Search Results (155)

Chlorophenylacetonitriles are known as one of the emerging nitrogenous disinfection byproducts (N-DBPs) in chlorinated drinking water due to their concerned cytotoxicity and genotoxicity compared to regulated carbonaceous DBPs. However, under low-dose exposure, the in vivo pathological consequences of chlorophenylacetonitriles remain largely unresolved. Here, C57BL/6J mice were exposed to 2-chlorophenylacetonitrile (2-CPAN) via drinking water (100 ug/L) for six months, and an integrated histopathological and genome-wide transcriptomic approach was employed to mechanistically characterize its multi-organ toxicological consequences. 2-CPAN ingestion significantly suppressed body weight (35.9 ± 2.0 g vs. 47.6 ± 11.6 g, p < 0.05) and induced severe gastroenteropathy—including gastric lamina propria inflammatory infiltration, intestinal villous blunting, crypt disorganization, transmural mononuclear infiltration, and abrogating epithelial barrier integrity. Intestinal barrier failure drove portal translocation of luminal PAMPs, potentially triggering splenic white pulp atrophy, red/white pulp boundary dissolution, and parenchymal changes consistent with fibrotic remodeling. Splenic RNA sequencing revealed a bipartite transcriptomic reprogramming: upregulated pathways were enriched in the ribosome, MAPK signaling, cytokine–cytokine receptor interaction, and chemokine signaling pathways. A proteotoxic stress module (Hspa1a, 9.4-fold; Hspa1b, 10.2-fold) and a chemokine effector hub (Ccl2, 3.43-fold; Ccl5, 2.9-fold; Ccl19, 2.58-fold; Ccl21a, 2.15-fold) were identified by the STRING network. Downregulated pathways converged on cell cycle suppression, with concurrent loss of Ccne1/Ccne2 and Cdc6 (G1/S block), Ccnb1 and Plk1 (G2/M arrest), and Rrm2/Tars3/TrnM (dNTP and aminoacyl-tRNA starvation), collectively forcing splenic lymphocytes into irreversible proliferative failure. These findings provide the first mechanistically resolved in vivo evidence that chronic 2-CPAN exposure drives a potential gut–spleen toxicological axis, underscoring the urgent need to incorporate organ endpoints by long-term exposure into N-DBP risk assessment. Full article

The overset grid adaptive method offers an efficient approach for the computational modeling of steady or transient three-dimensional compressible flow problems. When implementing this approach on parallel distributed memory computing systems, its scaling, load balancing, and partitioning must be addressed. In this study, we present a parallel, three-dimensional, finite volume compressible Navier–Stokes solver with block-based adaptive mesh refinement capability. The overset grid system consists of an Octree forest governed adaptive Cartesian off-body grid and a pre-partitioned body-conforming grid. To create, manage, and efficiently handle the load balancing and partitioning of the off-body grid, the developed solver utilizes the open source library of p4est. The communication between the partitions of the p4est governed off-body grid and the body-conforming grid is established by using an efficient spatial query algorithm. The parallel performance of the developed solver is evaluated by solving two benchmark problems: steady supersonic flow over a semi-infinite blunt-nose cylinder and the transient interaction of an incident planar shock with a sphere in quiescent air. The results show that the solver accurately captures and tracks the resultant flow shock structures while exhibiting good scalable parallel performance. Full article

Flow-field parameters of bow shocks in high-altitude rarefied flow are fundamental for seeker radiation noise evaluation and thermal-protection design. The conventional direct simulation Monte Carlo (DSMC) method is computationally expensive, making it difficult to achieve real-time prediction and massive sample generation of flow-field parameters. This paper presented a surrogate model adopting a convolutional neural network (CNN) to rapidly predict bow-shock reactive flow-field parameters. A blunt body with a nose radius of 0.1–1.0 m was investigated. The Latin hypercube sampling methodwas used to construct a sample space spanning altitudes of 80–150 km and Mach numbers of 15–35. DSMC-calculated data was segmented into training and test sets at a ratio of 4:1 and verified by the bow-shock ultraviolet experiments. An encoder–decoder CNN with a parallel decoder strategy was established to develop a bow-shock reactive flow surrogate model (CNN-BS) and conduct error evaluation. The results show that the mean absolute percentage errors for temperature, velocity, pressure, and nitric oxide number density are below 8%, with coefficients of determination close to 1. The average prediction time is 0.5 s, enabling online data generation. The CNN-BS model provides efficient support for radiation-noise evaluation and thermal-protection design of hypersonic blunt bodies. Full article

Background: Recovery after major head-and-neck reconstruction extends beyond flap survival and wound closure, involving swallowing, psychological adaptation, body image, and overall quality of life. Integrated multidimensional assessments remain limited in routine reconstructive outcomes research. Aim: The aim of this study was to characterize and compare six-month multidimensional recovery—clinical, functional, nutritional, psychological, and body-image outcomes—between microvascular free-flap and regional pedicled-flap reconstruction and to identify factors that stratify risk for persistent functional and psychosocial impairment. Methods: We conducted a single-center prospective cohort study at the “Victor Babeș” University of Medicine and Pharmacy, Timișoara, Romania, enrolling 87 adults undergoing major reconstructive surgery after ablative treatment of head-and-neck defects (52 microvascular free flaps; 35 regional pedicled flaps). Patients were assessed at baseline and 6 months using the SF-36, WHOQOL-BREF, Body Image Scale (BIS), HADS, PHQ-9, GAD-7, Functional Oral Intake Scale (FOIS), speech intelligibility, and PEG/tracheostomy dependence. Results: At 6 months, most SF-36 and WHOQOL-BREF domains improved with moderate effect sizes (d = 0.3–0.7; all p ≤ 0.009), and body image distress decreased significantly (ΔBIS −2.9 ± 4.6; p < 0.001), whereas social functioning showed no robust gain (p = 0.098; not surviving false-discovery-rate correction). Pedicled reconstruction was associated with higher PEG dependence (37.1% vs. 9.6%; p = 0.005) and worse FOIS (4.7 ± 1.4 vs. 5.6 ± 1.2; p = 0.003). Major complications were linked to blunted or worsening psychological trajectories and a threefold higher rate of clinically significant depression (HADS-D ≥ 11: 66.7% vs. 18.7%; p = 0.001). In a reduced four-predictor multivariable model, pedicled flap (aOR 4.6), adjuvant radiotherapy (aOR 2.8), major complication (aOR 3.3), and lower baseline FOIS (aOR 0.5 per point) were independently associated with PEG dependence (optimism-corrected AUC 0.79). Clustering identified three recovery phenotypes—functional/emotional responders, psychological/body-image responders, and global slow recovery—with significantly different PEG rates (5.9%, 21.4%, 40.0%; p = 0.006). Exploratory mediation analysis suggested that the association between reconstruction technique and mental quality-of-life recovery was partly statistically accounted for by swallowing and body-image improvement. Conclusions: Recovery after major head-and-neck reconstruction is multidimensional and heterogeneous. Baseline swallowing function, reconstruction technique, radiotherapy, and major complications jointly stratify risk for persistent functional and psychosocial impairment, supporting risk-adapted multidisciplinary rehabilitation and early psycho-oncologic screening. Full article

Shearing is a stressful procedure for sheep, combining isolation, restraint, and the mechanical action of shearing, which activates the hypothalamic–pituitary–adrenal axis and induces oxidative stress. This study investigated whether melatonin—a pleiotropic hormone with well-documented antioxidant properties—administration could modulate the stress response and oxidative stress in Sarda sheep during shearing. Forty lactating ewes (aged 3–5 years, mean body weight 41 ± 1.1 kg) were randomly assigned to four groups (n = 10 each): two groups received a subcutaneous melatonin implant (18 mg); two remained untreated as controls. Within each category, one group was shorn and the other subjected only to restraint. Blood samples were collected before, during, and after shearing to measure cortisol, glucose, reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), and oxidative stress index (OSI). Procedures elevated cortisol, glucose, ROMs, and OSI in all groups, but melatonin treatment significantly reduced these parameters and increased BAP relative to untreated animals at all sampling points (p < 0.05). No significant differences were observed between shorn and unshorn animals within the same treatment, suggesting that the handling, restraint, and isolation associated with the shearing procedure represent the major sources of stress, rather than the mechanical act of shearing itself. In conclusion, melatonin administration blunts the stress response and reduces oxidative stress in sheep during routine shearing-related handling procedures, suggesting its potential as a practical tool to improve animal welfare during routine management practices. Full article

Background: While maternal obesity is a well-established risk factor for labor induction failure, the specific impact of regional fat distribution and its direct influence on prostaglandin dose–response profiles remain under-investigated. Relying solely on generalized anthropometric metrics like Body Mass Index (BMI) may obscure the true physiological variations in tissue bioavailability. Therefore, this study aimed to compare dinoprostone-induced labor outcomes between obese pregnant women and non-obese controls, and to evaluate whether ultrasonographically measured abdominal subcutaneous fat thickness (ASFT) can serve as a more precise, independent predictor of induction success and cumulative prostaglandin dose requirements. Methods: This prospective two-center observational study was conducted with 200 single-term pregnant women, comprising an obese study group (n = 100, BMI ≥ 30 kg/m²) and a symmetrical non-obese control group (n = 100, BMI 18.5–29.9 kg/m²). Maternal ASFT was measured via high-resolution ultrasonography at the infraumbilical midline prior to labor induction. All participants initially received a 10 mg dinoprostone vaginal insert governed by a standardized institutional induction protocol. Primary outcomes included successful labor induction (defined as achieving vaginal delivery within 24 h) and cumulative prostaglandin dose requirements. Secondary analyses involved comparative evaluation stratified by obesity classes (Class 1 vs. Class 2–3) and an exploratory ASFT threshold (<30 mm vs. ≥30 mm). Results: Obese women demonstrated significantly lower successful labor induction rates (defined as vaginal delivery within 24 h) compared to the non-obese control group (59.0% vs. 86.0%, p = 0.001). The cumulative dinoprostone dose required for cervical ripening was significantly higher in the obese cohort than in controls (16.8 ± 4.5 mg vs. 12.4 ± 2.2 mg, p < 0.001). Similarly, induction-to-delivery intervals were significantly prolonged in obese parturients (19.2 ± 6.1 vs. 14.6 ± 4.8 h, p < 0.001). Subgroup analysis within the obese cohort revealed that patients with ASFT ≥ 30 mm required higher prostaglandin doses (18.08 ± 3.40 mg vs. 14.14 ± 3.08 mg, p < 0.001) and exhibited lower vaginal delivery rates (45.7% vs. 70.4%, p = 0.012) than those with ASFT < 30 mm. Multivariate logistic regression analysis encompassing the entire study population (n = 200) confirmed that ASFT remained a strong independent predictor of induction failure (Adjusted OR: 1.14; 95% CI: 1.05–1.24, p = 0.002). Conversely, generalized obesity metrics via BMI did not maintain independent significance in the multivariate model (p = 0.420). Conclusions: Increased maternal ASFT is directly associated with blunted drug responsiveness, higher cumulative dinoprostone requirements, and a lower likelihood of successful labor induction. Compared with generalized metrics such as BMI, ultrasonographic measurement of ASFT provides a more precise and clinically relevant assessment of regional maternal adiposity. These findings suggest that incorporating pre-induction ASFT evaluation into routine obstetric practice could improve risk stratification and help clinicians design individualized, precision-based dosing strategies for obese parturients. Full article

Fatal free falls (FFF) represent a distinct form of blunt force trauma and pose a significant challenge in forensic investigations, particularly in estimating fall height and differentiating between accidental and suicidal events. Postmortem computed tomography (PMCT) enables detailed assessment of skeletal injuries, including quantitative evaluation of skull fracture patterns. Total Cranial Fracture Length (TCFL), derived from three-dimensional CT skull fracture scoring (3D-CT-SF), has been proposed as an objective indicator of impact severity; however, available evidence remains limited. This study aimed to assess the relationship between TCFL and fall height in fatal free falls and to evaluate the influence of selected anthropometric and biomechanical variables on cranial fracture severity. A retrospective analysis of 76 fatal free-fall cases examined between 2016 and 2024 was conducted using PMCT and autopsy data. TCFL was measured on three-dimensional volume-rendered CT reconstructions of calvarial fractures. Statistical analyses were performed for the entire cohort and separately for accidental and suicidal falls. No significant correlation between TCFL and fall height was observed in the overall cohort or among suicide cases. In contrast, a significant negative correlation between TCFL and fall height category was identified in accidental falls. TCFL showed significant positive correlations with body mass, body mass index (BMI), and kinetic energy, particularly in the suicide subgroup. TCFL is a promising objective parameter for assessing the severity of cranial injury in fatal free-fall cases. While its utility in estimating fall height appears limited in suicidal falls, TCFL may support forensic interpretation of fall dynamics and contribute to distinguishing the manner of death, especially in accidental cases. Further studies in larger, more diverse populations are warranted. Full article

This study presents a surrogate-assisted evolutionary optimization framework for parametric design under limited data conditions, integrating computational fluid dynamics (CFD), machine learning, and evolutionary algorithms to optimize spiked blunt body geometries in supersonic flow. A dataset of CFD simulations covering a range of Mach numbers and geometric ratios, including spike length ($L/D$) and diameter ($d/D$), was used to train regression-based surrogate models.Among the evaluated models, the Gradient Boosting Regressor (GBR) achieved the highest predictive accuracy ($R^2=0.8909$, RMSE = 0.00775), effectively capturing the nonlinear relationship between flow conditions, geometry, and drag coefficient ($C_d$). The trained surrogate model was coupled with three evolutionary algorithms—Differential Evolution (DE), Covariance Matrix Adaptation Evolution Strategy (CMA-ES), and Genetic Algorithm (GA)—to identify optimal geometric configurations across different Mach regimes. To validate the proposed framework, the optimal solutions obtained from the surrogate-based optimization were re-evaluated using CFD simulations. A strong agreement between predicted and simulated drag coefficients was observed, confirming the reliability of the surrogate model for guiding optimization within the explored design space. The results reveal consistent geometric trends, with the optimal spike length ratio decreasing as Mach number increases, while the diameter ratio converges to a narrow range around $d/D\approx 0.17$. Additionally, SHapley Additive exPlanations (SHAP) analysis identified $L/D$ as the most influential parameter affecting drag, followed by Mach number and $d/D$, supporting the physical interpretation of the flow behavior. Overall, the proposed framework demonstrates that the integration of CFD, machine learning, and evolutionary algorithms provides an efficient and reliable approach for geometric optimization in supersonic applications, enabling accurate design exploration with a limited number of high-fidelity simulations. Full article

Background/Objectives: A blunted growth hormone (GH) response in stimulation tests (GHSTs) in obese patients is well documented, with less evidence for insulin-like growth factor-1 (IGF-1) concentrations. The aim of this study was to assess the relationships between nutritional status, GH peak in GHST, and IGF-1 concentrations, and to develop machine learning prediction models of GH deficiency (GHD) in children with short stature. Methods: A case–control study included 1592 children with short stature, whose height, weight, body mass index (BMI), GH peak in two GHSTs, IGF-1 concentration and bone age (BA) were assessed. The cut-off of GH peak in two GHSTs between GHD and idiopathic short stature (ISS) was 10.0 µg/L; additionally, a lower cut-off of 7.0 µg/L was used in repeated analysis. Univariate statistical analyses and classification models were used to identify variables related to the normal and subnormal results of GHST. Results: Depending on the cut-off of GH peak (10.0 vs. 7.0 µg/L), GHD was diagnosed in 604 vs. 279 patients (37.9% vs. 17.5%). Children with GHD had significantly lower (p < 0.001) BMI SDS and IGF-1 SDS than ones with ISS for both cut-offs of GH peak. Overnutrition was associated with the lowest GH peak but the highest IGF-1 SDS; the opposite results were observed in undernutrition. A decision tree predicted GHD in 156 patients, in 149 based on BMI SDS > 0.91. A Naïve Bayes classifier predicted GHD in 118 cases, with BMI SDS and IGF-1 SDS being the only significant variables. The best multilayer perceptron (MLP) neural network predicted GHD in 310 patients, while a logistic regression model did so in 269 patients. Conclusions: Interpretation of GHST should include the patient’s nutritional status in order to avoid overdiagnosis of GHD in overweight and obese children. Full article

Background: Circadian disruption exacerbates type 2 diabetes mellitus (T2DM). Time-restricted feeding (TRF) and exercise (EX) improve metabolic health, but their combinatory effect remains unclear. This study investigated whether combined TRF and EX additively ameliorates metabolism via circadian reprogramming in db/db mice. Methods: Eight-week-old male db/db mice were assigned to control (Con), diabetic model (DM), TRF (8 h feeding window), EX (treadmill, 60 min/day, 5 days/week), or combined TRF + EX groups for 8 weeks (n = 8/group). Body weight, glucose/insulin tolerance, and 24 h energy metabolism (CLAMS) were assessed. Mitochondrial function, oxidative stress, inflammation, and expression of mitophagy (Pink1, Park2, Bnip3, Fundc1) and thermogenic (Ucp1, Pgc1a, Prdm16, Cidea) genes were measured. Results: Compared with the con group, DM mice showed obesity, hyperglycemia and blunted circadian metabolic rhythm. The TRF and EX groups improved these defects. Specifically, combined TRF + EX reduced fasting blood glucose from 25.3 ± 3.1 mmol/L (DM) to 13.2 ± 1.8 mmol/L (p < 0.05), body weight from 49.8 ± 2.5 g to 39.5 ± 1.7 g (p < 0.05), and body fat percentage from 45.6 ± 3.2% to 32.1 ± 2.2% (p < 0.05). GTT area under the curve (AUC) decreased from 3711.0 ± 186.5 (DM) to 2118.0 ± 112.4 (p < 0.05), and ITT AUC decreased from 2617.5 ± 135.8 to 1260.0 ± 68.9 (p < 0.05). Notably, the combination of TRF + EX produced greater effects than either intervention alone: body weight, fasting blood glucose, and glucose/insulin tolerance were greatly improved (p < 0.05). In addition, compared with the DM group, the diurnal metabolic amplitude and phase were improved in the TRF or EX group; the combination group showed further improvements in these parameters. Furthermore, TRF and EX each resulted in significantly higher expression of key thermogenic genes (Ucp1, Pgc1a, Prdm16, Cidea) in white adipose tissue (WAT) and brown adipose tissue (BAT) (p < 0.05), and the TRF + EX group showed the highest expression levels. Combined intervention also restored skeletal muscle SOD activity (31.2 ± 2.9 U/mg prot vs. DM 20.1 ± 2.5 U/mg prot, p < 0.05) and reduced serum TNF-α (28.5 ± 4.5 pg/mL vs. DM 65.8 ± 8.5 pg/mL, p < 0.05) and IL-6 (21.6 ± 3.8 pg/mL vs. DM 50.3 ± 7.1 pg/mL, p < 0.05). Conclusions: TRF + EX additively restores metabolic homeostasis in diabetes by re-entraining circadian energy rhythms, improving mitochondrial quality, and activating adipose thermogenesis, supporting further investigation of integrated lifestyle timing as a potential therapeutic strategy. Full article

The mandible, due to its anatomical position, mobility, and functional role, is one of the bones most frequently involved in maxillofacial trauma, with fracture patterns influenced by impact mechanisms and anatomical characteristics. This study aimed to analyse the relationship between trauma mechanisms and affected anatomical subsites in patients with isolated mandibular fractures treated at a regional public hospital in Buenos Aires Province. A retrospective cross-sectional observational study was conducted using medical records, surgical reports, and diagnostic imaging of patients treated between 2011 and 2024. Isolated mandibular fractures were included, while pathological fractures, dentoalveolar injuries, and cases with incomplete data were excluded. Trauma mechanisms were classified as interpersonal aggression, vehicular accidents, falls from height, contact sports, and blows with blunt objects. Interpersonal aggression was the most frequent trauma mechanism, followed by falls from height and vehicular accidents. The mandibular angle, parasymphysis, and condyle were the most commonly affected anatomical sites. Multivariable analysis showed a higher probability of condylar fractures in falls from height (OR = 4.75; 95% CI: 2.24–10.3; p < 0.001) and vehicular accidents (OR = 3.02; 95% CI: 1.28–7.13; p = 0.01). Falls were also associated with a lower probability of mandibular angle fractures (OR = 0.16; 95% CI: 0.06–0.36; p < 0.001), while blunt object trauma showed a positive association with mandibular body fractures (OR = 3.12; 95% CI: 1.04–8.95; p = 0.04). These findings indicate that trauma mechanisms influence the anatomical distribution of mandibular fractures, providing relevant information for diagnostic assessment and surgical planning. Full article

Retinal detachments following blunt ocular trauma are challenging to predict due to the complex and transient biomechanical responses of the globe. This study combines an in vitro weight-drop experiment and finite element analysis (FEA) to evaluate the mechanical pathways leading to traumatic retinal detachment and to predict the spatial likelihood of injury. In the in vitro model, a cylindrical weight was impacted onto freshly enucleated mouse eyes (16 weeks old) supported on a rigid metal plate. Following impact, the eyes were sectioned and stained using hematoxylin and eosin (H&E) for histological assessment. A finite element model of a mouse eye, including the cornea, sclera, lens, zonule, vitreous body, aqueous humor, and retina, was reconstructed from the histological section and used to simulate the whole sequence of compression and rebound following the blunt impact. The simulation demonstrated that the lens retained a high momentum. It generated an alternating compressive (up to −6.57 × 10⁻³ MPa) and tensile (up to 1.62 × 10⁻³ MPa) radial stress at the posterior pole and sustained compressive stress at the peripheral region (up to −3.12 × 10⁻³ MPa) and tensile-compressive stress variation at the equatorial region of the retina. In addition, the regions experiencing tensile stress overlapped with the region exhibiting retinal detachment in the in vitro experiment. These findings highlight the spatiotemporal mapping of biomechanical stress to predict traumatic retinal detachment following blunt impact and provide an understanding of early biomechanical response following ocular trauma. Full article

Delayed effects of acute radiation exposure (DEARE), including radiation pneumonitis (lung-DEARE), develop weeks to months after radiation exposure. Pathway-targeted biomarkers that capture early oxidative stress and cell death could improve risk stratification and provide objective measures of mitigator efficacy. The objective was to test whether molecular lung imaging predicts long-term survival and mitigator response after irradiation. Rats received 13.5 Gy leg-out partial-body irradiation with a subset treated with the radiation-injury mitigator lisinopril. Rats underwent lung imaging at weeks 2 and 4 post-irradiation with ^99mTc-duramycin (cell death) and ^99mTc-HMPAO (oxidative stress). Plasma mitochondrial damage-associated molecular patterns (mtDAMPs) were also measured. Irradiation reduced survival with animals evidencing significant pleural effusion as an indication of radiation pneumonitis, which was mitigated with lisinopril as previously shown. Lung uptake of both imaging biomarkers increased in irradiated rats between weeks 2 and 4, consistent with worsening cell death and oxidative stress. Rats that succumbed by day 120 exhibited significantly larger increases in both biomarkers than the survivors. A predictive test was developed that predicted death by day 120 with ~70% sensitivity and specificity. Plasma mtDAMPs (ND1/2 and ATPase 6/8) increased following irradiation, and the D-loop increase from week 2 to 3 separated outcomes (increase in nonsurvivors versus decrease in survivors). Both imaging and mtDAMPs data from lisinopril-treated animals showed blunted responses. Early dual-tracer molecular lung imaging predicted long-term survival after radiation exposure and tracked mitigation with lisinopril. Circulating mtDAMPs may provide complementary systemic information to further strengthen early risk stratification after radiation exposure. Full article

Background/Objectives: Avoidant/restrictive food intake disorder (ARFID) and psychotic disorders are clinically distinct conditions yet occasionally co-occur in ways that complicate assessment and treatment. ARFID is characterised by avoidance of food due to sensory sensitivities, fear of aversive consequences, or low interest in eating, without body-image distortion. Recent meta-analytic evidence suggests that ARFID affects a substantial proportion of the population and is associated with a considerable social burden. Psychosis is characterised by positive symptoms (hallucinations and delusions), negative symptoms (avolition, blunted affect, and social withdrawal), and cognitive impairments affecting thought, perception, and behaviour. Methods: Across the limited literature, shared mechanisms between ARFID and psychotic disorders appear to converge on pathological avoidance, which may arise from sensory overstimulation, obsessive–compulsive features, or delusional beliefs about food. Case reports indicate that psychosis may both mimic ARFID and exacerbate food avoidance, while severe malnutrition can itself precipitate or worsen psychotic symptoms, blurring diagnostic boundaries. Results: Abnormalities in interoception, sensory sensitivity, and disrupted perception of bodily signals are manifestations of both ARFID and psychosis, suggesting a potential bridging pathway contributing to vulnerability and clinical overlap. Conclusions: Given the paucity of empirical studies and the reliance on isolated case reports, systematic investigation is mandatory and necessary to clarify shared mechanisms, refine differential diagnosis, and guide integrated treatment approaches. Given the heterogeneity of symptoms in comorbid patients, a personalised approach is suggested for treating these patients. Full article

Nutritional strategies based on sourdough fermented breads with wholemeal ancient grains and legumes are emerging as promising modulators of (neuro)immune processes. This study investigated whether prolonged consumption of a sourdough bread enriched with a mixture of ancient cereals and legumes, commercially available in Italy (Primus^® bread, P^®B), modulates neuroimmune systemic responses to repeated lipopolysaccharide (LPS) challenge in mice. For this study, male C57BL/6J mice were fed for 14 days with either a standard diet (SD) or P^®B. Animals then received intraperitoneal LPS (3 mg/kg/day for 3 days) or vehicle. Body weight and food intake were monitored throughout. Pain-like behaviours were assessed by von Frey, plantar and tail flick tests, and plasma cytokine (32-plex panel), splenocyte and peritoneal macrophage cytokine expression, and expression of pro-inflammatory cytokines in sciatic nerves, dorsal root ganglia (DRG) and the spinal cord were analyzed by Reverse Transcription–quantitative Polymerase Chain Reaction (RT-qPCR). P^®B prevented LPS-induced body weight loss and reduced splenomegaly. Unlike SD mice, which exhibited widespread plasmatic cytokine upregulation, P^®B-fed mice displayed only limited increases Interleukin (IL)-1β, IL-12p40 and Tumor Necrosis Factor (TNF)α. Ex vivo cultures of splenocytes and macrophages confirmed attenuated cytokine overexpression. LPS-induced hypersensitivity to mechanical, thermal and nociceptive stimuli was significantly reduced in P^®B mice. Molecular analyses revealed that the P^®B diet blunted the pro-inflammatory cytokine expression present after LPS challenge in the sciatic nerves and DRG, with partial attenuation in the spinal cord. Our findings highlight the great potential of functional foods as affordable dietary strategies to mitigate systemic immune and neuroimmune dysregulation. Full article