Search Results (276)

Proximal humerus fractures are frequent injuries that often require internal fixation. Conventional metallic plates, however, present significant drawbacks such as corrosion, secondary removal surgeries, and adverse reactions in patients with metal hypersensitivity. This study evaluates biocomposite plates fabricated from polylactic acid (PLA) and polyvinyl alcohol (PVA), reinforced with hydroxyapatite (HA) derived from sugar industry by-products (BCF) at 10% and 20% concentrations. These composites are compatible with both injection molding and 3D printing, enabling the design of patient-specific implants. Characterization by SEM, FTIR, XRD, and DSC confirmed that BCF incorporation enhances strength, stiffness, osteoconductivity, and biocompatibility. Mechanical testing showed that PVA/BCF exhibited greater tensile strength and stiffness, suggesting suitability for load-bearing applications, though their water solubility restricts use in humid environments and prevents filament-based 3D printing. PLA/BCF composites demonstrated better processability, favorable mechanical performance, and compatibility with both manufacturing routes. Finite element analysis highlighted the importance of plate–humerus contact in stress distribution and fixation stability. Compared with non-biodegradable thermoplastics such as PEI and PEEK, PLA/BCF and PVA/BCF offer the additional advantage of controlled biodegradation, reducing the need for secondary surgeries. Cell viability assays confirmed cytocompatibility, with optimal outcomes at 10% BCF in PVA and 20% in PLA. These results position PLA/BCF and PVA/BCF as sustainable, patient-tailored alternatives to metallic implants, combining adequate mechanical support with bone regeneration potential. Full article

Anecdotal reports have recently circulated suggesting that intramuscular injection of bacteriostatic saline (BS)—which contains benzyl alcohol (BnOH)—can reverse botulinum toxin type A (BoNTA)-induced brow ptosis. Given the well-established intracellular persistence of BoNTA’s light chain and its irreversible cleavage of SNAP-25, such rapid functional recovery challenges existing pharmacological understanding. This study employed high-resolution pharmacokinetic/pharmacodynamic (PK/PD) modelling using the AesthetiSim™ platform to systematically evaluate this hypothesis. A total of 30,000 virtual patients were randomized to receive BoNTA alone, BoNTA followed by BS injection, or BoNTA followed by normal saline (NS) at Day 7. The model incorporated BoNTA diffusion, internalization, SNAP-25 cleavage, neuromuscular output, and transient BS effects on membrane permeability and endosomal trafficking. Simulated recovery trajectories were tracked over 90 days. The primary outcome, time to 80% restoration of baseline frontalis muscle force (T₈₀), averaged 42.0 days in the BoNTA-only group and 35.5 days in the BS group (Δ = −6.5 days; p < 0.001). Only 13.9% of BS-treated patients reached the T₈₀ threshold by Day 30. Partial reactivation (T₃₀) occurred earlier with BS (21.8 ± 5.3 days vs. 27.3 ± 4.9 days), and the area under the effect curve (AUEC) was increased by 9.7%, reflecting higher overall muscle function over time. In molecular simulations, BnOH produced a minor rightward shift in the BoNTA–SNAP-25 dissociation curve, but receptor occupancy remained above 90% at therapeutic toxin concentrations, suggesting no meaningful impairment of binding affinity. A global Sobol sensitivity analysis demonstrated that the primary driver of recovery kinetics was intracellular LC degradation (49% of T₈₀ variance), while BS-modulated extracellular parameters collectively contributed less than 20%. These findings indicate that BS does not reverse the molecular action of BoNTA but may transiently influence recovery kinetics via non-receptor-mediated pathways such as increased membrane permeability or altered vesicular trafficking. The magnitude and variability of this effect do not support the notion of a true pharmacologic reversal. Instead, these results emphasize the need for mechanistic scrutiny when evaluating rapid-reversal claims, particularly those propagated through anecdotal or social media channels without supporting biological plausibility. Full article

Alcohol misuse can lead to alcohol-related brain damage (ARBD), a condition linked to long-term cognitive impairment and considerable disease burden. The pharmacological characteristics of alpha-lipoic acid (ALA) make it a promising candidate for the treatment of ARBD. In this study, adult male Wistar rats were divided into eight experimental groups. Four groups received a 20% (v/v) ethanol–tap water solution ad libitum for 15 weeks to induce early-stage ARBD, while the remaining received only tap water. After 14 weeks, all groups were administered daily injections for one week with either ALA, rivastigmine, or memantine. Behavioral testing included the step-through passive avoidance and rotarod performance tests. Whole-brain biochemical analyses assessed acetylcholinesterase activity, brain-derived neurotrophic factor, and oxidative stress biomarkers. Brain weight, relative brain weight, and brain histopathological changes were also evaluated. Results showed that, similar to memantine and rivastigmine, ALA improved STL at both 24 h and 8 days and reduced ethanol-induced Purkinje cell damage. It also decreased lipid peroxidation levels by 44%, unlike the reference drugs, and superoxide dismutase activity by 33%, similar to them. No other significant changes were detected. Albeit several limitations, this is the first study comparing ALA with rivastigmine and memantine in this experimental context. Full article

In this study, low-viscosity (<5 mm²·s⁻¹, fits European Biodiesel Standard-EN 14214) quaternary microemulsification fuels were developed and tested in a CRDI diesel engine to evaluate their effects on engine performance, injection, combustion, and emission characteristics. The fuels were formulated using 50% petro-diesel, 30% waste frying oil (without converting biodiesel), and a combination of 10% n-butanol with either 10% methanol or 10% ethanol. Engine tests were conducted at constant speed of 2000 rpm and five different engine loads. The results indicated that both microemulsified fuels exhibited increased brake specific fuel consumption by about 20% and brake specific energy consumption by around 8% compared to petro-diesel, while thermal efficiency decreased by about 8%. Injection timing for both pilot and main injections occurred earlier with the emulsification fuels, and higher injection amount and injection rate values were observed at all loads. As engine load increased, the peak cylinder pressures of the emulsified fuels surpassed those of petro-diesel, although the crank angles at which these peak values were attained were similar. The combustion duration was shorter for both quaternary fuels, with similar maximum pressure rise rates to petro-diesel. Emulsification fuels caused higher exhaust emissions (especially THC) and this difference increased with increasing load. When comparing two formulations, the methanol-containing fuel demonstrated slightly better results than the ethanol-containing blend. These findings suggest that microemulsified fuels containing bio-alcohols and waste frying oil can be sustainable fuel alternatives for partial petro-diesel substitution if the injection settings are adapted in accordance with the properties of these fuels. Full article

To encourage the use of alternative fuels while limiting the use of fossil fuels, researchers have focused on using more environmentally friendly fuels. Furthermore, the goal is to improve engine performance to increase energy efficiency. A four-stroke, single-cylinder, diesel engine with a common rail fuel injection system runs with diesel, biodiesel, and biodiesel–alcohol fuel blends. The tests were performed using a constant engine speed of 2000 rpm and three different gas pedal positions (20%, 50% and 80%). It was found that maximum cylinder gas pressure increased in all test fuels with increased gas pedal position (GPP) and advanced injection start time. In general, the maximum heat release rate increased in blended fuels compared to diesel fuel. In addition, it was seen that advanced injection timings caused an increase in ignition delay in all fuel types. In the same test conditions, it was observed that biodiesel–alcohol fuel blends caused an increase in ignition delay by more than 10% compared to diesel fuel (D100), while shortening combustion duration (CD) by more than 10%. A decreasing trend in CO and HC emissions was observed in the use of biodiesel fuel compared to diesel fuel. With the use of biodiesel–alcohol fuel blends, CO₂ emissions tend to decrease. Advanced injection timings caused high NO emissions. Full article

With aging, harsh working conditions or sports injuries, the meniscus can degrade, causing pains to the patient. Nowadays, the treatment consists of the surgical replacement of this cartilage. Since this procedure can lead to complications due to open wounds and potential infections, synthesizing a polyurethane-based injectable joint filler represents an interesting alternative. In this study, poly(δ-decalactone)triol oligomers and Lysine diisocyanate were chosen as starting monomers to create an isocyanate-based prepolymer, because of their biocompatibility and liquid state at room temperature. Nevertheless, to fully replace the meniscus, the joint filler must crosslink in vivo, and this should occur in a short time window. Accordingly, in this work, we studied the catalytic activity of a range of relatively safe compounds for the alcohol/isocyanate addition reaction. A preliminary ¹H NMR kinetic study of the catalyzed addition of 1-butanol or 3-pentanol on lysine diisocyanate ethyl ester at body temperature has been performed to reach this objective. Among catalysts, stannous octoate was the most effective with either primary or secondary alcohol, allowing them to reach 92 and 80% alcohol conversion, respectively. In addition, the conversion of the primary and secondary isocyanates of lysine diisocyanate ethyl ester was monitored for all the catalysts and revealed different behaviors depending on the catalyst employed. Stannous octoate, unlike the others, showed a similar reactivity for primary and secondary isocyanates with conversions of 49 and 47%, respectively. Finally, when employing the most effective catalyst, curing of the poly(δ-decalactone) triisocyanate with glycerol at 35 °C provided a polyurethane elastomer that exhibits an elastic modulus of 519 kPa and a swelling index lower than 3% in PBS, making it suitable for injectable polyurethane joint filler application. Full article

Prenatal alcohol exposure (PAE) causes neurobehavioral deficits and metabolic syndrome in later life. Prenatal choline supplementation (PCS) improves those behavioral deficits. Here we test whether PCS also ameliorates the attendant metabolic syndrome, using an established mouse model that mirrors aspects of alcohol-related neurodevelopmental disorders. Pregnant dams were exposed to alcohol (3 g/kg) from gestational days 8.5–17.5; some dams received additional choline (175% of requirement) by a daily injection. Offspring were followed through to the age of 86 wks with respect to their body composition and glucose tolerance. We found that PAE affected these outcomes in a sex-dependent manner. Male PAE offspring exhibited an increased fat mass, liver enlargement, elevated fasting glucose, and glucose intolerance. Female PAE offspring exhibited an increased fat mass, but the glucose tolerance and fasting values were unaffected. Regardless of sex, PCS attenuated all these metabolic measures. PCS was shown previously to elevate methyl-related choline metabolites and improve fetal growth, suggesting that it acts by attenuating the in utero stressors that otherwise program the fetus for metabolic syndrome in later life. Importantly, PCS also improved the adiposity, fasting glucose, and glucose tolerance in control offspring consuming the fixed-nutrient AIN-93G diet, suggesting that its choline content (1 g/kg) may be inadequate for optimal rodent health. Full article

Background/Objectives: Lidocaine is a widely used local anesthetic, but injections and topical creams are often painful or slow in onset. This study aimed to develop dissolving microneedles incorporating lidocaine hydrochloride for rapid and convenient local anesthesia. Methods: Six formulations were prepared with polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) and evaluated for mechanical strength, skin insertion, drug release, and transdermal permeability. Results: Sharp pyramidal microneedles were successfully fabricated, with PVP–PVA mixtures producing stronger needles than single polymers. The optimized F5 formulation showed high strength (>32 N), efficient skin insertion (four parafilm layers), and rapid release (>80% within 15 min). In ex vivo studies, F5 delivered >600 µg/mL lidocaine in 15 min, over three times the therapeutic level and much faster than Emla cream (5%). Conclusions: PVP–PVA microneedles represent a promising platform for painless, rapid local anesthesia, combining the benefits of injections and topical creams while minimizing their drawbacks. Full article

Urinary incontinence (UI) is a widespread worldwide gynecological pathology with a negative impact on women’s quality of life. We performed a narrative review and present a general, descriptive, and comprehensive perspective about surgical techniques for urinary incontinence in young women. Even though parity and vaginal births represent important risk factors for the occurrence of UI, it is also common among young women who are nulliparous. Lifestyle, obesity, smoking, alcohol consumption, and excessive stretching exercises can contribute to the occurrence of UI. Correct diagnosis and treatment may reduce the negative effects of UI on daily activities. Disease management varies depending on the three types of UI: stress, urge, and mixed. Conservative treatment involves lifestyle changes, pharmacological therapy, and pelvic floor muscle training. If symptoms persist, surgical techniques such as midurethral/suburethral slings, anterior colporrhaphy, and retropubic/laparoscopic colposuspension are necessary. Transvaginal tension-free vaginal tape obturator (TVT-O) is the most common surgical technique for the treatment of UI. Its effectiveness has been proven by reducing symptoms and improving quality of life. Alternative modern treatment methods are vaginal laser therapy, periurethral bulking agents injection, or local injection with autologous platelet-rich plasma. Surgical techniques for the treatment of UI are in continuous development and improvement considering the increased incidence of this pathology and the need of patients to improve symptoms and quality of life. Full article

Patients with concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) exhibit increased susceptibility to non-alcoholic steatohepatitis (NASH), advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. This study investigated the contribution of ketogenesis to T2DM-mediated NAFLD exacerbation and elucidated the therapeutic mechanism of cynaroside in NASH-complicated T2DM. Male C57BL/6J mice were given CDAHFD combined with streptozotocin to establish stage-specific NAFLD with T2DM models. Hepatic HMGCS2 expression was modulated via tail vein injection of adenoviral vectors for HMGCS2 overexpression or knockdown. Cynaroside was administered orally from week 5 to week 8. The results showed that concurrent T2DM accelerated NAFLD progression, accompanied by a dysregulated ketogenesis that was correlated with disease severity. Hepatic HMGCS2 expression paralleled circulating ketone body concentrations, indicating that HMGCS2-mediated ketogenic dysregulation contributed to NAFLD pathogenesis in T2DM contexts. HMGCS2 overexpression in NASH-T2DM models significantly attenuated steatohepatitis progression through the enhancement of ketogenesis. Cynaroside administration ameliorated hepatic pathology in NASH-T2DM mice by (1) reducing hepatocellular injury and lobular inflammation; (2) decreasing intrahepatic lipid accumulation; and (3) suppressing hepatocyte senescence and the secretion of SASP factors. Mechanistically, cynaroside exerted therapeutic effects via HMGCS2-mediated ketogenesis. Our data demonstrated that ketogenic modulation is a viable therapeutic strategy to delay T2DM-NAFLD progression. Full article

This study investigated the effects of six cap management protocols targeting contrasting oxidation-reduction potential (ORP) evolutions during alcoholic fermentation of Pinot noir wines. Treatments included twice-daily punch-downs (PD) and pump-overs (PO), 1 h air or N₂ injections (AirMix, N₂Mix), air injections triggered by ORP ≤ −40 mV (RedoxConAir), and equal N₂ injections concurrent to RedoxConAir wines (RedoxConN₂). AirMix wines maintained ORP values above 0 mV throughout fermentation, showed an oxidatively favored glutathione-to-glutathione disulfide ratio (GSH:GSSG) of 0.3:1, and had 21% lower total phenolics and 24% lower anthocyanins than PD wines. In contrast, N₂Mix wines maintained the lowest ORP, near −100 mV, and showed a reductively favored GSH:GSSG ratio (7:1). PD wines extracted 48% more flavan-3-ols than PO wines, consistent with greater berry integrity disruption and seed submersion. Volatile composition was also impacted: ethyl n-octanoate showed the highest OAV among esters, ranging from 147 in PO wines to 116 in AirMix wines. Results suggest the GSH:GSSG ratio served as an indicator of redox history, with potential implications for color and aroma preservation during aging. Inert gas mixings resulted in equal or greater total phenolic content, while excessive air injections may provide a tool to soften astringency. Full article

Conventional thermoplastic polymer composites are produced using energy-intensive equipment. From an environmental perspective, reducing energy and material consumption, as well as selecting polymers and fillers that biodegrade without harmful consequences for the environment, is considered good practice. In this work, polyvinyl alcohol (PVOH), a biodegradable and water-soluble polymer, was compounded with 30 w%, 40 µm long cellulose fibres. Conventional melt blending production and innovative cold processing were compared from a tensile testing, thermogravimetric, and life cycle assessment (LCA) perspective through primary data collection. The granule production process significantly affects the mechanical performance of injected samples, with a 23.4% drop in tensile strength and an increase of 67.9% in elongation at break. The thermogravimetric analysis reported slight differences due to an additional thermal process involved in the melt blending of PVOH. From an LCA perspective, the innovative cold blending of PVOH-based composites drops all environmental indicators by 58–92%, maximizing the reduction of the “Water use” indicator. The most impactful production phase in the analysed production processes was drying, accounting for 46% and 85% of the conventional melt blending and innovative cold-blending processes, respectively. Full article

This study investigates the recombinant Tarim red deer hepatocyte growth factor (HGF) in a mouse model to develop an HGF/c-Met-based regenerative therapy for alcoholic liver disease. We constructed a recombinant HGF fusion protein and expressed and purified it in Escherichia coli. The recombinant protein was administered via intravenous injection to treat mice with alcoholic liver disease induced by chronic alcohol feeding followed by acute alcohol gavage (NIAAA model). The therapeutic effects were evaluated based on liver tissue histology and biochemical indicators. The recombinant Tarim red deer HGF protein successfully reduced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in mice, increased serum albumin (ALB) levels, decreased hepatic steatosis and triglyceride (TG) levels, lowered hepatic malondialdehyde (MDA) levels, and increased the levels of the antioxidants glutathione (GSH) and superoxide dismutase (SOD) in the liver. Additionally, it enhanced the proliferation capacity of liver cells, thereby promoting liver regeneration. In conclusion, our study demonstrates that recombinant Tarim red deer HGF effectively reduces liver damage in a mouse model of alcoholic liver disease. Full article

The activity of the present work is part of a research project aimed at proposing a solution for off-grid charging stations relying on the adoption of a reciprocating engine fuelled with alternative renewable fuels. This technology has as its main advantage the zero-carbon emissions impact of biofuels with small modifications to current ICE technology and refuelling infrastructure. This research is founded on preliminary experimental tests carried out on a six-cylinder spark-ignition engine adapted to pure ethanol fuelling with a single-point injection system. The experimental results obtained at different engine loads have been useful to build and validate a CFD model by testing several kinetic mechanisms and for the proper calibration of a flame speed model. Nevertheless, due to the chemical and physical properties of alcohols such as ethanol, this type of fuelling system leads to a significant non-uniformity of the mixture among the cylinders, and in some cases, to rich air-to-fuel ratio; numerical simulations are performed to address such an issue, and to evaluate performance and exhaust emissions, in terms of CO, CO₂, and NO_x. Finally, a study on spark timing variation is presented as well, to study its effect on performance and pollutants. Full article

Background/Objectives: Levocetirizine (LCZ) is a second-generation antihistamine with minimal central nervous system effects. However, its short half-life necessitates daily dosing, potentially reducing adherence in pediatric populations. This study aimed to develop a long-acting injectable LCZ formulation by synthesizing lipophilic prodrugs and evaluating their physicochemical stability, enzymatic hydrolysis, and pharmacokinetics in vivo. Methods: Two prodrugs of LCZ, LCZ decanoate (LCZ-D) and LCZ laurate (LCZ-L), were synthesized via esterification with alkyl alcohols. The compounds were characterized using NMR, FT-IR, and DSC. Prodrugs were formulated with an oil-based vehicle (castor oil and benzyl benozate), and their hydrolysis was evaluated using porcine liver esterase (PLE) and rat plasma. Pharmacokinetic profiles were assessed in Sprague Dawley rats after oral or intramuscular administration. Stability was tested at 25 °C, 40 °C, and 60 °C for 6 weeks. Results: LCZ-D and LCZ-L exhibited first-order hydrolysis kinetics, with rates following the order of PLE (2.0 > 0.5 units/mL) > plasma > PLE (0.2 units/mL). The C_max of LCZ-D and LCZ-L were 13.95 and 5.12 ng/mL, respectively, with corresponding AUC_0–45d values of 6423.12 and 2109.22 h·ng/mL. Formulations containing excipients with lower log P values led to increased systemic exposure. All formulations maintained therapeutic plasma concentrations for over 30 days. The inclusion of the antioxidant BHT (0.03% v/v) improved oxidative stability, reducing degradation at 60 °C from 4.72% to 1.17%. Conclusions: All formulations demonstrated potential for the long-acting delivery of LCZ, maintaining therapeutic plasma levels for over 30 days. Moreover, the release behavior and systemic exposure could be effectively modulated by excipient selection. Full article