Three of the great public health challenges of our time converge at the hippocampus. The first, dementia, most commonly in the form of Alzheimer's disease, is well known to cause progressive hippocampal damage, resulting in the memory loss associated with the illness. The second, COVID-19 infection, has thus far been linked to hippocampal alterations across multiple studies. Lastly, the third, opioids-especially in the setting of misuse-have been associated with acute and persistent hippocampal injury; this review focuses on the collection of pre-clinical, clinical, and epidemiologic observations supporting this final relationship. Basic science work dating back decades has demonstrated a hypermetabolic response to opioids and associated damage to the hippocampus. The earliest cases recognized as opioid-associated amnestic syndrome (OAS) were subsequently identified in 2012 and reported as part of larger case series several years later. In 2019, a related but more fulminant syndrome involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) was first described. From these investigations, a growing body of data has since emerged to suggest that regular opioid use, particularly at higher doses or potency, may be connected to a reduction in hippocampal volume and greater risk of dementia. This review begins with a synthesis of data supporting the underlying pathological mechanisms of opioid-associated hippocampal injury (OAHI), then covers the clinical spectrum of this phenomenon. Lastly, we will close with implications of OAHI that warrant further study, including the future epidemiologic impact on related cognitive disorders in the wake of the opioid epidemic and potential therapeutic applications of opioid antagonism for mild cognitive impairment.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease marked by the destruction of pancreatic β-cells, resulting in lifelong dependence on exogenous insulin. Despite advances in insulin delivery and glucose monitoring technologies, patients remain at risk for acute and long-term complications, underscoring the need for curative strategies. Gene therapy and gene-editing technologies are emerging as transformative approaches capable of restoring β-cell function, modulating immune responses and potentially achieving durable remission. This review synthesizes basic science foundations and clinical trial evidence, focusing on five key protocols (NCT03162237, NCT05210530, NCT05241444, NCT05565248 and NCT06938334). Strategies include immune modulation (PD-L1, FOXP3), β-cell replacement (CRISPR-edited progenitors, xenotransplantation) and combination approaches. Early-phase clinical trials have demonstrated feasibility and safety; however, long-term efficacy, durability and scalability remain uncertain. Critical challenges include potential off-target effects in CRISPR editing, risks of insertional mutagenesis, safety concerns in xenotransplantation and achieving a balance between immune tolerance and protective immunity. Future directions emphasize combination therapies, personalized medicine and next-generation editing tools such as base and prime editing. Together, these efforts represent a paradigm shift from symptomatic insulin replacement toward curative interventions, while highlighting the considerable translational hurdles that must be overcome before routine clinical application.

CAQK is a homing peptide that targets sites of central nervous system injury and has previously demonstrated functional benefits in traumatic brain injury models. We recently demonstrated its localization to spinal cord injury (SCI) after intravenous administration and hypothesized that it could enhance motor recovery after SCI. Twelve female Sprague-Dawley rats underwent C5 right-sided spinal cord hemicontusion. Animals were randomized to receive intravenous CAQK (2.5mg/kg) or saline daily for 7 days, beginning 1 hour postinjury. Motor performance was assessed using the Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale, a scale from 0 to 9, with 9 being normal function. IBB score was assessed at five time points over 8 weeks, followed by histological analysis. An in vitro neuroprotection assay was also conducted to evaluate the neuroprotective effects of CAQK at various doses. All animals exhibited motor deficits immediately after injury. Compared with saline controls, CAQK-treated rats demonstrated significantly improved motor recovery at 1, 2, 5, and 8 weeks postinjury (week 8: IBB = 7 vs. 3; p = 0.01). Histologic analysis showed significantly reduced astroglial activation in the CAQK group (GFAP: treated = 0.1±0.01 vs. untreated = 0.7±0.2; p = 0.002) and increased axonal preservation (NFM: treated = 0.3±0.06 vs. untreated = 0.1±0.06; p = 0.03). In vitro, CAQK significantly enhanced neuronal network complexity compared with saline (p < 0.05). CAQK treatment significantly improved motor outcomes compared with saline-only treatment. Ex vivo analysis of spinal cord tissue showed enhanced tissue recovery in CAQK-treated rats. In vitro, neuroprotection was evident in cells treated with CAQK. Overall, these findings support CAQK's potential as a targeted therapeutic candidate for SCI. (J Trauma Acute Care Surg 2026;00:000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). Basic Science.

Precise knowledge of the anatomical course of the superior and inferior labial arteries is essential for ensuring the safety of surgical interventions and minimally invasive esthetic procedures involving the lips. However, despite their growing clinical importance, the available anatomical evidence remains heterogeneous and fragmented, which limits the development of consistent safety guidelines. To evaluate the anatomical distribution of the superior and inferior labial arteries in relation to the orbicularis oris muscle by integrating findings from a Brazilian cadaveric anatomical investigation with evidence synthesized through a systematic review and meta-analysis. The cadaveric component was performed using preserved Brazilian specimens and standardized anatomical landmarks, dividing the lips into midline and paramedian regions located 1 cm lateral to the midline. The position of the superior and inferior labial arteries relative to the orbicularis oris muscle was classified as submucosal, intramuscular, or subcutaneous. In parallel, a systematic review and meta-analysis were conducted according to PRISMA guidelines, with electronic databases searched without date restrictions for studies reporting the anatomical location of the labial arteries. Eligible studies were quantitatively synthesized using fixed- or random-effects models depending on the degree of heterogeneity. Four studies met the eligibility criteria for quantitative synthesis. The pooled analysis demonstrated that the superior labial artery in the upper lip was most frequently located in the submucosal plane (33.3-53.3%), followed by an intramuscular course (40.0-46.7%), whereas a subcutaneous position was uncommon (0.0-26.7%). In the lower lip, the inferior labial artery showed greater variability, with intramuscular positioning predominating in median regions (73.3%) and submucosal positioning ranging from 13.3 to 53.3%, while subcutaneous localization remained rare. Regional and sex-related differences contributed to moderate-to-high heterogeneity across the analyses. The cadaveric findings were consistent with the meta-analytic results, confirming the predominance of submucosal and intramuscular arterial courses, a consistent midline anastomosis, and increased positional variability in paramedian regions. The superior and inferior labial arteries demonstrate variable anatomical distribution patterns, most commonly occupying submucosal and intramuscular planes, while subcutaneous courses are uncommon. By integrating a Brazilian cadaveric study with systematic review and meta-analysis, this investigation provides comprehensive anatomical evidence with direct clinical implications for improving the safety of lip surgery and minimally invasive esthetic procedures, emphasizing that neither midline nor paramedian regions can be considered entirely risk-free. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Neurogenic lower urinary tract dysfunction (NLUTD), stemming from neurodegenerative diseases or injuries such as cerebrovascular accidents, spinal cord injuries, and Alzheimer's disease, significantly impacts quality of life. Symptoms, including urinary frequency, urgency, incontinence, and retention, are managed with devices ranging from catheters to sacral neuromodulation. This Neurogenic Bladder Research Group (NBRG) report explores the intersection between clinical, basic science, and engineering research in personalized NLUTD treatment, identifies critical gaps for future investigation, and examines how interdisciplinary collaboration can drive engineering solutions to improve care. In December 2024, NBRG convened its annual meeting, gathering experts from engineering, clinical practice, research, and patient advocacy to discuss challenges in NLUTD research and explore collaborative solutions. Enhanced collaboration between clinicians and engineers offers promise for improving NLUTD care. Clinicians provide critical insight into patient needs but often lack time for sustained research, while engineers contribute technical innovation yet may lack clinical exposure. Integrating patient perspectives emerged as a key theme, ensuring that technologies are practical, acceptable, and aligned with end-user needs. Discussions emphasized expanding programs that support cross-disciplinary, multi-institutional research and identifying funding pathways tailored to interdisciplinary efforts. Strategies to enhance patient involvement and foster inclusive research that reflects patient diversity and socio-demographic factors influencing care were also discussed. Institutional support, interdisciplinary collaboration, and the active engagement of patients are key to advancing clinical care and NLUTD treatments.

The aim of this study is to identify the anatomical location of the emergence point of the zygomaticotemporal nerve (EP) in the lateral orbital margin with reference to the marginal tubercle of zygomatic bone (MT), and to determine whether the MT can serve as a consistent landmark for zygomaticotemporal nerve (ZTN) block procedures. Thirty-six hemifaces from 20 cadavers were dissected. The spatial relationships of the EP with the MT and the lateral canthus (LC) were the main outcomes. Facial proportions were recorded as covariates. Cross-sectional relationships of the ZTN with the middle temporal vein (MTV) and the frontal branch of the facial nerve (FN) in fascial planes were also examined. The EP was consistently identified near the lateral orbital margin, located 4.5±1.6 mm superior to the MT and 17.6±2.7 mm lateral and 9.5±2.9 mm superior to the LC. The vertical distance to the MTV was 7.3±2.3 mm, with both structures positioned within the same fascial plane. In contrast, the FN coursed through a more-superficial layer. Correlation analyses indicated that while the facial proportions affected the absolute location of the ZTN, they did not alter its spatial relationship to the MT. The MT serves as a consistent palpable landmark for locating the EP, facilitating more-accurate regional nerve blocks for anesthesia, postoperative pain control, and neuralgia treatment. When the MT is not palpable, the LC can serve as an alternative landmark. Understanding their spatial relationships with surrounding structures-including the MTV and FN-may help prevent vascular injury and inadvertent FN blockade.Levels of Evidence: Basic science and clinical study.

Sixty years of adeno-associated virus (AAV) research illustrates a trajectory marked by basic science exploration, iterative innovation, persistent challenges, a number of clinical setbacks, as well as commercial therapeutic triumphs. This continual evolution has led to recombinant AAV (rAAV) becoming a cornerstone of modern gene therapy. Significant advancements in molecular design, process development, and manufacturing have been made over the past three decades; these improvements are expected to significantly improve the safety, efficacy, and economics of rAAV gene therapies. Beyond rare disease, rAAV vectors have the potential to be used in prevalent conditions such as arthritis, heart failure, diabetes, Alzheimer's disease, and Parkinson's disease. Meeting the vector demands of these disease treatments will require continued innovations in rAAV manufacturing, including further improvements in process optimization and molecular engineering. In addition, the adoption of process intensification and automation strategies, pioneered in other biologics such as monoclonal antibody manufacturing, should prove pivotal in advancing the scale, robustness, and efficiency of rAAV production.

IntroductionThe 13th Annual Conference of the Cholangiocarcinoma Foundation (CCF) took place on May 1-3, 2026, in Salt Lake City, USA; this year’s conference also celebrated CCF’s 20th Anniversary. Themed Strength in Community: Every Patient Counts, it convened leading researchers, clinicians, patients, caregivers, advocates, and industry partners to explore the latest basic science, translational and clinical advancements in cholangiocarcinoma (CCA) and foster collaboration across the community.The conference, co-chaired by Dr Tim F Greten (NIH, MD, USA) and Dr Luke Boulter (University of Edinburgh, UK), consisted of three keynote presentations: 1. Therapy Resistance and Combination Strategies in CCA: Navigating Adaptive Responses and Lineage States (Dr Nabeel El-Bardeesy, Harvard); 2. Beyond Immune Checkpoint Blockade: Emerging Strategies (Dr Tak Mak, Princess Margaret Hospital, Canada); and 3. Research in CCA: Accomplishments, Advances, and Aspirations (Dr Gregory Gores, Mayo Clinic). There was a focus on basic science on Day 1, with multidisciplinary clinical aspects on Days 2 and 3, covering surgery, and locoregional and systemic therapies, including novel targets and agents in development.The patient voice is a key feature of the Conference; in addition to a Patient Day (Day 1), patients and caregivers shared their experiences during the plenary sessions, participated in discussions, and learned about the latest research in the poster session and the Clinical and Science Poster Walks, with posters requiring a lay summary.CCF helps to develop the next generation of researchers. Plenary sessions were co-chaired by early career investigators; they also presented their research as posters. Some were selected for oral presentations or speed talks. The 2026 CCF Fellows were announced at the Awards Ceremony, and the 2025 CCF Fellows gave oral presentations of their research.This supplement contains all accepted abstracts (as of April 10, 2026). Please note that some abstracts may have been withdrawn or rescheduled at authors’ request. In addition, The Oncologist is not able to accept previously published encore abstracts. These have been removed, although the Cholangiocarcinoma Foundation is grateful that this information was shared at the meeting with the clinical and patient community.

Where Are the Women in Basic Science Research? Gender Trends in Abstracts Presented at the Academic Surgical Congress.

Silicone implants are widely used in rhinoplasty but often face issues such as displacement, tilting, sliding, and translucency. Additionally, their fixed sizes fail to meet individualized needs, and intraoperative carving increases surgical difficulty and time. 3D printing technology offers the potential for precise and personalized silicone nasal implants to address these challenges. To investigate whether 3D-printed silicone nasal implants can reduce implant displacement, sliding, tilting, and translucency, as well as shorten surgical time compared to traditional silicone implants. The dimensions of the implant were determined by measuring the nasal dorsum of experimental animals. 3D CT scanning was used to obtain nasal bone data, based on which personalized silicone implants were designed and fabricated to fit the bone surface. A rabbit nasal implantation model was used to compare outcomes between 3D-printed implants (3D group) and traditional silicone implants (control group). Additional implantation experiments were conducted on beagle dogs. The 3D-printed silicone nasal implants showed a tight fit with the nasal bone. Their rough surface and porous design promoted tissue ingrowth, reducing implant displacement. The porous structure also minimized light refraction and translucency. The implantation surgery required no carving, thus reducing operative time. 3D-printed silicone implants effectively address displacement and translucency issues associated with traditional implants, enable personalized design to meet individual patient needs, reduce surgery time, and improve surgical efficiency. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acute inflammation, when unresolved, can lead to complications that impair tissue repair and therapeutic outcomes. In this study, we employed a model of lipopolysaccharide (LPS)-induced acute subcutaneous abdominal inflammation in mice to investigate the modulatory effects of elastic compression. LPS administration elicited a robust inflammatory response, characterized by increased leukocyte infiltration, edema, and upregulation of pro-inflammatory mediators. Elastic compression significantly attenuated this response, reducing leukocyte counts in subcutaneous lavage, histological inflammatory infiltrates, and the expression of key pro-inflammatory genes and proteins, including NF-κB, IL-1β, and TNF-α, at both 24 and 72 hours post-induction. Mechanistically, these effects may result from the compressive force altering microvascular dynamics and modulating macrophage polarization and mechanotransduction pathways, including TLR4 and integrin signaling. Additionally, compression preserved redox homeostasis, as indicated by stable oxidative stress markers and antioxidant responses. To our knowledge, this is the first study to demonstrate that elastic compression modulates inflammation at molecular, cellular, and tissue levels in an acute inflammation model. These findings support the therapeutic potential of elastic compression as a non-pharmacological strategy for managing acute inflammation, with possible applications in postoperative care, traumatic edema, and other soft tissue inflammatory conditions. Further translational and clinical studies are warranted to validate these outcomes and guide evidence-based application protocols. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Atrophic acne scarring is a prevalent and psychologically distressing sequela of acne vulgaris, often resulting from insufficient matrix remodeling and collagen loss. While microneedling is a safe treatment, its efficacy as a monotherapy is often limited. Autologous platelet-rich plasma (PRP) is the current gold standard adjuvant, but its high cost and invasiveness restrict its use. Topical insulin has emerged as a cost-effective, non-invasive alternative to promote wound healing. A comprehensive search was conducted across PubMed, Web of Science, CENTRAL, Scopus, and Google Scholar for comparative studies published up to January 2026. Risk of bias was assessed using the RoB-2 and ROBINS-I tools. The primary outcome was significant clinical improvement (>50%). Secondary outcomes included changes in scar severity scores and adverse events. Risk ratios (RRs) and standardized mean differences (SMDs) were pooled with 95% confidence intervals (CIs). Trial sequential analysis was also performed. Five studies involving 256 patients were included. Microneedling with topical insulin was associated with a significantly higher rate of significant clinical improvement compared to PRP (RR = 1.96, 95% CI [1.30-2.95], p < 0.0001). However, the pooled analysis of changes in scar severity scores showed no significant difference between groups (SMD = -0.52, 95% CI [-1.44, 0.39], p = 0.26), with high heterogeneity. Regarding safety, there was no significant difference in the risk of post-inflammatory hyperpigmentation (RR = 0.72, 95% CI [0.14-3.62], p = 0.69), and no episodes of hypoglycemia were reported. Microneedling with topical insulin may achieve a higher rate of significant clinical improvement than PRP, with a comparable safety profile. However, given the inconclusive trial sequential analysis, high heterogeneity, and low overall certainty of evidence, these findings should be interpreted with caution. Further adequately powered trials are required to confirm this preliminary signal. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prevention of Hip Fractures in the Elderly A Public Health Problem. I. Basic Science.

To compare the accuracy and safety of 4 large language models on cornea and external disease multiple-choice questions (MCQs). DeepSeek-V3.2, GPT-5.2 (via ChatGPT), Gemini 3 Pro, and Claude Opus 4.5 were tested on American Academy of Ophthalmology (AAO) Ophthalmic News and Education (ONE) Network Cornea/External MCQs (114 text-only) and AAO Basic and Clinical Science Course Cornea/External study questions (38 text-only). Each item was queried once per model using a standardized prompt for the primary analysis. In secondary analyses, each item was requeried 5 times per model in independent sessions. Accuracy was compared using Cochran Q and pairwise exact McNemar tests with Holm adjustment. Potentially harmful wrong answers (HarmfulWrong) were independently coded using a prespecified rubric. In the AAO ONE dataset, accuracy was 65.8% for DeepSeek-V3.2, 93.0% for GPT-5.2, 93.9% for Gemini 3 Pro, and 92.1% for Claude Opus 4.5 (Cochran Q P < 0.001). DeepSeek-V3.2 was significantly less accurate than all other models; the other 3 did not differ significantly. In the Basic and Clinical Science Course dataset, accuracy was 57.9%, 76.3%, 94.7%, and 84.2%, respectively (Cochran Q P < 0.001); DeepSeek-V3.2 was significantly less accurate than Gemini 3 Pro and Claude Opus 4.5. Five-run retesting showed similar ranking but imperfect stability, particularly for DeepSeek-V3.2. HarmfulWrong responses were infrequent, and 2 cornea specialists achieved 98.0% and 97.4% overall accuracy without HarmfulWrong responses. GPT-5.2, Gemini 3 Pro, and Claude Opus 4.5 achieved similarly high accuracy on text-only cornea/external disease MCQs, whereas DeepSeek-V3.2 underperformed. Potentially harmful errors were uncommon but support continued clinician oversight.

Traumatic hemothorax (HTX) is a frequent complication of chest wall injury, with ~300,000 cases annually in the United States. Pain often signifies underlying inflammation and may contribute to secondary complications after chest wall injury. We hypothesized that HTX leads to local, intrapleural complement activation and release of proinflammatory cytokines that can prime neutrophils for inflammatory reactive oxygen species (ROS) release. Adult trauma patients (N=15) with chest wall injury and HTX were consented for the study with IRB approval. HTX fluid and corresponding blood plasma were obtained in 3.2% citrate. Multiplex assays for complement analytes and proinflammatory cytokines were performed. Neutrophils from healthy donors were obtained and co-incubated with control platelet-poor plasma (PPP), trauma PPP, or corresponding HTX fluid and then challenged with vehicle control or N-formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence of luminol, with ROS measured as luminescence over time. Pairwise comparisons were performed. Significance was set at p <0.05. Compared with circulating trauma PPP, HTX fluid had significant local elevations of complement components Ba, C3a, C4a, and sC5b-9 (all p <0.01). Inflammatory cytokines showed a similar local elevation in HTX relative to trauma PPP, including TNF-alpha, IFN-gamma, IL-8, and MCP-1 (all p <0.05). Neutrophils did not generate significant ROS in response to healthy PPP, trauma PPP, or HTX in the absence of fMLP. When challenged with fMLP, HTX co-incubated neutrophils generated marked ROS that was significantly greater than trauma PPP co-incubated neutrophils ( p <0.05), demonstrating marked local neutrophil priming in HTX, while plasma co-incubated neutrophils were not primed for ROS generation. Traumatic HTX is a highly inflammatory condition with locally enhanced complement activation, proinflammatory cytokine release, and inflammatory neutrophil priming for ROS production beyond that of circulating trauma plasma. Pain and secondary complications after chest wall injury with HTX may benefit from anti-inflammatory treatments in addition to pain control and drainage. ( J Trauma Acute Care Surg 2026;00:000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). Original Research. Basic Science; N/A.

Few conditions in reproductive medicine rival polycystic ovary syndrome (PCOS) in terms of clinical breadth and global impact. Affecting roughly 6-21% of women of childbearing age depending on which diagnostic criteria are applied PCOS sits at the intersection of endocrinology, metabolism, and gynecology, making it difficult to capture within any single disciplinary lens. Its hallmarks are well rehearsed: excess androgens, disrupted ovulation, and the characteristic follicular architecture seen on pelvic ultrasound. Yet what makes PCOS genuinely challenging is the degree to which these reproductive features overlap with far-reaching metabolic consequences, including insulin resistance, type 2 diabetes, lipid abnormalities, and a meaningfully elevated cardiovascular risk profile that persists well beyond the fertile years. Despite several decades of sustained investigation, the origins of PCOS remain imperfectly understood. Genetic susceptibility, epigenetic programming, environmental chemical exposures, and modern dietary habits all appear to play contributory roles, though no single culprit has emerged. The molecular picture is equally layered: aberrant insulin signaling feeds androgen overproduction, gonadotropin secretion goes out of balance, inflammatory cytokines accumulate, oxidative injury mounts, and more recently the gut microbial community has been implicated as an additional participant in this cascade. Diagnosis is further complicated by the phenotypic variability of the syndrome, with different criteria yielding meaningfully different patient populations. Treatment, in turn, requires individualization; lifestyle change, hormonal therapies, insulin sensitizers, and an expanding repertoire of repurposed drugs and plant-based agents each address different facets of a fundamentally heterogeneous disorder. This review provides a comprehensive and integrated account of PCOS across its full biological and clinical spectrum. It covers epidemiology, clinical presentation, risk factors, and current diagnostic frameworks. Pathophysiological mechanisms are examined in depth. A central and distinctive focus of this review is the experimental preclinical landscape. Established animal induction models, letrozole, dehydroepiandrosterone (DHEA), testosterone/dihydrotestosterone propionate, and high-fat diet protocols are critically evaluated for their translational relevance. Drawing on these models, we comprehensively catalogue protective agents across four systematic tables, encompassing both repurposed pharmaceuticals (metformin, GLP-1 receptor agonists, SGLT-2 inhibitors, statins, melatonin) and bioactive natural compounds (curcumin, berberine, quercetin, fisetin, myricetin, apigenin, and others), detailing their induction models, mechanistic pathways, and therapeutic outcomes. Together, this review aims to serve as a single, authoritative reference bridging basic science, translational pharmacology, and clinical practice in PCOS, while identifying the most promising avenues for future research and personalized therapeutic development.

ABSTRACTBackgroundChronic migraine (CM) is a debilitating neurological disorder with limited treatment options. Although acupuncture has demonstrated clinical efficacy in relieving CM symptoms, its cellular and molecular mechanisms remain poorly understood.ObjectiveThis study aimed to delineate the cell‐type‐specific transcriptional landscape and intercellular communication network reshaped by acupuncture.MethodsA rat model of CM was induced by repeated administration of nitroglycerin. Acupuncture was applied at GB8 and GB34 points. Single‐nucleus RNA sequencing (snRNA‐seq) was performed on the TNC region to profile transcriptomic changes across different cell types. Differential expression analysis, functional enrichment, and pseudotime trajectory inference were performed, along with intercellular communication analysis using CellChat.ResultsAcupuncture alleviated pain‐related behaviors and restored aberrant cell compositions in the TNC, especially among neurons, astrocytes, and microglia. It reversed the CM‐induced upregulation of inflammatory and oxidative stress‐related genes (e.g., Nfkbia, S100a8, S100a9, Penk). The imbalance between neuronal excitability and metabolism was rectified through the modulation of glutamatergic transmission and oxidative phosphorylation pathways. Microglial polarization shifted from pro‐inflammatory (M1/M5) to reparative ones (M2/M4), while astrocytic subtypes rebalanced toward anti‐inflammatory and metabolic repair states. CellChat analysis showed that acupuncture also remodeled neuron–glia communication disrupted by CM.ConclusionsThis study sheds light on the cellular and molecular mechanisms by which acupuncture alleviates CM, providing novel insights into its effects on oxidative stress, inflammation, and neuronal function in the TNC. These findings have important implications for both basic science and clinical practice, supporting the potential of acupuncture as a non‐invasive, adjunctive therapy for migraine treatment.

Basic science. The goal of this study was to investigate a novel therapeutic approach for treating degenerative disc disease (DDD) by enhancing anabolic signaling through ALK3 overexpression in the intervertebral disc, using a mouse tail compression model. Our previous data showed induction of BMP/Smad signaling in intervertebral disc tissue of DDD patients. The role of such induction is not fully understood, but previous literature indicates mostly protective effects of exogenous BMPs against DDD. ALK3 transgenic mice (ALK3 TG ) were crossed to tamoxifen-inducible Aggrecan-Cre (Acan-Cre ERt2 ) mice to assess the protective effect of tissue-specific ALK3 overexpression using a tail compression device in the caudal vertebrae to induce DDD. Cre+;ALK3 TG (GOF, n=40) and Cre-;ALK3 TG (Cre- control, n=40) mice were used. At four and eight weeks, tails were harvested and analyzed with histomorphometry and micro-computed tomography. In the male cohort, GOF mice showed significantly greater proteoglycan content compared with Cre- controls at four and eight weeks after tail compression. There was no difference proteoglycan content in the female compression cohort at either time point. In the male cohort, GOF mice trended towards having a larger disc area than Cre- controls at four weeks after tail compression, but no difference was observed at eight weeks. In the female cohort, disc area was significantly larger in GOF mice compared with Cre- controls at four and eight weeks after tail compression. Using a tail compression device to model DDD, we found that ALK3 overexpression in aggrecan-expressing disc cells enhanced BMP signaling and maintained higher proteoglycan content in male mice and increased disc area in female mice.

The multifaceted role of cAMP signalling in Leishmania pathogenesis and host immune modulation.

ObjectivesActive learning strategies, including case-based learning (CBL), problem-based learning (PBL) and team-based learning (TBL), have been extensively studied in clinical and basic science education; however, their application in public health programmes remains under-explored. Public health professionals address population-level challenges that differ substantially from clinical practice, making it necessary to evaluate whether these pedagogies are effective in this field. This review examines how CBL, PBL and TBL have been used in public health education and what outcomes have been reported.DesignScoping review was conducted using the Levac and Colquhoun framework, an adaptation of Arksey and O’Malley’s approach.Data sources, eligibility and extractionPubMed, Scopus and Google Scholar were searched for studies published between 2000 and 2025. Eligible studies included those involving students enrolled in undergraduate or postgraduate public health programmes, such as bachelor’s or master’s programmes in public health, epidemiology and biostatistics, global health, community medicine or health policy as well as employees working in public health-related fields. Data were extracted using a predefined template capturing study characteristics, population characteristics, student satisfaction and study objectives. All articles were thematically analysed.ResultsOverall, 22 studies were included. Of these, 11 focused on PBL, 2 on CBL, 3 on both CBL and PBL and 6 on TBL. Public health topics addressed included general public health practice (n=5), global health (n=3), health literacy or education (n=3) and occupational health or medicine (n=2); remaining studies covered leadership, nutrition, health behaviour, climate and health, ageing and mental health. Six themes emerged: skill development, real-world relevance, diversity and inclusion, blended learning, innovative approaches and challenges. Key challenges for PBL included cognitive overload and implementation constraints; for CBL, inequitable participation and resource-intensive implementation; and for TBL, increased student time burden and difficulty adapting to complex simulations.ConclusionActive learning methods enhance critical thinking and problem-solving in public health education but face implementation barriers, including faculty training requirements and resource constraints. Future research should examine long-term outcomes and the integration of emerging technologies.