Search Results (129)

Background: In pediatric practice, dose individualization often requires the manipulation of solid oral dosage forms, such as dispersing capsules in water and administering only part of the volume. Despite its frequent use, this practice is poorly documented and may lead to inaccurate dosing. Objectives: This study aimed to assess the actual dose administered when compounded hard gelatin capsules are dispersed in water and partially withdrawn, and to evaluate the influence of different manipulation protocols on dose recovery. Methods: Ten active pharmaceutical ingredients (APIs) routinely compounded as pediatric hard gelatin capsules were studied. Content uniformity was first verified according to European Pharmacopoeia (EP) requirements. One capsule was dispersed in 2 mL of water, and 1 mL was withdrawn using three protocols: (1) no mixing, (2) gentle manual mixing with immediate sampling, and (3) gentle manual mixing followed by a 10 s resting period before sampling. Drug content in the withdrawn volume was quantified using validated HPLC-UV methods. Results are expressed as the mean percentage of the theoretical dose ± standard deviation. Results: All capsules complied with EP content uniformity criteria. However, partial volume administration resulted in marked and protocol-dependent deviations from the theoretical dose. Without mixing, recovered doses ranged from 17% to 58% of the target dose, with high variability. Gentle mixing improved dose recovery, particularly for APIs forming solutions, such as captopril, thiamine hydrochloride, and clonidine hydrochloride, which achieved values close to 90%. In contrast, APIs forming suspensions consistently resulted in underdosing, even after mixing, with further reductions observed after a short resting period, indicating rapid sedimentation. Conclusions: Fractional administration of dispersed hard gelatin capsules leads to unpredictable and often clinically relevant underdosing, especially for poorly soluble APIs. Whenever possible, capsules should be compounded at the prescribed dose, and liquid formulations should be preferred when dose fractionation is required. Full article

The solubilization of poorly water-soluble drugs remains a critical challenge in pharmaceutical research. The formulation of solid dispersions employing mesoporous silica nanoparticles (MSN) constitutes a key strategy for enhancing the hydrophilicity and oral bioavailability of Biopharmaceutics Classification System (BCS) Class II drugs. Although several commercial mesoporous silica excipients have been approved for pharmaceutical use, there remains room for improvement regarding drug loading capacity, stability, and controllability of drug release. Methods: for this purpose, dendritic mesoporous silica nanoparticles (DMSN) with a radial dendritic structure and pH-responsive degradation properties were designed and synthesized using celecoxib (CEL) as the model drug, featuring a pore size of 21.51 nm. CEL was loaded onto DMSN and seven commercial solid dispersion excipients using the solvent evaporation method. Results: owing to its high surface area, pore volume, and radial structure, DMSN achieved 39.72% drug loading in an amorphous state, markedly improving wettability, dissolution, and physical stability. Accelerated stability tests showed that DMSN inhibited recrystallization, outperforming traditional solid dispersions. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of CEL-DMSN was 1.29-fold higher than that of commercial celecoxib capsules. Conclusions: in conclusion, these results confirmed the potential of DMSN in enhancing the stability, promoting oral absorption, and reducing gastrointestinal irritation of poorly soluble drugs. Full article

Orchid pollination is traditionally considered to rely on intact pollinarium transfer by animal vectors. Species lacking a functional viscidium are generally classified as obligately autogamous. In this study, we investigated the reproductive biology of Epipactis bugacensis, a taxon long regarded as strictly self-pollinating. Floral visitor activity was assessed through repeated field observations, and pollinator dependence was tested using a pollinator-exclusion (net-covering) experiment at two Hungarian populations, combined with measurements of fruit set, capsule volume, seed number, and seed density. We documented a previously unreported pollen-transfer mechanism in E. bugacensis, whereby halictid bees fragment pollinia and transfer these fragments in their scopa to neighboring flowers enabling geitonogamous deposition and suggesting the potential for xenogamous pollen transfer. Other visitor taxa showed no evidence of effective pollen transport. Mesh coverage increased fruit set, capsule volume, and seed number, while seed density remained unchanged. Reproductive output declined from basal to apical positions along flowering shoots, revealing strong internal resource-allocation constraints. Overall, E. bugacensis is predominantly self-pollinating but not strictly obligate autogamous, and its reproductive success is governed primarily by microhabitat quality rather than pollinator availability. Full article

The aims of this study were to evaluate the impact of probiotics (added as a starter sourdough and microcapsules) on gluten-free (GF) rice–amaranth steamed bread (SB) regarding physicochemical characteristics, sensory attributes, probiotic viability, and volatile organic compounds (VOCs). Also, probiotic viability, pH, total titratable acidity (TTA), moisture content, water activity, and texture were determined for 10 days of storage. GF-SB based on rice and amaranth was formulated and cooked at 90 ± 2 °C for 40 min. Three types of GF-SB were studied: control, with 30% sourdough fermented using Lactiplantibacillus plantarum NRRL B-4496 (GF-P), and with sourdough and encapsulated Limosilactobacillus reuteri DSM 17938 (GF-PC). The encapsulation yield was 94.9%. The viability of both probiotics was drastically reduced after steamed cooking, with losses ranging from 6 to 8 log₁₀ CFU/g. Sourdough decreased the pH (from 6.04 to 5.48–5.71) and hardness (control 46 N, sourdough ~25 N) while increasing lactic and acetic acids, moisture content (control 38%, sourdough ~46%), and water activity. Sourdough and probiotic capsules did not affect volume (~1.24 cm³/g), width-to-height ratio (~2.4), color, or sensory attributes. The VOCs revealed higher relative abundances of certain yeast-derived higher alcohols and oxidation-related carbonyl-trapping derivatives in control GF-SB, whereas bread with sourdough showed higher levels of long-chain hydrocarbons and esters, such as heptacosane and decanoic acid decyl ester. During the storage, Lpb. plantarum increased to ~3 log₁₀ CFU/g and Lim. reuteri remained steady. pH and TTA (0.03–0.04%) remained constant during storage. After 10 days of storage, hardness increased significantly (p < 0.05) in all GF-SB, doubling the initial values. Moisture content remained constant, while water activity decreased in GF-P (Δ = 0.025) and the control (Δ = 0.015). The use of sourdough in GF-SB improved texture, moisture content, and VOCs without modifying physical and sensory properties. Full article

Background/Objectives: The COVID-19 pandemic profoundly disrupted gastric cancer care, reducing access to screening, delaying diagnosis, and altering therapeutic pathways worldwide. Beyond clinical challenges, it exposed structural weaknesses in healthcare systems but also accelerated innovation. Methods: We conducted a narrative review supported by a structured literature search (PubMed/MEDLINE, Scopus, Web of Science; 1 January 2014–30 November 2025), with a narrative synthesis of observational studies, registry analyses, and meta-analyses addressing COVID-19–related changes in gastric cancer epidemiology, diagnosis, treatment, vaccination, and telemedicine. A PRISMA-style flow diagram was used to illustrate study selection. Results: Elective endoscopy volumes fell by up to 80%, leading to diagnostic backlogs and increased proportions of advanced-stage gastric cancer. Surgical postponements, modified chemotherapy and radiotherapy schedules, and reduced molecular/genetic testing further compromised outcomes. Conversely, vaccination, telemedicine, capsule endoscopy, and adaptive triage frameworks enabled partial recovery of services. Geographical variations were observed in the recovery of gastric cancer care services, with regions that had established screening infrastructure generally resuming activity more rapidly, whereas others experienced ongoing delays and diagnostic backlogs. Conclusions: This review integrates epidemiological, diagnostic, and therapeutic evidence to demonstrate how COVID-19 redefined gastric cancer care. By highlighting regional disparities and outlining a conceptual model for oncologic resilience, it provides an innovative framework for future crisis preparedness. The lessons of the pandemic—digital health integration, flexible treatment protocols, and international collaboration—represent a foundation for more robust, equitable gastric cancer management in the post-pandemic era. Full article

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, characterized by persistent inattention, hyperactivity, and impulsivity. This narrative review aims to synthesize and critically evaluate recent large-scale magnetic resonance imaging (MRI) studies to clarify the neuroanatomical and functional brain alterations associated with ADHD in children. By addressing current gaps in understanding, this work seeks to identify reliable neurobiological markers that could improve diagnostic accuracy and guide personalized interventions. The literature reveals that large-scale structural MRI studies consistently report abnormal development in total cortical volume and surface area, prefrontal cortex volume, and basal ganglia volume in children with ADHD. Moreover, gray matter alterations show significant age-dependent effects, with the degree of impairment potentially serving as neurobiological markers. Diffusion magnetic resonance imaging studies reveal disrupted white matter microstructures in regions such as the left uncinate fasciculus, superior and inferior longitudinal fasciculi, corpus callosum, cingulum, and internal capsule. Importantly, these white matter abnormalities often persist into adulthood, highlighting their clinical relevance. Functional MRI findings indicate reduced global connectivity within core hubs of the default mode network in children with ADHD. Furthermore, deficits in inhibitory control identified via fMRI may represent one of the neurofunctional signatures that differentiates ADHD from typically developing controls. By consolidating evidence from large-scale multimodal MRI studies, this review provides a comprehensive understanding of the neurodevelopmental alterations in ADHD and underscores their potential utility for improving diagnosis and treatment. Full article

Background: Recent research suggests that damage to right hemisphere regions homotopic to the left hemisphere language network affects language abilities to a greater extent than previously thought. However, few studies have investigated acute disruption of language after lesion to the right hemisphere. Here, we examined lesion correlates of acute speech deficits following left and right hemisphere ischemic stroke to clarify the neural architecture underlying early language dysfunction. Methods: We retrospectively analyzed 410 patients (225 left, 185 right hemisphere lesions) from the Stroke Outcome Optimization Project dataset. Presence and severity of speech deficits was measured using the National Institute of Health Stroke Scale Best Language subscore within 48 h of onset. Manual lesion masks were derived from clinical MRI scans and normalized to MNI space. Lesion-symptom mapping was conducted using voxelwise and region-of-interest analyses with permutation correction (5000 iterations; p < 0.05), controlling for total lesion volume. Results: Speech deficits were observed in 53.7% of the cohort (58.2% left, 48.1% right hemisphere lesions). In the full sample, the presence of speech deficits was associated with bilateral subcortical and perisylvian damage, including the external and internal capsules, insula, putamen, and superior fronto-occipital fasciculus. Severity of speech deficits localized predominantly to left hemisphere structures, with peak associations in the external capsule (Z = 6.39), posterior insula (Z = 5.64), and inferior fronto-occipital fasciculus (Z = 5.43). In the right hemisphere cohort, the presence and severity of speech deficits were linked to homologous regions, including the posterior insula (Z = 3.70) and external capsule (Z = 3.63), although with smaller effect sizes relative to the left hemisphere cohort. Right hemisphere lesions resulted in milder deficits despite larger lesion volumes compared with left hemisphere lesions. Conclusions: Acute speech impairment following right hemisphere stroke is associated with damage to a homotopic network encompassing perisylvian cortical and subcortical regions analogous to the dominant left hemisphere language network. These findings demonstrate that damage to the right hemisphere consistently results in acute speech deficits, challenging the traditional left-centric view of post-stroke speech impairment. These results have important implications for models of bilateral language representation and the neuroplastic mechanisms supporting language recovery. Full article

Background/Objectives: Breast cancer remains a major cause of cancer-related mortality among women worldwide, highlighting the need for new therapeutic strategies. Pyrimidine derivatives have shown promise in oncology due to their ability to modulate immune responses and influence tumor growth pathways. Methods: Cytotoxicity of Xymedon was evaluated using MTT and colony formation assays on cancer MCF-7, NCI-H322M, HCT-15 cells, and primary human foreskin fibroblasts. In vivo efficacy was assessed in an orthotopic MCF-7 xenograft model in female Balb/c nude mice. Xymedon was administered orally at 410 mg/kg daily alone or in combination with intraperitoneal doxorubicin (1 mg/kg weekly). Hematological, histological, and immunohistochemical analyses were performed. Results: In vitro, Xymedon (up to 3 mM) showed no cytotoxicity against cancer cell lines or human skin fibroblasts. In vivo, Xymedon significantly increased tumor necrosis (44.1% vs. 28.5%, p < 0.01) and enhanced intratumoral infiltration of CD3+, CD8+, and CD20+ lymphocytes, with peritumoral counts increasing 2.2–5.3-fold. It mitigated Doxorubicin-induced myelosuppression by improving red blood cell counts, hemoglobin, and hematocrit levels, while platelet recovery remained limited. Combination therapy with Xymedon did not affect tumor volume or weight, but resulted in a non-significant trend toward improved survival (80% vs. 30%, p ≈ 0.11; Hazard Ratio [HR] = 0.268, 95% CI: 0.07082 to 1.012) without affecting fibrous capsule formation. Conclusions: These results suggest that Xymedon is a non-cytotoxic immunomodulator with potential as an adjuvant to enhance antitumor immunity and reduce hematologic toxicity associated with chemotherapy. Further studies are needed to elucidate the molecular pathways and confirm clinical efficacy. Full article

Background/Objectives: Anterior segment optical coherence tomography (AS-OCT) is a non-invasive imaging modality used to evaluate anterior segment features. This report aims to inform clinicians of best practices to obtain high-resolution AS-OCT images of anterior segment features of eyes implanted with the Port Delivery Platform (PDP). Methods: In PDP trials, AS-OCT imaging of the anterior segment was performed using Heidelberg Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) equipped with the Anterior Segment Module. Images from over 2500 separate study visits were obtained using standardized imaging parameters. The following stepwise approach was recommended to properly orient the volume scans over the extrascleral flange of the PDP ensuring that the scans are centered on the implant with adequate depth: (1) the volume scan was aligned such that: (i) the long axis of the scan was oriented parallel to the implant flange long axis, (ii) the imaging field was centered on the implant septum center, and (iii) it covered the entirety of the implant, with equal margins on either side of the implant flange; (2) the depth of the scan focus was adjusted to ensure that the conjunctiva and Tenon’s capsule over the overmold, as well as sclera under the implant flange, and the septum of the implant, were captured; and (3) Steps 1 and 2 were then repeated after the scan orientation was changed so that the short-axis scans were oriented parallel to the implant flange short axis. Results: Utilization of AS-OCT during clinical development of the PDP allowed visualization of anterior segment features, including the conjunctiva, Tenon’s capsule, and sclera, surrounding the PDP. Overall, these best practices enabled detailed structural imaging of the implant’s interface with surrounding ocular tissues. Common errors resulting in poor AS-OCT image acquisition included off-center raster scans, scans not being aligned parallel to the long and/or short axes of the PDP implant, or not being oriented along the implant axes, and inappropriate scan depths. Conclusions: Application of a standardized AS-OCT imaging procedure was used to obtain high-quality, high-resolution images of anterior segment features in the presence of the PDP implant. The best practices reported are not a requirement for managing eyes with the PDP, but a recommendation for how to obtain high-quality images of the anterior segment of eyes with the PDP implant. Full article

Background: Rhodiola rosea (RR) is marketed as an adaptogen; however, evidence for acute/short-term effects—and especially dose–response effects—in trained adults across performance and cognition is limited. Objective: Test whether RR improves resistance performance (strength, power) and executive function in resistance-trained adults using a randomized crossover with placebo and a capsule-free baseline. Methods: In a randomized, double-blind, crossover trial with four conditions—no-capsule control (CON), placebo (PL), low-dose RR (LDRR), and high-dose RR (HDRR). Twenty-seven resistance-trained adults completed the conditions. Day-7 testing included bench press (BP) and leg press (LP) 1-repetition maximum (1RM); a third set to failure at 60% 1RM with set-3 volume; Tendo mean/peak power; a 30 s Wingate; and the Stroop Color–Word Test. Secondary endpoints were Rating of Perceived Exertion (RPE), Readiness to perform using a Visual Analog Scale (VAS), and hemodynamics. Results: Versus CON, LDRR increased BP 1RM (+5.59 kg; p = 0.003), set-3 repetitions (+4.30; p < 0.001), set-3 volume (+168.6 kg; p < 0.001), and mean power (+29.7 W; p = 0.026). HDRR increased set-3 repetitions (+2.78; p = 0.005) and peak power (+34.2 W; p = 0.026), with a trend for set-3 volume (p = 0.086). LP 1RM exceeded CON with LDRR (+35.7 kg; p < 0.001) and HDRR (+47.7 kg; p < 0.001); contrasts vs. PL were significant. Wingate outcomes showed no consistent effects. Stroop improved vs. CON across all sections: Word +10.5 to +17.4 counts (p < 0.05), Color +6.1 to +12.0 (p ≤ 0.03), and Color–Word +10.2 to +18.9 (p < 0.001). Conclusions: Short-term RR consumption, regardless of dose or gender, improved resistance performance and significantly enhanced Stroop outcomes, with minimal changes in anaerobic cycling and RPE, and no consistent acute hemodynamic effects. Full article

Background and Objectives: The anesthetic nerve block test is a surgical technique that can assist in the differential diagnosis of forefoot pain. The MTP joint, enclosed by its capsule, may act as a sealed cavity with predictable contrast dispersion, whereas the IM space, lacking clear boundaries and containing bursae and the plantar digital nerve, favors diffuse spread. Due to the high rate of false positives in suspected cases of Morton’s neuroma with the anesthetic block current procedure in the intermetatarsal space, the aim of this study was to propose an alternative to the current procedure. Material and Methods: Six fresh cadaveric feet were used. Under ultrasound guidance, the 2nd–4th MTP joints received stepwise intra-articular injections of radiopaque contrast. The third common digital nerve was injected within the third intermetatarsal space. Standard radiographs were obtained to assess distribution and proximal spread. Results: A volume of 0.3 mL was sufficient to fully reach the intra-articular cavity and potentially induce effective localized anesthesia. When the third common digital plantar nerve was injected in an anatomically healthy region, the contrast medium showed a proximal diffusion pattern extending up to the mid-diaphyseal level of the third and fourth metatarsal bones. On radiographs, the intra-articular infiltration lines appear sharply demarcated, supporting the interpretation of the metatarsophalangeal joint as a sealed compartment. Conclusions: Low intra-articular anesthetic volumes may yield targeted effects, while Morton’s neuroma injections spread proximally, risking loss of diagnostic specificity; this technique may improve decision-making accuracy and reduce failures. Full article

Background/Objectives: Adnexal masses are commonly encountered in the routine practice of gynecologists, and transvaginal ultrasonography is the preferred imaging modality for assessing the masses in size and complexity. There has been a notable lack of focus on comparative studies concerning benign adnexal tumors. This study aimed to define and compare the specific morphological and vascular characteristics of ovarian mature cystic teratomas (MCTs) and endometriomas using transvaginal ultrasound and Doppler analysis. Methods: This retrospective analysis included 93 patients who underwent surgical intervention for benign adnexal masses at the Obstetrics and Gynecology Clinic Narodni Front from 1 January 2020 to 1 January 2022. Morphological parameters included the appearance of tumors, the largest diameter, volume, capsule thickness, and the presence of fluid in the pouch of Douglas. Hemodynamic parameters included the localization and quantity of blood vessels within the mass, Resistance Index (RI), peak systolic velocity (Vmax), and end-diastolic velocity (Vmin) within detectable tumor vessels. Flow was also assessed in the uterine arteries, calculating the AURI (uterine artery RI) on both the tumor and contralateral sides. Results: There were 46 patients with ovarian mature cystic teratomas, as well as 46 patients with endometriomas; 1 patient presented with both tumors. There were significant differences in ultrasonographic morphological appearance between the two groups. MCTs most frequently presented as multilocular solid cysts (51.0%) or unilocular solid cysts with hyperechoic content (20.4%). Conversely, the majority of endometriomas were classified as unilocular cysts with ground-glass echogenicity (45.5%). A significant difference was identified in the RI of intracystic vessels and the RI of the ipsilateral uterine artery (AURI). Endometriomas presented elevated RI values (0.57 vs. 0.54, p = 0.04) and reduced AURI (0.81 vs. 0.83, p = 0.02) compared to teratomas. Conclusions: These findings confirm that specific morphological and Doppler parameters, particularly the RI and AURI, can assist in distinguishing between endometriomas and mature cystic teratomas. This suggests a potential role for Doppler analysis in improving diagnostic precision for common benign adnexal tumors in clinical practice. Full article

Deeply implanted biomedical devices like leadless pacemakers require an antenna with minimal volume and high radiation efficiency to ensure reliable in-body communication and long operational time within the human body. This paper introduces a novel implantable antenna designed to significantly reduce the spatial requirements within an implantable capsule while maintaining high radiation efficiency in lossy media like heart tissue. The design principles of the proposed antenna are outlined, followed by antenna parameters and an equivalent circuit study that demonstrates how to fine-tune the antenna’s resonant frequency. The radiation characteristics of the antenna are thoroughly investigated, revealing a radiation efficiency of up to 28% at the Medical Implant Communication System (MICS) band and 56% at the 2.4 GHz ISM band. The transmission efficiency between two deeply implanted antennas within heart tissue has been improved by more than 15 dB compared to the current state of the art. The radiation and transmission performance of the proposed antennas has been validated through comprehensive simulations using anatomical human body models, phantom measurements, and in vivo animal experiments, confirming their superior radiation performance. Full article

Cataract surgery is the most common eye operation worldwide and is regarded as one of the safest procedures in medicine. Yet, despite its low complication rates, it generates a disproportionate share of litigation. The gap between excellent safety profiles and rising medico-legal claims is driven less by surgical outcomes than by patient expectations, often shaped by healthcare marketing and the promise of risk-free recovery. This narrative review explores the clinical and legal dimensions of cataract surgery, focusing on complications, perioperative risk factors, and medico-legal concepts of predictability and preventability. Particular emphasis is given to European frameworks, with the Italian Gelli-Bianco Law (Law No. 24/2017) providing a model of accountability that balances innovation and patient safety. Analysis shows that liability exposure spans all phases of surgery: preoperative (inadequate consent, poor documentation), intraoperative (posterior capsule rupture, zonular instability), and postoperative (endophthalmitis, poor follow-up). Practical strategies for risk reduction include advanced imaging such as macular OCT, rigorous adherence to updated guidelines, systematic video recording, and transparent perioperative communication. Patient-reported outcomes further highlight that satisfaction depends more on visual quality and dialogue than on spectacle independence. By translating legal principles into clinical strategies, this review offers surgeons actionable “surgical–legal pearls” to improve outcomes, strengthen patient trust, and reduce medico-legal vulnerability in high-volume cataract surgery. Full article

Bone marrow-derived mononuclear cells (BMMCs) have shown beneficial effects on tissue repair, largely attributed to the paracrine action of bioactive mediators such as lysophosphatidic acid (LPA). This study aimed to evaluate the effects of BMMC treatment in a rat model of renal ischemia/reperfusion (I/R) injury, focusing on LPA-related molecular pathways. Male Wistar rats were divided into three groups: control; I/R, subjected to bilateral renal artery clamping for 30 min followed by 24 h of reperfusion; and I/R + BMMC, which received 1 × 10⁶ BMMCs per kidney directly into the renal capsule post-ischemia. During reperfusion, the rats were placed in metabolic cages for urine collection, renal function and protein expression. BMMC treatment did not reverse the I/R-induced increase in urine volume or decrease in glomerular filtration rate, serum potassium, or filtered sodium load. However, it prevented proteinuria, increased blood urea nitrogen, and enhanced urinary potassium excretion. Mechanistically, BMMC treatment prevented I/R-induced upregulation of LPAR1, downregulated LPAR2 and LPAR3, restored plasma LPA levels, and reduced renal autotaxin content. These results suggest that BMMCs modulate harmful LPA-related signaling and may contribute to renal protection through paracrine mechanisms in the setting of acute I/R injury. Full article