Search Results (666)

Vitamin B1 (thiamine) is a water-soluble B vitamin. As a cofactor of many enzymes, it is essential for the proper functioning of many body systems and organs, including metabolic and energy metabolism. In extreme cases, vitamin B1 deficiency causes neurodegenerative disorders, including beri-beri, or cognitive impairment resulting from encephalopathy. B1 avitaminosis may result from increased demand, dietary errors, malabsorption, or excessive loss. Thiamine supplementation is used in cases of vitamin B1 deficiency or for preventative measures in situations of increased demand. Vitamin B1 can be administered enterally or parenterally (intravenously, intramuscularly, subcutaneously). The route and dose depend on the individual patient’s clinical situation. Hypersensitivity to vitamin B1 is rare and appears to be primarily associated with rapid intravenous infusion of large doses of thiamine hydrochloride over a short period (intravenous bolus). Hypersensitivity to thiamine administered by routes other than intravenous or intramuscular injection appears to be an incidental phenomenon. Thiamine should also be considered as an occupational allergen. The mechanism of thiamine hypersensitivity has not been clearly elucidated. However, considering the clinical nature and dynamics of the reaction, the most likely reaction seems to be an immediate type of hypersensitivity reaction (immunoglobulin E (IgE)-dependent), in which thiamine (but not its metabolites) acts as a hapten. Diagnosing hypersensitivity to vitamin B1 is difficult due to the lack of validated tests for additional testing. In individuals requiring thiamine supplementation who have experienced hypersensitivity to intramuscular or intravenous administration of this vitamin, switching to oral administration may be considered (provided this does not reduce treatment efficacy). This form of supplementation is usually well tolerated by individuals allergic to parenteral thiamine. However, if enteral supplementation does not guarantee the maintenance of therapeutic potential, thiamine desensitization may be considered, which seems to be an effective therapeutic method in such a clinical situation. Full article

Background/Objectives: Canine Diffuse Large B-cell Lymphoma (cDLBCL) is characterized by a high prevalence of MHC II DR (DLA-DR) antigen overexpression. Murine anti-pan-DLA-DR monoclonal antibodies (mAbs) B5 and E11 have been previously observed to promote death of cDLBCL cells in vitro and in vivo. Consequently, DLA-DR antigens are considered a prospective target for passive immunotherapy aside from CD20. While infusion of anti-pan MHC II mAbs has demonstrated tumor suppression in cDLBCL xenografted immunodeficient mice, the relative contributions of direct cellular versus immune-mediated mechanisms to this therapeutic effect remain undefined. This study aimed to dissect these potential mechanisms of mAb E11. Methods: Canine lymphoma and leukemia cell lines CLBL1 and CLB70 were incubated with full E11 antibody or its F(ab′)2 and Fab fragments and cell viability was assessed with sub-G1 assay then, NOD-SCID mice were xenotransplanted with 1.5 × 10⁷ canine CLBL1 cells expressing nanoluciferase and were infused either with mAb E11 or its fragments, each at 1 mg/kg body mass, twice weekly for three consecutive weeks. Tumor burden was monitored by assessing body weight, nanoluciferase activity in blood, and by flow cytometric analyses of bone marrow tumor cell content. Time to tumor progression (TTP) was calculated based on weight loss and luminescence measurements. Results: We observed cytotoxic activity of monovalent E11-Fab fragments in vitro and in vivo. The mean TTP for mice treated with irrelevant mouse IgG antibodies was 9.8 ± 4.65 days. In contrast, treatment with E11 Fab fragments resulted in a TTP of 19.1 ± 2.67 days, which was similar to that achieved with the full E11 mAb (19.5 ± 1.73 days) and E11 F(ab′)2 fragments (18.1 ± 2.9 days). Conclusions: Our findings demonstrate a potent antibody cytotoxicity mechanism that operates in vivo and is independent of cell surface MHC II crosslinking or Fc engagement. These data support the promising potential of E11-Fab fragments for further clinical development as a therapeutic agent in canine lymphoma. Full article

Bovine endometritis negatively impairs fertility and milk production. Taurine maintains cellular integrity and exerts anti-inflammatory and antioxidant effects. However, whether taurine can treat endometritis remains unclear. This study aimed to investigate taurine’s effect on endometritis and explore its mechanism in vivo. Endometritis models were established in mice via intrauterine lipopolysaccharide (LPS) infusion, followed by 25, 50, and 100 mg/kg taurine treatment. Taurine attenuated inflammation by mitigating histopathological damage, suppressing uterine serum cytokine levels, and preserving tight-junction integrity. It ameliorated oxidative stress by reducing malondialdehyde content, restoring antioxidant activities, and recovering levels of oxidative-stress-related proteins. Apoptosis was alleviated by diminishing the apoptosis ratio and normalizing apoptosis-related proteins. 16S analysis revealed taurine restored uterine microbiota composition by reversing the changes in the abundances of Firmicutes, Bacteroidetes, Nocardioides, Ruminococcus, and Acidibacter. The abundances of Muribacter and Rodentibacter were positively correlated with inflammation. The abundances of Akkermansia and Streptococcus were negatively correlated with inflammation. RNA sequencing showed that the differentially expressed genes were mainly related to immunity. Phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signaling pathways were indicated as pivotal mechanisms for taurine’s therapeutic efficacy against endometritis with transcriptomic profiling analysis. This study confirms that taurine alleviates LPS-induced endometritis in mice by modulating PI3K–AKT, MAPK, and NF-κB signaling pathways, indicating its potential as a therapeutic agent for bovine endometritis. Full article

Inflammatory bowel disease (IBD) is a chronic condition whose pathogenesis is not entirely clear. Impaired immune regulation has been hypothesized as the mechanism responsible for the abnormal response of adoptive immunity to enteric microbial antigens. Regulatory T cells (Tregs) have been regarded as the crucial element of immune regulation, since the discovery that humans lacking Tregs due to mutation of FOXP3 develop autoimmune disorders, including severe bowel inflammation. The existing publications concerning T regulatory cells in human IBD have been reviewed, and current evidence does not clearly indicate quantitative disturbances or functional defects of Tregs in human inflammatory bowel disease. The possible mechanisms explaining immunoregulatory failure in IBD have been summarized. So far, only one clinical trial with Tregs infusion has been completed, and its results do not provide sufficient data on the efficacy or safety of Tregs-based therapies in IBD. It will probably be difficult to implement them in clinical practice in the near future. Full article

Despite the widespread use of experimental acute pain models, little exploration has been undertaken on the acute pain proteome in humans. We resolved to explore molecular alterations evoked by hypertonic saline (HS)-induced acute muscle pain and to map the spread of mechanical hyperalgesia. This study used a two-cohort design in healthy participants. Cohort one (n = 16) underwent intermittent blood sampling prior to, during, and following intramuscular HS (5%) infusion to allow for the discovery of the proteomic and cytokine profile of acute muscle pain. Cohort two (n = 10) underwent bilateral sensory testing during HS infusion, to map the spread of mechanical hyperalgesia. Molecular analysis in cohort one revealed a broad array of proteins and cytokines showing altered expression in response to acute muscle pain. Particularly, these alterations were linked to metabolism and immune response pathways suggestive of systemic effects of acute pain. Cohort two revealed a significant mechanical hyperalgesia which emerged in a distributed pattern over the ipsilateral limb to HS infusion. However, despite systemic molecular alterations, no such mechanical hyperalgesia was observed in the contralateral limb. This study demonstrates systemic molecular alterations resultant from acute HS-induced muscle pain, accompanied by spatially constrained sensory interactions. This dissociation implies that, at least in acute sensitization, widespread molecular changes may not necessarily translate into a correspondingly widespread sensory phenotype. Full article

A 15-year-old female developed refractory Complex Regional Pain Syndrome (CRPS) Type I of the left hand following metacarpal fixation. Conservative therapy and hand rehabilitation failed, resulting in persistent allodynia and functional loss. She was admitted for multimodal analgesia combining subanesthetic ketamine infusion, gabapentin, and a tunneled supraclavicular continuous nerve catheter delivering ropivacaine. Pain decreased from 7/10 at rest to 0/10 within 48 h. Allodynia has resolved, and motor function has fully recovered. The catheter was removed nine days later without complication, and pain remission persisted. This case demonstrates a safe and effective multimodal strategy for adolescent CRPS integrating central and peripheral desensitization mechanisms. Full article

Basic physiology and molecular mechanisms accounting for the maldistribution of fluid that is characteristic of the “third fluid space” (V_t2) have been known for several decades but have been poorly integrated into the clinical literature. Today, the maldistribution can be quantified and simulated in living humans by using volume kinetic mathematics, which introduces possibilities to validate interventions designed to mitigate the pathophysiology. Fluid accumulation in V_t2 occurs both in fluid overload and inflammation, and both are largely influenced by interstitial fluid pressure. This is normally slightly sub-atmospheric but increases during volume loading to eventually exceed the ambient air pressure, whereby the loss of vacuum allows pools of fluid to appear in the interstitial gel. Opening of V_t2 due to fluid overload can be delayed/minimized by lowering the infusion rate, hemorrhage, and the use of hyper-oncotic fluid. Accumulation of fluid in V_t2 during acute inflammation and tissue injury can be explained by disruption of the cell–matrix interactions that actively regulate the interstitial pressure. Inflammatory mediators, mostly tissue cytokines, cause release of tensile forces that disrupt integrin-dependent adhesion between interstitial fibroblasts and collagen fibers. This disruption causes the interstitial space to expand, which results in a deep negative (suction) pressure. These events can be modulated by α-trinositol and insulin. Full article

Background: Intraoperative high-volume diuresis is a frequent but underrecognized complication in cardiac surgery, potentially leading to hypovolemia, electrolyte imbalances, and hemodynamic instability. Its mechanisms remain poorly defined. This study investigated the hormonal and biochemical regulation of urine output during off-pump coronary artery bypass grafting (OPCABG). Methods: For this single-center observational cohort study, 70 patients undergoing OPCABG were enrolled (diuresis: urine output > 5 mL/kg/h, n = 38; normal, n = 32). Hormonal markers and osmolality parameters were measured perioperatively. Logistic regression was used to identify independent predictors, and receiver operating characteristic (ROC) curves was used to assess model performance. Results: Intraoperative high-volume diuresis occurred in 54.2% of patients. Logistic regression identified a low Body Mass Index (BMI) (OR 0.72, p = 0.002), reduced albumin (OR 0.75, p = 0.014), and lower copeptin (OR 0.43, p = 0.037) as independent predictors (AUC 0.855). Perioperatively, NT-proBNPT0 rose in both groups, aldosterone increased only in the diuresis group, and copeptin showed a slight nonsignificant rise. Plasma sodium was higher in cases of diuresis at the end of surgery (148.4 vs. 144.9 mmol/L, p < 0.001). Despite greater urine output and fluid infusion, the rates of intensive care unit (ICU) admission and hospital stays were similar. Conclusions: Intraoperative high-volume diuresis in OPCABG is strongly associated with reduced antidiuretic hormone activity, suggesting a partial central diabetes insipidus-like mechanism. Although not affecting short-term outcomes, it posed challenges for intraoperative fluid and electrolyte management. Larger multicenter studies are needed for validation. Full article

Plant growth-promoting bacteria (PGPB) can act as biostimulants, improving the growth of plants in sustainable agriculture systems that seek to reduce synthetic agrochemical input. Bacteria present in seeds are closely associated with vertical transmission and thus represent a potential trove of biostimulants. Capsicum species are notable for producing capsaicin, a compound with antimicrobial activity that may influence microbial communities associated with pepper fruits and seeds. Using Luria–Bertani (LB) media infused with capsaicin, we isolated bacteria from bell peppers, jalapeno peppers, and habanero peppers, which we verified to have different levels of capsaicin through high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Minimum inhibitory concentration (MIC) assays indicated that the capsaicin resistance of isolated bacteria did not correlate with the pungency level of the host pepper variety. Of the total isolated bacteria, four showed promise as plant growth promoters; two belong to the genera Pseudomonas, one Agrobacterium, and one Bacillus. Our isolates tested positively for potassium and phosphate solubilization, urease production, and indole-3-acetic acid (IAA) phytohormone production. Inoculation of these bacteria into surface-sterilized red clover (Trifolium pratense) and Kentucky bluegrass (Poa pratensis) showed significant improvements in germination rate, seedling root length, and seedling shoot height. These results show that the pungency of peppers does not influence the capsaicin resistance of isolated bacteria. Additionally, seedborne PGPB have the potential for plant growth improvement through various mechanisms, reducing the need for synthetic chemicals. Full article

Graphene oxide (GO) has been successfully used as a filler to modify various properties of polymers and fiber-reinforced composites. The resulting properties depend on the filler content and on the distribution of GO in the polymer matrix. In this work, for the first time, we introduced GO into the highly viscous DEN-438 epoxy novolac resin and investigated rheological properties of the resulting compositions. In particular, we studied the functions of complex viscosity, storage and loss moduli, and mechanical loss tangent on temperature and GO content. The unusual behavior of the newly prepared formulations compared to typical GO/epoxy mixtures was discovered. At low GO content, introduction of GO led not to an increase, but to a decrease in the resin viscosity, with the minimum registered at 0.29 wt.% GO. After this threshold value, viscosity increased with GO content, which we explained by formation of the liquid crystalline structure. At higher GO concentrations, the formulations changed their state from solid-like at rest to liquid-like under load, with the properties being highly desired for film binders. The discovered properties of the GO/novolac epoxy resin formulations suggest their potential use as the new generation of film binders for Resin Film Infusion technology. Full article

Background: Severe traumatic brain injury (TBI) often leads to elevated intracranial pressure (ICP) that requires aggressive management. Inducing burst suppression with deep sedation is an established therapy for refractory intracranial hypertension. Traditionally, barbiturate coma has been used to achieve burst-suppression EEG in TBI patients, but alternative sedative agents (propofol, midazolam, ketamine, dexmedetomidine) are increasingly utilized in modern neurocritical care. This review compares barbiturates with these alternatives for inducing burst suppression in adult TBI, focusing on protocols, mechanisms, efficacy in controlling ICP, safety profiles, and impacts on neurological outcomes. Methods: A search of the literature was performed, including clinical trials, observational studies, and guidelines on deep sedation for ICP control in adult TBI. Studies comparing high-dose barbiturates to other sedatives (propofol, midazolam, ketamine, dexmedetomidine) in the context of burst suppression or severe TBI management were included. Data on sedative protocols (dosing and EEG targets), mechanisms of action, ICP-lowering efficacy, complications, and patient outcomes were extracted and analyzed qualitatively. Results: High-dose barbiturates (e.g., pentobarbital or thiopental) and propofol are both effective at inducing burst-suppression EEG and reducing ICP via cerebral metabolic suppression. Barbiturate coma remains a third-tier intervention reserved for ICP refractory to other treatments. Propofol infusion has become first-line for routine ICP control due to rapid titratability and shorter half-life, though it can also achieve burst suppression at high doses. Midazolam infusions provide sedation and seizure prophylaxis but yield less metabolic suppression and ICP reduction compared to barbiturates or propofol, and are associated with longer ventilation duration and delirium. Ketamine, once avoided for fear of raising ICP, has shown neutral or lowering effects on ICP when used in ventilated TBI patients, thanks to its analgesic properties and maintenance of blood pressure; however, ketamine alone does not reliably produce burst-suppression patterns. Dexmedetomidine offers sedative and anti-delirium benefits with minimal respiratory depression, but it is generally insufficient for deep burst-suppressive sedation and has only a modest effect on ICP. In comparative clinical evidence, propofol and barbiturates both effectively lower ICP, but neither has demonstrated clear improvement in long-term neurological outcome when used prophylactically. Early routine use of barbiturate coma may increase complications (hypotension, immunosuppression), and thus, current practice restricts it to refractory cases. Modern sedation protocols emphasize using the minimal necessary sedation to maintain ICP < 22 mmHg, with continuous EEG monitoring to titrate therapy to a burst-suppression target (commonly 2–5 bursts per minute) when deep coma is employed. Conclusions: In adult TBI patients with intracranial hypertension, propofol-based sedation is favored for first-line ICP control and can achieve burst suppression if needed, whereas high-dose barbiturates are reserved for ICP crises unresponsive to standard measures. Compared to barbiturates, alternative agents (propofol, midazolam, ketamine, dexmedetomidine) offer differing advantages: propofol provides potent, fast-acting metabolic suppression; midazolam adds anticonvulsant sedation for prolonged use at the cost of slower wake-up; ketamine supports hemodynamics and analgesia; dexmedetomidine aids lighter sedation and delirium control. The choice of agent is guided by the clinical scenario, balancing ICP reduction needs against side effect profiles. While all sedatives can transiently reduce ICP, careful monitoring and a tiered therapy approach are essential, as no sedative has conclusively improved long-term neurological outcomes in TBI. EEG monitoring for burst suppression and meticulous titration is required when employing barbiturate or propofol coma. Ongoing research into optimal combinations and protocols may further refine sedation strategies to improve safety and outcomes in severe TBI. Full article

Dexmedetomidine improves pulmonary function in dogs and humans, but evidence in horses is scarce. This study evaluated dexmedetomidine infusion on oxygenation and respiratory mechanics in anesthetized horses. Twenty horses undergoing elective surgery were included in a prospective, non-randomized, observational study. Horses received either lidocaine alone (1.3 mg/kg over 15 min, then 3 mg/kg/hour; LIDO) or combined with dexmedetomidine (1.75 μg/kg over 15 min, then 1.75 μg/kg/hour; DL). Respiratory mechanics, gas exchange, and cardiovascular variables were recorded at baseline, post-loading, and after 30, 60, and 90 min. Data were analyzed using mixed-effects linear models with horse as a random effect and time and treatment and their interaction as fixed effects (p ≤ 0.05). Peak inspiratory pressure increased over time with both treatments but was lower with DL at 90 min (−1.26 mmHg, p = 0.046). There was no evidence that arterial oxygen pressure or oxygenation ratio improved over time with DL (p > 0.75). Shunt fraction did not significantly change over time or between treatments (Wald χ² = 4.77, p = 0.85). Heart rate with DL decreased from baseline (p ≤ 0.001) but remained higher than LIDO overall (p = 0.001). Dexmedetomidine infusion showed no benefit on oxygenation or respiratory mechanics in anesthetized horses. Full article

Nearly 10% of IVF patients experience repeated implantation failure (RIF). Although several meta-analyses report improved outcomes following peripheral blood mononuclear cell (PBMC) administration, the uterine mechanisms remain poorly understood. We first analyzed PBMC composition and cytokine secretion in a preliminary cohort (n = 18), followed by endometrial immune profiling in a larger cohort (n = 70) before and after PBMC treatment. Embryo transfer was performed in 41 women, enabling the assessment of associations between immune profiles and implantation success. Successful implantation occurred in 16 of 41 embryo transfers (39%). PBMCs were predominantly composed of lymphocytes (60.7%), with T helper cells as the predominant T cell subset (Th/cytT ratio 1.44). Cytokine assays confirmed secretion of TNF-α, IL-6, IL-4, and IL-10. C-reactive protein levels remained below the threshold for systemic inflammation and were unaffected by PBMC administration. In the full cohort, PBMC infusion significantly enriched stromal macrophages and T helper cells, reflected by higher Th/T, Th/MΦ, and Th/cytotoxic T cell ratios and a reduced cytotoxic T/T cell ratio (all p ≤ 0.001). Importantly, women with successful implantation exhibited a significantly higher macrophage/T cell ratio (1.15 vs. 0.74; p = 0.024). These findings suggest that PBMC administration reshapes the endometrial immune landscape and that the macrophage/T cell ratio may serve as a promising biomarker of treatment efficacy. Full article

Aerogels combine ultralow density with high surface area, yet their brittle, open networks preclude tensile deformation and hinder integration into wearable electronics. Here we introduce a prestrain-enabled coaxial architecture that converts a brittle conductive aerogel into a highly stretchable fiber. A porous thermoplastic elastomer (TPE) hollow sheath is wet-spun using a sacrificial lignin template to ensure solvent exchange and robust encapsulation. Conductive polymer-based precursor dispersions are infused into prestretched TPE tubes, frozen, and lyophilized; releasing the prestretch then programs a buckled aerogel core that unfolds during elongation without catastrophic fracture. The resulting TPE-wrapped aerogel fibers exhibit reversible elongation up to 250% while retaining electrical function. At low strains (<60%), resistance changes are small and stable (ΔR/R₀ < 0.04); at larger strains the response remains monotonic and fully recoverable, enabling broad-range sensing. The mechanism is captured by a strain-dependent percolation model in which elastic decompression, contact sliding, and controlled fragmentation/reconnection of the aerogel network govern the signal. This generalizable strategy decouples elasticity from conductivity, establishing a scalable route to ultralight, encapsulated, and skin-compatible aerogel fibers for smart textiles and deformable electronics. Full article

Background and Objectives: Analgesia and sedation are a major challenge in pediatric intensive care. The COMFORT-B scale and the Bispectral Index (BIS) are commonly used to assess the degree of sedation. The aim of this study was to investigate the correlation between the COMFORT-B and BIS and to evaluate the predictive validity of the BIS scale. Materials and Methods: Mechanically ventilated children (n = 41) diagnosed with acute bronchiolitis and treated with fentanyl and midazolam were included in the study. COMFORT-B and BIS scores were recorded over a 7-day observation period. Patients were divided into subgroups based on chronological age, neuromuscular blocker use, and level of sedation. Statistical analyses included correlation analysis by subject and time, simple moving average trend analysis, linear mixed-effects modeling and random forest. Results: Conventional correlation analysis revealed a weak to moderate correlation between the two scales in the entire cohort (Spearman rho of patients’ means 0.42, p = 0.007). The longitudinal correlation analysis by individual patient showed no significant relationship between the two scales in the entire cohort (CCF 0-lag 0.23; p = 0.33) or any subgroup. Linear mixed-effects model analysis showed that BIS score was associated with COMFORT-B score (slope = 0.799, p = 0.0002). The random forest model explained 19.6% of the variance. Both models yielded similar prediction errors (RMSE 10.6 and 11.3, respectively). Conclusions: We found a weak correlation between the two scales, which does not allow for reliable and valid predictions between the two scales. The BIS scale is suitable for the assessment of deep sedation, whereas the COMFORT-B scale is suitable for the assessment of moderate sedation. Full article