Mater Research

This study examined nuanced preferences and unmet needs for bereavement care of mothers who experienced stillbirth or neonatal death. Cross-sectional survey. The Philippines. A total of 169 bereaved mothers aged 18 years or older who had experienced stillbirth or neonatal death on or after 30 January 2020 in the Philippines. Response patterns to nine self-administered questions about desired bereavement care and the care they received were analysed using latent class analysis. Measurement invariance was assessed across participant types and urbanicity. Multinomial logistic regression was used to examine the associations between latent classes, demographics and perinatal loss information. Desired type of bereavement care and unmet need for bereavement care. We identified three mutually exclusive stable latent classes related to desired care and unmet needs. For desired bereavement care, one class was characterised by a strong preference for seeing, holding, spending time with, and naming the baby, but low desire in memory making (25.1%). This preference was more common among mothers from urban areas (aOR = 3.04) and those who experienced stillbirth (aOR = 3.07), compared to those from rural areas and who experienced neonatal death, respectively. Regarding unmet need for bereavement care, one class reported unmet needs for memory making (28.3%), with preterm mothers (aOR = 3.11) three times more likely to belong to this class than those who delivered full-term. This study offers novel insights into the complex bereavement care preferences and needs of mothers who experienced perinatal loss. The findings can inform future frameworks and guide the development of culturally appropriate, context-specific interventions for mothers and families.

Abstract Expression of the Csf1r gene in cells of the mononuclear phagocyte lineage is regulated by a conserved enhancer, the fms-intronic regulatory element (FIRE). In mice with a germ-line deletion of FIRE ( Fireko ) CSF1R expression is undetectable in bone marrow progenitors and classical monocytes. Fireko mice lack subpopulations of macrophages in the brain and periphery but develop normally. Here we show that loss of CSF1R expression in Fireko mice is partly overcome by CSF2 in vitro and inflammatory recruitment in vitro. Analysis of heterozygous mutant mice and deletion of the conserved AP1 motif in FIRE provide evidence that continuous receptor synthesis determines CSF1 responsiveness. The absence of macrophages in kidney and heart of Fireko mice was not associated with detectable loss of physiological function. In a model of renal injury macrophage recruitment and histopathology were similar in WT and Fireko mice. Tissue resident macrophages that were depleted in Fireko mice, including microglia, were replaced by donor-derived cells following intraperitoneal adoptive transfer of wild-type bone marrow at weaning. The Fireko mouse provides a novel platform to dissect the functions of tissue resident macrophages in development, homeostasis and pathology. Summary Statement This study describes a unique model of selective tissue resident macrophage deficiency arising from dysregulated expression of the mouse Csf1r gene.

Abstract Vincristine-induced peripheral neuropathy (VIPN) is a frequent and dose-limiting complication of cancer therapy, yet the upstream mechanisms coupling vascular activation to neuroinflammation remain poorly defined. Here we identify E-selectin as a critical orchestrator of vincristine-induced neuropathy. Systematic interrogation of endothelial adhesion molecules in a murine model of VIPN revealed that blockade of E-selectin, but not ICAM-1, PECAM-1 or P-selectin, completely prevented mechanical hypersensitivity and markedly reduced F4/80⁺ immune cell accumulation in dorsal root ganglia and peripheral nerves. Genetic deletion of E-selectin conferred equivalent protection, despite the absence of structural loss of intraepidermal or myelinated fibres, indicating a predominantly functional neuroimmune pathology. Spatial transcriptomics demonstrated that vincristine induces a conserved stress and neuroinflammation-associated transcriptional programme in dorsal root ganglia, with immune and stromal populations acting as dominant signalling hubs. Genetic or pharmacological perturbation of E-selectin did not abolish injury-associated pathways but redistributed cell–cell communication networks, reducing immune-cell dominance and reshaping interferon and metabolic signalling states without inducing Sele expression. Mechanistically, E-selectin exerted non-canonical effects beyond endothelial adhesion. Local E-selectin administration was sufficient to induce macrophage-dependent mechanical hypersensitivity that was abolished in Fut4/7-deficient mice and following phagocyte depletion. In macrophages, E-selectin enhanced vincristine-driven NF-κB activation, NLRP3 inflammasome assembly and IL-1β release. Together, these findings position E-selectin as an upstream regulator of IL-1β–dependent neuroinflammation in VIPN and identify selective targeting of E-selectin–mediated immune–neuron interactions as a therapeutic strategy for chemotherapy-induced neuropathy.

Antidepressant treatment remains a trial-and-error process: one-third of people with major depressive disorder (MDD) report inefficacy of first-line medications. Predictors of prescription patterns are needed to improve prescribing precision. To investigate phenotypic and genetic heterogeneity of MDD subgroups defined by antidepressant prescription patterns. This was a retrospective cohort study of Australian Genetics of Depression Study (2017-2018) adult participants (aged ≥18 years) with lifetime MDD who filled 1 or more prescriptions of the 10 most commonly used antidepressants across 4.5 years (2013-2017). Data were analyzed from August 2024 to October 2025. Treatment complexity was assessed as number of different antidepressant classes in prescriptions filled in 4.5 years. Sustained-use 360 groups were defined as 360 or more cumulative days (in 4.5 years) of a single antidepressant. Participants with genome-wide genotypes were contrasted across mutually exclusive sustained-use 360 groups. Associations of 44 self-reported phenotypes and polygenic scores (PGSs) for 15 traits with sustained-use 360 subgroups. Genome-wide association studies (GWASs) were conducted for selective serotonin reuptake inhibitor (SSRI) or SSRI/serotonin-norepinephrine reuptake inhibitor sustained use contrasted to other participants. Of 12 074 participants (9041 [75%] female with a mean [SD] age of 41.8 [14.6] years; 3022 [25%] male with a mean [SD] age of 47.7 [14.6] years) with 1 or more prescriptions and lifetime MDD, 8898 had genotyping data. High treatment complexity was significantly associated with 37 of 44 self-reported phenotypes (eg, higher rates of smoking, recurrent MDD, suicidal ideation, chronic pain, and circadian and atypical depression subtypes) and higher PGSs for psychiatric traits (MDD PGS: β, 0.04; 95% CI, 0.03-0.06; P = 1.2 × 10-8; ADHD PGS: β, 0.03; 95% CI, 0.02-0.05; P = 2.1 × 10-5 ; bipolar disorder PGS: β, 0.03; 95% CI, 0.01-0.04. P = 1.2 × 10-4 ; neuroticism PGS: β, 0.02; 95% CI, 0.01-0.04; P = 1.3 × 10-3). A total of 5453 (61%) met criteria for an exclusive antidepressant sustained-use 360 group. These groups had distinct phenotypic profiles, including associations with body mass index, suicidal ideation, and co-occurring conditions. GWASs identified novel loci, including an immune-related gene SLAMF3/LY9, for which single-nucleotide variant rs4656934 was associated with reduced odds of sustained SSRI use (G allele; odds ratio, 0.81; 95% CI, 0.75-0.87; P = 3.5 × 10-8). This study found that phenotypic factors were associated with sustained antidepressant use and treatment complexity. PGSs for traits studied were associated with treatment complexity but showed little association with sustained-use 360 groups. These findings support further research to guide treatment selection and to identify patients at risk of difficult-to-treat depression, informing precision psychiatry and early intervention in MDD.

Tuberculosis (TB) and type 2 diabetes mellitus (T2DM) are highly prevalent diseases resulting in high mortality rates globally. Furthermore, T2DM increases susceptibility to TB and vice versa, worsening disease outcomes. This comorbidity is, however, not well described nor understood, despite its rising prevalence globally. This investigation aimed to better characterize the urinary metabolic profiles of patients with the TB and T2DM comorbidity in a South African cohort, to better understand its metabolic basis and associated clinical implications. Using untargeted GCxGC-TOFMS metabolomics, urine samples from 17 patients with TB and T2DM and 34 healthy controls were analyzed and statistically compared to identify significantly altered urinary metabolites. TB-T2DM comorbid patients were characterized by altered metabolism of: (1) tryptophan and kynurenine (reduced kynurenic acid, anthranilic acid, picolinic acid) associated with changes to NAD+ synthesis and a redox imbalance, (2) nucleotides (reduced 3-aminoisobutyric acid, orotic acid, thymine, β-alanine, adenine, hypoxanthine), (3) tyrosine (reduced 3,4-dihydroxyphenylglycol, 4-hydroxy-3-methoxyphenylglycol, hydroxyphenylpyruvate), (4) lipids (reduced dec-2-enedioate, adipic acid, methylmalonic acid), (5) reduced concentrations of various glycine conjugates associated with glycine depletion, and (6) reduced urinary concentrations of various gut microbial metabolites indicative of microbial dysbiosis. These results indicate several metabolic disruptions to amino acids, nucleotides, lipids, NAD⁺ homeostasis and the host microbiome, in TB-T2DM patients, mainly driven by inflammation and oxidative stress. Overall, the findings indicate synergistic amplification of metabolic stress, associated with immune suppression and TB-T2DM disease progression, and subsequently suggests how TB increases T2DM susceptibility and vice versa, as foundation for further investigations.

This article introduces a framework of contextual effectiveness to reconcile the persistent gap between patients' positive experiences with treatments and negative clinical trial outcomes in palliative care. Using medicinal cannabis as an illustrative example, we challenge the statistical assumption that averaging patient responses yields a reliable "true effect" for subjective outcomes like quality of life. We argue that treatment effects vary not only between patients but also within the same patient across contexts and time. While averaging approaches remain valid for discrete symptoms (e.g., pain), a patient's reported improvement in overall well-being in specific situations may reflect genuine contextual effectiveness rather than placebo or misattribution. Highly individualized findings complicate guideline and funding decisions; hence, we propose a dual-pathway model for evidence generation: traditional randomised controlled trials (RCTs) for population-level efficacy, followed by post-trial contextual surveillance studies (CSS) that empower individualized patient-clinician decisions. This framework maintains scientific rigor while enabling more person-centered care. By recognizing that a patient may be both a "responder" and "non-responder" depending on life context, we offer a paradigm shift in how subjective outcomes are understood, evaluated, and applied in palliative care practice.

Epilepsy is a prevalent chronic neurological disorder marked by recurrent seizures, affecting over 70 million people worldwide. This review offers an up-to-date guide for general physicians, general practitioners and general neurology trainees on diagnosing and managing epilepsy, emphasising the importance of early referral to specialist teams. It discusses the epidemiology, significant societal burden and common comorbidities-including cognitive, psychiatric and cardiovascular conditions-which contribute to reduced quality of life and increased mortality, including sudden unexpected death in epilepsy. The article outlines a structured approach to first seizures and their mimics, emphasising the role of electroencephalographyand neuroimaging in diagnosis. Medical management centres on seizure control through anti-seizure medications (ASMs), but up to one-third of patients develop drug-resistant epilepsy, necessitating specialist interventions such as epilepsy surgery or neuromodulation. Accurate seizure classification and tailored treatment plans, including consideration of ASM teratogenicity in women of childbearing age, are essential. Case vignettes illustrate complex scenarios requiring specialist multidisciplinary evaluation. This review reinforces that timely specialist input can significantly enhance outcomes in patients with challenging or refractory epilepsy.

Ferroelectric materials are poised to drive the next technological leap through their emergent functionalities, including negative capacitance and resistance, charge accumulation without transport, and spontaneous polarization switching. The discovery of ferroionic material-systems that combine room-temperature ferroelectricity and fast ionic conductivity has opened an unprecedented avenue for multifunctional devices that merge the territories of electronics and ionics. These hybrid materials enable the direct coupling of ionic and electronic order parameters, allowing long-range electrostatic interactions, wireless field communication, and energy transduction across solid–solid and solid–air interfaces. Such capabilities offer potential solutions to long-standing challenges, including the Boltzmann limit in transistor subthreshold operation, voltage amplification without power dissipation, and nonvolatile polarization states with ionic reconfigurability. Beyond conventional applications, ferroionics support a new generation of quantum sensors and adaptive devices, spanning optical, electrical, mechanical, thermal, and magnetic domains. This review provides a comprehensive overview of the conceptual foundations, theoretical frameworks, and experimental progress underlying ferroionic systems, highlighting their role as a bridge between ferroelectrics, solid electrolytes, and correlated quantum materials. Finally, perspectives are offered on how ferroionic coupling may reshape device physics and enable sustainable, self-powered information and energy technologies.