The present prospective study investigated whether elevated total serum homocysteine concentration is a risk factor for cognitive decline. The outcomes were compared to the possible relation between ...cognition and vitamin B12 or folic acid. Cognitive performance of 144 normal aging individuals (aged 30-80 years) was tested at baseline and after six years of follow-up. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test) and verbal learning and memory (Word Learning Test Total; Delayed Recall). Serum concentrations of homocysteine, folic acid and vitamin B12 were determined. Serum concentrations of homocysteine correlated negatively with cognitive performance on the Word Learning tests at baseline, independent of age, sex, education level or folic acid concentration. Homocysteine concentration at baseline correlated negatively with cognitive performance on the Stroop and Word Learning tests during the whole six-year follow-up period. The folic acid concentration correlated to the Delayed Recall test at baseline only and no correlations were observed for vitamin B12. Thus, while a relation between vitamin B12 or folic acid and cognition was almost absent, elevated homocysteine concentrations were associated with prolonged lower cognitive performance in this normal aging population.
Molecular defects in genes encoding enzymes involved in homocysteine metabolism may account for mild hyperhomocysteinemia, an independent and graded risk factor for cardiovascular disease (CVD). We ...examined the relationship of two polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, the 677C-->T and 1298A-->C variants, to MTHFR activity, homocysteine concentrations, and risk of CVD in a population of 190 vascular disease patients and 601 apparently healthy controls. The mean specific and residual MTHFR activities were significantly lower in 677CT and 677TT individuals (both P<0.001). The 1298A-->C mutation alone showed no effect on MTHFR activities. However, when the 677C-->T genotype was taken into account, the 1298A-->C mutation also caused a significant decrease in MTHFR activities, which was observed in both the homozygous 1298CC (P<0.001) and the heterozygous 1298AC states (P=0.005). Both the 677TT as the 677CT genotypes were associated with significantly higher fasting and postload homocysteine levels than 677CC (P<0.001 and P=0.003, respectively). The 1298A-->C mutation had no effect on fasting or postload homocysteine levels. Since homocysteine itself is considered to be positively associated with the risk of CVD, these findings indicate that the 1298A-->C mutation cannot be considered a major risk factor for CVD.
In Europe, survival-rates after out-of-hospital cardiac arrest (OHCA) vary widely between regions. Whether a system dispatching First Responders (FRs; main FR-types: firefighters, police officers, ...citizen-responders) is present or not may be associated with survival-rates. This study aimed to assess the association between having a dispatched FR-system and rates of return of spontaneous circulation (ROSC) and survival across Europe.
Results of an inventory of dispatched FR-systems for OHCA in Europe were combined with aggregate ROSC and survival data from the EuReCa-TWO study and additionally collected data. Regression analysis (weighted on number of patients included per region) was performed to study the association between having a dispatched FR-system and ROSC and survival-rates to hospital discharge in the total population and in patients with shockable initial rhythm, witnessed OHCA and bystander cardiopulmonary resuscitation (CPR; Utstein comparator group). For regions without a dispatched FR-system, the theoretical survival-rate if a dispatched FR-system would have existed was estimated.
We included 27 European regions. There were 15,859 OHCAs in the total group and 2,326 OHCAs in the Utstein comparator group. Aggregate ROSC and survival-rates were significantly higher in regions with an FR-system compared to regions without (ROSC: 36% 95%CI 35%-37% vs. 24% 95%CI 23%–25%; P<0.001; survival in total population N=15.859: 13% 95%CI 12%–15% vs. 5% 95%CI 4%–6%; P<0.001; survival in Utstein comparator group N=2326: 33% 95%CI 30%–36% vs. 18% 95%CI 16%–20%; P<0.001), and in regions with more than one FR-type compared to regions with only one FR-type. All main FR-types were associated with higher survival-rates (all P<0.050).
European regions with dispatched FRs showed higher ROSC and survival-rates than regions without.
This project/work has received funding from the European Union's Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381 (IO, HLT and MTB) and the European Union's COST programme under acronym PARQ, registered under grant agreement No CA19137 (IO, DC, HLT, MTB). HLT and MTB were supported by a grant from the Netherlands CardioVascular Research Initiative, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organization for Health Research and Development, Royal Netherlands Academy of Sciences - CVON2017-15 RESCUED (HLT), and CVON2018-30 Predict2 (HLT and MTB).
Objective
The limited number of large fetal cohort studies on common arterial trunk (CAT) impedes prenatal counseling at midgestation. This study evaluates the prognosis of CAT from a fetal ...perspective.
Method
Fetuses with a prenatally diagnosed CAT were extracted from the PRECOR registry (2002–2016). We evaluated fetal and postnatal survival and the presence of additional morbidity at last follow‐up. Literature databases were searches systematically for additional cases.
Results
Thirty‐eight cases with a prenatal diagnosis of CAT were identified in our registry, of which 18/38 (47%) opted for pregnancy termination (TOP). Two cases resulted in spontaneous intrauterine demise (10%, 2/20), six cases demised postnatally (33%, 6/18), leaving 60% (12/20) alive, after exclusion of TOP, at a mean age of six (range: 2–10 years).
Additional morbidity was found in 42% (5/12) of survivors, including 22q11.2 deletion syndrome, Adams‐Oliver syndrome and intestinal atresia, whereas 8% (1/12) had developmental delay. The remaining 30% (6/12) of survivors appeared isolated with normal development. All of whom six required replacement of the initial right ventricle to pulmonary artery conduit. Additionally, we reviewed 197 literature cases on short‐term outcome.
Conclusion
The risk of fetal and neonatal demise, as well as significant morbidity amongst survivors, should be included in prenatal counseling for CAT.
Key Points
What's already known about this topic?
Postnatal cohort studies have reported generally good postoperative results for common arterial trunk (CAT)
Prenatal counseling relies primarily on these selected cohorts, due to the lack of prenatal follow‐up studies
What does this study add?
A large cohort study evaluating outcome of fetal CAT beyond the neonatal period and with regard to the presence of genetic diagnoses, extracardiac malformations and neurodevelopment
The first systematic literature review on short‐term outcome following a prenatal diagnosis of CAT
Background
Chronic urticaria (CU) is a skin condition driven by mast cells and basophils. The exact responsiveness profile of these cells, especially regarding the anti‐IgE treatment, Omalizumab, is ...not fully investigated. We sought to characterize the surface activation profile of basophils in CU during Omalizumab treatment and their responsiveness to IgE and non‐IgE stimulation.
Methods
Whole blood basophils from 11 CU patients and 10 healthy controls were stimulated with either medium, anti‐IgE, fMLP, C5a, or Substance P for 30 min and characterized by flow cytometry.
Results
CU patients showed a broad range of basophil count as opposed to healthy subjects. An increased number of unstimulated CD69+ (p = 0.05), but not CD63+ basophils was observed in CU groups in comparison to healthy. The expression of CD203c and CD200R were comparable between all groups, whilst the FcεRI was reduced with the treatment. Both IgE and non‐IgE mediated stimulations upregulated CD63, CD203c and CD200R, but not CD69 in all groups, however, no difference between the groups was observed. Among unstimulated basophils, expression of MRGPRX2 was higher in CU patients after Omalizumab treatment than in the healthy group (2.4% vs. 1.5%, p = 0.01). The anti‐IgE stimulation increased the number of MRGPRX2‐expressing basophils in the CU group before and after omalizumab as compared to the healthy (p = 0.003; p = 0.005). The fMLP and C5a stimulations showed a similar effect to the IgE‐mediated stimulation. The MRGPRX2 ligand, Substance P did not activate basophils.
Conclusion
CU basophils show increased expression of MRGPRX2 after IgE and non‐IgE stimulation.
The role of basophils as the effector cells in CU is widely recognized, however, several aspects of their biology, phenotype, or function, require further investigation. Basophils in CU showed resting expression of substance P receptor, MRGPRX2, that was significantly increased with IgE and non‐IgE dependent stimulations, indicating a role of the MRGPRX2 pathway in CU. Moreover, a partially preactivated profile defined by the increased expression of the CD69 activation marker was observed on unstimulated (resting) basophils in CU patients.
Injection of adipose-derived mesenchymal stromal cells (ASCs) into murine knee joints after induction of inflammatory collagenase-induced osteoarthritis (CiOA) reduces development of joint pathology. ...This protection is only achieved when ASCs are applied in early CiOA, which is characterized by synovitis and high S100A8/A9 and IL-1β levels, suggesting that inflammation is a prerequisite for the protective effect of ASCs. Our objective was to gain more insight into the interplay between synovitis and ASC-mediated amelioration of CiOA pathology.
CiOA was induced by intra-articular collagenase injection. Knee joint sections were stained with hematoxylin/eosin and immunolocalization of polymorphonuclear cells (PMNs) and ASCs was performed using antibodies for NIMP-R14 and CD271, respectively. Chemokine expression induced by IL-1β or S100A8/A9 was assessed with qPCR and Luminex. ASC-PMN co-cultures were analyzed microscopically and with Luminex for inflammatory mediators. Migration of PMNs through transwell membranes toward conditioned medium of non-stimulated ASCs (ASC
-CM) or IL-1β-stimulated ASCs (ASC
-CM) was examined using flow cytometry. Phagocytic capacity of PMNs was measured with labeled zymosan particles.
Intra-articular saline injection on day 7 of CiOA increased synovitis after 6 h, characterized by PMNs scattered throughout the joint cavity and the synovium. ASC injection resulted in comparable numbers of PMNs which clustered around ASCs in close interaction with the synovial lining. IL-1β-stimulation of ASCs
strongly increased expression of PMN-attracting chemokines CXCL5, CXCL7, and KC, whereas S100A8/A9-stimulation did not. In agreement, the number of clustered PMNs per ASC was significantly increased after 6 h of co-culturing with IL-1β-stimulated ASCs. Also migration of PMNs toward ASC
-CM was significantly enhanced (287%) when compared to ASC
-CM. Interestingly, association of PMNs with ASCs significantly diminished KC protein release by ASCs (69% lower after 24 h), accompanied by reduced release of S100A8/A9 protein by the PMNs. Moreover, phagocytic capacity of PMNs was strongly enhanced after priming with ASC
-CM.
Local application of ASCs in inflamed CiOA knee joints results in clustering of attracted PMNs with ASCs in the synovium, which is likely mediated by IL-1β-induced up-regulation of chemokine release by ASCs. This results in enhanced phagocytic capacity of PMNs, enabling the clearance of debris to attenuate synovitis.
Abstract
Background and Hypothesis
The social deafferentation hypothesis (SDA) has been proposed as an explanatory mechanism of hallucinations, based on the theory that social withdrawal triggers the ...initial phase of schizophrenia. The current study tests the SDA by assessing how loneliness is associated with different types of hallucinations. Under the SDA, increased loneliness is hypothesized to affect the occurrence of hallucinations that carry social meaning, but not of nonsocial hallucinations.
Study Design
As part of an online survey, 2038 adolescents and young adults from the general population (median age 21 years; 75% female) filled out the Questionnaire for Psychotic Experiences, and the shortened De Jong Gierveld Loneliness Scale. Binomial logistic regression was used to investigate the effects of loneliness severity on past month prevalence of hallucinations, and on the presence of social versus nonsocial hallucinations.
Study Results
Loneliness increased the prevalence of hallucinations across modalities in the past month. Moreover, stronger degree of loneliness increased the likelihood of hearing voices or laughter, and of hallucinating being touched. Conversely, loneliness decreased the likelihood of experiencing the nonsocial hallucination of a tingling feeling. As expected, loneliness did not increase the prevalence of experiencing nonsocial hallucinations. Surprisingly, neither was loneliness associated with experiencing felt presence.
Conclusions
Our results are novel in showing that loneliness specifically increases the likelihood of hearing human sounds such as voices or laughter, or feeling a human touch. Hallucinations without social meaning were not more likely to be experienced with increasing loneliness. This forms a confirmation of the SDA.
Micro- and macrovascular complications are common among persons with type 2 diabetes. Recently there has been growing interest to investigate the potential of circulating small non-coding RNAs ...(sncRNAs) as contributors to the development of diabetic complications. In this study we investigate to what extent circulating sncRNAs levels associate with prevalent diabetic kidney disease (DKD) in persons with type 2 diabetes.
Plasma sncRNAs levels were determined using small RNA-seq, allowing detection of miRNAs, snoRNAs, piRNAs, tRNA fragments, and various other sncRNA classes. We tested for differentially expressed sncRNAs in persons with type 2 diabetes, with DKD (n = 69) or without DKD (n = 405). In secondary analyses, we also tested the association with eGFR, albuminuria (UACR), and the plasma proteome.
In total seven sncRNAs were negatively associated with prevalent DKD (all P
≤ 0.05). Including one microRNA (miR-143-5p), five snoRNAs (U8, SNORD118, SNORD24, SNORD107, SNORD87) and a piRNA (piR-019825 | DQ597218). Proteomic analyses showed that the seven sncRNAs, and especially the piRNA piR-019825, were associated with plasma levels of 24 proteins of which several have known associations with kidney function including TNF sR-I (TNFRFS1A), DAN (NBL1) and cystatin C (CST3).
We have identified novel small non-coding RNAs, primarily from classes other than microRNAs, that are associated with diabetic kidney disease. Our results show that the involvement of small non-coding RNAs in DKD goes beyond the already known microRNAs and also involves other classes of sncRNA, in particular snoRNAs and the piRNA piR-019825, that have never been studied before in relation to kidney function.
Colchicine reduces risk of cardiovascular events in patients post–myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of ...onset of treatment following an acute coronary syndrome (ACS).
This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status.
The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed.
In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio HR: 0.81; 95% confidence interval CI: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59).
The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease LoDoCo2 ACTRN12614000093684)
Display omitted
PDF
