Search Results (3,043)

Background/Objectives: Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the ocular conjunctiva. Tacrolimus (TCR), a potent calcineurin inhibitor, is limited by poor aqueous solubility and low ocular bioavailability. This study aimed to develop TCR-loaded cubosomes (TCR-Cubs) incorporated into HPMC/PVP K90 dissolving microneedles (MNs) to enhance their therapeutic efficacy. Methods: TCR-Cubs were prepared using a modified top-down fragmentation method with glyceryl monooleate and poloxamer 407, optimized via Box–Behnken design, and incorporated into dissolving MNs. The system was evaluated in vitro, ex vivo, and in vivo using a rabbit model of allergic conjunctivitis. Results: The optimized formulation exhibited the smallest particle size (210 ± 0.91 nm), polydispersity index (0.29 ± 0.03), zeta potential (−21 ± 0.87 mV), and the highest entrapment efficiency (% 93.3 ± 0.45). The optimized formulation was incorporated into MNs via micro molding. Scanning electron microscopy (SEM) confirmed well-defined, sharp microneedles, with low height reduction (<10%) by mechanical testing and high penetration efficiency (>85–90%). In vitro release studies revealed sustained drug release of (~75–80%) over 24 h, compared to (~40%) from the TCR suspension, following diffusion-controlled kinetics. Ex vivo permeation studies showed a (~2–3-fold) enhancement in corneal drug flux. In vivo pharmacodynamic evaluation using an ovalbumin-induced allergic conjunctivitis model demonstrated significant reductions in inflammatory mediators, including inflammatory markers (TNF-α, IL-1β, IL-6, NLRP3), which were reduced by (~50–75%), with modulation of CPA3, BCL2, and TGF-β1 by qRT-PCR. Histopathology and TLR4 analysis confirmed reduced inflammation without irritation. Conclusions: This dual-delivery system offers a promising, non-invasive platform for enhanced ocular delivery of tacrolimus with superior anti-inflammatory efficacy in allergic conjunctivitis. Full article

Background/Objectives: Progressive collapsing foot deformity (PCFD) is driven by multiplanar peritalar instability. This study evaluated the clinical and radiographic outcomes of a standardized four-component reconstruction protocol designed to facilitate immediate postoperative weight-bearing in Stage 1a/1b PCFD. Methods: This single-center retrospective study included 20 patients treated between 2015 and 2023 with medializing calcaneal osteotomy, spring ligament repair, flexor digitorum longus (FDL) tendon transfer with internal brace augmentation, and subtalar arthroereisis. Clinical (VAS, AOFAS) and radiographic parameters (anteroposterior and lateral Meary angles, calcaneal pitch, and talonavicular coverage angle) were assessed longitudinally, with subgroup analysis comparing implant removal versus retention. Results: The protocol yielded significant overall improvements. Mean VAS decreased by 4.37 points (p < 0.001), and final AOFAS reached 84.7 ± 7.6 at the final follow-up. Although subtalar arthroereisis was removed in 45% of patients due to symptomatic irritation, subgroup analysis revealed no significant loss of radiographic correction (p > 0.05). Notably, a significant interaction effect was observed for VAS scores (p = 0.002) and AOFAS scores (p = 0.041), with the removal group demonstrating a pronounced functional recovery trajectory following explantation. No major complications occurred. Conclusions: A standardized four-in-one reconstruction provides reliable multiplanar correction in Stage 1a/1b PCFD. The maintenance of structural alignment despite a high implant removal rate supports the role of arthroereisis as a temporary but valuable adjunct for early mobilization. This strategy offers a reproducible framework for joint-preserving PCFD management. Full article

Irritable bowel syndrome (IBS) and mental health disorders represent common and significant health concerns in pediatric populations. Objectives: This study aimed to evaluate psychological and social risk factors associated with IBS in children and to identify correlations with their gastrointestinal symptoms. Materials and Methods: Children aged 4 to 18 years diagnosed with IBS according to Rome IV criteria were eligible for inclusion. Both patients and parents completed a comprehensive questionnaire detailing gastrointestinal symptom characteristics. Additionally, all children underwent psychological assessment. Results: The study included 24 children with IBS, with a mean age of 12.7 ± 3.4 years. Anxiety was present in 54.2% of cases, and depression in 12.5%. Comparing children with IBS and anxiety to those without these, no statistically significant differences emerged regarding the duration and frequency of abdominal pain; however, abdominal pain intensity was significantly higher in children without anxiety (p = 0.04). The duration of IBS symptoms did not significantly differ in children with or without anxiety (p = 0.21). Impaired emotional self-regulation was identified in 54.2% of participants, and 41.6% exhibited vegetative symptoms in response to stress. Furthermore, 70.8% of parents and/or children reported experiencing a negative family event. Conclusions: The findings suggest that psychological characteristics and adverse family events are important risk factors associated with pediatric IBS. These factors should be systematically considered as integral components of clinical assessment and management. Full article

Ocular fungal diseases are associated with severe infection and pain and, in advanced stages, can lead to vision loss. Current treatment options are limited to the topical application of conventional drugs, and the bioavailability of these drugs is quite limited due to ocular barriers. In this study, a dual-drug nanodelivery system was developed to improve intraocular drug delivery by combining antifungal and anti-inflammatory therapies. Posaconazole (PSC), a broad-spectrum triazole antifungal agent, and dexketoprofen trometamol (DKP), a rapidly acting nonsteroidal anti-inflammatory drug, were co-loaded onto polymeric micelles and then incorporated into electrospun poly(vinyl alcohol)/poly(vinylpyrrolidone) (PVA/PVP) nanofiber intraocular implants. DSC, XRD, FTIR, and FESEM analyses showed that both APIs were successfully converted into nanofiber form without disrupting the micelle structure. Comparative studies with DKP solution and PSC commercial oral suspension (Noxafil^® 40 mg/mL) showed that the produced micelle-loaded nanofibers provided sustained release and significantly increased ex vivo ocular permeation and penetration. In vitro antifungal activity tests demonstrated efficacy against Candida albicans, and HET-CAM toxicity tests showed that the micelle-loaded nanofibers were non-irritating and suitable for ocular application. Overall, the micelle-loaded electrospun nanofiber ocular inserts developed in this study represent a promising platform for combined antifungal and anti-inflammatory ocular therapy. Full article

Background/Objectives: Compounded vaginal creams are widely used for conditions such as hormone replacement therapy, vaginal dryness, low libido, vaginal infections, etc. Recent research highlights the potential of using anhydrous bases to extend shelf life, particularly when combined with self-emulsifying and mucoadhesive properties that improve mucosal retention and enhance drug bioavailability. This study provides in vitro and ex vivo evaluation of an anhydrous vaginal base. Methods: Key quality indicators such as irritation potential, leakage potential, pH compatibility, mucoadhesion, and self-emulsification were assessed using the chorioallantoic membrane Hen’s Egg Test, MTT assay, texture analysis, and fluorescence microscopy. Results: The anhydrous vaginal base demonstrated high cell viability (>78%) and non-irritant potential (IS = 2.5) in in vitro assays. It maintained physiological vaginal pH (4.56 ± 0.05), showed strong mucoadhesive properties comparable to commercial products, and exhibited minimal leakage. Ex vivo studies confirmed its prolonged retention on vaginal tissues. The anhydrous vaginal base formed stable emulsions upon contact with vaginal fluid simulant, effectively distributing both lipophilic and hydrophilic compounds. Conclusions: Compared to water-containing bases, an anhydrous vaginal base shows advantages: longer retention time and lower leakage; adaptability to varying vaginal fluid levels; and efficient dispersion of both hydrophilic and lipophilic active pharmaceutical ingredients. These features support its potential use in compounded vaginal products, minimizing stability risks and enhancing patient compliance and therapeutic outcomes. Full article

Background/Objectives: Mental fatigue in adolescents is a growing concern in educational contexts, positioning physical education (PE) teachers as key agents in designing effective mitigation strategies. This study examined the perceptions of Spanish high school PE teachers regarding the causes, consequences, and potential countermeasures for students’ mental fatigue. Methods: A total of 116 in-service teachers (81 males and 35 females; mean teaching experience 7.8 ± 5.3 years) from 12 autonomous communities throughout Spain completed a comprehensive 34-item electronic questionnaire. The instrument assessed the perceived existence, etiology, and outcomes of mental fatigue through multiple-choice, dichotomous (yes/no), and five-point Likert scale questions, with particular attention given to the role of physical activity (PA) in symptom alleviation. A quantitative frequency analysis was conducted to examine the data. Results: The main findings reveal a strong consensus among the teachers (77.6% to 87.9%) on the prevalence of mental fatigue, with its primary causes attributed to academic pressure and sedentarism. The consequences were identified as increased irritability and reduced cognitive performance. The teachers overwhelmingly endorsed moderate intensity PA as the most effective countermeasure. However, a significant gap was identified between this theoretical awareness and the systematic implementation of targeted strategies within schools. Conclusions: These results underscore the critical need for professional development programs and structural support to translate teacher knowledge into practical intervention, suggesting important directions for future research. Full article

Background: While previous studies indicate an association between chest pain and favorable clinical outcomes in patients with pulmonary embolism (PE), the extent and underlying mechanisms of this effect remain inadequately defined. Methods: We investigated the prognostic value of chest pain with regard to in-hospital adverse outcomes and the association of chest pain with age and sex in consecutive patients with confirmed PE enrolled in a single-center registry between 2008 and 2019. Results: Of 858 patients (52% female) included in this study, 435 (51%) had chest pain at presentation. Chest pain was more prevalent in younger individuals aged 18–34 years (74%) compared to patients >34 years (46%). The prevalence of coronary artery disease (CAD) was similar in patients with and without chest pain (17.0% vs. 16.1%). Chest pain patients less frequently presented with elevated troponin levels (p < 0.001) or signs of right heart strain (RHS; p = 0.007) but more frequently exhibited imaging signs of pulmonary infarction (p = 0.001). Chest pain was associated with lower risk of adverse outcome (OR 0.35 [95% CI: 0.19–0.65]) and in-hospital mortality (OR 0.31 [95% CI: 0.13–0.74]). Multivariable models confirmed a prognostic effect independent of sex, comorbidities and results of risk stratification algorithms. Conclusions: In acute PE, chest pain is a favorable prognostic marker irrespective of sex. Chest pain patients are less likely to suffer from myocardial ischemia or show signs of RHS but more frequently show imaging signs of pulmonary infarction, suggesting pleuritic irritation rather than myocardial ischemia as the likely cause of pain. Full article

Background: Plant-derived essential oils possess valuable bioactivities, but their application is limited by volatility and irritation, which may be addressed through natural polymer encapsulation. This study aimed to investigate the bioactivity of Hedychium coronarium rhizome essential oil and evaluate the effect of microencapsulation on its physicochemical characteristics, biological stability, and irritation profile. Methods: Essential oil was extracted from H. coronarium rhizomes by hydrodistillation and chemically characterized. Enzyme inhibitory activities against elastase, hyaluronidase, and tyrosinase were assessed. Microencapsulation was performed using gum Arabic or maltodextrin at 1–5% w/w oil loadings. The resulting powders were evaluated for morphology, entrapment efficiency, hygroscopicity, water activity, biological stability, and irritation potential using the hen’s egg test on the chorioallantoic membrane. Results: The essential oil demonstrated strong enzyme inhibition, particularly against hyaluronidase (IC₅₀ = 0.1 ± 0.0 µg/mL), along with notable elastase and tyrosinase inhibition. Encapsulation significantly reduced irritation scores from 13.3 ± 1.4 for the free oil to 3.6–4.2 for encapsulated systems (p < 0.05). Gum Arabic produced rough, porous particles with lower hygroscopicity, while maltodextrin yielded smoother particles with lower water activity. Both encapsulated powders significantly enhanced biological stability compared with the ethanolic solution. Conclusions: Natural polymer-based microencapsulation effectively reduced the irritation potential and improved the handling properties of H. coronarium essential oil, supporting its potential application in topical bioactive delivery systems. Full article

Massage relieves stress and anxiety, but also helps to reduce musculoskeletal problems, decreasing tension, in all stages of life. For pediatric use, organoleptic properties, cosmetic safety and user acceptability of topical products are important given the higher frequency of irritative or allergic episodes in young skin. We evaluate for the first time the comprehensive cosmetic performance of Physiorelax Forte Plus natural formulation in cream, spray and roll-on applied regularly in healthy and active children/adolescents. 210 healthy volunteers were included (150 adults with sensitive skin and 60 children and adolescents [6–16 years]). This three-part, sequential, observational, non-comparative pilot design monitored user experience under real-world conditions: (I) Open-label testing to assess skin compatibility in adults (N = 60); (II) In-use testing in adults for cosmetic acceptability and safety over 14 days (N = 90); (III) In-use testing in children/adolescents for 14 days (N = 60). Outcomes were dermatological assessments for tolerability and user (and/or parents/caregiver(s)-reported) satisfaction/acceptability and perceived benefits. No control group or objective efficacy measures were included. Among pediatric participants, no cutaneous reactions were observed at application sites after 14 days of use. Proxy reporting about consumer satisfaction and acceptability for the range were generally high. Principal component analysis revealed a clear three-cluster structure (sensory, functional, practicality), with roll-on driving the strongest differentiation across items and spray aligning most closely with sensory attributes, while cream showed an intermediate functional profile. The Physiorelax Forte Plus range demonstrated a favorable cosmetic safety profile and consumer acceptability in pediatric use under real-world conditions. Findings are limited by the observational, unblinded design, absence of a control group, and reliance on subjectively reported outcomes; no clinical or pharmaceutical claims are implied. Future controlled studies incorporating objective dermatologic endpoints, benchmark products, and direct child/adolescent reporting are warranted. Full article

New benzazole–sesamol derivatives 6a–8c were synthesized via an easily accessible reaction based on the coupling of Sesamol with in situ generated electrophilic N-alkoxycarbonylbenzazolium ions. This strategy successfully integrated benzothiazole, benzimidazole, and 5,6-dimethylbenzimidazole fragments with the biologically active natural lignan Sesamol. The structural integrity and the specific position of the newly formed C–C bond was confirmed by ¹H-, ¹³C{¹H}-, HSQC-NMR, FTIR, and HRMS analyses. The obtained compounds with yields in the range of 71–95% were evaluated for their in vitro radical scavenging activity and subjected to in silico predictions of mutagenicity and toxicity. Radical scavenging activity studies demonstrate that the introduction of a benzothiazoline ring (compounds 6a and 6b) enhances radical scavenging activity compared to Sesamol in the DPPH assay, outperforming the benzimidazole analogues. In silico analyses identified compounds 7b, 7c, 8a, 8b, and 8c as promising molecules due to the absence of mutagenic and irritant effects and their low toxicity profiles. In particular, compounds 7a, 7b, and 8a were found to be significantly safer than Sesamol. Compound 7a exhibited the highest safety profile, characterized by an LD₅₀ value of 3046.92 mg/kg. Full article

Purpose: The objective of this study was to engineer and optimize a mucoadhesive, positively charged stearylamine-enriched liposomal platform, termed Aminosomes, to circumvent the biophysical barriers limiting the ocular bioavailability of Brimonidine Tartrate (BT), an alpha-2 adrenergic receptor agonist for glaucoma management. Methods: Aminosomes were synthesized using a tailored ethanol injection technique and optimized via a 3² × 2¹ full factorial design. Molecular integrity and crystallinity were assessed using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The mucoadhesive potential was validated through a mucin interaction assay based on zeta potential shifts. In vitro release kinetics were evaluated using the dialysis membrane diffusion technique, while the therapeutic potential and ocular safety were validated through in vivo pharmacodynamic profiling of intraocular pressure (IOP) reduction, alongside comprehensive biocompatibility assessments via Draize irritancy protocol and histopathological examination. Results: The optimized Aminosomes exhibited nanometric dimensions, monodisperse size distribution, robust positive surface charge, and superior drug loading. FTIR and XRD analyses confirmed the chemical compatibility of the formulation components, as well as the successful encapsulation of BT and its transition to an amorphous state within the lipidic matrix. The mucoadhesion test demonstrated a high binding affinity for mucin. The in vitro release profile demonstrated a sustained-release pattern (78.8% over 12 h). Non-compartmental pharmacodynamic analysis of IOP-reduction data revealed a 2.8-fold increase in AUC_0–24h, 3.5-fold extension in t_1/2, and 5.2-fold prolongation in mean residence time (MRT) relative to the standard solution. Conclusions: The optimized Aminosomes demonstrated superior mucoadhesive anchoring, enhanced and sustained therapeutic flux without inducing ocular toxicity, offering a robust strategy for enhancing the pharmacodynamics of BT. Full article

Vulvodynia is a chronic gynecological condition characterized by unexplained vulvar pain, which may significantly impact every aspect of women’s quality of life, encompassing physical, psychological, and social well-being. Due to its heterogeneous clinical presentation and associated comorbidities, vulvodynia is often misdiagnosed and/or not adequately treated. This descriptive observational study was conducted using an anonymous questionnaire, which was distributed through social media channels and included 29 questions (25 multiple-choice and four open-ended questions) and aimed to investigate participants’ most frequent symptoms, comorbidities, impact on quality of life, and treatment efficacy and costs. Analyzing a total of 221 answers, we found that burning (85%) and abrasion/irritation sensation (73%) are the most common symptoms, and they are most frequently localized in the vestibular area, while irritable bowel syndrome (35%) is the most common comorbidity. A significant negative effect on individual functioning was confirmed, also due to a noticeable diagnostic delay (4.5 years on average) and treatments’ prohibitive costs potentially impairing participants’ compliance. Our study provides valuable insights into self-reported aspects of women affected by vulvodynia, raising healthcare professionals’ awareness of this issue. Better knowledge of peculiar aspects of vulvodynia may help improve its diagnosis and promote a more personalized and efficient therapeutic approach. Full article

Endometriosis affects a large number of women of reproductive age, and its pathogenesis is still unclear. It causes severe chronic pelvic pain, which is often misdiagnosed as irritable bowel syndrome, or other disorders. Metabolomics and transcriptomic approaches enable the study of changes in various physiological or pathological pathways to identify new potential biomarkers. We employed gas chromatography–mass spectrometry (GC–MS) to investigate metabolic alterations, and quantitative real-time polymers-chain reaction (RT-qPCR) to assess changes in miR-451a and miR-125b in saliva in endometriosis. Serum and saliva samples of patients with symptomatic endometriosis and volunteers without it were collected and subjected to GC–MS and qPCR-RT analysis, respectively. Multivariate and univariate statistical analyses were performed. Orthogonal partial least squares discriminant analysis has shown the differences between the two groups. Eicosadienoic acid, arachidonic acid, and miR-451a increased significantly in endometriosis patients. Machine learning methods were used to build the predictive model, which can be used in early low-invasive diagnostics of endometriosis. Receiver operating characteristics analysis has tested the diagnostic power of metabolites. The combination of metabolic and microRNA profiling may improve our knowledge of the pathophysiological and signaling mechanisms in endometriosis and the discovery of new efficient biomarkers of endometriosis. Full article

Many female athletes experience menstrual cycle issues. We investigated clary sage (Salvia sclarea L.) essential oil inhalation’s effect on dysmenorrhea-related symptoms, antioxidant capacity, and salivary hormone levels in female collegiate athletes. This randomized crossover trial included 20 female collegiate athletes (mean age: 20.2 ± 1.2 years). The participants were randomly assigned to one of two conditions: clary sage essential oil (intervention) or water (control) inhalation. Each condition lasted for one menstrual cycle, with inhalation administered at bedtime for 60 min using a diffuser. Dysmenorrhea-related symptoms and their impact on athletic performance were assessed using a visual analog scale. Biochemical analyses included salivary antioxidant capacity and cortisol, estradiol, and progesterone level measurements. Data from 12 participants who completed the study were analyzed. Compared with water inhalation, clary sage essential oil inhalation significantly reduced menstrual pain, sleep disturbances, irritability, and anxiety (all p < 0.05). The impact of dysmenorrhea-related symptoms on performance and total symptom scores was also significantly lower in the intervention condition than in the control condition (both p < 0.05). Additionally, salivary antioxidant capacity was significantly higher following clary sage essential oil inhalation than after water inhalation (p < 0.05). However, no significant differences were observed in the salivary cortisol, estradiol, or progesterone levels between the intervention and control conditions. Clary sage essential oil inhalation may be an effective nonpharmacological approach for alleviating dysmenorrhea-related symptoms and enhancing antioxidant capacity in female collegiate athletes. The results highlight its potential as a noninvasive and easy-to-use daily method for managing menstrual symptoms. Full article

Quantitative sensory testing (QST), including temporal summation of pain (TSP) and pressure pain threshold (PPT) assessments, was conducted to evaluate the diagnostic validity and immediate therapeutic efficacy of the manual therapy technique Fascial Counterstrain (FCS). A single patient with persistent lower back and referred leg pain was evaluated and treated by a certified FCS practitioner. A clinical diagnosis of left S1–S2 radiculitis (FCS criteria) was established and corroborated by elevated pre-treatment TSP and reduced PPT measures in the affected dermatomes, indicating nerve root irritation and central sensitization. Immediate post-treatment TSP and PPT assessments demonstrated near-complete normalization of wind-up in the involved S1 and S2 dermatomes, along with a substantial improvement in three-trial-average PPT measurements of the S1–S2 musculature from 2.4 kg/cm² to 6.1 kg/cm². This case report provides preliminary evidence supporting the diagnostic process and immediate post-treatment efficacy of FCS in patients with lower back pain and central sensitization. Full article