coli (E. coli) and five Gram (+) inoculums. 14-O-((5-amino-benzimidazole-2-yl) thioacetyl) mutilin (3) was the most active compound and showed highest antibacterial activities. Furthermore, we evaluated the inhibition activities of compound 3 on short-term S. aureus and MRSA growth and cytochrome P450 (CYP). The bioassay results indicate that compound 3 could be considered potential antibacterial agents but with intermediate inhibition of CYP3A4.
production and release of endothelin‐1 from the gut and spleen in portal hypertension due to cirrhosis

This study was aimed to evaluate the source of endothelin‐1 (ET‐1) in cirrhotic patients. ET‐1 is implicated in the pathogenesis of portal hypertension. However, the mechanism and source for increased plasma ET‐1 in cirrhotic patients are still obscure. Plasma ET‐1 levels in systemic (SV), superior mesenteric (SMV), and splenic venous (SPV) blood were measured in 23 patients with cirrhosis and 8 controls with normal liver. Fourteen removed spleens were immunohistochemically studied for ET‐1, CD34, CD68, and CD20. In situ hybridization was done to localize ET‐1 messenger RNA (mRNA). In cirrhosis, ET‐1 levels in both SMV and SPV were higher than in SV. ET‐1 in SV and SPV were significantly higher in cirrhotic patients than in control patients. Three groups of cells in the spleen expressed both protein and mRNA of ET‐1: endothelial cells in the sinus, which were also stained for CD34; cells in the germinal center; and cells in the marginal zone of lymphoid sheaths and follicles, which were also stained for CD20 but not for CD34 and CD68. The ET‐1 concentration released from the spleen was in parallel with the grade of ET‐1 expression in the spleen. The spleen is one of the major sites of ET‐1 release in cirrhotic patients. Endothelial cells of the splenic sinus and possibly B lymphocytes in the germinal center and marginal zone of lymphoid sheaths and follicles seem to be the sites of ET‐1 production in the spleen.
Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme

Alterations in the signal transduction pathways are key mechanisms in the pathogenesis of de novo glioblastoma multiforme (GBM), which are also involved in the resistance to chemo‐ and radiotherapy. Here, we analyzed the methylation status and mRNA expression of suppressor of cytokine signaling (SOCS)1‐2‐3, 3 of the most important inhibitory molecules of the signal transduction circuitry, in 46 GBM specimens. The relationship between methylation status of SOCS1‐2‐3 and clinical outcome was investigated. Using methylation‐specific PCR (MS‐PCR) and sequencing, after bisulphite modification, we found that the promoter of SOCS1‐2‐3 was methylated in 24, 6.5 and 35% of GBM, respectively. Real‐time analysis showed that in methylated GBM, mRNA expression for SOCS1‐2‐3 was reduced by 5, 3 and 7‐folds, respectively, when compared with unmethylated GBM. Moreover, methylation of SOCS3 promoter significantly associated with an unfavorable clinical outcome (p < 0.0002). Our data suggest that methylation of SOCS3 may be involved in the pathogenesis of GBM and in the resistance of this neoplasm to conventional treatment. © 2008 Wiley‐Liss, Inc.
Protective effects of cariporide on endothelial dysfunction induced by high glucose

AbstractAim:To explore the effects of cariporide, a selective sodium-hydrogen antiporter inhibitor, on endothelial dysfunction induced by high glucose.Methods:Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation and biochemical parameters including malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) were measured in rat isolated aorta.Results:A 6-h incubation of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition of EDR, but had no effects on endothelium-independent relaxation. After the 6-h incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1 μmol/L) with high glucose, cariporide prevented the inhibition of EDR caused by high glucose in concentration-dependent manners. Similarly, high glucose decreased SOD activity and contents of NO, and increased MDA concentration in aortic tissue. Cariporide (1 μmol/L) significantly resisted the decrease of NO content and SOD activity, and elevation of MDA concentration caused by high glucose in aortic tissues. Mannitol (44 mmol/L) or cariporide (1 μmol/L) alone had no effect on EDR, endothelium-independent relaxation and biochemical parameters.Conclusion:Cariporide significantly prevented endothelial dysfunction induced by high glucose. The mechanisms of endothelial dysfunction induced by high glucose may involve the activation of sodium-hydrogen antiporter and the generation of oxygen-free radicals, but it is not related to the change of osmolarity.
Racial/Ethnic Disparities in Preventive Care Practice Among U.S. Nursing Home Residents

Objective: To assess racial/ethnic disparities in preventive care practices among U.S. nursing home residents. Method: To implement the Institute of Medicine definition of health care disparity, we used the rank-and-replace adjustment method to assess the disparity in receipt of eight preventive care services among residents and evaluate trends in disparities. The sampling design (stratification and clustering) was accounted for using Stata 11. Results: The 2004 National Nursing Home Surveys data show White residents were more likely to have pain management, scheduled toilet plan/bladder retraining, influenza vaccination, and pneumococcal vaccination than Black residents. White residents were also more likely to have scheduled toilet plan/bladder retraining than residents of Other race/ethnicity. Significant Black–White disparities in receipt of influenza vaccination and pneumococcal vaccination were found. Time trend analysis showed that disparities were neither exacerbated nor reduced. Conclusion: Persistent racial/ethnic disparities in preventive care among nursing home residents exist. We urge the development and implementation of targeted interventions to improve the quality of preventive care in nursing homes.
Improving Students Public Speaking Skill through Instagram

Public speaking in English is a needed skill for leaders and staffs in any offices and companies in Indonesia. In this globalization era, skill to communicate effectively and efficiently in English during a meeting or a teleconference with foreigners is needed, such as for company product promotion, or during building cooperation. Therefore, public speaking course is occupied by employees since they have an important role for the company development. Since the needs of this skill is high, universities in Indonesia have started providing course of Public Speaking in English. One of them is English Department in Politeknik Negeri Padang. In teaching public speaking, the teacher must teach them to overcome their fear, show their confident, perform perfectly, and used good English. Unfortunately, performing in their reguler class, infront of their classmates and lecturers did not build any of them. An action was taken by asking the students to upload their performance in their personal instagram application. Instagram was chosen since the application provides a variety of video that get shared to instagram daily. View, comment, and like from the viewers would be the important part of building the character of the students to be like a professional public speaker. From several times presenting their public speaking activities in instagram, Categories ‘state in purpose’ ‘organize the content’, and ‘summarize the main idea’ are in level 5 (high) which means highest improvement. Category ‘speak clearly with appropriate vocabulary and information’, ‘uses tone, speed, and volume as tool’, and ‘appears comfortable with audiences’ in level 4 which is between high and average. Meanwhile, it still can be seen that students need more on English knowledge such their numbers of vocabularies and English structure. In conclusion, instagram application can be one of the media for improving students’ public speaking skill especially in building the character of a public speaker. Keywords-public speaking; instagram; teaching
Women in the Field: America's Pioneering Women Naturalists

My Personal Review: These biographies of American women naturalists bring to light the large number of women who made important contributions to the natural history of North America, often receiving little credit for their work. As a woman who has long waited through the raising of a family for the opportunity to become a field biologist, I found the stories of these women's bold expeditions, often made alone, through tropics, across wild rivers, and over steep mountains, searching for undiscovered plants, insects, and birds inspiring. The women in these accounts practiced patient and exact science in their studies, and won credit for their work despite prevailing prejudices against women as scientists. What prejudices still exist today? What self-doubts still remain for women naturalists today? This book inspires me with confidence in my new direction. I would recommend it for all women naturalists amateur and professional, and especially for those in their teens who are considering a career in natural sciences.
Predictors of post-caesarean section pain and analgesic consumption

Background: Ideally, the intensity of postoperative pain should be predicted so as to customize analgesia. The objective of this study was to investigate whether preoperative electrical and pressure pain assessment can predict post-caesarean section pain and analgesic requirement. Materials and Methods: A total of 65 subjects scheduled for elective caesarean section, who gave written informed consent, were studied. Preoperatively, PainMatcher® was used to evaluate electrical pain threshold, while manual PainTest™ FPN 100 Algometer and digital PainTest™ FPX 25 Algometer determined pressure pain threshold and tolerance. Postoperatively, numerical rating scales were used to assess pain at regular time intervals. Patients received intramuscular pethidine (100mg, 6 hourly), rectal diclofenac (100mg, 12 hourly), and oral paracetamol (1g, p.r.n.) for pain relief. Statistical analysis was conducted using PASW Statistics 18 software. Results: Preoperative electrical pain threshold correlated significantly with post-caesarean pain scores at 6 and 24 hours (r = –0.26, P < 0.02; r = –0.23, P < 0.04, respectively), and with the quantity of paracetamol consumed by the patient within 48 hours of surgery (r = –0.33, P < 0.005). Preoperative pressure pain tolerance measured by PainTest™ FPX 25 Algometer was significantly correlated with pain scores 6 hours postsurgery (r = –0.21, P < 0.05). Pain scores 6 hours post-caesarean section correlated significantly with anesthesia—general or spinal (F = 4.22, v1 = 1, v2 = 63, P < 0.05). Conclusions: The predictive methods proposed may aid in identifying patients at greater risk for postoperative pain. Electrical pain threshold could be useful in personalizing the postoperative analgesic protocol.
CD4+ and CD8+ T-cell kinetics in aviremic HIV-infected patients developing Hodgkin or non-Hodgkin lymphoma

Objective:The risk of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is increased in HIV-infected individuals. We studied the kinetics of lymphocyte subsets in patients who subsequently developed HL or NHL while on virologically suppressive antiretroviral therapy (ART). Design:Using a nested case–control design, cases of HIV+ HL or NHL were selected from two prospective clinical studies. Aviremia was defined as less than 200 HIV-RNA copies/ml for at least 6 months prior to lymphoma diagnosis. Each case was matched to three aviremic HIV+ controls without lymphoma. Results:In the 81 cases (50 HL and 31 NHL), prediagnostic CD4+ T cells and CD8+ T cells displayed discordant kinetics compared with controls. Within the last and within the next-to-last year preceding HL diagnosis, mean CD4+ T cells decreased by −168 and by −2 cells/&mgr;l, compared with an increase of +44 and +73 cells/&mgr;l in the controls, respectively. Mean CD8+ T cells decreased by −352 and −115 cells/&mgr;l, compared with nonsignificant changes of −29 and ±0 cells/&mgr;l in the controls, respectively. T-cell kinetics demonstrated a marked inter-individual variability. Kinetics of CD4+ and CD8+ T cells were also discordant between NHL cases and controls. Conclusion:This study on a large number of aviremic patients developing HL and NHL who were carefully matched with controls, gives insights to prediagnostic kinetics of immune parameters. The discordant kinetics of both CD4+ and CD8+ T cells are already seen 1–2 years prior to lymphoma diagnosis, are more pronounced during the last year and in patients developing HL but are also seen in NHL.
Reverse myocardial effects of intermedin in pressure‐overloaded hearts: role of endothelial nitric oxide synthase activity

Intermedin (IMD) is a cardiac endogenous peptide upregulated in several models of heart disease. We show a depressant effect of IMD1−47 on contractility of the normal myocardium, mediated by increased nitric oxide (NO) production due to endothelial nitric oxide synthase (eNOS) phosphorylation. In rat models of cardiac hypertrophy or NO deficiency, IMD1−47 enhances contractility and hastens relaxation associated with phospholamban phosphorylation. This opposing response in normal and diseased myocardium is due to impairment of IMD1−47‐induced eNOS phosphorylation. The results reveal distinct myocardial effects and subcellular mechanisms for IMD1−47 in the hypertrophic heart, suggesting a key role of cardiac endothelial dysfunction with potential pathophysiological relevance.