Medical research archives最新文献

{"title":"Translating Combined Mother-Baby Interaction Therapy and Interpersonal Psychotherapy for Postpartum Depression from In-Person to Digital Delivery via <i>MommaConnect</i>.","authors":"June A Horowitz, Bobbie Posmontier, Pamela A Geller, Mary McDonough, Kayla Alvares, Yiqi Wang, Mona Elgohail, Katie Chang, Tony Ma","doi":"10.18103/mra.v14i2.7298","DOIUrl":"10.18103/mra.v14i2.7298","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and purpose: &lt;/strong&gt;Postpartum depression (PPD) is a common childbirth complication that impairs the mother-infant relationship and contributes to long-term developmental challenges among children. Although PPD treatment reduces depressive symptoms, it is not necessarily sufficient to improve maternal-infant interaction. In addition, several barriers preclude timely access to care including mental health stigma, limited specialized providers, and challenges with navigating the healthcare system and securing necessary childcare and transportation. Our team developed a 12-session patient- and clinician-facing digital platform, &lt;i&gt;MommaConnect&lt;/i&gt; that combines evidence-based therapies-- Mother Baby Interaction Therapy and Interpersonal Psychotherapy-- to improve PPD symptoms and mother-infant interaction, address barriers to care, and provide support between therapy sessions. The purpose of this article is to describe the translation of our in-person approach to treating PPD and improving mother-baby interaction to our &lt;i&gt;MommaConnect&lt;/i&gt; digital platform that integrates core psychotherapy components into a user-centered platform.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Our methods were guided by the PRECEDE-PROCEED Model and three stages of a nine-stage digital platform development process. In stage 1, we conducted focus groups to understand the needs of postpartum mothers who had experienced PPD and in-depth interviews to understand the concerns of perinatal mental health clinicians. We analyzed the qualitative data with thematic content analysis. In stage 2, we used component mapping to translate treatment modalities into the digital platform. Finally in stage 3, we used co-design, prototyping, and user-interface design to build the &lt;i&gt;MommaConnect&lt;/i&gt; prototype.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Results from the focus groups identified four themes including (1) barriers to accessing care, (2) preferences and needs in mental health care delivery, (3) feedback on the &lt;i&gt;MommaConnect&lt;/i&gt; App, and (4) broader challenges and experiences. The in-depth interviews with the clinicians resulted in six themes including (1) assessment and early intervention, (2) barriers to care, (3) role of technology in treatment, (4) building a therapeutic alliance, (5) community and social support, and (6) addressing comorbid conditions. Additionally, the team translated the in-person treatment modality to a 12-session format and designed the current version of the &lt;i&gt;MommaConnect&lt;/i&gt; prototype, which has both patient-facing and clinician-facing components.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and implications: &lt;/strong&gt;&lt;i&gt;MommaConnect&lt;/i&gt; offers an innovative, accessible approach that combines Mother Baby Interaction Therapy and Interpersonal Psychotherapy to treat PPD and improve the quality of mother-infant interaction. Its digital adaptation provides a treatment platform for mothers and clinicians to work together in real time and communicate between sessions. &lt;","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"14 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-IsdB Antibody-Secreting Cells Found in S. aureus-Infected Periprosthetic Bone Marrow: Case Series of Total Hip Arthroplasty Patients.","authors":"John R Owen, Gowrishankar Muthukrishnan, David J Topham, John L Daiss, Edward M Schwarz, Stephen L Kates","doi":"10.18103/mra.v14i1.7191","DOIUrl":"10.18103/mra.v14i1.7191","url":null,"abstract":"<p><p>Staphylococcus aureus periprosthetic joint infection is notoriously difficult to treat and is often associated with septic death. Results from the V710 Phase IIB/III clinical trial and subsequent research have demonstrated that non-neutralizing antibodies against the iron-regulated surface determinant protein B (IsdB) facilitate bacterial entry into leukocytes, generating \"Trojan horse\" leukocytes and the dissemination of surgical-site infections. In contrast, anti-glucosaminidase (Gmd) antibodies, which mediate opsonophagocytosis of bacterial clusters, are associated with protection from S. aureus osteomyelitis in both mice and humans. To further test whether anti-IsdB antibodies are pathogenic and anti-Gmd antibodies are protective in infected patients, we performed a clinical pilot study of three healthy patients undergoing primary total hip arthroplasty and a patient undergoing revision arthroplasty for S. aureus infection to assess the feasibility of quantifying anti-IsdB and anti-Gmd antibody-secreting cells in blood and periprosthetic bone marrow. We also assessed anti-IsdB and anti-Gmd antibody levels in serum, blood plasma, bone marrow plasma, and cell culture supernatant collected after six days with and without a previously established memory B-cell stimulation cocktail. The frequencies of memory B-cells and antibody-secreting plasmablasts were measured using IgG ELISpot. Consistent with our hypothesis, we found large numbers of anti-IsdB antibody-secreting cells in unstimulated periprosthetic bone marrow from the infected patient, which increased with stimulation. However, these cells were only detectable in peripheral blood mononuclear cells following stimulation. Furthermore, anti-Gmd antibody-secreting cells were undetectable in the bone marrow of this infected patient at the time of revision surgery. This patient also had very high titers of anti-IsdB antibodies in serum, blood plasma, and bone marrow plasma. Anti-IsdB and anti-Gmd antibody-secreting cells were only detected in bone marrow for one of the uninfected patients. Collectively, the results are consistent with the hypothesis that anti-IsdB antibodies are associated with disease and related to the presence of IsdB-specific memory B-cells and plasmablasts. This case series demonstrates the utility of ELISpot to assess local vs. systemic antigen-specific humoral responses in total hip arthroplasty patients and support a larger study to test the hypothesis that anti-IsdB antibody-secreting cells proximal to S. aureus infected implants are associated with recalcitrant infections and septic death.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytohormone Signaling Induces Dormancy and Apoptosis in Prostate Cancer Disseminated Tumor Cells.","authors":"Agustina Rodriguez, Younghun Jung, Keshab Raj Parajuli, Russell S Taichman","doi":"10.18103/mra.v14i1.7240","DOIUrl":"10.18103/mra.v14i1.7240","url":null,"abstract":"<p><p>Prostate cancer remains a major health concern, ranking as the second leading cause of cancer-related deaths in men in the United States. The dissemination of tumor cells from the prostate, their entry into circulation, and subsequent skeletal metastasis involve complex mechanisms that are not fully elucidated. Notably, disseminated tumor cells demonstrate a remarkable ability to home to the hematopoietic stem cell niche within bone marrow, where they may remain dormant for years. Key signaling pathways implicated in dormancy include TGF-β, BMP4/BMP7, GAS6/TAM receptors, and Wnt5a, each influencing cell cycle arrest, survival, and phenotype adaptation. Recent research has explored analogies between dormancy mechanisms in cancer and plant biology, particularly focusing on phytohormones such as abscisic acid and gibberellins, which regulate plant stress responses and developmental dormancy. While plants utilize PYR1/PYL/RCAR receptors for abscisic acid, mammals rely on LANCL2 and PPARγ. This study evaluated the effects of abscisic acid, gibberellic acid, and the ABA agonist pyrabactin on human and murine prostate cancer cell lines. Results demonstrated that gibberellic acid lacked proliferative effects and could not counteract ABA-induced growth arrest. In contrast, pyrabactin potently induced growth arrest and apoptosis, activating SMAC/Diablo cell death pathways independently of LANCL2 and PPARγ signaling. Further, the activity of abscisic acid and pyrabactin depended on cellular uptake via SLC4AE2 and SLC4A3 anion exchangers; downregulation of these transporters partially reversed their inhibitory effects. These findings suggest a mechanistic parallel between phytohormone-induced dormancy in plants and regulated dormancy and apoptosis in PCa, opening new avenues for therapeutic targeting of dormancy pathways in cancer metastasis.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital health and consumer health informatics: past and future.","authors":"Xia Jing, Hua Min, Yang Gong","doi":"10.18103/mra.v14i1.7206","DOIUrl":"10.18103/mra.v14i1.7206","url":null,"abstract":"<p><p>This perspective paper introduces digital health and consumer health informatics, their focus areas, origins, current trends, and future challenges. The paper aims to elaborate on the differences and their connections within the broader context of biomedical and health informatics. The goal is to provide a better and clearer navigation system for readers and researchers in the fields of digital health and consumer health informatics.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Profiling of GLP-1-Mediated Cardioprotection in a Large Animal Model of Chronic Coronary Artery Disease.","authors":"Clark Zheng, Christopher Stone, Kelsey Muir, Dwight Harris, Frank W Sellke","doi":"10.18103/mra.v13i11.7114","DOIUrl":"10.18103/mra.v13i11.7114","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery disease (CAD) imposes marked morbidity on patients, with many afflicted with debilitating residual symptoms despite optimal application of the available medical and surgical options. Glucagon-like peptide-1 (GLP-1) agonists have emerged from the resultant search for adjuncts as promising cardioprotective candidates in clinical trials.</p><p><strong>Aims: </strong>We have previously characterized the augmented myocardial functional response to GLP-1 agonism; in this experiment, we aim to elucidate the molecular basis of this augmentation using highly sensitive proteomic analysis.</p><p><strong>Methods: </strong>Yorkshire swine underwent surgical induction of CAD-associated ischemic cardiomyopathy through ameroid constrictor placement. Postoperatively, all were allocated either to receive semaglutide (n=6), or no drug (n=10) for 5 weeks, whereupon animals underwent myocardial resection and sectioning. The most ischemic ventricular sections were identified, from which tissue aliquots were fractionated using high-performance liquid chromatography and analyzed using mass spectrometry.</p><p><strong>Results: </strong>There were 594 upregulated and 90 downregulated proteins identified in the semaglutide cohort compared with control cohort. Enrichment analysis revealed marked upregulation of multiple central metabolic pathways, including the glycolytic and tricarboxylic acid cycle pathways. The significantly downregulated proteomic fraction was found within pathways relevant to the induction of dilated and hypertrophic cardiomyopathy.</p><p><strong>Conclusions: </strong>Myocardial sections taken from semaglutide-treated animals exhibited a striking and multifaceted increase in metabolic flexibility. This result implicates enhanced resilience against the energetic strain imposed by ischemic disease as a mechanistic account of GLP-1-mediated cardioprotection.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12916146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Community Engagement to explore Surrogate Decision-Making for HIV+ African Americans: a pilot study.","authors":"Mei Ching Lee, Randy Woods, Mian Bazle Hossain, Ila Mulasi, Renard Murray, Carla S Alexander, Frank Oldham, Steven Eveland, Robyn Palmiero Lcsw","doi":"10.18103/mra.v13i11.6823","DOIUrl":"10.18103/mra.v13i11.6823","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Patient-centered communication and trusting relationships are central to effective clinical management for anyone living with chronic illness. For those able to access and continue effective medications, aging with the human immunodeficiency virus (HIV) is now like aging with any chronic illness. Advance Care Planning (ACP) has been a recognized strategy to improve health outcomes for individuals with serious illnesses. Despite its importance, African Americans living with HIV (AAHIV) often experience barriers to ACP, including having lived in a syndemic environment where low health literacy and historical mistrust of the healthcare system are inherent. Our clinically translational pilot study aimed to evaluate the feasibility and acceptability of discussing surrogate decision-making and ACP within an urban syndemic using a community-engaged research approach to improve individual outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a one-year translational research pilot, to tryout a newfound academic-community research team formed during COVID-19 in one eastern urban setting. We used Community Engagement in Research (CEnR) and mixed methods to evaluate the impact of community input on Focus Group activities. Participants were recruited through local HIV/AIDS service organizations. A 19-item survey assessed ACP awareness and behaviors (n=75) and focus group discussion (n=34) explored barriers and facilitators of surrogate decision-making prompted by a community-generated scenario. Data analysis included descriptive statistics for the survey and thematic analysis for focus group discussions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;DECIDE survey results indicated that after the COVID pandemic, 45% of participants had never heard of ACP, and, of those with prior knowledge, 73% had discussed their treatment preferences, only 37% had created an ACP document. Approximately 49% of participants had named a health proxy, although only 45% of those individuals had discussed their values with the proxy. Use of a community-constructed scenario led to rapid assembly and valuable discourse among focus group participants despite the discussion being about dying. Focus group findings revealed a strong desire for more opportunities to rehearse ACP conversations and a persisting mistrust of healthcare systems. Participants expressed the need for continued, community-based educational efforts to address these issues.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The DECIDE translational pilot endorses the literature that community engagement is feasible, acceptable and effective in syndemic settings. Use of a community-generated scenario rapidly engaged participants in meaningful talk about surrogate decision-making among African Americans living with HIV. CEnR accelerated data collection about a potentially avoided topic for participants living in syndemic settings. Future research should address systemic barriers, trust-building, and community engagem","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matricellular Regulation of Alveolar Epithelial Cell Plasticity in Neonatal Lung Injury: Insights from CCN5 and Beyond.","authors":"Najla Fiaturi, Heber C Nielsen, John Castellot","doi":"10.18103/mra.v13i10.6931","DOIUrl":"10.18103/mra.v13i10.6931","url":null,"abstract":"<p><p>Neonatal lung injury remains a major cause of morbidity among preterm infants and is a leading antecedent of bronchopulmonary dysplasia (BPD), a condition characterized by arrested alveolar development, inflammation, and extracellular matrix (ECM) remodeling. Despite significant advances in neonatal care, the mechanisms governing lung repair and regeneration remain incompletely understood. Recent research highlights the crucial role of matricellular proteins that orchestrate cell signaling, differentiation, and tissue remodeling in modulating-epithelial responses to injury. Among these, the CCN (CYR61/CTGF/NOV) family of proteins has emerged as a pivotal regulator of epithelial mesenchymal communication, with diverse and context-dependent functions in development, fibrosis, and regeneration. This review examines the distinct role of <b>CCN5 (WISP2)</b> within this family as a modulator of alveolar epithelial cell (AEC) plasticity in neonatal lung injury. We integrate findings from our own work with recent advances in CCN biology to elucidate how CCN5 influences epithelial survival, epithelial-mesenchymal transition (EMT), mitochondrial homeostasis, and intercellular signaling in hyperoxic injury. The review also contrasts CCN5 with other CCN members implicated in fibrotic lung diseases and situates it within broader matricellular signaling networks. By defining how CCN5 mediates epithelial resilience and tissue homeostasis, we propose it as a potential therapeutic target for mitigating BPD and enhancing regenerative outcomes in premature infants.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammatory Mechanisms and Vocalization Biomarkers in the <i>Pink1</i>-/- Preclinical Model of Parkinson's Disease.","authors":"Sarah A Lechner, Cynthia A Kelm-Nelson","doi":"10.18103/mra.v13i10.6972","DOIUrl":"10.18103/mra.v13i10.6972","url":null,"abstract":"<p><p>Parkinson's disease is a progressive neurodegenerative disorder with an unclear etiology and a long preclinical phase. The multitude of challenges of studying this in humans highlight the need for robust preclinical animal models that accurately reflect the disease's preclinical progression. While traditional neurotoxin models fail to capture the slow, genetic nature of PD, genetic models, such as the phosphatase and tensin homolog-induced putative kinase 1 (<i>Pink1</i>-/-) knockout rat, offer a preclinical, translational approach. This review synthesizes the current understanding of the <i>Pink1</i>-/- rat model, focusing on two key aspects: neuroinflammation and vocalization deficits. The <i>Pink1</i>-/- rat presents early non-motor symptoms, including vocalization deficits, which can serve as a non-invasive, objective, and longitudinal biomarker of disease progression. This review further proposes a direct link between the model's neuroinflammatory profile, characterized by chronic glial activation and the upregulation of inflammatory pathways, and the observed vocal dysfunctions. By bridging these two critical areas, neuroinflammation as a pathological mechanism and vocalizations as a functional readout, this review provides a framework for future investigations into the diagnosis and treatment of Parkinson's disease and suggests that targeting specific inflammatory pathways could be a viable therapeutic strategy.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective versus Risk Factors for 18-month Outcomes in a multi-decade sample of preterm infants age 23-30 weeks.","authors":"Ted S Rosenkrantz, Ruth M McLeod, R Holly Fitch","doi":"10.18103/mra.v13i10.7027","DOIUrl":"10.18103/mra.v13i10.7027","url":null,"abstract":"<p><p>This paper summarizes risk and protective factors modulating cognitive, language and motor outcomes in a cohort of preterm infants from Connecticut Children's Medical Center and University of Connecticut Health Center. Infants were born at 23-30 weeks gestational age and admitted to the neonatal unit (1991 - 2017). Extracted and de-identified patient data included sex, gestational age (GA), birthweight, maternal health conditions (pre-eclampsia, diabetes, etc.), presence of necrotizing enterocolitis, intra-ventricular hemorrhage and grade, maternal magnesium sulfate (MGS) treatment, and administration of the methylxanthine (MX) adenosine antagonists (caffeine or theophylline) and timing (< 48 hrs from birth (early) or > 48 hrs (late)). Outcome measures were obtained at 18-month follow-up evaluations (Bayley Scale and/or Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale). Scores on different components of the tests were z-scored and averaged into 3 categories for each infant as Language, Cognitive, and Motor indices. Significant risk factors for <i>poor</i> outcomes were found to include: (1) being male, (2) extremely low birthweight (a better predictor of poor outcome than low GA), (3) positive inflammatory perinatal profile; and (4) MGS exposure in males, particularly when followed by early MX treatment. Factors leading to significantly <i>better</i> outcomes included: (1) MX exposure within 48 hours of birth, <i>particularly</i> in infants with inflammation (but excluding males with prior MGS exposure); and (2) perinatal MGS exposure, <i>particularly</i> in lower birthweight females (but excluding early MX-treated males). This novel evidence of sub-group specific therapeutic benefits and harms emphasizes a serious need for additional research on individualized therapeutic interventions for at-risk preterm infants and reveals a novel deleterious interaction between magnesium sulfate exposure and subsequent treatment with methyxanthines (e.g., caffeine) within 48 hours of birth for preterm boys.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of endocannabinoid signaling in the cytoskeleton functionality in migrating neurons.","authors":"Yury M Morozov, Pasko Rakic","doi":"10.18103/mra.v13i10.7041","DOIUrl":"10.18103/mra.v13i10.7041","url":null,"abstract":"<p><p>A fraction of neurons migrating through the developing brain are known to show nuclear envelope rupture and herniation of the chromatin in cytoplasm. We recently reported powerful streams of chromatin rupturing nuclear envelopes together with the plasma membranes in migrating cerebral neurons in mouse embryos. Such chromatin streams represent a novel form of cell pathology, which we named 'piercing nuclear hernia' (PNH). Simultaneous piercing of the nuclear and plasma membranes exposes nucleoplasm and cytoplasm to the intercellular space and may result in accidental cell death which, in contrast to the programed cell death mechanisms, are not detectable using biochemical or immunochemical markers for apoptosis, autophagy, or necrotic type of cell death. We also showed that the disfunction of the endocannabinoid system increases the probability of nuclear membrane rupture and chromatin herniation in developing brain. Indeed, about 40% of migrating neurons in cannabinoid type 1 receptor knock-out mouse embryos and wild type embryos exposed to two different agonists of the cannabinoid receptor show nuclear envelope ruptures or/and PNHs. This indicates that deviations from optimal functioning of the endocannabinoid system in under- or over-activity may trigger analogous mechanisms increasing the membrane's vulnerability and chromatin herniation. The role of increased intranuclear pressure and cytoskeleton malfunction in the mechanism of nuclear envelope rupture is documented and commonly accepted. In accordance, our results provide evidence that optimal endocannabinoid signaling plays a role in cytoskeleton functionality in migrating neurons. In a fraction of neurons, catastrophic rupture of the nuclear and plasma membranes provokes ultrastructural pathology in the mitochondria and other organelles. At the same time, other neurons with PNH show generally normal ultrastructure that may indicate a mechanism of neuronal cell body repair. Further studies of neuronal cell body recovery may identify yet unknown molecular mechanisms and become instrumental for increasing regenerative capacity of neurons during neurodegenerative diseases, after traumatic brain injury and ischemic conditions. On the other hand, the demonstrated novel pathology of PNH in migrating cells and the procedure of its upregulation may be useful for inducing breaks of the plasma membrane and death of metastatic tumor cells.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}