Nonimmune Hydrops Fetalis.

Nonimmune hydrops fetalis (NIHF) poses a significant challenge in perinatal care due to its high mortality rates and diverse etiologies. This comprehensive review examines the pathophysiology, etiology, antenatal diagnosis and management, postnatal care, and outcomes of NIHF. NIHF arises from numerous underlying pathologies, including genetic disorders, cardiovascular causes, and fetal infections, with advances in diagnostic techniques improving identification rates.

Scoring Central Nervous System Inflammation, Demyelination, and Axon Injury in Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a common immune-based model of multiple sclerosis (MS). This disease can be induced in rodents by active immunization with protein components of the myelin sheath and Complete Freund's adjuvant (CFA) or by the transfer of myelin-specific T effector cells from rodents primed with myelin protein/CFA into naïve rodents. The severity of EAE is typically scored on a 5-point clinical scale that measures the degree of ascending paralysis, but this scale is not optimal for assessing the extent of recovery from EAE.

Mechanisms and consequences of sex differences in immune responses.

Biological sex differences refer to differences between males and females caused by the sex chromosome complement (that is, XY or XX), reproductive tissues (that is, the presence of testes or ovaries), and concentrations of sex steroids (that is, testosterone or oestrogens and progesterone). Although these sex differences are binary for most human individuals and mice, transgender individuals receiving hormone therapy, individuals with genetic syndromes (for example, Klinefelter and Turner syndromes) and people with disorders of sexual development reflect the diversity in sex-based biology. The broad distribution of sex steroid hormone receptors across diverse cell types and the differential expression of X-linked and autosomal genes means that sex is a biological variable that can affect the function of all physiological systems, including the immune system.

Potential biological contributers to the sex difference in multiple sclerosis progression.

Multiple sclerosis (MS) is an immune-mediated disease that targets the myelin sheath of central nervous system (CNS) neurons leading to axon injury, neuronal death, and neurological progression. Though women are more highly susceptible to developing MS, men that develop this disease exhibit greater cognitive impairment and accumulate disability more rapidly than women. Magnetic resonance imaging and pathology studies have revealed that the greater neurological progression seen in males correlates with chronic immune activation and increased iron accumulation at the rims of chronic white matter lesions as well as more intensive whole brain and grey matter atrophy and axon loss.

Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA individuals without a systemic autoimmune rheumatic disease diagnosis.

Background: Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA individuals and investigated their utility as biomarkers of clinical progression.

Effect of puberty on the immune system: Relevance to multiple sclerosis.

Puberty is a dynamic period marked by changing levels of sex hormones, the development of secondary sexual characteristics and reproductive maturity. This period has profound effects on various organ systems, including the immune system. The critical changes that occur in the immune system during pubertal onset have been shown to have implications for autoimmune conditions, including Multiple Sclerosis (MS).

Immune Cell Contributors to the Female Sex Bias in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS) that leads to axonal damage and accumulation of disability. Relapsing-remitting MS (RR-MS) is the most frequent presentation of MS and this form of MS is three times more prevalent in females than in males. This female bias in MS is apparent only after puberty, suggesting a role for sex hormones in this regulation; however, very little is known of the biological mechanisms that underpin the sex difference in MS onset.

Peroxisome Proliferator-Activated Receptor-δ Deficiency in Microglia Results in Exacerbated Axonal Injury and Tissue Loss in Experimental Autoimmune Encephalomyelitis.

Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear receptor that functions to maintain metabolic homeostasis, regulate cell growth, and limit the development of excessive inflammation during immune responses. Previously, we reported that PPAR-δ-deficient mice develop a more severe clinical course of experimental autoimmune encephalomyelitis (EAE); however, it was difficult to delineate the role that microglia played in this disease phenotype since PPAR-δ-deficient mice exhibited a number of immune defects that enhanced CNS inflammation upstream of microglia activation. Here, we specifically investigated the role of PPAR-δ in microglia during EAE by using mice where excision of a floxed allele was driven by expression of a tamoxifen (TAM)-inducible CX3C chemokine receptor 1 promoter-Cre recombinase transgene (: ).

Pro-inflammatory adiponectin in pediatric-onset multiple sclerosis.

Background: Being obese is associated with both increased risk of developing multiple sclerosis (MS) and greater MS disease activity.

Objectives: The objective of this study is to investigate levels and potential pathophysiologic contribution of serum adipose-hormones (adipokines) in pediatric-onset MS.

Methods: Following a Luminex adipokine screen, adiponectin (APN) and its isoforms were quantified by enzyme-linked immunosorbent assay (ELISA) in 169 children with incident acquired demyelinating syndromes (ADS), prospectively ascertained as having either MS or other forms of inflammatory central nervous system (CNS) demyelination.

Thioredoxin deficiency exacerbates vascular dysfunction during diet-induced obesity in small mesenteric artery in mice.

Objective: Thioredoxin (Trx) is a small cellular redox protein with established antioxidant and disulfide reductase properties. We hypothesized that Trx deficiency in mice would cause increased oxidative stress with consequent redox imbalance that would exacerbate obesity-induced vascular dysfunction.

Methods: Non-transgenic (NT, C57BL/6) and dominant-negative Trx (dnTrx-Tg, low levels of redox-active protein) mice were either fed a normal diet (NC) or high fat diet plus sucrose (HFS) diet for 4 months (3-month HFD+ 1-month HFS).

Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis.

The cysteine protease inhibitor Cystatin C (CST3) is highly expressed in the brains of multiple sclerosis (MS) patients and C57BL/6J mice with experimental autoimmune encephalomyelitis (EAE; a model of MS), but its roles in the diseases are unknown. Here, we show that CST3 plays a detrimental function in myelin oligodendrocyte glycoprotein 35-55 (MOG)-induced EAE but only in female animals. Female Cst3 null mice display significantly lower clinical signs of disease compared to wild-type (WT) littermates.

COVID-19 and Religious Ethics.

The editors of the solicited short essays on the COVID-19 pandemic from a group of scholars of religious ethics that reflected on how the field might help them make sense of the complex religious, cultural, ethical, and political implications of the pandemic, and on how the pandemic might shape the future of religious ethics.

Aged hind-limb clasping experimental autoimmune encephalomyelitis models aspects of the neurodegenerative process seen in multiple sclerosis.

Experimental autoimmune encephalomyelitis (EAE) is the most common model of multiple sclerosis (MS). This model has been instrumental in understanding the events that lead to the initiation of central nervous system (CNS) autoimmunity. Though EAE has been an effective screening tool for identifying novel therapies for relapsing-remitting MS, it has proven to be less successful in identifying therapies for progressive forms of this disease.

Peroxisome Proliferator-Activated Receptor-δ Acts within Peripheral Myeloid Cells to Limit Th Cell Priming during Experimental Autoimmune Encephalomyelitis.

Peroxisome proliferator-activated receptor (PPAR)-δ is a fatty acid-activated transcription factor that regulates metabolic homeostasis, cell growth, and differentiation. Previously, we reported that mice with a global deficiency of PPAR-δ develop an exacerbated course of experimental autoimmune encephalomyelitis (EAE), highlighting a role for this nuclear receptor in limiting the development of CNS inflammation. However, the cell-specific contribution of PPAR-δ to the more severe CNS inflammatory response remained unclear.

Voluntary wheel running reveals sex-specific nociceptive factors in murine experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an inflammatory, neurodegenerative autoimmune disease associated with sensory and motor dysfunction. Although estimates vary, ∼50% of patients with MS experience pain during their disease. The mechanisms underlying the development of pain are not fully understood, and no effective treatment for MS-related pain is available.

Peroxisome Proliferator-Activated Receptor-δ Supports the Metabolic Requirements of Cell Growth in TCRβ-Selected Thymocytes and Peripheral CD4 T Cells.

During T cell development, progenitor thymocytes undergo a large proliferative burst immediately following successful TCRβ rearrangement, and defects in genes that regulate this proliferation have a profound effect on thymus cellularity and output. Although the signaling pathways that initiate cell cycling and nutrient uptake after TCRβ selection are understood, less is known about the transcriptional programs that regulate the metabolic machinery to promote biomass accumulation during this process. In this article, we report that mice with whole body deficiency in the nuclear receptor peroxisome proliferator-activated receptor-δ (PPARδ) exhibit a reduction in spleen and thymus cellularity, with a decrease in thymocyte cell number starting at the double-negative 4 stage of thymocyte development.

Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection.

T cells represent a critical effector of cell-mediated immunity. Activated T cells engage in metabolic reprogramming during effector differentiation to accommodate dynamic changes in energy demands. Here, we show that the hormone, insulin, and downstream signaling through its insulin receptor shape adaptive immune function through modulating T cell metabolism.

Prenatal intent and postpartum receipt of long-acting reversible contraception among women receiving medication-assisted treatment for opioid use disorder.

Background: Many women with opioid use disorder (OUD) do not use highly effective postpartum contraception such as long-acting reversible contraception (LARC). We evaluated factors associated with prenatal intent and postpartum receipt of LARC among women receiving medication-assisted treatment (MAT) for OUD.

Study Design: This was a retrospective cohort study of 791 pregnant women with OUD on MAT who delivered at an academic institution without immediate postpartum LARC services between 2009 and 2012.

Unintended hysterotomy extension during caesarean delivery: risk factors and maternal morbidity.

We conducted an observational retrospective cohort study to evaluate the risk factors and the maternal morbidity associated with unintended extensions of the hysterotomy during caesarean delivery. We evaluated 2707 women who underwent low-transverse caesarean deliveries in 2011 at an academic, tertiary-care hospital. Hysterotomy extensions were identified through operative reports.

Decreased EDHF-mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high-fat sucrose diet.

High-fat sucrose (HFS) diet in aged individuals causes severe weight gain (obesity) with much higher risk of cardiovascular diseases such as hypertension or atherosclerosis. Endothelial dysfunction is a major contributor for these vascular disorders. We hypothesize that prolonged ingestion of HFS diet by aged mice would accentuate endothelial dysfunction in the small resistance arteries.

Noncovalent Protein Arginine Deiminase (PAD) Inhibitors Are Efficacious in Animal Models of Multiple Sclerosis.

Peptidyl arginine deiminases have been shown to be hyperactive in neurodegenerative diseases including multiple sclerosis. An α-amino acid-based core structure, derived from a hydantoin core, with unique heterocycles on the side chains were synthesized as potential noncovalent inhibitors of PAD enzymes. Among the various heterocycles investigated, compound 23, carrying an imidazole moiety, exhibited the highest potency in this series with some selectivity for PAD2, and was further investigated in vivo.