Search Results (7,315)

Background: Endometriosis is a chronic inflammatory condition affecting 10–15% of women of reproductive age. Genome-wide association studies (GWASs) have accounted for only a fraction of its high heritability, indicating the need for alternative approaches to identify rare genetic variants contributing to its etiology. To this end, we performed whole-exome sequencing (WES) in a multi-affected family. Methods: A multigenerational family was studied, comprising three sisters, their mother, grandmother, and a daughter, all diagnosed with endometriosis. WES was conducted on the three sisters and their mother. We used the enGenome-Evai and Varelect software to perform our analysis, which mainly focused on rare, missense, frameshift, and stop variants. Results: Bioinformatic analysis identified 36 co-segregating rare variants. Six missense variants in genes associated with cancer growth were prioritized. The top candidates were c.3319G>A (p.Gly1107Arg) in the LAMB4 gene and c.1414G>A (p.Gly472Arg) in the EGFL6 gene. Variants in NAV3, ADAMTS18, SLIT1, and MLH1 may also contribute to disease onset through a synergistic and additive model. Conclusions: We identified novel candidate genes for endometriosis in a multigenerational affected family, supporting a polygenic model of the disease. Our study is an exploratory family-based WES study, and replication and functional studies are warranted to confirm these preliminary findings. Full article

Background: Concerns over women’s mental health have intensified globally, especially among mothers managing dual careers and family responsibilities. Positive Psychology Interventions (PPIs), such as gratitude journaling and well-being workshops, have demonstrated promise in enhancing mental health; however, their applicability in Arab contexts remains underexplored. This study aims to investigate the effectiveness of PPIs on mothers’ well-being, gratitude, depression, anxiety, and stress in Saudi Arabia. Methods: This quasi-experimental, one-group pretest–posttest study assessed the effects of a four-week PPI on 37 Saudi working mothers (aged 21–50 years) employed at a private school in Riyadh. The intervention included guided gratitude journaling thrice weekly and two workshops on positive psychology and gratitude. Pre- and post-intervention assessments used validated Arabic versions of the Depression Anxiety Stress Scale (DASS-21), WHO-5 Well-being Index, and Gratitude Questionnaire (GQ-6). Results: Significant improvements were found post-intervention: depression, anxiety, and stress scores decreased (p < 0.001), while well-being and gratitude increased (p = 0.001). However, participants with lower household income (<50,000 SAR) showed less improvement, indicating a potential moderating effect of socioeconomic status. Conclusions: The intervention demonstrated promising short-term improvements in mental health and well-being among Saudi mothers. The findings underscore the importance of culturally appropriate PPIs and highlight the need for further research using controlled, long-term designs. Limitations include the small, non-random sample, absence of a control group, and restriction to a single geographic region. Full article

Background/Objectives: Antimicrobial resistance (AMR) contributes to millions of deaths globally each year, creating an urgent need for new therapeutic agents. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their potential to combat AMR pathogens. This study aimed to evaluate the antimicrobial activity of an AMP from a soil-derived bacterial isolate against Gram-negative bacteria. Method: Soil bacteria were isolated and screened for antimicrobial activity. The bioactive peptide was purified and determined its structure and antimicrobial efficacy. Genomic analysis was conducted to predict the biosynthetic gene clusters (BGCs) responsible for AMP production. Results: Genomic analysis identified the isolate as Paenibacillus sp. Na14, which exhibited low genomic similarity (61.0%) to other known Paenibacillus species, suggesting it may represent a novel species. The AMP from the Na14 strain exhibited heat stability up to 90 °C for 3 h and retained its activity across a broad pH range from 3 to 11. Structural analysis revealed that the Na14 peptide consisted of 14 amino acid residues, adopting an α-helical structure. This peptide exhibited bactericidal activity at concentrations of 2–4 µg/mL within 6–12 h, and its killing rate was concentration-dependent. The peptide was found to disrupt the bacterial membranes. The Na14 peptide shared 64.29% sequence similarity with brevibacillin 2V, an AMP from Brevibacillus sp., which also belongs to the Paenibacillaceae family. Genomic annotation identified BGCs associated with secondary metabolism, with a particular focus on non-ribosomal peptide synthetase (NRPS) gene clusters. Structural modeling of the predicted NRPS enzymes showed high similarity to known NRPS modules in Brevibacillus species. These genomic findings provide evidence supporting the similarity between the Na14 peptide and brevibacillin 2V. Conclusions: This study highlights the discovery of a novel AMP with potent activity against Gram-negative pathogens and provides new insight into conserved AMP biosynthetic enzymes within the Paenibacillaceae family. Full article

The agony of medical negligence for all involved is well documented. Health practitioners involved in harm events are described in the literature as “second victims”. Injured patients report that clinical negligence litigation is traumatic, slow, expensive, and does not meet their needs. Clinical negligence lawyers have complained that healthcare injury cases are so complex and expensive that many firms do not accept these cases. This article uses a qualitative case study research design to analyse two cases from the United States of America (US) to explore the promise of an alternative resolution process: the communication-and-resolution program (CRP). CRPs involve the hospital disclosing the healthcare injury, investigating and explaining what happened, apologising and, sometimes, offering compensation to injured patients and families. In the US, CRPs have not replaced tort law. The two case studies analysed in this article offer a rare insight into the accounts of those who have experienced clinical negligence and an alternative non-litigation approach. The case study approach delves into the detail, providing an in-depth glimpse into the complexity of healthcare injuries in their real-life context. The case studies provide valuable lessons for reshaping resolution processes to better meet injured patients’ needs. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Background: Neurogenic bladder (NB) in children may lead to recurrent urinary tract infections (UTIs), renal deterioration, and a reduced quality of life. Clean intermittent catheterization (CIC) is the standard of care, but in some patients, CIC may be unfeasible due to anatomical, sensory, or compliance issues. Button cystostomy (BC) has emerged as a minimally invasive, bladder-preserving alternative. This study aimed to assess the feasibility, safety, and outcomes in the long-term of BC in pediatric NB patients. Methods: Retrospective analysis was conducted on children with NB who underwent endoscopic BC placement between January 2020 and December 2024 in a tertiary pediatric center. Demographic data, operative time, complications, and follow-up outcomes were collected. All procedures used an endoscopic approach with cystoscopic guidance for safe device placement. Results: Thirty-three patients (25 males; median age 7.96 years) underwent BC placement. Most had spinal dysraphism (63.6%). The mean operative time was 48.5 ± 6 min. During a mean follow-up of 2.1 ± 1.4 years, five patients (15.2%) had febrile UTIs and two had minor leakage. No major complications occurred. Four buttons were removed due to clinical improvement (N = 1), the fashioning of a continent derivation (N = 1) and implantation of a sacral neuromodulator (N = 2); two patients accepted CIC. Satisfaction was reported by 93.9% of families. Conclusions: BC is an effective, minimally invasive alternative for urinary drainage in children with NB, even when compared to continent diversion techniques such as the Mitrofanoff, due to its lower invasiveness, greater feasibility, and lower complication rate. Broader adoption may be warranted, but prospective studies are needed to confirm long-term outcomes. Full article

The COVID-19 pandemic precipitated unprecedented social isolation measures, profoundly disrupting daily life, educational routines, and mental health worldwide. University students, already susceptible to psychological distress, encountered intensified challenges under remote learning and prolonged confinement. This longitudinal study examined fluctuations in anxiety and mood among 102 Brazilian university students during the pandemic, distinguishing between those solely engaged in academic pursuits and those simultaneously balancing work and study. Data collected via the Brunel Mood Scale and State-Trait Anxiety Inventory in April and July 2021 revealed that students exclusively focused on studies exhibited significant increases in depressive symptoms, anger, confusion, and anxiety, alongside diminished vigor. Conversely, participants who combined work and study reported reduced tension, fatigue, confusion, and overall mood disturbance, coupled with heightened vigor across the same period. Notably, women demonstrated greater vulnerability to anxiety and mood fluctuations, with socioeconomic disparities particularly pronounced among females managing dual roles, who reported lower family income. These findings suggest that occupational engagement may serve as a protective factor against psychological distress during crises, underscoring the urgent need for tailored mental health interventions and institutional support to mitigate the enduring impacts of pandemic-related adversities on the student population. Full article

The genus Anisosciadium, belonging to the Apiaceae family, has been traditionally recognized for its anti-inflammatory, antioxidant, and antimicrobial properties. However, scientific research on this genus is still limited, highlighting the need for a comprehensive review of its chemical composition and pharmacological characteristics. A comprehensive compilation of data was conducted using major databases such as Google Scholar, Research Gate, Web of Science, Scopus, and ScienceDirect. In this review, we collected and organized the available information of identified compounds from different species of the genus Anisosciadium, covering the literature from 2003 to 2024. In total, 64 phytoconstituents were detected. The findings suggest that the traditional therapeutic properties of Anisosciadium are well supported by the reported pharmacological activities from previous studies. Notably, these studies highlight its antioxidant, antibacterial, and cytotoxic effects, emphasizing the potential of this genus in the development of new therapeutic agents. Nonetheless, the lack of comparative studies among Anisosciadium species and the scarcity of in vivo studies and clinical trials limit the full realization of its therapeutic potential. Specifically, comparative studies could be crucial in identifying species with unique chemical profiles and understanding how variations in secondary metabolite compositions may influence their pharmacological activities. Full article

Background: Cochlear implantation (CI) in pediatric patients with cochlear nerve deficiencies (CND) remains controversial due to a highly variable clinical population, lack of evidence-based guidelines, and mixed research findings. This study assessed current clinical perspectives and practices regarding CI candidacy in children with CND among hearing healthcare professionals in the USA. Methods: An anonymous 19-question online survey was distributed to CI clinicians nationwide. The survey assessed professional background, experience with aplasia and hypoplasia, and perspectives on CI versus auditory brainstem implant (ABI) candidacy, including imaging practices and outcome expectations. Both multiple-choice and open-ended responses were analyzed to identify trends and reasoning. Results: Seventy-two responses were analyzed. Most clinicians supported CI for hypoplasia (60.2%) and, to a lesser extent, for aplasia (41.7%), with audiologists more likely than neurotologists to favor CI. Respondents cited lower risk, accessibility, and the potential for benefit as reasons to attempt CI before ABI. However, many emphasized a case-by-case approach, incorporating imaging, electrophysiological testing, and family counseling. Only 22.2% considered structural factors the best predictors of CI success. Conclusions: Overall, hearing health professionals in the USA tend to favor CI as a first-line option, while acknowledging the limitations of current diagnostic tools and the importance of individualized, multidisciplinary decision-making in CI candidacy for children with CND. Findings reveal a high variability in clinical perspectives on CI implantation for pediatric aplasia and hypoplasia and a lack of clinical consensus, highlighting the need for more standardized assessment and imaging protocols to provide greater consistency across centers and enable the development of evidence-based guidelines. Full article

Background: Social and financial services are essential for the inclusion and well-being of people with disabilities (PWDs), who often rely on family caregivers to access these systems. In Saudi Arabia, where disability inclusion is a strategic goal under Vision 2030, understanding caregiver experiences is crucial to identifying service gaps and improving accessibility. Objectives: This study aimed to explore caregivers’ perspectives on awareness, perceived barriers, and accessibility of social and financial services for PWDs in Saudi Arabia. The analysis is grounded in Andersen’s Behavioural Model of Health Service Use and the WHO’s International Classification of Functioning, Disability and Health (ICF) framework. Methods: A cross-sectional survey was conducted with 3353 caregivers of PWDs attending specialised day schools. The survey collected data on demographic characteristics, service awareness, utilisation, and perceived obstacles. Exploratory Factor Analysis (EFA) identified latent constructs, and Structural Equation Modelling (SEM) was used to test relationships between awareness, barriers, and accessibility. Results: Findings reveal that over 70% of caregivers lacked awareness of available services, and only about 3% had accessed them. Key challenges included technological barriers, complex procedures, and non-functional or unclear service provider platforms. Both User Barriers and Service Barriers were negatively associated with Awareness and Accessibility. Awareness, in turn, significantly predicted perceived Accessibility. Caregiver demographics, such as age, education, gender, and geographic location, also influenced awareness and service use. Conclusions: There is a pressing need for targeted awareness campaigns, accessible digital service platforms, and simplified service processes tailored to diverse caregiver profiles. Inclusive communication, decentralised outreach, and policy reforms are necessary to enhance service access and promote the societal inclusion of PWDs in alignment with Saudi Arabia’s Vision 2030. Full article

Background: The progression of Alzheimer’s Disease (AD) deeply affects not only the diagnosed person but also their close relatives, who are often called to take on the role of informal caregivers. This transition is frequently unplanned and emotionally complex, yet poorly understood in its deeper processual dimensions. This study aims to explore and theorize the transition experienced by a family member becoming the primary informal caregiver for a person with advanced AD. Methods: A qualitative study based on the Constructivist Grounded Theory according to Charmaz’s approach (2006) was conducted. In-depth interviews were carried out with 10 participants who had become informal caregivers for a loved one with advanced AD. Data were analyzed using initial coding, focused coding, the constant comparative method, and theoretical coding. Results: Ten caregivers (mean age 39 years, range 35–54; nine females) of patients with advanced AD participated in the study. The analysis revealed a complex, emotionally intense caregiving experience marked by sacrifice, feelings of powerlessness, identity loss, and the necessity of sharing caregiving responsibilities. A core category emerged: A Silent and Certain Willingness to Care, representing the caregivers’ deep, often unconscious commitment to prioritize the care of their loved ones above their own needs. Four interconnected phases characterized the caregiving process: (1) The Changing Daily Life—involving significant sacrifices in personal and social life; (2) Feeling Powerless—confronting the inevitable decline without means to alter the course; (3) Losing Oneself—experiencing physical and psychological exhaustion and a sense of identity loss; and (4) Sharing with Others—seeking external support to sustain caregiving. These findings highlight the evolving nature of becoming a caregiver and the enduring dedication that sustains this role despite the challenges. Conclusions: The progression of AD deeply transforms the lives of caregivers, who become co-sufferers and active participants in the disease’s management. The results underscore the urgency of designing integrative care strategies—including psychological, social, and potentially technological support—that can enhance both patient outcomes and caregiver resilience. Grounded in real-world experiences, this study contributes to the broader neurodegeneration discourse by emphasizing caregiving as a critical factor in long-term disease management and therapeutic success. Full article

Physiological levels of reactive oxygen species (ROS) play a crucial role as intracellular signaling molecules, helping to maintain cellular homeostasis. However, when ROS accumulate excessively, they become toxic to cells, leading to damage to lipids, proteins, and DNA. This oxidative stress can impair cellular function and lead to various forms of cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis. Despite their significance, the role of ROS in autosis (an autophagy-dependent form of cell death) remains largely unexplored. In this review, we gather current knowledge on autotic cell death and summarize how oxidative stress influences the activity of Beclin-1 and the Na⁺,K⁺-ATPase pump, both of which are critical effectors of this pathway. Finally, we discuss the theoretical potential for ROS to modulate this type of cell death, proposing a possible dual role for these species in autosis regulation through effectors such as HIF-1α, TFEB, or the FOXO family, and highlighting the need to experimentally address cellular redox status when working on autotic cell death. Full article

Background: Family caregivers are a vital yet often under-recognized part of the healthcare system. They provide essential emotional, physical, and logistical support to individuals with illness, disability, or frailty, and their contributions improve continuity of care and reduce system strain. However, many healthcare and social service providers are not equipped to meaningfully engage caregivers as partners. In Alberta, stakeholders validated the Caregiver-Centered Care Competency Framework and identified the need for a three-tiered education model—Foundational, Advanced, and Champion—to help providers recognize, include, and support family caregivers across care settings. This paper focuses on the development and early evaluation of the Advanced Caregiver-Centered Care Education modules, designed to enhance the knowledge and skills of providers with more experience working with family caregivers. The modules emphasize how partnering with caregivers benefits not only the person receiving care but also improves provider effectiveness and supports better system outcomes. Methods: The modules were co-designed with a 154-member interdisciplinary team and grounded in the competency framework. Evaluation used the first three levels of the Kirkpatrick–Barr health workforce education model. We analyzed pre- and post-surveys from the first 50 learners in each module using paired t-tests and examined qualitative feedback and SMART goals through inductive content analysis. Results: Learners reported a high level of satisfaction with the education delivery and the knowledge and skill acquisition. Statistically significant improvements were observed in 53 of 54 pre-post items. SMART goals reflected intended practice changes across all six competency domains, indicating learners saw value in engaging caregivers as partners. Conclusions: The Advanced Caregiver-Centered Care education improved providers’ confidence, knowledge, and skills to work in partnership with family caregivers. Future research will explore whether these improvements translate into real-world practice changes and better caregiver experiences in care planning, communication, and navigation. Full article

Saffron (Crocus sativus L.) is a vegetatively propagated crop of high economic and cultural value, potentially affected by viral infections that may impact its productivity. Despite Iran’s dominance in global saffron production, knowledge of its virome remains limited. In this study, we conducted the first nationwide virome survey of saffron in Iran employing a high-throughput sequencing (HTS) approach on pooled samples obtained from eleven provinces in Iran and one location in Afghanistan. Members of three virus families were detected—Potyviridae (Potyvirus), Solemoviridae (Polerovirus), and Geminiviridae (Mastrevirus)—as well as one satellite from the family Alphasatellitidae (Clecrusatellite). A novel Potyvirus, tentatively named saffron Iran virus (SaIRV) and detected in three provinces, shares less than 68% nucleotide identity with known Potyvirus species, thus meeting the ICTV criteria for designation as a new species. Genetic diversity analyses revealed substantial intrapopulation SNP variation but no clear geographical clustering. Among the two wild Crocus species sampled, only Crocus speciosus harbored turnip mosaic virus. Virome network and phylogenetic analyses confirmed widespread viral circulation likely driven by corm-mediated propagation. Our findings highlight the need for targeted certification programs and biological characterization of key viruses to mitigate potential impacts on saffron yield and quality. Full article

Telomeres are terminal regions of chromosomes that protect and stabilize chromosome structures. Telomeres are usually composed of specific DNA repeats (motifs) that are maintained by telomerase and a complex of specific proteins. Telomeric DNA sequences are generally highly conserved throughout the evolution of different groups of eukaryotes. The most common motif in insects is TTAGG, but it is not universal, including in the large order Hemiptera. In particular, several derived telomeric motifs were identified in this order by analyzing chromosome-level genome assemblies or by FISH screening the chromosomes of target species. Here, we analyzed chromosome-level genome assemblies of 16 species from three hemipteran suborders, including Sternorrhyncha (Coccoidea: Planococcus citri, Acanthococcus lagerstroemiae, and Trionymus diminutus; Aphidoidea: Tuberolachnus salignus, Metopolophium dirhodum, Rhopalosiphum padi, and Schizaphis graminum), Auhenorrhyncha (Cicadomorpha: Allygus modestus, Arthaldeus pascuellus, Aphrophora alni, Cicadella viridis, Empoasca decipiens, and Ribautiana ulmi), and Heteroptera (Gerromorpha: Gerris lacustris; Pentatomomorpha: Aradus depressus and A. truncatus). In addition, scaffold-level genome assemblies of three more species of Heteroptera (Gerromorpha: Gerris buenoi, Microvelia longipes, and Hermatobates lingyangjiaoensis) were examined. The presumably ancestral insect motif TTAGG was found at the ends of chromosomes of all species studied using chromosome-level genome assembly analysis, with four exceptions. In Aphrophora alni, we detected sequences of 4 bp repeats of TGAC, which were tentatively identified as a telomeric motif. In Gerris lacustris, from the basal true bug infraorder Gerromorpha, we found a 10 bp motif TTAGAGGTGG, previously unknown not only in Heteroptera or Hemiptera but also in Arthropoda in general. Blast screening of the scaffold-level assemblies showed that TTAGAGGTGG is also likely to be a telomeric motif in G. buenoi and Microvelia. longipes, while the results obtained for H. lingyangjiaoensis were inconclusive. In A. depressus and A. truncatus from the basal for Pentatomomorpha family Aradidae, we found a 10 bp motif TTAGGGATGG. While the available data allowed us to present two alternative hypotheses about the evolution of telomeric motifs in Heteroptera, further data are needed to verify them, especially for the yet unstudied basal infraorders Enicocephalomorpha, Dipsocoromorpha, and Leptopodomorpha. Full article