ObjectiveWhen caring for patients with life-threatening disease, the family caregivers' life and health are affected. This study aimed to culturally adapt and validate the content of the Carer Support Needs Assessment Tool (CSNAT) and to identify support needs in family caregivers of patients receiving home-based palliative care in Chile.MethodsThis cross-sectional study was conducted between May and December 2023 in two Chilean healthcare institutions. It involved three phases: (a) translation/adaptation of the Spanish-CSNAT, (b) cultural adaptation of the CSNAT by an expert committee, and (c) caregivers pretesting CSNAT followed by interviews. Experts and caregivers evaluated the content (clarity and relevance) of the sixteen CSNAT domains. Caregivers reported their support needs and whether CSNAT should include additional needs.ResultsNine experts and thirty-six caregivers participated. The experts found linguistic issues in four domains, which were revised by the CSNAT team-UK. A large proportion of experts (67-100%) and caregivers (90-100%) reported each of the CSNAT domains as clear. The domain with the highest average relevance-score was 'looking after your own health'. Cognitive interviews with caregivers showed high acceptability of CSNAT. 'Knowing what to expect in the future' was the need caregivers most often wished more support for (77%). Emotional support, lack of free time and financial support were identified as needs not covered by CSNAT.ConclusionThe Spanish CSNAT showed good content validity for detecting support needs in family caregivers of patients receiving home-based palliative care in Chile. Therefore, we recommend its use in clinical practice and palliative care research.
Cardiac toxicity from QT-prolonging drugs can precipitate malignant ventricular arrhythmias in susceptible individuals, and family screening may clarify inherited risk. We report a 33-year-old woman with a history of postpartum cardiac arrest treated with a secondary-prevention implantable cardioverter-defibrillator (ICD) who developed an electrical storm after self-administration of a single low dose of amitriptyline (12.5 mg). ICD interrogation documented 176 episodes of ventricular fibrillation requiring repeated shocks, followed by complete battery depletion, hemodynamic collapse, and the need for venoarterial extracorporeal membrane oxygenation and continuous renal replacement therapy. The admission electrocardiogram showed marked QT prolongation (QTc 651 ms), with previously documented prolonged baseline QTc values. Targeted next-generation sequencing identified a novel SCN5A missense variant (NM_000335.5:c.5738G > A) and a rare pathogenic KCNQ1 splice variant (NM_000218.3:c.1032G > C), cascade testing across the family demonstrated variable expressivity among carriers. Given a suspected contribution of late sodium current, a mechanism-based strategy was implemented with mexiletine added to propranolol and overdrive pacing (90 bpm). This case underscores the risk of malignant ventricular arrhythmias after exposure to QT-prolonging agents even at low doses, and supports genotype-informed, mechanism-based therapy to mitigate arrhythmic risk in patients with marked QT prolongation.
Wilson disease (WD) is a hereditary autosomal recessive disorder of copper metabolism, which results from mutations in the ATP7B gene. It is a monogenic disorder characterized by significant clinical heterogeneity in patients with renal, ocular, hepatic, and neurological involvement, complicating its clinical diagnosis. This study involves examination of an Iranian family with a child diagnosed with WD. After various clinical tests, Whole Exome Sequencing (WES) and Sanger sequencing were carried out on the proband to identify the cause of the disease and verify the results. Segregation analysis was also performed. The next step was the study of protein conservation and its alterations after mutation. The WES analysis revealed that the c.1883_1884del [p. His628ArgfsTer126] and c.2145 C > T variations in the ATP7B gene, in compound heterozygous form, were linked to WD in the proband. The analysis also determined that the proband inherited c.1883_1884del [p. His628ArgfsTer126] from his mother's side and c.2145 C > T from his father. A decrease in the amount of translated protein compared to the wild-type leads to the appearance of clinical symptoms in the affected individuals. This study added criteria PP1, PP4 and PS4 to c.1883_1884del [p. His628ArgfsTer126] according to the ACMG guidelines and also supports a potential reclassification of c.2145 C > T variant from variant of uncertain significance (VUS) to likely pathogenic by adding PP4 and PM3. These findings will significantly help specialists in their decision-making about these variants.
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Timely, individually tailored support for family caregivers of cancer patients is stressed, reinforcing the importance of implementing screening tools in clinical practice. This study aims to evaluate the validity and reliability of the Swedish CancerSupportSource-Caregiver among 145 Swedish family caregivers of persons diagnosed with cancer. We evaluated the validity and reliability of the Swedish CancerSupportSource-Caregiver among 145 Swedish family caregivers of persons diagnosed with cancer who responded to the Swedish CancerSupportSource-Caregiver, sociodemographic questions, and the Hospital Anxiety and Depression Scale. Psychometric analyses were performed using descriptive statistics and classical test theory to evaluate data quality, targeting, scaling assumptions, and internal validity. Construct validity was assessed through confirmatory factor analysis; criterion validity through concurrent validity; and reliability through internal consistency. Overall, in the sample, evaluations demonstrated generally satisfactory psychometric properties with respect to data quality, targeting, and scaling assumptions. The hypothesized five-domain model showed an acceptable fit to the data, although there were indices that it could be improved. Item loadings were generally high, supporting the proposed construct structure. Further, assessments of the criterion validity were satisfactory. However, the evaluations of internal validity and internal consistency indicated redundancy, mainly within the emotional well-being domain. The Swedish CancerSupportSource-Caregiver demonstrated preliminary satisfactory abilities to screen for support needs and psychological distress among Swedish family caregivers of persons diagnosed with cancer. Further evaluations in larger samples, using Rasch measurement theory, could provide a deeper understanding of the functioning of items and response options.
Information regarding risk factors among service member families for different child maltreatment types is needed to improve prevention efforts. To identify factors associated with first occurrences of 4 child maltreatment types and examine child age-related changes in risk for each type among active duty service member families. This population-based retrospective cohort study used data from the Child Maltreatment in Military Families Life Course Study on active duty service member families with a first occurrence of child maltreatment in fiscal years 2009 through 2018 and a representative sample of active duty families without child maltreatment incidents. Data were analyzed from August 2023 to February 2026. One or more parents serving as an active duty service member. First documented occurrences of neglect, physical abuse, emotional abuse, and sexual abuse, identified using Family Advocacy Program data. Associations between sociodemographic, family, and military-related characteristics and first occurrences of maltreatment types were examined in univariable and multivariable logistic regressions. The study included 618 101 active duty service member families (28 684 [4.64%] with a first occurrence of child maltreatment and 589 417 [95.36%] without child maltreatment incidents), consisting of 1 070 510 family-months (FM); the total weighted sample was 65 142 809 FM (59 031 293 male service member FM [90.62%]; mean [SD] age, 32.74 [6.97] years). Crude rates of child maltreatment were highest for child neglect (22.16 per 100 000 FM) followed by physical abuse (10.97 per 100 000 FM), emotional abuse (4.23 per 100 000 FM), and sexual abuse (2.66 per 100 000 FM). Factors associated with higher odds of all child maltreatment types in multivariable models were female service member families (eg, sexual abuse: odds ratio [OR], 1.39 [95% CI, 1.18-1.64]; physical abuse: OR, 1.82 [95% CI, 1.70-1.95]), early parenting (age <21 years) (eg, neglect: OR, 1.32 [95% CI, 1.22-1.41]; sexual abuse: OR, 2.12 [95% CI, 1.75-2.56]), larger number of dependent children (≥3) (eg, emotional abuse: OR, 1.63 [95% CI, 1.48-1.79]; sexual abuse: OR, 2.32 [95% CI, 2.06-2.61]), and never-deployed status (eg, sexual abuse: OR, 1.90 [95% CI, 1.55-2.32]; emotional abuse: OR, 3.76 [95% CI, 3.09-4.57]). Risk rates peaked at 3 months of age for neglect (48.61 per 100 000 FM) and physical abuse (25.49 per 100 000 FM). Risk of emotional and sexual abuse peaked in middle childhood (age 5-12 years) and adolescence but was generally lower (<6 per 100 000 FM) than risk of other child maltreatment types across all ages. In this cohort study, families with female service members, never-deployed service members, 3 or more children, and young parents had higher risk of child maltreatment. Dynamic prevention approaches appear to be needed to address evolving risk factors across the family life course.
ObjectiveTo analyze the effectiveness of a virtual educational intervention on care performance and knowledge of family caregivers of older adults with stroke sequels, when compared with usual guidance.MethodsA randomized pragmatic trial was carried out with 58 family caregivers of older adults with stroke sequels, randomized to the Intervention Group and Management Group. For Intervention Group a massive, open, online course was made available to equip caregivers with the necessary tools to assist older adults in activities of daily living after discharge. Moreover, telecommunication consultations were held on the seventh, thirtieth, sixtieth and eightieth days to check the course progress and possible difficulties. The course and telephone calls were made by research nurses. Caregiver assessment was carried out close to hospital discharge, before the intervention, and 90 days later, using three indicators of the outcome "Caregiver Performance: Direct Care" and six indicators of the outcome "Knowledge: Stroke Management" of the Nursing Outcomes Classification.ResultsA significant improvement was observed in intragroup assessment in Intervention Group for the indicator "Assists with care recipient's activities of daily living needs" (p < 0.001) of the outcome "Caregiver Performance: Direct Care" and for the indicator "Causes and contributing factors" (p = 0.021) of the outcome "Knowledge: Stroke Management". The indicator "Strategies to maintain skin integrity" of the outcome "Knowledge: Stroke Management" showed statistical significance in intergroup assessment, with better results for Control Group (p = 0.040), in addition to a significant improvement in intragroup assessment for Intervention Group (p = 0.008).ConclusionsThe intervention was effective for Intervention Group members, improving performance and knowledge about care for older adults when comparing baseline and final assessments.Implications for PracticeThe use of a massive, open, online course and telephone monitoring improves outcomes in care for older adults after discharge, which reflects the importance of nurses' educational. Registered in Clinical Trials (NCT05553340).DescriptorsStroke; Family Caregiver; Educational Technology; Standardized Nursing Terminology; Geriatric Nursing; Transition from Hospital to Home.
The use of restorative practices may be an alternative approach to responding to patients and families harmed by medical racism. Little research has explored its implementation in health care settings or the perspectives of residents and fellows (ie, medical learners) regarding its use in academic clinical settings. To elicit perspectives from medical learners on using restorative practices to address patient and family concerns about racism and other identity-based harms in the health care context. This qualitative study consisted of one-on-one semistructured interviews with residents and fellows between May and July 2024. Participants were invited from 76 adult and pediatric training programs affiliated with the University of Washington. The interview guide was developed by the study team, and interviews were conducted via videoconferencing and lasted approximately 30 minutes. Each participant received a $50 gift card as compensation. Medical learners' perspectives and concerns about implementing restorative practices to address racism in health care settings. Thematic analysis was used to identify these perspectives. Interviews were conducted until thematic saturation was reached. A total of 20 medical learners were interviewed. These participants had a mean (SD) age of 32.3 (3.2) years; 13 (65%) were women and 8 (40%) identified as Asian, 4 (20%) as Black, and 8 (40%) as White individuals. Eight participants (40%) had heard of restorative practices, mostly in the criminal justice and educational settings; 5 (25%) were confident in explaining what restorative practices entailed; and 2 (10%) had participated in restorative circles. In general, medical learners were supportive of using restorative practices to address medical racism and other harms experienced by patients and families. However, medical learners identified important concerns regarding preparation for this work (prework and intention setting), burden of participation (time barriers and personal and professional risks), and goals and outcomes (patient and family willingness, goals identification, and healing and harm mitigation). This qualitative study found that medical learners were open to working with patients and families using restorative practices to address medical racism and other identity-based harms; these participants also identified additional concerns regarding implementation such as preparation, barriers and risks, and meaningful goals and outcomes. Future studies should investigate potential solutions to these concerns as well as include perspectives from patients and families to support evidence-based implementation.
Killer cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands regulate the functions of natural killer (NK) cells. However, extensive sequence homology within the KIR family limits the ability of monoclonal antibodies to selectively recognise individual receptors, and no KIR2DS1-specific reagent is available to date. Here, we comprehensively delineate the binding profile of the monoclonal antibody S22019F. Using Ba/F3 cells, NK cell clones, and primary NK cells, we demonstrate that S22019F selectively binds KIR2DS1. Moreover, functional assays reveal that binding of S22019F to KIR2DS1 is preserved upon activation by its HLA-C ligand. We further confirm that S22019F does not cross-react to KIR2DL3*005 allotypes and we extend its application to the analysis of KIR2DS1+ T cells. Collectively, these findings underscore the value of S22019F as a reagent that selectively recognises KIR2DS1, enabling improved analyses of KIR2DS1-bearing lymphocytes in fundamental and clinical research.
Langerhans cell histiocytosis (LCH) is a myeloid dendritic cell neoplasm causing inflammation and tissue destruction. Clinical features vary from single bone involvement to a multi-system, life-threatening disease. A 3-year-old presented with bilateral osteolytic lesions, advanced alveolar and basal bone loss, widened inferior alveolar canal, and displacement of tooth buds. Clinical findings revealed the presence of multiple ulcerative lesions on the gingival region of the mandibular posterior teeth, the palatal region of the maxillary posterior teeth, and the right submandibular lymphadenopathy with cranial pain. Patient's family history revealed a sibling with multiple osteolytic lesions, and systemic symptoms. Histopathologic examination demonstrated infiltration by S100-CD1a-positive histiocytes accompanied by eosinophils, consistent with LCH. This case report outlines the difficulties in early diagnosis of jaw lesions, their differential diagnosis, and early biopsy to guide multidisciplinary management.
Oral and maxillofacial pathology (OP) and oral medicine (OM) are recognized specialties in Brazil and worldwide. Identifying dental students' intentions to pursue these fields and understanding the factors influencing their career choices may provide insights into the future of the specialties. Therefore, this study aimed to determine the intention of Brazilian final-year dental students to pursue the professional career in OP and OM. Final-year undergraduate dental students, from various public and private institutions in Brazil, were invited to voluntarily complete a self-administered and anonymous virtual questionnaire. The questionnaire consisted of 11 questions. The statistical analysis consisted of describing the absolute and relative numbers, and performing analytical statistics using Pearson's chi-squared test for categorical variables. A total of 358 students participated of the study. The majority were female (75.1%), with a mean age of 25.27 years, mainly from public universities (52%). The main careers pursued were restorative dentistry (39.1%), dental implantology (37.7%), prosthodontics (33%), and orofacial harmonization (31.3%). The main reasons for choosing specialization were to stand out in the profession and to perform better in the profession with better clinical outcomes. OM was reported as a career choice by 17% of students and OP by 7.5%. The motivations for such choice were vocation and influence from professors, colleagues, or family members. The results revealed a surprising and concerning finding: interest in the fields of OP and OM, which are fundamental for diagnosing and treating complex conditions of the oral cavity, was relatively low.
A novel bacterial strain, designated MF1-13ᵀ, was isolated from tidal-flat sediment collected in Gochang, Republic of Korea. Cells of strain MF1-13ᵀ are Gram-stain-negative, facultatively anaerobic, motile, and short rod-shaped to ovoid, forming pale yellow colonies on marine agar. The strain produces catalase and oxidase. It grows at 25-30 °C (optimum, 30 °C), at pH 6-8.0 (optimum, pH 7.0), and in the presence of 0-5% (w/v) NaCl, with optimal growth at 2% (w/v). Phylogenetic analysis based on 16 S rRNA and genome sequences placed strain MF1-13ᵀ within the family Roseobacteraceae (class Alphaproteobacteria), showing highest sequence similarity to Pseudooceanicola nitratireducens JLT1210ᵀ (97.2%), Pseudooceanicola onchidii XY-99ᵀ (96.8%) and Pseudooceanicola flagellatus DY470ᵀ (97.2%). The major polar lipids are phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. The genome of strain MF1-13ᵀ is 4.24 Mbp in size, with a G + C content of 61.2%. The strain hydrolyzes starch, gelatin, and Tween 20, 40, and 80, but do not hydrolyze casein or DNase. The predominant cellular fatty acids are C16:0, C18:1 ω7c 11-methyl, and Summed Feature 8 (C18:1 ω7c/C18:1 ω6c). Genomic comparisons (ANI, AAI, and dDDH) between strain MF1-13ᵀ and related taxa were well below species delineation thresholds, supporting its classification as a novel species. Based on polyphasic taxonomic analysis, strain MF1-13ᴛ represents a novel species of the genus Pseudooceanicola, for which the name Pseudooceanicola aestuariicola sp. nov. is proposed. The type strain is MF1-13ᵀ (= KEMB 21563ᵀ = KCTC 8775ᵀ = JCM 37675ᵀ).
The increasing incidence of Alzheimer's disease (AD) coupled with emerging diagnostics and treatments underscores the need for early detection of AD, yet identifying these individuals remains challenging. This US study sought to examine community-based physician attitudes regarding diagnosis and treatment of early AD (mild cognitive impairment [MCI] due to AD and mild AD). A total of 177 primary care physicians (PCPs) and 147 neurologists recruited through a national physician panel were surveyed about early AD diagnostic and treatment processes, and self-confidence in identifying and managing the condition. Physicians identified patient and family/caregiver involvement as critical in triggering the diagnostic process. Patterns of use of neurocognitive assessments, structural imaging tests, and AD-specific biomarkers varied between PCPs and neurologists. Confidence diagnosing and managing early AD was a concern across specialties, although was greater among PCPs. Programs promoting awareness of early AD symptoms, and emerging technologies and treatments are critical to timely management.
Esophageal carcinoma is very rare in young people, particularly during pregnancy. We present a rare fatal case of esophageal adenocarcinoma in a 26.-year old pregnant woman with the full-term delivery of a healthy baby. Alarming symptoms despite being considered hyperemesis gravidarum raised suspicion of the upper digestive system neoplasia, which was confirmed by subsequent diagnostic work-up, including endoscopy, biopsy, and histopathology. Although the deceased's family suspected possible medical negligence, it was not proven, but was evaluated and interpreted as an unintended outcome. Namely, the pregnant woman did not want to undergo a diagnostic examination of the digestive system in the 20th week of pregnancy, but almost towards the end of the pregnancy, when a malignant neoplasm of the esophagus was diagnosed. After delivery of health baby, she died two months later. This unfortunate case underscores the necessity of maintaining a high index of suspicion for malignancy in persistent gastrooesophageal symptoms during pregnancy. The refusal of diagnostic and therapeutic procedures by the patient dictated the dissemination of the disease and the fatal outcome, which could not be influenced by the professional malpractice, and therefore certainly has a forensically and clinically interesting discussion.
Women harboring pathogenic variant (PV) in the BRCA1 or BRCA2 genes (= BRCA) have an elevated lifetime risk for breast cancer (BC). One of the main options for active BC risk reduction is bilateral risk-reducing mastectomy (RRM). Understanding the factors influencing that decision is important for genetic-counselling and risk mitigation strategy planning. A structured questionnaire was circulated to BRCA carriers, members of the Good Genes NGO in Israel. Data on RRM uptake and timing, factors previously reported to be associated with decision to undergo RRM (e.g., psychosocial, family history, counselling/health-system factors) were obtained. Comparison between carriers who elected to undergo RRM with those who opted for early detection schemes were performed using logistic regression and chi square statistical analyses. Of cancer free women (n = 391), 272 (69.6%) elected to adhere to the recommended surveillance scheme and 119 (30.4%) elected to undergo RRM. The major reasons for electing RRM over surveillance were active BC risk reduction (4.96 ± 0.23), fear of developing BC (4.86 ± 0.50), and having at least one relative with BC diagnosed under age 45 years. Support group discussions emerged as a stronger determinant of RRM uptake than primary care physician or religious guidance. In conclusion, among healthy Israeli BRCA carriers the decision to undergo RRM was influenced by a complex interplay of factors-active BC risk reduction, fear of cancer diagnosis in the context of having one relative with early onset BC and support group discussions were the major drivers of RRM in Israeli BRCA1 carriers.
The global regulator LaeA is widely recognized as a master activator of secondary metabolism and development in filamentous fungi. Yet its role under genetically buffered or metabolically stable conditions-where canonical phenotypes are masked-remains poorly understood. This study aimed to characterize the LaeA ortholog (ThlaeA) in Trichoderma hypoxylon and to elucidate its regulatory role in a ΔThtri5 background, where trichodiene synthase function is disrupted. We constructed single and double knockout mutants (ΔThlaeA, ΔThtri5, and ΔThlaeAΔThtri5) and performed integrated metabolomic and transcriptomic analyses to assess global regulatory effects. Additional assays evaluated oxidative stress responses and biocontrol activity. The deletion of ThlaeA alone had negligible effects on secondary metabolite production, whereas disruption of ThlaeA in the ΔThtri5 background restored biosynthesis of major terpenoid compounds abolished in ΔThtri5. Metabolomics revealed that ThlaeA regulates 48.4% of metabolites in the wild-type but 31.3% in ΔThtri5, while transcriptomics showed restoration of 16.7% of gene expression dysregulated in ΔThtri5. Phenotypically, ThlaeA deletion reinstated oxidative stress sensitivity and partially attenuated biocontrol efficacy. ThlaeA acts as a conditional repressor that counterbalances Thtri5-dependent perturbations to maintain metabolic homeostasis. This work redefines the LaeA paradigm and provides a framework for understanding the context-dependent regulation of secondary metabolism in fungi. LaeA plays compelling roles in secondary metabolism and development in filamentous fungi. However, related research also found that genetic operations of LaeA have no obvious effect on the metabolic spectrum in some fungal species. Many attempts have been made to decipher the phenomenon and to explain how about the function of LaeA in these cases. Here, we identified a ThlaeA in Trichoderma hypoxylon. The deletion of ThlaeA alone did not alter secondary metabolism but restored metabolite production in a ΔThtri5 background. Integrated metabolomic and transcriptomic analyses revealed that ThlaeA modulates metabolic homeostasis by compensating for Thtri5-related perturbations. ThlaeA-Thtri5 interaction regulates oxidative stress responses and membrane transport pathways, coupling secondary metabolism with physiological adaptation. This regulatory model broadens the understanding of the LaeA protein family. Fine-tuning this pathway can enhance the environmental adaptability and agricultural biocontrol potential of Trichoderma strains, while boosting bioactive secondary metabolite production and optimizing fungal cell factories. This study advances fundamental insights into fungal metabolic regulation and provides a rational basis for strain improvement and biotechnological applications in agriculture and industry.
Camalexin is a phytoalexin produced by plants of the Brassicaceae family, including the model species Arabidopsis thaliana, and its biosynthesis is tightly regulated to balance growth and defense. Here, we identify BASIC PENTACYSTEINE 1 (BPC1) as a key negative regulator of camalexin biosynthesis. Transcriptome analyses of bpc1-1 and bpc1-1;bpc2-1 mutants revealed both distinct and overlapping functions of BPC1 and BPC2, with BPC1-specific differentially expressed genes being highly enriched for camalexin biosynthetic processes. Consistently, multiple camalexin pathway genes were upregulated in bpc1-1, leading to increased camalexin accumulation. Analysis of publicly available ChIP-seq data together with mutant expression profiles showed that several BPC1-regulated camalexin biosynthetic genes are enriched for the repressive histone mark, H3K27me3 and are de-repressed in Polycomb Repressive Complex 2 (PRC2) mutants, indicating PRC2-dependent transcriptional silencing. ChIP-qPCR analyses further demonstrated that BPC1 directly binds GA-rich cis-elements in camalexin pathway genes, including CYP71A12 and CYP71B15. Furthermore, epigenome profiling showed that the BPC1 locus itself is embedded within an active chromatin environment enriched in H3K4me2/3, H3K36me3, and histone acetylation. Loss-of-function mutants of histone H3 methyltransferases like ATX1, ATX2, ATXR7, and EFS exhibited reduced BPC1 expression, whereas a knock-out mutant of a histone H3 acetyltransferase gene, HDA9, hda9-1 displayed elevated H3ac levels and increased BPC1 transcript abundance, indicating that BPC1 transcription is epigenetically modulated by both histone methylation and acetylation dynamics. Together, our findings establish BPC1 as an epigenetically regulated transcriptional repressor that partners with PRC2 to suppress camalexin biosynthesis, revealing a previously unrecognized regulatory module controlling the basal suppression of specialized defensive metabolism in Arabidopsis.
SUMMARYEffective immunity requires the ability to mount strong pathogen defenses while minimizing detrimental effects on organismal fitness. To achieve this balance, many immune genes are maintained in a transcriptionally repressed but responsive state, ensuring rapid induction upon infection and timely repression once the threat subsides. This dynamic regulation is controlled by transcription factors and chromatin remodelers that fine-tune the accessibility of immune loci. The nematode Caenorhabditis elegans provides a powerful model for dissecting these mechanisms in non-professional immune cells. Its antiviral RNA interference (RNAi) pathway serves as a rapid, sequence-specific silencing system targeting viral RNA. Complementing RNAi, the intracellular pathogen response represents a specialized, inducible transcriptional program that protects C. elegans from intracellular pathogens, including viruses and microsporidia. In addition, pathways regulated by STAT family transcription factors coordinate immune activation in a pathogen- and tissue-specific manner, providing further regulatory diversity. This review explores how transcriptional and chromatin mechanisms coordinate these distinct immune programs to maintain effective yet balanced immune responses. Investigating these pathways in C. elegans continues to uncover both conserved and novel principles of immune regulation, offering insight into how organisms integrate transcriptional control with physiological constraints to thrive in a pathogen-rich environment.