-
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 -
International Urology and Nephrology Jun 2024This study evaluates the effectiveness of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system in predicting postoperative complications...
INTRODUCTION
This study evaluates the effectiveness of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system in predicting postoperative complications following radical cystectomy (RC).
MATERIALS AND METHODS
In this single-center retrospective study, we analyzed data from patients who underwent open RC for muscle-invasive bladder cancer by a single surgeon between 2008 and 2023. Cases involving cystectomy for non-urothelial carcinoma or urinary diversion other than ileal conduit were excluded. We recorded patient demographics, body mass index (BMI), history of abdominal/retroperitoneal surgery, ASA score, performance status (PS), and pre-existing conditions, such as hypertension (HT), coronary artery disease (CAD), diabetes mellitus (DM), and chronic kidney disease (CKD). Intraoperative data included surgery duration, blood loss, and need for blood transfusion. Post-operative complications were classified using the Clavien-Dindo system. E-PASS score was calculated using the Preoperative Risk Score (PRS), Surgical Stress Score (SSS), and Comprehensive Risk Score (CRS).
RESULTS
The study included 252 patients. Patients who experienced postoperative complications had higher age, BMI, prior surgical history, ASA score, PS, and rates of CAD, HT, DM, and CKD compared to those who did not. Surgery duration, blood loss, blood transfusion requirement, and E-PASS scores (PRS, SSS, CRS) were also higher in this group. The ROC curve for CRS revealed a predictive cutoff of 0.4911 (AUC = 0.905, p < 0.001). Independent risk factors for postoperative complications included high BMI (p = 0.031), longer surgery duration (p < 0.001), HT (p = 0.042), CKD (p = 0.017), and CRS > 0.4911 (p < 0.001).
CONCLUSION
E-PASS system effectively predicts postoperative complications in RC patients.
PubMed: 38918284
DOI: 10.1007/s11255-024-04134-1 -
Transplantation Reviews (Orlando, Fla.) Jun 2024Pancreatic islet transplantation for type 1 diabetes mellitus (T1DM) is efficacious in supressing severe hypoglycaemic episodes (SHE) and restoring glycaemic regulation,... (Review)
Review
BACKGROUND
Pancreatic islet transplantation for type 1 diabetes mellitus (T1DM) is efficacious in supressing severe hypoglycaemic episodes (SHE) and restoring glycaemic regulation, which are both pivotal in increasing health-related quality of life (HRQoL). Therefore, a systematic assessment of reports detailing HRQoL outcomes is warranted to better understand the benefits of islet transplantation. To this end, we performed a systematic review of the literature to assess the impact of islet transplantation on HRQoL in individuals with T1DM, whether as a standalone procedure (ITA) or following renal transplantation (IAK).
METHOD
All studies providing a quantitative assessment of HRQoL following ITA or IAK were included. Selected studies had to meet the following criteria: they had to (i) involve adult recipients of islet grafts for T1DM, (ii) use either generic or disease-specific QoL assessment tools, (iii) provide a comparative analysis of QoL metrics between the pre- and post-transplantation state or between the post-transplantation state and other pre-transplant patients or the general population.
RESULTS
Seven studies that met the inclusion criteria provided data on 205 subjects. In the included studies, HRQoL was measured using both generic instruments, such as the 36-item Short Form Health Survey (SF-36) and the Health Status Questionnaire (HSQ) 2.0, and disease-specific instruments, such as the Diabetes Distress Scale (DDS), the Diabetes Quality of Life Questionnaire, and the Hypoglycaemia Fear Survey (HFS). These instruments cover physical, mental, social, or functional health dimensions. We found that pancreatic islet transplantation was associated with improvements in all HRQoL dimensions compared with the pre-transplant baseline.
CONCLUSIONS
Our systematic review demonstrates that islet transplantation significantly enhances quality of life in individuals with T1DM who are experiencing SHE. To our knowledge, this is the most extensive systematic review conducted to date, evaluating the impact of islet transplantation on HRQoL.
PubMed: 38917621
DOI: 10.1016/j.trre.2024.100870 -
PloS One 2024Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general...
Changes in blood catecholamines during induction of general anesthesia in patients with post-induction hypotension undergoing laparoscopic cholecystectomy: A single-center prospective cohort study.
BACKGROUND
Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy.
METHODS
This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH.
RESULTS
Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH.
CONCLUSION
The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension.
TRIAL REGISTRATION
ChiCTR2200055549, 12/01/2022.
Topics: Humans; Cholecystectomy, Laparoscopic; Male; Female; Anesthesia, General; Middle Aged; Prospective Studies; Hypotension; Adult; Catecholamines; Blood Pressure; Aged; Norepinephrine; Epinephrine
PubMed: 38917102
DOI: 10.1371/journal.pone.0305980