La pintura habla en la poesía y la Poesía calla en la pintura

In der vorliegenden Arbeit soll, dem Leitmotiv „ut pictora poesis“ Folge leistend, ein Zusammenhang zwischen den Künsten Malerei und Poesie am Beispiel Lope de Vegas und Vicente Carduchos geschaffen werden.Die Silva Lope de Vegas in erster Linie, sowie die Diálogos de la pintura im Weiteren, stehen, wie ihre Verfasser, exemplarisch für einen interdisziplinären Zugang zur Kunst im goldenen Zeitalter Spaniens."Ut pictora poesis" is the motive assigned to the present analysis, which represents the attempt to create a coherence between the art of poetry and painting. The poem "Silva de Frey Lope Félix de Vega Carpio", together with the "Diálogos de la pintura" incorporate the means to this end and stand for the successful collaboration of painter and poet in the spanish Golden Age

AT2 receptor agonist LP2 restores respiratory function in a rat model of bleomycin-induced lung remodelling

This study aimed to evaluate the prophylactic and therapeutic potential of angiotensin II type 2 receptor peptide agonist LP2 in bleomycin-induced airway and cardiac remodeling in rats. Male Wistar rats were intratracheally instillated with bleomycin. Animals of a prophylactic arm received LP2 from day 0 at intraperitoneal doses of 1, 3 or 10μg/kg/d, whereas animals from a therapeutic arm received this LP2 treatment from day 7. On day 28 direct lung mechanics were determined and cardiac and lung tissues were collected and (histo)morphologically assessed. Prophylactic LP2 at 1µg/kg/d with bleomycin, versus bleomycin alone, significantly improved the airway pressure responses at fixed inflation of 4ml (p&lt;0.05) and 7ml volume (p&lt;0.05), static compliance (p&lt;0.01), inspiratory capacity (p&lt;0.05), lung tolerance of increased volume (p&lt;0.0001), right to left ventricular hypertrophy (p&lt;0.05). Therapeutic regime showed a similar trend as the prophylactic arm but was less effective, mostly lacking significance. However, and importantly, therapeutic LP2 at 1µg/kg/d significantly decreased mRNA expression of collagen 1A1 (p&lt;0.01), of Connective Tissue Growth Factor 1 (p&lt;0.05) and of Tissue MetalloPeptidase inhibitor 1 (p&lt;0.05). In conclusion, a very low dose of 1µg/kg/d LP2 has capacity to counter bleomycin-induced impairment of lung functioning and consequent cardiac remodeling.</p

KOGNITIIVIS-BEHAVIORAALISET INTERVENTIOT TYÖUUPUMUKSEN HOIDOSSA

Työuupumus on yleinen, mutta silti alidiagnosoitu vaiva väestössämme, ja se on muodostunut työelämän kiihtymisen myötä merkittäväksi kansanterveydelliseksi ongelmaksi. Jopa neljänneksen työssäkäyvistä arvioidaan kärsivän vähintään lievästä työuupumuksesta. Työuupumuksen diagnostisia kriteerejä ei ole standardisoitu, ja sitä myös mitataan hyvin erilaisilla mittareilla. Kognitiivis-behavioraaliset menetelmät ja terapiat ovat lupaavia työuupumuksen hoitotapoja. Niiden käyttöä työuupumuksen hoidossa on tutkittu runsaasti, ja tulokset ovat olleet lupaavia. Tämän systemaattisen kirjallisuuskatsauksen tarkoituksena on antaa ajankohtainen katsaus kognitiivis-behavioraalisten menetelmien ja terapioiden hyödyllisyydestä työuupumuksen hoidossa, ja antaa ehdotuksia tulevien interventiotutkimusten laadun parantamiseen, jotta tulevaisuudessa voidaan parantaa työuupuneiden potilaiden tunnistamista ja hoitoa. Katsauksen aineistona toimivat alan keskeisistä PubMed- ja PsycInfo-tietokannoista kerätyt interventiotutkimukset. Laajoin hakulausekkein haetuista tutkimuksista valikoitui ennaltamääritettyjen kriteerien mukaan 23 hoito- tai sekundaaripreventiotutkimusta, joissa hoitomuotona käytettiin kognitiivis-behavioraalisia menetelmiä ja terapioita. Tässä katsauksessa esitellään artikkelien tutkimustuloksia ja pohditaan artikkeleista muodostuvaa kokonaiskuvaa ja sitä, miten tutkimustuloksia voidaan yhdistellä ja hyödyntää työuupumuksesta kärsivien potilaiden hoidossa. Kognitiivis-behavioraalisilla menetelmillä ja terapioilla vaikuttaa olevan selkeää tehoa työuupumuksen hoidossa, mutta tutkimusnäyttö ei ole kiistatonta. Useissa tutkimuksissa interventioryhmän ja kontrolliryhmän välille ei muodostu tilastollisesti merkitseviä eroja työuupumuksesta toipumisessa. Kognitiivis-behavioraalisten menetelmien ja terapioiden tehon kiistattoman varmentamisen esteeksi muodostuu muun muassa interventiotutkimusten kontrolliryhmien rakentamisen vaikeus, työuupumuksen heterogeeninen määrittely, diagnosointi ja mittaaminen sekä kognitiivis-behavioraalisten menetelmien monimuotoisuus. Lisää tutkimuksia aiheesta tarvitaan, ja erityisesti yhtenäistettyjen työuupumuksen diagnoosikriteerien ja mittarien kehittyminen olisi tärkeää työuupumuspotilaiden hoidon kehittymisen mahdollistamiseksi

Being Born Large for Gestational Age is Associated with Increased Global Placental DNA Methylation

Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001)

Pre-Interventional Kynurenine Predicts Medium-Term Outcome after Contrast Media Exposure Due to Coronary Angiography

Background/Aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application. Methods: In this prospective cohort study 245 patients undergoing coronary angiography were analyzed. Blood samples were obtained at baseline, 24h and 48h after contrast media (CM) application to diagnose CI-AKI. Patients were followed for 120 days for adverse clinical events including death, the need for dialysis, and a doubling of plasma creatinine. Occurrence of any of these events was summarized in the combined endpoint MAKE. Results: Preinterventional plasma kynurenine was not associated with CI-AKI. Patients who later developed MAKE displayed significantly increased preinterventional plasma kynurenine levels (p<0.0001). ROC analysis revealed that preinterventional kynurenine is highly predictive for MAKE (AUC=0.838; p<0.0001). The optimal cutoff was found at ≥3.5 µmol/L Using this cutoff, the Kaplan-Meier estimator demonstrated that concentrations of plasma kynurenine ≥3.5 µmol/L were significantly associated with a higher prevalence of MAKE until follow up (p<0.0001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. Conclusion: Preinterventional plasma kynurenine might serve as a highly predictive biomarker for MAKE up to 120 days after coronary angiography

25(OH)VitD and human endocrine and functional fertility parameters in women undergoing IVF/ICSI

Background: Vitamin D plays an important role in reproduction. Evidence shown that free 25-hydroxyvitamin D (25(OH)VitD) was more accurate than total 25(OH)VitD in reflecting the status of 25(OH)VitD during pregnancy. However, the relationship between free 25(OH)VitD and female fertility parameters has not been reported yet. Therefore, this study aims to compare the correlation of free and total 25(OH)VitD with fertility parameters in infertility females undergoing in vitro fertilization and embryo transfer (IVF-ET) or intracytoplasmic sperm injection (ICSI). Methods: According to the inclusion and exclusion criteria, 2569 infertility patients who received IVF-ET or ICSI treatment for the first time participated in this study. Five milliliter peripheral blood samples of the patients were collected on the day before embryo transfer (ET). Enzyme linked immunosorbent assay (ELISA) kits was used to detect free 25(OH)VitD and total 25(OH)VitD, and clinical information was collected. Spearman’s rho was used to evaluate the association between the variables. Results: The median (IQR) of free 25(OH)VitD was 4.71 (4.11-5.31) pg/mL and total 25(OH)VitD was 19.54 (16.52-22.83) ng/m. The correlation between them, however, was week (rho=0.311). Compared to total 25(OH)VitD, free 25(OH)VitD was slightly better correlated with basal follicle-stimulating hormone (FSH) (rho=0.041, P=0.036), basal estradiol (E2) (rho=0.089, P<0.001), anti-Müllerian hormone (AMH) (rho=-0.057, P=0.004), antral follicle count (AFC) (rho=-0.053, P=0.007), E2 (rho=-0.080, P<0.001), number of oocytes retrieval (rho=-0.079, P<0.001) and progesterone (P)/E2 on hCG trigger day (rho=0.081, P<0.001). Conclusions: Overall, there was only a rather weak correlation of free as well as total 25(OH)VitD with human endocrine and functional fertility parameters in women undergoing IVF/ICSI. Neither free nor total 25(OH)VitD seems to play a major role in human embryo implantation

Endothelin‐receptor antagonists for diabetic nephropathy: A meta‐analysis

AimEndothelin‐receptor antagonists may be a novel therapeutic strategy for diabetic nephropathy, but their use remains controversial. This meta‐analysis seeks to evaluate the effectiveness and safety of endothelin‐receptor antagonists for patients with diabetic nephropathy.MethodsLiterature reviews of the PubMed, EMBASE and CENTRAL databases were conducted to identify randomized controlled trials (RCTs) comparing endothelin‐receptor antagonist treatment with placebo in patients with diabetic nephropathy. Quality assessment was performed by using the Cochrane Handbook's tools for assessing risk of bias; meta‐analysis was conducted by RevMan 5.3.ResutlsFive RCTs (n = 2034 patients) were included for analysis. Compared with placebo, endothelin‐receptor antagonists showed significant benefits for lowering albuminuria (five trials, n = 2034 patients; SMD 0.66 95% confidence interval (CI) 0.56 to 0.76), but there was no significant difference in the risk of death (two trials, n = 1674 patients; RR 1.49 95% CI 0.81 to 2.76). In addition, risk of cardiovascular events and other serious adverse events were significantly higher in the endothelin‐receptor antagonists group than the placebo group (four trials, n = 1956 patients; RR 1.45 95% CI 1.07 to 1.97; five trials, n = 2034 patients; RR 1.32 95% CI 1.10 to 1.58).ConclusionEndothelin‐receptor antagonists can reduce albuminuria in patients with diabetic nephropathy, although use resulted in more serious adverse events compared with placebo. There is a potential need for further RCTs, which has larger sample size and longer duration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111994/1/nep12442.pd

Empagliflozin reduces kidney fibrosis and improves kidney function by alternative macrophage activation in rats with 5/6-nephrectomy

Background Sodium glucose cotransporter 2 (SGLT2) inhibitors originally developed for the treatment of type 2 diabetes are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. Methods We generated single-cell transcriptomes of kidneys from rats with 5/6 nephrectomy before and after SGLT2 inhibitors treatment by single-cell RNA sequencing. Findings Empagliflozin treatment decreased BUN, creatinine and urinary albumin excretion compared to placebo by 39.8%, 34.1%, and 55%, respectively (p < 0.01 in all cases). Renal interstitial fibrosis and glomerulosclerosis was likewise decreased by 51% and 66.8%; respectively (p < 0.05 in all cases). 14 distinct kidney cell clusters could be identified by scRNA-seq. The polarization of M2 macrophages from state 1 (CD206-CD68- M2 macrophages) to state 5 (CD206+CD68+ M2 macrophages) was the main pro-fibrotic process, as CD206+CD68+ M2 macrophages highly expressed fibrosis-promoting genes and can convert into fibrocytes. Empagliflozin remarkably inhibited the expression of fibrosis-promoting (IFG1 and TREM2) and polarization-associated genes (GPNMB, LGALS3, PRDX5, and CTSB) in CD206+CD68+ M2 macrophages and attenuated inflammatory signals from CD8+ effector T cells. The inhibitory effect of empagliflozin on CD206+CD68+ M2 macrophages polarization was mainly achieved by affecting mitophagy and mTOR pathways. Interpretation We propose that the beneficial effects of empagliflozin on kidney function and morphology in 5/6 nephrectomyiced rats with established CKD are at least partially due to an inhibition of CD206+CD68+ M2 macrophage polarization by targeting mTOR and mitophagy pathways and attenuating inflammatory signals from CD8+ effector T cells. Fundings A full list of funding bodies that contributed to this study can be found in the Acknowledgements section

DNA methylation of the glucocorticoid receptor gene promoter in the placenta is associated with blood pressure regulation in human pregnancy

BACKGROUND: Blood pressure (BP) regulation during pregnancy is influenced by hormones of placental origin. It was shown that the glucocorticoid system is altered in hypertensive pregnancy disorders such as preeclampsia. Epigenetic mechanism might influence the activity of genes involved in placental hormone/hormone receptor synthesis/action during pregnancy. METHOD: In the current study, we analyzed the association of 5'-C-phosphate-G-3' (CpG) site methylation of different glucocorticoid receptor gene (NR3C1) promoter regions with BP during pregnancy. The study was performed as a nested case-control study (n = 80) out of 1045 mother/child pairs from the Berlin Birth Cohort. Placental DNA was extracted and bisulfite converted. Nested PCR products from six NR3C1 proximal promoter regions [glucocorticoid receptor gene promotor region B (GR-1B), C (GR-1C), D (GR-1D), E (GR-1E), F (GR-1F), and H (GR-1H)] were analyzed by next generation sequencing. RESULTS: NR3C1 promoter regions GR-1D and GR-1E had a much higher degree of DNA methylation as compared to GR-1B, GR-1F or GR-1H when analyzing the entire study population. Comparison of placental NR3C1 CpG site methylation among hypotensive, normotensive and hypertensive mothers revealed several differently methylated CpG sites in the GR-1F promoter region only. Both hypertension and hypotension were associated with increased DNA methylation of GR-1F CpG sites. These associations were independent of confounding factors, such as family history of hypertension, smoking status before pregnancy and prepregnancy BMI. Assessment of placental glucocorticoid receptor expression by western blot showed that observed DNA methylation differences were not associated with altered levels of placental glucocorticoid receptor expression. However, correlation matrices of all NR3C1 proximal promoter regions demonstrated different correlation patterns of intraregional and interregional DNA methylation in the three BP groups, putatively indicating altered transcriptional control of glucocorticoid receptor isoforms. CONCLUSION: Our study provides evidence of an independent association between placental NR3C1 proximal promoter methylation and maternal BP. Furthermore, we observed different patterns of NR3C1 promoter methylation in normotensive, hypertensive and hypotensive pregnancy

Increased global placental DNA methylation levels are associated with gestational diabetes

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus regarding placental epigenetic changes in GDM was set on gene-specific DNA methylation analyses. Studies that robustly investigated placental global DNA methylation are lacking. However, several studies showed that tissue-specific alterations in global DNA methylation are independently associated with type 2 diabetes. Thus, the aim of this study was to characterize global placental DNA methylation by robustly measuring placental DNA 5-methylcytosine (5mC) content and to examine whether differences in placental global DNA methylation are associated with GDM. METHODS: Global DNA methylation was quantified by the current gold standard method, LC-MS/MS. In total, 1030 placental samples were analyzed in this single-center birth cohort study. RESULTS: Mothers with GDM displayed a significantly increased global placental DNA methylation (3.22 ± 0.63 vs. 3.00 ± 0.46 %; p = 0.013; ±SD). Bivariate logistic regression showed a highly significant positive correlation between global placental DNA methylation and the presence of GDM (p = 0.0009). Quintile stratification according to placental DNA 5mC levels revealed that the frequency of GDM was evenly distributed in quintiles 1-4 (2.9-5.3 %), whereas the frequency in the fifth quintile was significantly higher (10.7 %; p = 0.003). Bivariate logistic models adjusted for maternal age, BMI, ethnicity, recurrent miscarriages, and familiar diabetes predisposition clearly demonstrated an independent association between global placental DNA hypermethylation and GDM. Furthermore, an ANCOVA model considering known predictors of DNA methylation substantiated an independent association between GDM and placental DNA methylation. CONCLUSIONS: This is the first study that employed a robust quantitative assessment of placental global DNA methylation in over a thousand placental samples. The study provides large scale evidence that placental global DNA hypermethylation is associated with GDM, independent of established risk factors