Search Results (7,119)

Severe adverse reactions induced by non-ionic contrast media remain an uncommon complication in veterinary medicine. This report describes the clinical manifestations and sequential computed tomography alterations indicative of acute shock captured during 2 min and 4 min delayed phases in a 10-year-old, castrated male Maltese dog. The patient, previously diagnosed with a cutaneous mast cell tumor on the lip exhibiting incomplete histopathological margins, underwent CT for metastatic evaluation. The patient had no clinical evidence of systemic disease, and no anesthetic adverse events were observed during past patellar luxation surgery. However, the 2 min delayed CT scan revealed suspected hepatic congestion, vascular collapse, marked esophageal wall edema, and intense intestinal mucosal contrast enhancement. Subsequently, the 4 min delayed CT scan demonstrated diffuse contrast medium stagnation within the cardiac chambers and renal parenchyma, accompanied by the absence of the renal excretory phase. During anesthetic recovery, severe hypotension and respiratory failure emerged, suggesting the development of hypersensitivity. Following immediate intervention with cardiopulmonary resuscitation, epinephrine, and dexamethasone, the patient temporarily exhibited facial edema, hematochezia, diarrhea, and transient ataxia. However, dobutamine administration successfully restored systemic blood pressure and tissue perfusion, returning the patient to a normal clinical status. Consequently, this case highlights potential pathophysiological mechanisms, key CT findings, and emergency management considerations for contrast-induced hypersensitivity. Notably, sequential CT imaging documented evolving shock-related changes before the onset of overt clinical deterioration, suggesting that these findings may represent early imaging indicators of contrast-induced hypersensitivity. Full article

Pott’s disease, also known as tuberculous spondylodiscitis, accounts for 50% of all forms of skeletal tuberculosis. It is rare in children, especially in low-burden TB countries. We present a case of Pott’s disease with miliary tuberculosis in a 22-month-old child. Furthermore, we provide an exploratory literature review of pediatric cases published in PubMed and Scopus between January 2000 and August 2025, including patients aged 0 to 17 years with confirmed or clinically diagnosed tuberculous spondylodiscitis. Sixty-four cases were included. Most cases (81.3%) involved children from highly endemic countries, particularly India. Median age was 10 years, with a median diagnostic delay of 141.4 days. The most common signs and symptoms were back pain (79.6%), followed by difficulty walking (68.4%). The thoracic spine was the most affected segment (60.3%). Sixty-three received anti-TB therapy, 58% required surgical intervention, and treatment led to overall clinical recovery in 96.9% of cases. Neurological deficits were reported in 46% (paresthesia) and 68.4% (motor weakness), with permanent motor sequelae in 8.1% and persistent spinal deformity (kyphosis) in 14.5%. Our case highlights the importance of considering the suspicion of tuberculous spondylodiscitis, even in low-endemic countries, to achieve early diagnosis and appropriate therapeutic management. Early MRI combined with microbiological confirmation is essential to reduce the risk of severe complications, including neurological sequelae, progressive spinal deformities, and potentially life-threatening outcomes in growing patients. Full article

Anaphylaxis is a severe systemic hypersensitivity reaction characterized by rapid onset, unpredictable clinical course, and potentially fatal outcomes. Although its diagnosis remains primarily clinical, the identification of biomarkers capable of improving risk stratification and understanding disease mechanisms remains an important unmet need. Among the mediators implicated in anaphylaxis, platelet-activating factor (PAF) has emerged as a key effector molecule involved in vascular permeability, bronchoconstriction, platelet activation, and cardiovascular dysfunction. The biological activity of PAF is tightly regulated by platelet-activating factor acetylhydrolase (PAF-AH), the enzyme responsible for its degradation, making the PAF–PAF-AH axis a potentially important determinant of reaction severity. OBJECTIVES: The present review summarizes current knowledge regarding the biology of PAF and PAF-AH and examines their role in the pathophysiology of anaphylaxis, with particular emphasis on Hymenoptera venom allergy (HVA). The therapeutic potential of targeting the PAF pathway is also discussed. Experimental and clinical evidence consistently suggests an association between increased PAF activity, reduced PAF-AH activity, and more severe anaphylactic reactions. However, methodological limitations, biological variability, and conflicting findings across studies currently limit the clinical applicability of these molecules as standalone biomarkers. Overall, the PAF–PAF-AH axis represents a biologically plausible link between molecular mechanisms and clinical severity in anaphylaxis. Further studies are required to standardize measurements, validate clinical utility, and define the role of this pathway as both a biomarker and therapeutic target; hence gaining insight into PAF’s role in various biological processes is critical. Full article

Post-COVID symptoms frequently include cognitive complaints, yet evidence on objectively measured cognitive performance in large samples of young adults remains limited. This study examined associations between self-reported post-COVID consequences and objective cognitive performance in university students, with particular attention to acute COVID-19 severity. The sample comprised 7482 students aged 17–23 years: 3945 reported no previous COVID-19, 1676 reported previous COVID-19 without post-COVID consequences, and 1861 reported previous COVID-19 with post-COVID consequences. Visuospatial working memory was assessed using the Corsi Block Tapping Test (CTB), and choice-response performance was assessed using accuracy and mean correct-response latency in a four-choice reaction time task. Analyses accounted for age, sex, and clustering by university; among previously infected participants, models additionally adjusted for perceived acute COVID-19 severity. The primary adjusted analyses included 7117 participants for CTB and 6361 participants for the cleaned choice-response accuracy and latency analyses. In the three-group analysis, students reporting post-COVID consequences had slightly lower CTB scores than those without previous COVID-19 (B = −0.146, 95% CI [−0.277, −0.015], p = 0.029), although the effect was small and was not fully robust in an ordinal sensitivity model (OR = 0.91, 95% CI [0.82, 1.00], p = 0.052). No reduction in choice-response accuracy or robust slowing of response latency was observed in the post-COVID consequence group. Among previously infected participants, post-COVID consequences were not significantly associated with CTB performance (B = −0.149, 95% CI [−0.311, 0.013], p = 0.071), choice-response accuracy (OR = 0.80, 95% CI [0.60, 1.07], p = 0.126), or response latency (−0.79%, 95% CI [−2.06%, 0.49%], p = 0.224) after adjustment for acute severity, age, and sex; none of these associations remained significant after false discovery rate correction. Acute COVID-19 severity was likewise not significantly associated with the cognitive outcomes. Overall, self-reported post-COVID consequences were associated with, at most, small and outcome-dependent differences in objective cognitive performance in this young university sample. The findings do not support a broad objective cognitive deficit associated with self-reported post-COVID consequences after accounting for acute disease severity and demographic factors. Full article

Background/Objectives: The oxidation of low-density lipoprotein (LDL) is a crucial step in atherogenesis. Beta-Caryophyllene (BCP) is a natural compound with established anti-oxidative and anti-inflammatory properties as shown in animal and cell culture studies. We examined whether BCP can impede LDL oxidation in an in vitro model. Methods: The anti-oxidative effect of BCP was evaluated in different concentrations (0, 25, 50, 100, and 150 µg/mL) with regard to scavenging reactive oxygen species (ROS) during LDL oxidation, which was initiated by the addition of copper chloride (CuCl₂) in a concentration of 10 µmol/L. Lipid hydroperoxides (LPO), malondialdehyde (MDA), dienes, cell viability, and reactions of BCP with ROS according to Gibbs free energies were applied to determine the oxidation state of LDL. Results: Our findings indicated that BCP is highly efficient in inhibiting LDL oxidation in a dose-dependent manner in this in vitro model. The lipid hydroperoxide content in oxLDL was significantly lower in the presence of 100 µg/mL BCP compared to oxLDL without BCP (p < 0.0001). This corresponds to the MDA levels, which were significantly lower in the presence of 100 µg/mL BCP compared to oxLDL without BCP (p = 0.0393). Furthermore, a dose-dependent inhibition of diene formation in the LDL particle was observed in the presence of ascending BCP concentrations which corresponds to a decrease in the cytotoxicity of oxLDL in EA.hy926 cells in the presence of increasing concentrations of BCP. Moreover, BCP’s anti-oxidant effectiveness exceeds that of the widely recognized anti-oxidant spermidine at equivalent concentrations. Our quantum chemical calculations showed that the reactions between BCP and hydroxyl radicals, hydroperoxyl radicals, or hydrogen peroxide are exergonic. We therefore conclude that BCP impedes the oxidation of LDL by its capability to scavenge (at least) these three reactive oxygen species. Conclusions: Our results indicate that BCP impedes the oxidation of LDL in vitro and therefore presumably has the potential to serve as an appropriate therapeutic agent to prevent atherogenesis and related (cardio)vascular diseases by balancing vascular oxidative stress. For this purpose, more prospective clinical studies in humans are required to assess the potential atheroprotective and health-promoting effects of BCP. Full article

Background/Objectives: Polyglutamine (polyQ) expansion induces protein misfolding, aggregation, and neurodegeneration; however, effective strategies for aggregate clearance remain limited. This study evaluated the effect of metformin, resveratrol, and curcumin on polyQ proteotoxicity using an engineered Dictyostelium discoideum model expressing 80Q repeats, and investigated their autophagy-related mechanism. Methods: In this study, 80Q-expressing Dictyostelium discoideum (D. discoideum) cells were treated with metformin, resveratrol, or curcumin. Cell viability and proliferation were assessed by growth curve and doubling-time analyses. Developmental assays examined restoration of multicellular morphology. PolyQ aggregation was analyzed using brightfield microscopy, fluorescence microscopy, Thioflavin T (ThT), and Congo Red assays. Quantitative real-time polymerase chain reaction (qRT-PCR) evaluated AMP-activated protein kinase (AMPK) and autophagy-related gene expression. Molecular docking and molecular dynamics (MD) simulations were performed to assess interactions between the compounds and AMPK. Results: All three compounds significantly improved viability and reduced doubling time in 80Q-expressing cells. Treated strains displayed improved developmental morphology and culmination compared to untreated controls. Thioflavin T (ThT) and Congo Red assays demonstrated a marked reduction in amyloid-like polyQ aggregates following treatment. Gene-expression analysis revealed the upregulation of AMP-activated protein kinase (AMPK) and core autophagy genes, indicating activation of an AMPK-linked pro-autophagy pathway involved in aggregate clearance. Computational studies further confirmed stable, energetically favorable interactions of metformin, resveratrol, and curcumin with AMPK. Conclusions: Metformin, resveratrol, and curcumin effectively reduce polyQ-associated proteotoxicity in D. discoideum and are associated with modulation of AMP-activated protein kinase (AMPK) signaling and autophagy-related pathways. These findings support the therapeutic potential of metabolic modulators against protein aggregation and establish D. discoideum as a valuable platform for screening autophagy-targeted interventions relevant to neurodegenerative diseases. Full article

Food adulteration is a critical global threat to public health, economic stability, and social welfare. It primarily occurs in two forms: intentional and incidental. Intentional adulteration, or economically motivated adulteration, involves deliberately adding fraudulent or toxic substances such as hazardous ripening agents and harmful coloring to increase profitability. Substitution of food species is also a widely practiced form. Such adulteration can cause severe acute and chronic health issues, ranging from gastrointestinal distress to cancer and organ failure. Incidental adulteration happens through accidental contamination during processing, storage, or distribution, involving hazards such as heavy metals, mycotoxins, and pesticides. Such contaminants also lead to severe chronic diseases and dangerous allergic reactions. Food adulteration also triggers massive socio-economic consequences. Food safety incidents such as the melamine milk crisis and the horsemeat scandal caused billions of dollars in losses due to healthcare costs, product recalls, damaged brand reputation, and disrupted international trade. Global entities such as the WHO, WTO, and Codex Alimentarius have established robust legislative frameworks. However, effective enforcement remains a significant challenge in many countries. To mitigate such harmful impacts, it is essential to strengthen global surveillance systems, enhance rapid analytical detection methods, and strictly enforce compliance with existing food safety regulations. Full article

Food allergy is a growing global health concern associated with significant dietary restrictions, impaired quality of life, and risk of severe allergic reactions. Dupilumab, a monoclonal antibody targeting the interleukin-4 receptor alpha (IL-4Rα), inhibits IL-4 and IL-13 signaling and has demonstrated efficacy across multiple type 2 inflammatory diseases. This systematic review aimed to evaluate the effects of dupilumab on food allergy outcomes in pediatric and adult patients. Across studies, dupilumab treatment was consistently associated with reductions in total immunoglobulin E (IgE) and food-specific IgE levels, indicating modulation of allergic sensitization and type 2 inflammation. However, these immunologic improvements were not consistently accompanied by clinically meaningful desensitization or acquisition of food tolerance. In a phase II trial of peanut allergy, dupilumab monotherapy reduced immunologic markers but did not improve oral food challenge outcomes. When combined with oral immunotherapy, dupilumab modestly enhanced desensitization rates but did not substantially reduce treatment-related allergic reactions. Current evidence suggests that dupilumab favorably affects immunologic markers associated with food allergy, particularly total and allergen-specific IgE levels. Nevertheless, there is insufficient evidence to conclude that dupilumab alone induces sustained clinical tolerance to food allergens. Larger randomized controlled trials incorporating standardized oral food challenges and long-term follow-up are required to clarify the clinical role of dupilumab in food allergy management. Full article

Background/Objectives: Although kidney transplantation improves survival and quality of life in children with end-stage kidney disease, neurocognitive and motor impairments acquired during chronic kidney disease (CKD) may persist after transplantation. Cognitive–motor evaluations in this population remain limited. This study compared cognitive function, manual dexterity, grip strength, reaction time, and balance between pediatric kidney transplant recipients and healthy peers. Methods: This study included 30 pediatric kidney transplant recipients aged 8–18 years and 30 age- and sex-matched healthy controls. Cognitive function was assessed using the Stroop Color–Word Test. Fine and gross manual dexterity were evaluated using the Nine-Hole Peg Test and Box and Block Test, respectively. Handgrip strength was measured with a JAMAR dynamometer, reaction time with the FitLight Trainer™ system, and balance with the Pediatric Balance Scale. Results: Compared with healthy controls, pediatric kidney transplant recipients showed poorer executive function, demonstrated by longer Stroop completion times and more color–word errors (all p < 0.05). Manual dexterity was reduced, with a significantly lower Box and Block Test score for the dominant hand (p = 0.020) and longer Nine-Hole Peg Test completion times for both hands (both p < 0.001), whereas the between-group difference in the non-dominant Box and Block Test did not reach statistical significance (p = 0.055). Dominant-hand reaction time and reaction time during the cognitive task were significantly prolonged (p = 0.018 and p = 0.046, respectively). Handgrip strength and Pediatric Balance Scale scores did not differ significantly between groups (both p > 0.05). Conclusions: Pediatric kidney transplant recipients exhibit persistent impairments in executive function, manual dexterity, and cognitive–motor performance despite transplantation. Long-term follow-up should incorporate cognitive and motor assessments to support early rehabilitation and optimize functional outcomes. Full article

Background/Objectives: Epstein–Barr virus (EBV) is a ubiquitous pathogen responsible for significant malignancies and autoimmune diseases, yet no prophylactic vaccine is available. The viral entry glycoproteins gL/gH and gB are essential for infection, but soluble forms are poorly immunogenic and fail to elicit durable neutralizing antibodies. Moreover, EBV infects both B cells and epithelial cells, demanding broad neutralization. This study aimed to develop a virus-like particle (VLP) platform that displays gL/gH and gB in a dense, repetitive array to overcome these barriers. Methods: We conjugated recombinant gL/gH and gB to Acinetobacter phage AP205 VLPs using SpyTag/SpyCatcher covalent linkage, generating monovalent and bivalent chimeric nanoparticles (co-displaying both antigens on the same particle). Mice were immunized with these VLP constructs or alum-adjuvanted soluble proteins, and antibody responses, neutralization titres against B-cell and epithelial-cell infection, as well as germinal centre responses and durability, were assessed over a four-month period. Results: AP205-conjugated nanoparticles elicited significantly higher antigen-specific IgG titres than soluble proteins. The chimeric VLP, co-displaying gL/gH and gB, induced the stronger neutralising antibodies, effectively blocking EBV entry into both B cells and epithelial cells. Mechanistically, VLP immunization drove robust and sustained germinal centre reactions, resulting in increased plasma and memory B cells, and maintained neutralising activity for at least four months. Conclusions: Precision nanoscale assembly of EBV entry glycoproteins on a synthetic VLP programs high-magnitude, broad-spectrum, and durable humoral immunity. The AP205-SpyTag platform offers a versatile and promising strategy for developing an effective prophylactic EBV vaccine. Full article

Persistence, coexistence, competitive exclusion, and global asymptotic stability (GAS) are closely related problems in mathematical epidemiology that are often treated by model-specific arguments. We develop a unified approach to GAS based on Perron–Volterra Lyapunov functions $L_p$, for multi-strain epidemic reaction networks. For bilinear m-strain models with irreducible rank-one infection blocks and block-diagonal next-generation structure, these functions yield a generic competitive-exclusion partition of parameter space into at most $m+1$ regions: either the disease free equilibrium is GAS, or exactly one dominant strain persists and its boundary endemic equilibrium is GAS; see non-generic tie surfaces on which the corresponding reproduction numbers coincide. We also prove a second complete GAS partition, for two-strain models with increasing concave incidence and scalar, non-interacting strain blocks, extending the Rahman–Zou result beyond rational saturating incidence. In this class, the disease-free, single-strain, and coexistence equilibria may all occur, and explicit Lyapunov functions provide the full exclusion/coexistence partition among the four possible equilibrium supports. The construction combines five ingredients: siphons, which determine forward-invariant boundary faces; triangular Jacobian structure on siphon faces; the Metzler property of transversal Jacobians and their Perron eigenvectors; regular next-generation splittings, whose spectral radii determine invasibility; and boundary transcritical invasion relays linking eigenvalue crossings to the emergence of equilibria on adjacent faces. The resulting Perron–Volterra functions combine Volterra entropy terms for resident variables with Perron-weighted linear functionals for absent strain blocks. These constructions are implemented in the Mathematica package EpidCRN, which computes siphons, transversal blocks, invasion data, Perron weights, and candidate Lyapunov functions. For the two model classes considered here, these candidates are proved to be genuine Lyapunov functions and yield complete generic GAS partitions. Full article

Background/Objectives: To assess the acceptance of, attitudes towards, and concerns regarding allogeneic serum eye drops (Allo-SEDs) among patients treated with autologous serum eye drops (ASEDs). Methods: We conducted this investigator-initiated, cross-sectional, single-center survey at the Department of Ophthalmology, University Hospital Zurich, Switzerland. We consecutively recruited all patients using ASEDs during routine visits, who anonymously completed a 9-item questionnaire comprising eight 11-point Likert-scale items and one open numerical item on the daily application frequency. We assessed perceived ASED effectiveness, willingness to switch to Allo-SEDs under different scenarios, and concerns regarding safety, efficacy, and immunological risks. Results: Of 202 eligible patients, 107 returned the questionnaire (53.0%). The full eligible cohort had a median (IQR) age of 63.5 (49.2–75.0) years and a median ASED treatment duration of 4.0 (1.0–8.0) years. They rated ASEDs as highly effective (median 9, IQR 8.2–10.0) and applied them a median of 7 (5–10.5) times daily. Willingness to switch was low without clinical need (median 3, IQR 0–6; p = 1.0), increased when autologous production was no longer feasible (median 7, IQR 5–9; p < 0.001), and was intermediate for general openness (median 5, IQR 2–8; p = 0.7). Concerns regarding infectious disease transmission, immunological reactions, and therapeutic efficacy correlated with lower willingness to switch (all r = −0.29 to −0.46). Daily application frequency did not correlate with acceptance. Conclusions: Patients were highly satisfied with ASEDs but were reluctant to switch to Allo-SEDs unless autologous production was no longer feasible. Among the domains assessed, concerns regarding infection, immunological reactions, and efficacy were the main barriers to acceptance, supporting targeted patient education. Full article

Background/Objective: Bartonella henselae, the causative agent of cat-scratch disease (CSD), usually causes a self-limiting zoonotic infection. Osteomyelitis is a rare but increasingly recognized manifestation, particularly in children, and may closely mimic malignant or other infectious bone diseases. We present a case of multifocal pediatric Bartonella henselae osteomyelitis and discuss the associated diagnostic and therapeutic challenges in the context of the current literature. Case presentation: We report the case of a previously healthy 10-year-old girl who presented with a one-month history of fever, fatigue, limping, and progressive thigh and groin pain following cat-scratch exposure. During the course of the illness, she developed unilateral facial nerve palsy and Parinaud oculoglandular syndrome. Initial laboratory investigations demonstrated elevated inflammatory markers and reactive thrombocytosis. Serological testing for Bartonella henselae was positive for both IgM and IgG antibodies, whereas polymerase chain reaction (PCR) testing of both peripheral blood and the bone biopsy specimen was negative. Plain radiographs were unremarkable; however, magnetic resonance imaging (MRI) revealed multifocal lesions involving the right femoral diaphysis, right pubic bone, and left iliac wing, together with focal hepatic and splenic lesions suggestive of disseminated disease. Because of the radiological suspicion of malignancy, a femoral bone biopsy was performed and demonstrated osteomyelitis with necrosis and microabscess formation, without evidence of malignancy. Following targeted antimicrobial therapy, the patient showed rapid clinical and laboratory improvement, with progressive regression of the lesions on follow-up MRI. Conclusions: Bartonella henselae osteomyelitis should be considered in the differential diagnosis of multifocal bone lesions in children, particularly in patients with a history of cat exposure. Because the disease may closely mimic malignancy both clinically and radiologically, establishing the diagnosis requires careful integration of epidemiological, clinical, serological, radiological, molecular, and histopathological findings. Early recognition and appropriate antimicrobial treatment are associated with an excellent prognosis. Full article

Parkinson’s disease (PD) is associated with alterations in gait symmetry and plantar loading that can be examined using vertical ground reaction force (VGRF) recordings. This study presents a confidence-stratified, physiology-anchored multiple-instance learning framework with concept-bottleneck-inspired pathways (implementation identifier: DRO-PAS-MIL-CBM; hereafter, PAS-MIL) for retrospective session-level PD-versus-control classification. Each gait session is represented as a bag of temporal windows. Eight predefined bilateral signal descriptors are combined with eight learned latent temporal dimensions, aggregated through attention-based pooling, and processed by concept-guided, prototype, anchor-only, and static-feature expert pathways. The evaluation used five-fold person-grouped cross-validation on 306 sessions from 165 participants in the PhysioNet Gait in Parkinson’s Disease database.Inner person-grouped out-of-fold ExtraTrees probabilities were used to construct the confidence strata and distillation targets. PAS-MIL achieved a pooled session-level area under the receiver operating characteristic curve of 0.771, average precision of 0.890, and a mean fold AUC of $0.826\pm 0.041$. Relevance analysis identified C05 (asymmetry variability) and C08 (bilateral change mismatch) as the highest-weighted predefined physiological anchor descriptors. Protocol-stratified sensitivity analysis showed variation across the three source sub-studies, with AUCs ranging from 0.740 to 0.790. Probability calibration remained suboptimal after temperature scaling (mean per-fold ECE, $0.291\pm 0.042$). The results demonstrate the feasibility of integrating physiology-informed descriptors, temporal representation learning, and session-level aggregation. The study is a retrospective proof of concept and does not establish external robustness or clinical deployment readiness. Full article

Nicotinamide adenine dinucleotide (NAD⁺) is a fundamental metabolic cofactor and signaling molecule that supports redox reactions, DNA repair, chromatin regulation, stress adaptation, inflammation, and neuronal maintenance. Age-associated NAD⁺ decline has been implicated in brain aging and neurodegenerative disorders, but the causal node and limiting compartment differ across tissues and disease states. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) catalyzes the final step in NAD⁺ biosynthesis and represents the major nuclear isoform of the mammalian NMNAT family. Direct human genetic evidence establishes NMNAT-1 as a causal gene in inherited retinal degeneration, whereas evidence linking endogenous NMNAT-1 to broader brain aging or sporadic neurodegeneration is mainly convergent preclinical, preliminary, or indirect. Beyond NAD⁺ synthesis, biochemical and Drosophila studies suggest possible chaperone-like and proteostasis-supporting functions, but a separable NAD⁺-independent function of endogenous mammalian NMNAT-1 has not yet been established in vivo. Here, we review the molecular structure, localization, and regulation of NMNAT-1, emphasizing calibrated distinctions among catalytic nuclear NAD⁺ supply, engineered axonal protection, pathway-adjacent NAD⁺ interventions, and putative non-catalytic protection. We further discuss how NMNAT-1 dysfunction may contribute to aging-associated genomic instability, neuroinflammation, synaptic impairment, retinal degeneration, selected neurodegenerative models, and glioma biology. Finally, we evaluate therapeutic strategies targeting NMNAT-1 and NAD⁺ pathways, noting that no human trial has yet established efficacy for an NMNAT-1-directed neurological therapy. A compartment-aware and evidence-stratified view is therefore essential for translating NMNAT-1 biology into interventions for age-related neural disease. Full article