Miracle-dz/UniFAR-FTUs huggingface dataset:
Heart Failure in Women With Hypertensive Disorders of Pregnancy

Supplemental Digital Content is available in the text. Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84–2.35], P=0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50–2.68, P<0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (Pinteraction=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.
disorders: State of the art on ethical and legislative aspects in 40 European countries Review/Meta-analysis

Background. Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. Methods. The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. Results. We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. Conclusions. We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
Keratoconus staging by decades: a baseline ABCD classification of 1000 patients in the Homburg Keratoconus Center

Background This retrospective cross-sectional study aims to analyse the keratoconus (KC) stage distribution at different ages within the Homburg Keratoconus Center (HKC). Methods 1917 corneae (1000 patients) were allocated to decades of age, classified according to Belin’s ABCD KC grading system and the stage distribution was analysed. Results 73 per cent (n=728) of the patients were males, 27% (n=272) were females. The highest KC prevalence occurred between 21 and 30 years (n=585 corneae, 294 patients). Regarding anterior (A) and posterior (B) curvature, the frequency of A was significantly higher than B in all age groups for stage 0, 1 and 2 (A0>B0; A1>B1; A2>B2; p<0.03, Wilcoxon matched-pairs test). There was no significant difference between the number of A3 and B3, but significantly more corneae were classified as B4 than A4 in all age groups (p<0.02). The most frequent A|B combinations were A4|B4 (n=451), A0|B0 (n=311), A2|B4 (n=242), A2|B2 (n=189) and A1|B2 (n=154). Concerning thinnest pachymetry (C), most corneae in all age groups were classified as C0>C1>C2>C3>C4 (p<0.04, Wilcoxon matched-pairs test). For the best distance visual acuity (D), a significantly higher number of corneae were classified as D1 compared to D0 (p<0.008; D1>D0>D2>D3>D4). Conclusion The stage distributions in all age groups were similar. Early KC rather becomes manifest in the posterior than the anterior corneal curvature whereas advanced stages of posterior corneal curvature coincide with early and advanced stages of anterior corneal curvature. Thus, this study emphasises the necessity of posterior corneal surface assessment in KC as enabled by the ABCD grading system.
Expression of CRMPs family mRNA in the development of rat hippocampus

Aim:To investigate the expression rule of CRMPs family mRNA in the development of rat hippocampus. Methods: The mRNA of CRMPs was detected using RT-PCR.Results: Limpid electrophoresis strips located in the contrived position.The expression of β-actin was similar in all rats.The most expression of CRMP-1 was in neogentic and juvenile rats,and the least was in adult rats(P0.05). The expression of CRMP-2 be inclined to increase gradually from embryonic to juvenile rats,and the adult rats were less than the others(P0.05). Compared with CRMP-1 and CRMP-2,juvenile and adult rats expressed more CRMP-3,the most was in juvenile rats(P0.05),but the least was in embryonic rats(P0.05). The expression of CRMP-4 was almost in embryonic,neogentic and juvenile rats,but weaker expression in adult rats(P0.05). The expression of CRMP-5 was more in all period and mainly in the neogentic and adult rats,the most was in adult rats(P0.05),the least was in embryonic(P0.05). Conclusion:Exclusive of CRMP-4 stabilized high expression,from embryonic to juvenile,the other members had the tendency to raise gradually.CRMP-3 and CRMP-5 kept up higher expression in adult rats among the family.
Modulation of the Association of Hypobicarbonatemia and Incident Kidney Failure With Replacement Therapy by Venous pH: A Cohort Study.

RATIONALE & OBJECTIVE Studies showing an association between lower bicarbonate levels and worse renal prognosis have not accounted for the influence of pH. It remains unknown whether this association is consistent across a wide range of blood pH. This study sought to assess how pH modifies the relationship between hypobicarbonatemia and incident kidney failure requiring replacement therapy (KFRT). STUDY DESIGN Retrospective cohort study SETTING & PARTICIPANTS: 1,058 Japanese patients with eGFR less than 60 mL/min/1.73m2 EXPOSURE: Baseline venous bicarbonate levels and venous pH. OUTCOME KFRT defined as initiation of renal replacement therapy ANALYTICAL APPROACH: Cox proportional hazards model assessing the interaction between baseline bicarbonate levels and venous pH on incident KFRT RESULTS: In the lowest bicarbonate quartile (≤21.5 mEq/L), 59% of patients had acidemia (pH<7.32), whereas 38% had a venous pH within the normal range and 3% had alkalemia (pH>7.42). Over a median follow-up of 3.0 years, 374 patients developed KFRT. Venous pH modified the association between bicarbonate and the rate of KFRT (P for interaction=0.04). After adjustment for potential confounders, including capacity for respiratory compensation, the lowest (versus the highest) quartile of bicarbonate was associated with a 2.29-fold [95% confidence interval (CI) 1.10-4.77; P=0.03] higher rate of KFRT among patients with acidemia (pH<7.32). In contrast, among patients without acidemia (pH≥7.32), no significant association was found between bicarbonate and KFRT. In an exploratory analysis, patients with higher respiratory compensation capacity had a lower rate of KFRT (hazard ratio 0.90 per 0.1 increase in respiratory compensation capacity; 95% CI 0.87-0.94; P<0.001). LIMITATIONS Observational study design; Blood gas measurements were performed in a selected patient population. CONCLUSIONS Venous pH modified the association of hypobicarbonatemia with progression of chronic kidney disease (CKD) to KFRT. Measurement of venous pH may be valuable for identifying patients with CKD and hypobicarbonatemia and may inform treatment.
Plasma lipidomic analysis of sphingolipids in patients with large artery atherosclerosis cerebrovascular disease and cerebral small vessel disease

Abstract Background: Sphingolipids mainly consist of ceramides (Cer), sphingomyelins (SM) and glycosphingolipids. Sphingolipids are related with coronary heart disease and metabolic disease, but there’re few studies about cerebrovascular disease. The purpose was to detect sphingolipids in plasma of patients with large artery atherosclerosis (LAA) cerebrovascular disease and cerebral small vessel disease (CSVD) to explore the similarities and differences of pathogenesis of the two subtypes. Methods: 20 patients with LAA cerebrovascular disease, 20 patients with age-related CSVD, 10 patients with Fabry disease and 14 controls were enrolled from October 2017 to January 2019. Ultra-high performance liquid chromatography-quadruple-time-of-flight mass spectrometry/mass spectrometry was used to determine sphingolipids. Univariate combined with multivariate analysis was used for comparison. Receiver operating characteristic curves were used to determine sensitivities and specificities. Results: 276 sphingolipids were detected, including 39 Cer, 3 ceramide phosphates, 72 glycosphingolipids and 162 SM. (1) Cer (d36:3), Cer (d34:2), Cer (d38:6), Cer (d36:4) and Cer (d16:0/18:1) were increased in LAA; SM (d34:1), Cer (d34:2), Cer (d36:4), Cer (d16:0/18:1), Cer (d38:6), Cer (d36:3) and Cer (d32:0) were increased in age-related CSVD. (2) Cer (d36:4) and SM (d34:1) were increased in age-related CSVD compared with LAA. (3) Total trihexosyl ceramides were increased in Fabry group compared with control (P<0.05); SM (d34:1) was increased in Fabry group. Conclusions: Ceramides are increased in both LAA and age-related CSVD, which may be related to similar risk factors and pathophysiological process of arteriosclerosis; SM is increased in both age-related CSVD and Fabry disease, suggesting that increased SM may be associated with CSVD. Glycosphingolipids, trihexosylceramides in particular, are increased in Fabry disease.
Beneficial Features of a mHealth Asthma App for Children and Caregivers: Qualitative Study

Background mHealth and uHealth apps are available for children with asthma and their caregivers. However, previous studies on mHealth apps for children older than 7 years old with asthma are limited, and most studies on asthma apps do not consider interactions involving communication between children and caregivers. Therefore, a prototype mHealth child asthma app was developed for children and their caregivers, with features of tailored feedback messages in continuing self-management and interactions between children and caregivers. Objective The aim of this study was to identify the beneficial features of a prototype mHealth app developed for children with asthma and their caregivers. Methods Children diagnosed with persistent asthma by allergy specialists at the National Center for Child Health and Development were recruited. The features of a prototype mHealth app for children with asthma and their caregivers were investigated using semistructured interviews after they tried the app. Data were analyzed using thematic analysis. Content-characteristic words were named and grouped together as categories to explore themes. Results We recruited 27 children with asthma aged 2 to 12 years and 26 their caregivers. Findings on the good aspects of the app for children older than 7 years old and caregivers suggested 4 themes (confirmation of asthma knowledge, child-caregiver interaction, design of the app, and child’s interest), and 6 categories were identified. Findings on the good aspects of app for children 7 to 12 years old and caregivers suggested 5 themes (new knowledge, manga as a Japanese-style comic, child’s interest, trigger of self-management, and design and operability), and 11 categories were identified. Findings on the beneficial features of app suggested 6 themes (asthma knowledge, elements for continuous, universal design, notification, monitoring, and functions), and 12 categories were identified. Conclusions Children with asthma and their caregivers perceived that the good aspects of the app were learning asthma knowledge with fun, including manga; interaction between child and caregiver; and easy-to-read design, such as colors. They wanted not only the asthma knowledge but also the universal design and enhanced elements, monitoring, and notification functions of the app.
Allosteric alpha1-adrenoceptor antagonism by the conopeptide rho-TIA

A peptide contained in the venom of the predatory marine snail Conus tulipa, rho-TIA, has previously been shown to possess alpha1-adrenoreceptor antagonist activity. Here, we further characterize its pharmacological activity as well as its structure-activity relationships. In the isolated rat vas deferens, rho-TIA inhibited alpha1-adrenoreceptor-mediated increases in cytosolic Ca2+ concentration that were triggered by norepinephrine, but did not affect presynaptic alpha2-adrenoreceptor-mediated responses. In radioligand binding assays using [125I]HEAT, rho-TIA displayed slightly greater potency at the alpha1B than at the alpha1A or alpha1D subtypes. Moreover, although it did not affect the rate of association for [3H]prazosin binding to the alpha1B-adrenoreceptor, the dissociation rate was increased, indicating non-competitive antagonism by rho-TIA. N-terminally truncated analogs of rho-TIA were less active than the full-length peptide, with a large decline in activity observed upon removal of the fourth residue of rho-TIA (Arg4). An alanine walk of rho-TIA confirmed the importance of Arg4 for activity and revealed a number of other residues clustered around Arg4 that contribute to the potency of rho-TIA. The unique allosteric antagonism of rho-TIA resulting from its interaction with receptor residues that constitute a binding site that is distinct from that of the classical competitive alpha1-adrenoreceptor antagonists may allow the development of inhibitors that are highly subtype selective.
Persistent high levels of immune activation and their correlation with the HIV-1 proviral DNA and 2-LTR circles loads, in a cohort of Mexican individuals following long-term and fully suppressive treatment.

OBJECTIVES The aim of this study was to investigate the correlation between the HIV-1 reservoir and the levels of immune activation in chronic patients under fully suppressive cART. METHODS We quantified the HIV proviral DNA and 2-LTR circles loads from PBMCs, the levels of CD38+ and Ki-67+ T-cells, and the levels of IL-7 in a cohort of patients with more than 5 years of ART at enrollment and after 1 year. RESULTS In 29 participants with a median of 8 years (IQR, 6.9-9.4) under suppressive cART we found higher levels of CD8+ CD38+ T-cells after 1-year (P = .000). There was a non-statistically significant poor correlation between the levels of immune activation and the proviral DNA of CD4+ and CD8+ T-cells. Ki-67+ T-cells declined without significant differences, and there was no significant correlation with the proportion of CD38+. IL-7 decreased at the follow-up observation (P = .094), but there was no correlation with the levels of CD38+ and Ki-67+ T-cells. CONCLUSIONS We found a weak but non-statistically significant correlation of the levels of T-cell activation with the proviral DNA and 2-LTR circles. This suggests the likely occurrence of further mechanisms driving chronic versus early immune activation other than viral replication by itself in chronic patients.
Transfer and Transcriptomic Profiling in Liver and Brain of European Eels (Anguilla anguilla) After Diet‐borne Exposure to Gold Nanoparticles

A nanometric revolution is underway, promising technical innovations in a wide range of applications and leading to a potential boost in environmental discharges. The propensity of nanoparticles (NPs) to be transferred throughout trophic chains and to generate toxicity was mainly assessed in primary consumers, whereas a lack of knowledge for higher trophic levels persists. The present study focused on a predatory fish, the European eel (Anguilla anguilla) exposed to gold NPs (AuNPs; 10 nm, polyethylene glycol–coated) for 21 d at 3 concentration levels in food: 0 (NP0), 1 (NP1), and 10 (NP10) mg Au kg−1. Transfer was assessed by Au quantification in eel tissues, and transcriptomic responses in the liver and brain were revealed by a high‐throughput RNA‐sequencing approach. Eels fed at NP10 presented an erratic feeding behavior, whereas Au quantification only indicated transfer to intestine and kidney of NP1‐exposed eels. Sequencing of RNA was performed in NP0 and NP1 eels. A total of 258 genes and 156 genes were significantly differentially transcribed in response to AuNP trophic exposure in the liver and brain, respectively. Enrichment analysis highlighted modifications in the immune system–related processes in the liver. In addition, results pointed out a shared response of both organs regarding 13 genes, most of them being involved in immune functions. This finding may shed light on the mode of action and toxicity of AuNPs in fish. Environ Toxicol Chem 2020;39:2450–2461. © 2020 SETAC
Optimization of test conditions: heparinase and lithium chloride can reduce the inhibition effect of haparin on β-actin amplifications during RT-PCR.

Objective To investigate whether heparinase and lithium chloride can reduce the inhibitory effect of heparin on β-actin amplifications when reverse transcription-polymerase chain reaction (RT-PCR) was run in heparinized blood samples.Methods After total RNAs were isolated from 20 clinical heparinized blood samples and identified by electrophoresis, each portion of RNA was divided into three parts; One part did not receive any treatment( group Ⅰ), one part was treated with heparinase Ⅰ 0.4U or 0.5U for very short time, 10 minutes or 60 minutes(group Ⅱ), the third part was treated with lithium chloride at -20℃ for 10 minutes, 60 minutes or overnight(group Ⅲ). RNAs were then reversely transcribed into cDNAs, and housekeeping gene β-actin amplifications were performed by RT-PCR, target fragments obtained were compared on 1% EB-agarose gel electrophoresis.Results Total RNAs were isolated from 20 clinical heparinized blood samples, if their integrity identified by electrophoresis was good, RT-PCR was performed. β-actin amplifications were not observed in group Ⅰ; in group Ⅱ, β-actin amplifications were observed only in sample treated with heprinaseⅠ0.5U for 60 minutes; β-actin amplifications were observed in all the 3 subgroups of group Ⅲ, with β-actin amplified at the greatest intensity in sample treated overnight. Heparinase and lithium chloride were equally effective in reducing the inhibitory effect of heparin during RT-PCR, β-actin amplification quantity were not significantly different between the two groups.Conclusion We found that heparinase Ⅰand lithium chloride can reduce inhibitory effect of heparin on β-actin amplifications when RT-PCR was run in heparinized blood samples, we compared their advantages and disadvantages so that test result can be improved.
Longitudinal analysis of subjective well-being in preadolescents: The role of emotional intelligence, self-esteem and perceived stress

Subjective wellbeing has been conceptualized as a person’s cognitive and affective evaluation of their life. In this line, life satisfaction and somatic complaints may be outstanding indicators of well-being. The aim of this longitudinal study was to analyze the combined contribution of trait emotional intelligence, self-esteem and perceived stress to well-being. Participants were 381 pupils aged 12–16 years (56.1% female). Hierarchical regression models and a fuzzy-set qualitative comparative analysis (QCA) were conducted. Trait emotional intelligence, self-esteem and low perceived stress were related in the expected direction to life satisfaction and somatic complaints. Findings support a specific pathway to improve wellbeing in preadolescents.
A Case of Kikuchi-Fujimoto Disease in a 7-Year-Old African American Patient: A Case Report and Review of Literature

Patient: Female, 7-year-old Final Diagnosis: Kikuchi-Fujimoto lymphadenitis Symptoms: Lymphadenopathy Medication:— Clinical Procedure: Biopsy Specialty: Immunology • Rheumatology Objective: Rare disease Background: Kikuchi-Fujimoto disease (KFD) is a rare self-limited necrotizing lymphadenitis which is likely under-diagnosed in pediatric patients who present with fever of unknown origin and lymphadenopathy. Definitive diagnosis is challenging as it requires an invasive open lymph node biopsy or lymph node needle aspiration cytology that shows pathologic findings of histiocytic necrotizing lymphadenitis. Case Report: We report the case of one of the youngest patients diagnosed with KFD in the United States, at the age of 7 years. KFD has a higher prevalence in patients of Asian descent, but this patient was an African American. This case report shows the often convoluted and complicated course these patients undergo with their presenting complaints of fever of unknown origin and lymphadenopathy and highlights particular clinical findings that suggest KFD. Conclusions: This patient is one of the youngest persons diagnosed with KFD in the United States, with an atypical ethnic background. It is likely that KFD is under-recognized and under-diagnosed in this population. With a broad differential diagnosis for fever of unknown origin and lymphadenopathy, awareness of KFD as a potential diagnosis may reduce other unnecessary investigations. The increased risk of patients with KFD of developing systemic lupus erythematosus (SLE) accentuates the importance of an accurate diagnosis and appropriate referral for heightened surveillance after recovery.
Funktionelle Charakterisierung des 19S regulatorischen Komplexes des 20S Proteasoms sowie Analyse der Biogenese des 20S Proteasoms

V Abkürzungsverzeichnis . VI 1 Einleitung . 1 1.1 Das 20S Proteasom . 1 1.1.1 Aufbau und Struktur des 20S Proteasoms. 1 1.1.2 Katalytische Aktivitäten des Proteasoms . 3 1.1.3 Assemblierung und Reifung des 20S Proteasoms. 5 1.2 Regulatorische Komplexe des 20S Proteasoms . 8 1.2.1 Der regulatorische 19S Komplex . 8 1.2.1.1 Der Aufbau des regulatorischen 19S Komplexes. 8 1.2.1.2 Die Funktionen des 19S Komplexes und seiner Untereinheiten . 9 1.2.2 Der 11S Regulator . 11 1.3 Zelluläre Funktion der proteasomalen Komplexe.11 1.4 Intrazelluläre Lokalisation des Proteasoms.12 1.5 Zielsetzung.12 2 Materialien und Methoden. 14 2.1 Chemikalien . 14 2.2 Oligonukleotide, Vektoren, Stämme und Zellinien.14 2.2.1 Oligonukleotide . 14 2.2.2 Vektoren . 16 2.2.3 E. coli-Stämme . 17 2.2.4 S. cerevisiae-Stämme . 17 2.2.5 Humane Zellinien.18 2.3 Kultur von Mikroorganismen.18 2.3. 1 Medien für E. coli-Kulturen.18 2.3. 2 Medien für S. Cerevisiae-Kulturen . 18 2.3. 3 Kultur von E. coli-Stämmen. 19 2.3. 4 Kultur von Hefezellen . 19 2.3. 5 Kryokonservierung.19 2.4 Zellkultur.19 2.4. 1 Medien für humane Zellinien . 19 2.4. 2 Kultur von humanen Zellinien (Suspensionszellen). 20 2.4. 3 Anlegen von Dauerkulturen (Kryokonservierung). 20 2.5 Molekularbiologische Methoden . 20 2.5. 1 Allgemeine Methoden.20 2.5. 2 DNA-Fällung . 20