Blood lipid concentrations are standard clinical biomarkers of cardiovascular disease risk. Replacing dietary saturated fat with unsaturated fat is expected to lower blood lipids. However, meta-analyses are lacking regarding quantifiable differences in blood lipid response between comparable diets rich in mono-(MUFA) and polyunsaturated fat (PUFA), considering food sources and dose-response.

The objective was to compare the effects of "high PUFA" compared with "high MUFA" diets on fasting blood lipids.

PubMed and Web of Science were searched through February 2025 for randomized clinical trials comparing "high PUFA" (≥10% of energy intake from PUFAs) and "high MUFA" (≥15% of energy intake from MUFAs) diets in adults. Reviewers extracted fasting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG). Eligible studies were pooled using random-effects models and expressed as mean differences with 95% confidence interval.

Fifty-three records were included, representing 1690 adult participants. "High PUFA" diets reduced TC [-5.71 (-8.02, -3.40) mg/dL], LDL cholesterol [-3.31 (-5.39, -1.24) mg/dL], HDL cholesterol [-0.77 (-1.27, -0.26) mg/dL], and TG [-6.59 (-8.77, -4.42) mg/dL] compared with "high MUFA" diets. Subgroup analyses showed that the effects of LDL cholesterol (P = 0.03), and TG (P = 0.03) were stronger with oil compared with nut or diet interventions. Metaregressions revealed that the benefit of consuming a "high PUFA" compared with a "high MUFA" diet increases with total fat intake, with a ∼0.5 mg/dL greater reduction in TC (P = 0.01) and LDL cholesterol (P = 0.01) for every 1% increase in energy intake from fat. Cochrane Risk of Bias tool identified some concerns in most of the included records.

High PUFA diets have a small, but significant, advantage for lowering blood lipids compared with high MUFA diets and may be a valuable strategy for improving blood lipids in some populations. This trial was registered at PROSPERO as CRD42023474301 (https://www.crd.york.ac.uk/PROSPERO/view/CRD42023474301).

The incidence of maternal cardiac arrest is rising, paralleling the escalating maternal morbidity and mortality rates in the United States. Effective management of cardiac arrest in pregnancy requires timely initiation of a resuscitative cesarean delivery when indicated. Understanding the history, indications, maternal physiology, and surgical principles of resuscitative cesarean delivery is essential for all clinicians caring for pregnant patients. Resuscitative measures during maternal cardiac arrest have evolved through the centuries-beginning as a burial practice for both mother and baby, evolving further to attempt fetal salvage, and now, to maternal rescue. During this evolution, performing resuscitative cesarean delivery was most effective if initiated within 4 minutes of maternal cardiac arrest. This concept led to the term "4-minute rule" or the principle of initiating a resuscitative cesarean delivery within 4 minutes of arrest to optimize maternal and fetal outcomes. Furthermore, the terminology has also progressed. "Resuscitative cesarean delivery" is now preferred over "perimortem cesarean delivery," emphasizing the goal of maternal resuscitation rather than fetal salvage. Successful maternal resuscitation may occur from resuscitative cesarean delivery due to relieving aortocaval compression by the gravid uterus, thus restoring venous return and cardiac output. Additional benefits include an autotransfusion effect from the uteroplacental circulation and improved oxygenation. Due to this aspect of maternal physiology, resuscitative cesarean delivery is indicated when maternal cardiac arrest occurs at 20 weeks' gestation or greater, or when the fundus is at the level of the umbilicus and should be considered immediately upon cardiac arrest in term patients or in those arriving pulseless from the prehospital setting. Rapid bedside initiation of resuscitative cesarean delivery is critical; transporting the patient to the operating room causes harmful delays. Training multidisciplinary teams to perform resuscitative cesarean delivery at the site of arrest can improve adherence to the "4-minute rule" and survival rates. Surgical technique prioritizes speed and simplicity, favoring a vertical midline skin incision and a vertical uterine incision to minimize vascular injury and facilitate rapid uterine evacuation. Postprocedure, recovery is optimized by proper wound management via broad-spectrum antibiotics and consideration of delayed wound closure, stabilization of uterine hemostasis, and careful application of critical care in the postpartum setting. In summary, resuscitative cesarean delivery is a critical, life-saving intervention during maternal cardiac arrest, providing physiological decompression, enhancing maternal resuscitation efforts, and improving neonatal outcomes. Resuscitative cesarean delivery substantially improves the chances of maternal return of spontaneous circulation and fetal survival in cases of maternal cardiac arrest. Given the persistent rise in maternal morbidity and mortality, increased awareness and readiness to perform resuscitative cesarean delivery using protocolized training and interdisciplinary coordination are imperative to improving maternal and perinatal outcomes in the modern healthcare landscape.

Several illicit drugs have been reported to be associated with ischemic stroke and myocardial infarction. However, the underlying mechanisms remain poorly investigated. In this study, we focused on N-Ethylpentylone (NEP), a synthetic cathinone with potent hallucinogenic property and explored its role in platelet activation.

Platelet function assays and flow cytometry were used to evaluate the effects of NEP on platelet aggregation, spreading, clot retraction, and integrin αIIbβ3 activation. The role of the 5-Hydroxytryptamine2A receptor (5-HT2AR) in NEP-mediated platelet responses was investigated using the selective 5-HT2AR antagonist M100907 in both ex vivo and in vivo. Phosphoproteomics identified NEP-regulated phosphorylation sites, and Western blotting validated mitogen-activated protein kinase (MAPK) pathway activation by targeting key phosphorylation nodes.

NEP significantly potentiated platelet aggregation, spreading, clot retraction, and integrin αIIbβ3 activation in a concentration-dependent manner. The NEP potentiated platelet responses were suppressed by M100907 in both ex vivo and in vivo models, confirming the critical regulatory role of 5-HT2AR. Phosphoproteomics revealed NEP-triggered phosphorylation upregulation, enriched in MAPK pathways. Western blotting confirmed selective ERK and p38 phosphorylation, with no effect on JNK.

NEP directly enhances agonist-induced platelet activation by targeting 5-HT2AR on platelet membranes. The findings of this study provide valuable insights for elucidating the hematotoxic mechanisms of NEP and other illicit drugs.

Thrombosis, when considering all its manifestations including myocardial infarction, stroke, and venous thromboembolism, constitutes the leading cause of death world-wide. Treatment of thrombotic diseases has been revolutionised by direct oral anticoagulants (DOACs) targeting thrombin and FXa. However, the therapeutic or prophylactic use of DOACs is not without limitations, including persistent and significant bleeding risks. In this review, we summarise and discuss current state-of-the-art of novel and experimental anticoagulation and fibrino/thrombolytic therapies beyond DOACs. In particular, we review studies investigating contact pathway inhibition, including in-vitro and in-vivo studies of FXIIa and FXIa inhibition, and clinical trials of contact pathway inhibition. We review in-vitro and in-vivo studies investigating inhibition of common pathway coagulation targets, including FV, FVIII, and FIX. This is followed by analysis of options for the therapeutic targeting of fibrin or fibrinogen, and FXIII. Next, we explore opportunities for the therapeutic harnessing of naturally occurring anticoagulant pathways as well as fibrinolytic mechanisms. The current state-of-the-art research for each of these mechanisms is summarised, including whether studies have progressed from in-vitro to in-vivo experimentation, and whether clinical trials have been performed. We highlight particularly novel areas of interest and include evaluation of the relative preclinical and clinical trial progress for the selected targets. The increased understanding of mechanisms driving thrombosis holds promise for future developments in novel anticoagulants that may contribute to reducing the impact and burden of thrombotic diseases while improving safety of current therapeutic options.

Rupture of atherosclerotic plaques and subsequent acute cardiovascular complications remain a major cause of morbidity and mortality throughout the world. Despite recent advances in treatment, we have not yet identified the means to prevent atherosclerotic vascular disease has not been met. It remains a challenge to determine at an early stage whether an atherosclerotic plaque will become unstable and vulnerable. Therefore, this study aim to identify key risk factors associated with the stability and vulnerability of carotid artery plaques, which may offer valuable insights for the early prevention of cardiovascular and cerebrovascular diseases.

We enrolled a total of 136 patients with stable atherosclerotic plaques and 635 with vulnerable plaques.Arterial stiffness and endothelial dysfunction were assessed using a cardiovascular function monitor and the Endo-PAT2000 device (Itamar Medical Ltd.), respectively. Differences between groups were compared using the Student's t-test for normally distributed data and the chi-square test for non-normally distributed data. We developed a logistic regression to analysed the association of these factors with carotid plaque stability.

Carotid femoral-pulse wave velocity and the reactive hyperaemia index were not different between the stable and unstable plaque groups (cf-PWV: 9.48±2.07, 9.59±1.79, p>0.05; RHI: 1.58±0.57, 1.62±0.39, p>0.05). The male sex, a smoke history, ejection and duration were risk factors for plaque stability. Correlation analysis showed that lipids were not correlated with plaque stability and aortic haemodynamic parameters were correlated with plaque vulnerability. Multivariate logistic regression analysis demonstrated that sex (OR: 0.1759, P<0.001, 95%CI: 0.1077 - 0.2874), Aortic AIx (OR: 1.0366, P<0.001, 95%CI:1.0175 - 1.0560), SEVR (OR:0.9626, P<0.001, 95%CI: 0.9535 - 0.9717) and Distance (OR:0.9854, P<0.001, 95%CI: 0.9804 - 0.9903) were independently correlated with plaque vulnerability.

There was insufficient evidence to indicate that RHI, cf-PWV were related to plaque stability. However, male, decreased of SEVR ,increased of Aortic AIx, and the shorter the distance between carotid-femoral artery had the greater the possibility of vulnerable plaque, which provides a reference for the early prevention of cardiovascular and cerebrovascular diseases.

BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare pediatric condition that can present with rapidly progressive glomerulonephritis and is characterized by necrotizing crescentic glomerulonephritis. While there are no specific pediatric treatment guidelines, rituximab has shown promising benefits in the management of pediatric AAV. This report presents a case of AAV in a 6-year-old girl treated with rituximab and mycophenolate mofetil, resulting in remission that was maintained at 5-year follow-up. CASE REPORT A 6-year-old girl with eczema herpeticum presented with progressive bilateral lower extremity pain, weakness, and intermittent fever and later developed microscopic hematuria. Initial workup revealed proteinuria, elevated inflammatory markers, and renal biopsy findings of pauci-immune crescentic glomerulonephritis, with positive perinuclear ANCA and myeloperoxidase antibodies, confirming AAV. She was initially treated with corticosteroids without improvement, but subsequent rituximab induction followed by mycophenolate mofetil maintenance resulted in clinical improvement. At 5-year follow-up, she remained in remission while receiving enalapril and annual rituximab therapy. CONCLUSIONS This report presents a rare occurrence of AAV in a pediatric patient and demonstrates the challenges in treating this condition given the lack of pediatric-specific treatment protocols. Further research and case reports are essential in the development of standardized and evidence-based treatment strategies tailored to the pediatric population. This case highlights that AAV, while rare in children, can be effectively managed with rituximab and mycophenolate mofetil to achieve long-term remission.

Human pluripotent stem cell (hPSC)-derived GABAergic neurons offer potential for treating neurological disorders by restoring disrupted inhibitory circuits, yet current differentiation methods show limited efficiency, purity, and subtype specificity. We present an approach for generating lateral/caudal ganglionic eminence (LGE/CGE) organoids (LCOs) from hPSC-derived brain organoids (BOs) without external signal induction. LCOs bud from the BO surface and are predominantly composed of LGE/CGE-type GABAergic neurons that mature into functional inhibitory neurons. LCOs and BOs exhibit distinct subtype compositions: LCOs contain both LGE-type neurons, with the capacity to form striatal medium spiny neurons, and abundant CGE-type neurons, whereas BOs contain fewer CGE-type neurons. Single-cell transcriptomic analysis reveals that LCOs closely resemble human embryonic LGE/CGE neurons at gestational weeks 12-13. We also developed a method to selectively enrich CXCR4⁺ CGE-type neurons from LCOs. This platform enables efficient generation of human LGE/CGE-type GABAergic neurons for disease modeling and cell therapy development.

Peripheral immune tolerance is a cardinal feature of the adaptive immune system, which makes self-nonself discrimination and unresponsiveness toward self-antigens. Disruption in the regulation of these processes leads to damage to self-tissues and serious consequences, including autoimmune diseases. In the T cell compartment, the family of regulatory T cells (Treg cells) is the main component for the induction and maintenance of immune tolerance and preventing autoimmune diseases. Forkhead box P3 (FOXP3) is the key transcription factor for the function and Treg cell programming. Importantly, FOXP3 by itself is insufficient to completely specify the Treg cell program, suggesting that additional accessory transcription factors are involved both upstream and downstream, as well as alongside FOXP3, in directing Treg cell specification and its expression is controlled through various regulatory factors and epigenetic modifications. In the current review, we examine new insight into the regulatory mechanisms of Treg cell functions and programming with an emphasis on FOXP3, which opens new avenues for future therapeutic strategies of autoimmune disorders.

Early Life Stress (ELS) increases the risk for mental health issues in humans, notably in major depression and anxiety disorders. ELS is frequently modeled in laboratory rodents by disrupting the early postnatal environment. Literature on ELS is expanding, yet studies on sex-specific differences remain mixed. We utilized a novel ELS protocol that subjected mouse pups of both sexes to maternal separation and removed pup-to-pup contact comfort during postnatal days 10 to 17. We hypothesized that this ELS protocol would induce depressive and anxiety-like phenotypes persisting into adulthood, with greater vulnerability in females. A second cohort reared under normal conditions until adulthood was subjected to forced swim, mimicking adult-onset stress (AS). ELS, AS, and control animals (reared under normal conditions) underwent open field, social interaction, and tail suspension tests. In open field, AS mice spent significantly less time in center than controls. Social interaction showed significant effects of treatment and sex, with stress exposure increasing familiar-mouse interaction time and reducing the sex difference observed in controls. Tail suspension testing revealed a significant decrease in latency to immobility for stress groups compared to controls. Total time immobile showed significant group and interaction effects, with stress groups showing more time immobile. Both social interaction and tail suspension revealed a sex difference in controls, eliminated in stress groups. This ELS protocol produces lasting alterations in adult social and coping-related behaviors and demonstrates multiple sex-specific outcomes.

Women’s Mental Health @Obstetrics and Gynecology (WMH @Ob/Gyn) is a novel, insurance-based clinical model integrated in Ob/Gyn practices that offers approachable, acceptable, available, and affordable mental healthcare to women across the lifespan. Women seen by Ob/Gyn physicians for physical healthcare needs are referred to the WMH @Ob/Gyn service based on patient request, provider observation, and/or results on universal depression screening. WMH@Ob/Gyn’ services include mental health screening, psychotherapy, psychopharmacology and support groups, all embedded into Ob/Gyn. Here, we sought to evaluate utilization rates of mental health services as an outcome of increased access resulting from real-world implementation of WMH @Ob/Gyn.

This prospective observational cohort study followed all patients referred to WMH @Ob/Gyn from 02/2020 to 12/2022. Data were obtained from a clinical registry and patient electronic health records. Utilization was estimated on initiation (proportion of women who attended at least one mental health visit), and sustainment (proportion of women who attended three or more visits).

2,661 women were referred to WMH @Ob/Gyn; 65% initiated, out of which 36% sustained treatment. Hispanic/Latina/Spanish women were less likely to initiate treatment. Of those who initiated, women whose insurance was non-participating in mental healthcare, women that were not pregnant, and younger women, had lower odds of sustaining treatment.

WMH @Ob/Gyn facilitates the initiation and sustainment of mental health treatment at rates considerably higher than those observed in comparable perinatal-integrated programs or the general population. However, persistent systemic barriers, including disparities in physical and mental health insurance coverage, continue to constrain equitable, sustained access to mental healthcare.

The online version contains supplementary material available at 10.1007/s00737-025-01652-4.