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International Journal of Molecular... Jun 2024Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought...
Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Fetal biometric data and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β = 0.39, < 0.05), while the amniotic laeverin level correlated well with the abdominal circumference of the fetus (β = 0.44, < 0.05). Furthermore, laeverin level in the amnion correlated positively with the estimated fetal weight (β = 0.48, < 0.05) and with the placental volume (β = 0.32, < 0.05). Logistic regression analyses revealed that a higher circulating Gal-13 level represents a slightly significant risk factor (OR: 1.01) for hypertension-related diseases during pregnancy. It is a novelty that laeverin can be detected in the amniotic fluid, and amnion laeverin concentration represents a potential biomarker of fetoplacental growth.
Topics: Humans; Pregnancy; Female; Adult; Galectins; Placenta; Amniotic Fluid; Biomarkers; Pre-Eclampsia; Fetal Development; Gestational Age; Pregnancy Proteins; Metalloproteases
PubMed: 38928055
DOI: 10.3390/ijms25126347 -
Biomolecules Jun 2024The origin of pre-existing cognitive impairment in stroke patients remains controversial, with a vascular or a degenerative hypothesis.
BACKGROUND
The origin of pre-existing cognitive impairment in stroke patients remains controversial, with a vascular or a degenerative hypothesis.
OBJECTIVE
To determine whether endothelial dysfunction is associated with pre-existing cognitive problems, lesion load and biological anomalies in stroke patients.
METHODS
Patients originated from the prospective STROKDEM study. The baseline cognitive state, assessed using the IQ-CODE, and risk factors for stroke were recorded at inclusion. Patients with an IQ-CODE score >64 were excluded. Endothelial function was determined 72 h after stroke symptom onset by non-invasive digital measurement of endothelium-dependent flow-mediated dilation and calculation of the reactive hyperemia index (RHI). RHI ≤ 1.67 indicated endothelial dysfunction. Different biomarkers of endothelial dysfunction were analysed in blood or plasma. All patients underwent MRI 72 h after stroke symptom onset.
RESULTS
A total of 86 patients were included (52 males; mean age 63.5 ± 11.5 years). Patients with abnormal RHI have hypertension or antihypertensive treatment more often. The baseline IQ-CODE was abnormal in 33 (38.4%) patients, indicating a pre-existing cognitive problem. Baseline IQ-CODE > 48 was observed in 15 patients (28.3%) with normal RHI and in 18 patients (54.6%) with abnormal RHI ( = 0.016). The RHI median was significantly lower in patients with abnormal IQ-CODE. Abnormal RHI was associated with a significantly higher median FAZEKAS score (2.5 vs. 2; = 0.008), a significantly higher frequency of periventricular lesions ( = 0.015), more white matter lesions ( = 0.007) and a significantly higher cerebral atrophy score ( < 0.001) on MRI. Vascular biomarkers significantly associated with abnormal RHI were MCP-1 ( = 0.009), MIP_1a ( = 0.042), and homocysteinemia ( < 0.05).
CONCLUSIONS
A vascular mechanism may be responsible for cognitive problems pre-existing stroke. The measurement of endothelial dysfunction after stroke could become an important element of follow-up, providing an indication of the functional and cognitive prognosis of stroke patients.
Topics: Humans; Male; Female; Middle Aged; Stroke; Aged; Endothelium, Vascular; Prospective Studies; Cognitive Dysfunction; Biomarkers; Magnetic Resonance Imaging; Risk Factors
PubMed: 38927124
DOI: 10.3390/biom14060721 -
Reproductive Health Jun 2024Endometriosis is a chronic and debilitating disease that can affect the entire reproductive life course of women, with potential adverse effects on pregnancy. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis is a chronic and debilitating disease that can affect the entire reproductive life course of women, with potential adverse effects on pregnancy. The aim of the present study is to investigate the association between hypertensive disorders in pregnancy and endometriosis.
METHOD
Relevant articles were searched from the Cochrane Library, PubMed, Scopus and Web of Science from inception up to December 2023. The full-text observational studies published in English that had a confirmed diagnosis of endometriosis were included. The case group included pregnant women diagnosed with endometriosis at any stage, while the control group consisted of pregnant women who had not been previously diagnosed with endometriosis. Two authors extracted and analyzed the data independently. Disagreements were reconciled by reviewing the full text by a third author. Endnote X9 was used for screening and data extraction. We used fixed and random effects models in Review Manager 5.3 to analyze the pooled data. The quality of the included studies was assessed using the Downs and Black checklist.
RESULTS
Out of the 9863 articles reviewed, 23 were selected for meta-analysis. According to the results of this study, there was an association between endometriosis and gestational hypertension (OR = 1.11, 95% CI: 1.06, 1.16; I = 45%, P < 0.00001; N = 8), pre-eclampsia (OR = 1.26, 95% CI: 1.18, 1.36; I = 37%, P < 0.00001; N = 12), and hypertensive disorders in pregnancy (OR = 1.13, 95% CI: 1.06, 1.21; I = 8%, P = 0.0001; N = 8).
CONCLUSIONS
This study confirmed that endometriosis may elevate the risk of developing gestational hypertensive disorders. Raising awareness of this issue will help to identify effective strategies for screening and early diagnosis of hypertensive disorders in pregnancy.
Topics: Humans; Female; Pregnancy; Endometriosis; Hypertension, Pregnancy-Induced; Pre-Eclampsia
PubMed: 38926850
DOI: 10.1186/s12978-024-01833-x -
International Journal of Developmental... Jun 2024Autism spectrum disorder (ASD) is a set of neurobehavioral manifestations that impose poor social interaction and stereotyped repetitive patterns. Several mircoRNA...
Autism spectrum disorder (ASD) is a set of neurobehavioral manifestations that impose poor social interaction and stereotyped repetitive patterns. Several mircoRNA (miRNA) dysregulations underpin ASD pathophysiology via impairing the neurogenic niches. For instance, miR-146a and miR-106 differential expressions are linked to deregulation of ASD-related genes and the severity of clinical symptoms, respectively. Breastfeeding provides newborns with many bioactive compounds that support their neurodevelopment including miRNA. Our pilot study evaluated the expression pattern of miR-106a and miR-146a in human milk (HM) of nursing mothers (n = 36) having autistic children compared to age-matched counterparts (n = 36) with neurotypical children as controls. Under sterile conditions, breast milk samples were collected using manual sucking pumps and centrifuged to separate the fat layer. Total RNA was extracted from the lipid fraction, and the expression profiles of both miR-106a and miR-146a were evaluated using quantitative real-time polymerase chain reaction. Among the test group, we reported some factors that were previously linked to HM miRNA perturbations: gestational diabetes, hypertension, and cesarean delivery. HM miR-106a showed comparable expression levels in both mother groups (p = 0.8681), whereas HM miR-146a was significantly downregulated in mothers with autistic children compared to controls (p = 0.0399). Alternatively, HM miR-106 levels were positively associated with two ASD clinical parameters: Childhood Autism Rating Scale (CARS) and communication and language domain of Autism Diagnostic Interview-Revised (ADI-R) (r = 0.6452, p = 0.0003 and r = 0.3958, p = 0.0410, respectively). The receiver operating characteristic (ROC) curves of both maternal HM miR-106a and miR-146a showed poor fitness as predictive biomarkers for ASD. Our findings suggest that the miR-146a differential expression in ASD children may originate at infancy during the lactation period. Thus, maternal pre- and postnatal health care is critical to maintain optimal miRNome in breast milk.
PubMed: 38922970
DOI: 10.1002/jdn.10353 -
Neurology International May 2024: This study aims to develop and validate the Futile Recanalization Prediction Score (FRPS), a novel tool designed to predict the severity risk of FR and aid in pre- and...
Introducing the Futile Recanalization Prediction Score (FRPS): A Novel Approach to Predict and Mitigate Ineffective Recanalization after Endovascular Treatment of Acute Ischemic Stroke.
: This study aims to develop and validate the Futile Recanalization Prediction Score (FRPS), a novel tool designed to predict the severity risk of FR and aid in pre- and post-EVT risk assessments. : The FRPS was developed using a rigorous process involving the selection of predictor variables based on clinical relevance and potential impact. Initial equations were derived from previous meta-analyses and refined using various statistical techniques. We employed machine learning algorithms, specifically random forest regression, to capture nonlinear relationships and enhance model performance. Cross-validation with five folds was used to assess generalizability and model fit. The final FRPS model included variables such as age, sex, atrial fibrillation (AF), hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, cognitive impairment, pre-stroke modified Rankin Scale (mRS), systolic blood pressure (SBP), onset-to-puncture time, sICH, and NIHSS score. The random forest model achieved a mean R-squared value of approximately 0.992. Severity ranges for FRPS scores were defined as mild (FRPS < 66), moderate (FRPS 66-80), and severe (FRPS > 80). : The FRPS provides valuable insights for treatment planning and patient management by predicting the severity risk of FR. This tool may improve the identification of candidates most likely to benefit from EVT and enhance prognostic accuracy post-EVT. Further clinical validation in diverse settings is warranted to assess its effectiveness and reliability.
PubMed: 38921949
DOI: 10.3390/neurolint16030045 -
European Journal of Investigation in... Jun 2024the objective of this longitudinal study (from pregnancy to the end of the sixth month postpartum) is to elucidate the association between maternal self-efficacy,...
BACKGROUND
the objective of this longitudinal study (from pregnancy to the end of the sixth month postpartum) is to elucidate the association between maternal self-efficacy, defined as a mother's confidence in her ability to breastfeed, and breastfeeding outcomes.
METHODS
This prospective cohort study was conducted among high-risk pregnant women (including those with conditions such as gestational diabetes, hypertension, pre-eclampsia, and other pathological medical conditions) and normal-risk pregnant women in Greece. The high-risk group included 164 women, while the normal-risk group comprised 154 women. Data were collected using validated psychometric scales, including the Breastfeeding Self-Efficacy Scale-Short Form, State-Trait Anxiety Inventory, Edinburgh Postnatal Depression Scale, Maternal Antenatal Attachment Scale, and Iowa Infant Feeding Attitude Scale.
RESULTS
Higher maternal self-efficacy was significantly associated with a longer duration and greater exclusivity of breastfeeding. A statistically significant relationship between the type of breastfeeding and the degree of breastfeeding self-efficacy was observed at multiple postpartum milestones: in the first and third 24 h postpartum, and at the end of the sixth week, third month, and sixth month postpartum.
CONCLUSION
The findings underscore the critical role of maternal self-efficacy in breastfeeding success, influenced by individual psychological factors and broader socio-cultural contexts. Strengthening maternal self-efficacy is essential for improving breastfeeding outcomes.
PubMed: 38921085
DOI: 10.3390/ejihpe14060119 -
Frontiers in Immunology 2024Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit...
INTRODUCTION
Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit cytotoxic responses against malignant B cells. However, efficacy is often compromised due to a suppressive microenvironment that interferes with cellular immune responses. To overcome this suppression, agonists of pattern recognition receptors have been studied which promote direct cytotoxicity or elicit anti-tumoral immune responses. NOD2 is an intracellular pattern recognition receptor that participates in the detection of peptidoglycan, a key component of bacterial cell walls. This detection then mediates the activation of multiple signaling pathways in myeloid cells. Although several NOD2 agonists are being used worldwide, the potential benefit of these agents in the context of antibody therapy has not been explored.
METHODS
Primary cells from healthy-donor volunteers (PBMCs, monocytes) or CLL patients (monocytes) were treated with versus without the NOD2 agonist L18-MDP, then antibody-mediated responses were assessed. In vivo, the Eµ-TCL1 mouse model of CLL was used to test the effects of L18-MDP treatment alone and in combination with anti-CD20 antibody.
RESULTS
Treatment of peripheral blood mononuclear cells with L18-MDP led to activation of monocytes from both healthy donors and CLL patients. In addition, there was an upregulation of activating FcγR in monocytes and a subsequent increase in antibody-mediated phagocytosis. This effect required the NF-κB and p38 signaling pathways. Treatment with L18-MDP plus anti-CD20 antibody in the Eµ-TCL model of CLL led to a significant reduction of CLL load, as well as to phenotypic changes in splenic monocytes and macrophages.
CONCLUSIONS
Taken together, these results suggest that NOD2 agonists help overturn the suppression of myeloid cells, and may improve the efficacy of antibody therapy for CLL.
Topics: Nod2 Signaling Adaptor Protein; Animals; Humans; Receptors, IgG; Mice; Macrophages; Leukemia, Lymphocytic, Chronic, B-Cell; Acetylmuramyl-Alanyl-Isoglutamine; Female; Mice, Inbred C57BL; Signal Transduction; Phagocytosis; Rituximab
PubMed: 38919608
DOI: 10.3389/fimmu.2024.1409333 -
Frontiers in Cardiovascular Medicine 2024High blood pressure is a major risk factor for cardiac remodeling and left ventricular hypertrophy, increasing cardiovascular risk and leading to heart failure with...
BACKGROUND
High blood pressure is a major risk factor for cardiac remodeling and left ventricular hypertrophy, increasing cardiovascular risk and leading to heart failure with preserved ejection fraction (HFpEF). Since renal sympathetic denervation (RDN) reduces blood pressure in the long term, we aimed to investigate the long-term effect of RDN in patients with HFpEF in the present analysis.
METHODS
Patients previously enrolled in a local RDN registry who underwent high-frequency RDN with the use of the Symplicity Flex® renal denervation system between 2011 and 2014 were followed up. The patients were assessed by 24-h ambulatory blood pressure measurement, transthoracic echocardiography, and laboratory tests. We used the echocardiographic and biomarker criteria of the Heart Failure Association (HFA)-PEFF (Pre-test assessment, Echocardiography and Natriuretic Peptide Score, Funkctional testing, and Final aetiology) score to identify patients with HFpEF.
RESULTS
Echocardiographic assessment was available for 70 patients at a 9-year long-term follow-up. Of these patients, 21 had HFpEF according to the HFA-PEFF score. We found a significant reduction of the HFA-PEFF score from 5.48 ± 0.51 points at baseline to 4.33 ± 1.53 points at the 9-year follow-up ( < 0.01). This decrease was due to a greater reduction in morphological and biomarker subcategories [from 1.95 ± 0.22 to 1.43 ± 0.51 points ( < 0.01) and from 1.52 ± 0.52 to 0.90 ± 0.63 points ( < 0.01), respectively] than in the functional one. Morphologically, there was a reduction in left ventricular hypertrophy and left atrial dilation.
CONCLUSIONS
The present analysis suggests that RDN may lead to a regression of the extent of HFpEF beyond a reduction in blood pressure and thus possibly contribute to an improvement in prognosis. More detailed information will be provided by ongoing randomized sham-controlled trials.
PubMed: 38919545
DOI: 10.3389/fcvm.2024.1408547 -
Clinical Kidney Journal Jun 2024This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum...
BACKGROUND
This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum calcification propensity (T50 time) and decrease calciprotein particle (CPP) load in hemodialysis patients with secondary hyperparathyroidism.
METHODS
In this single-arm, prospective, dose-escalation proof-of-principle study, hemodialysis patients received etelcalcetide at 2.5 mg/dialysis session with increments of 2.5 mg every 4 weeks to a maximum dose of 15 mg three times a week or until a pre-specified safety endpoint was reached, followed by an 8-week wash-out phase.
RESULTS
Out of 36 patients recruited (81% male, 62 ± 13 years), 16 patients completed the study per protocol with a mean maximum tolerated dose of etelcalcetide of 9.5 ± 2.9 mg/dialysis session. With escalating doses of etelcalcetide, PTH and serum calcium levels significantly decreased (< 0.0001). While there was no significant change in T50 times or serum phosphate levels, etelcalcetide did yield significant and consistent reductions in serum levels of endogenous calciprotein monomers [-35.4 (-44.4 to -26.5)%, < 0.0001], primary [-22.4 (-34.5 to -10.3)%, < 0.01] and secondary CPP [-29.1 (-45.7 to -12.4)%, < 0.01], an effect that was reversed after therapy withdrawal. Serum levels of osteoclastic markers significantly decreased with escalating doses of etelcalcetide, while levels of the osteoblastic marker remained stable.
CONCLUSIONS
Lowering of PTH with etelcalcetide did not result in statistically significant changes in T50. By contrast, homogenous reductions in serum levels of calciprotein monomers, primary and secondary CPP were observed.
PubMed: 38919277
DOI: 10.1093/ckj/sfae097 -
Scientific Reports Jun 2024A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder... (Observational Study)
Observational Study
A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses. To assess the population prevalence of iciHHV-6, we studied whole-genome sequencing data from blood-derived DNA of 3421 biobank subjects. Any herpes viral DNA was detected in only two (0.37%) PE and one (0.14%) control sample (OR 2.74, 95% CI 0.25-30.4). One PE sample contained iciHHV-6B and another HHV-7 DNA. The control's DNA was of iciHHV-6B; the fetus having growth restriction and preterm birth without PE diagnosis. Placentas showed no herpesviruses. In the biobank data, 3 of 3421 subjects (0.08%) had low level HHV-6B but no iciHHV-6. While iciHHV-6 proved extremely rare, both fetuses with iciHHV-6B were growth-restricted, preterm, and from a pregnancy with maternal hypertension. Our findings suggest that human herpesviruses are not a significant cause of PE, whereas iciHHV-6 may pose some fetal risk.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Adult; Herpesvirus 6, Human; Cohort Studies; Fetal Blood; Finland; DNA, Viral; Placenta; Herpesviridae
PubMed: 38918446
DOI: 10.1038/s41598-024-65386-6