Search Results (139)

Cystic fibrosis (CF), the most common hereditary lung disease in Caucasians, is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). We evaluated CFTR function using a newly developed Ussing chamber system, the Multi Trans Epithelial Current Clamp (MTECC), in an in vitro model of human airway epithelia. Air–liquid interface (ALI) cultures were established from nasal brushings of healthy controls (HC) and CF patients with biallelic CFTR variants. ALI layer thickness was similar between groups (HC: 62 ± 13 µm; CF: 55 ± 9 µm). Immunofluorescence showed apical CFTR expression in HC, but reduced or absent signal in CF cultures. MTECC enabled continuous measurement of transepithelial resistance (Rt), potential difference (PD), and conductance (G_t). G_t was significantly reduced in CF cultures compared to HC (0.825 ± 0.024 vs. −0.054 ± 0.016 mS/cm²), indicating impaired cAMP-inducible ion transport by CFTR. Treatment of CF cultures with elexacaftor, tezacaftor, and ivacaftor (Trikafta^®) increased G_t, reflecting partial restoration of CFTR function. These findings demonstrate the utility of MTECC in detecting functional differences in CFTR activity and support its use as a platform for evaluating CFTR-modulating therapies. Our model may contribute to the development of personalized treatment strategies for CF patients. Full article

Cystic Fibrosis Screen Positive Inconclusive Diagnosis/CFTR-related Metabolic Syndrome (CFSPID/CRMS) presents a significant clinical challenge due to its variable diagnostic outcomes and uncertain disease progression. Current diagnostic strategies, including sweat chloride testing and genetic analysis fall short in delivering clear guidance for clinical decision-making and risk assessment. Here, we comment on the potential of CFTR functional tests in patient-derived intestinal organoids (PDIOs) to enhance early risk stratification in CFSPID/CRMS cases. Using four hypothetical cases based on real-world data, we illustrate diverse clinical trajectories: diagnosis of cystic fibrosis (CF), reclassification as a CFTR-related disorder (CFTR-RD), non-CF designation, and persistent diagnostic uncertainty. Organoid-based assays—such as forskolin-induced swelling (FIS), steady-state lumen area (SLA) analysis, and rectal organoid morphology analysis (ROMA)—offer functional insights into CFTR activity and drug responsiveness. Compared to existing CFTR functional tests, such as Intestinal Current Measurement (ICM) and Nasal Potential Difference (NPD), these assays are more accessible, highly reproducible, and when needed support personalized medicine approaches. PDIO-based assays could help identify infants at high risk of disease progression, facilitating earlier interventions while minimizing unnecessary follow-ups for those unlikely to develop CF-related symptoms. Although not yet widely implemented, these assays hold promise for refining CFSPID diagnostics and management. Future research should focus on establishing standardized protocols allowing validation of clinical utility. Full article

Quercetin (Que) is widely recognized for its antioxidant and neuroprotective properties; however, its clinical potential remains limited due to poor solubility and low oral bioavailability. Nasal powders have emerged as a promising strategy to overcome these limitations, taking advantage of nose-to-brain delivery, offering a direct, non-invasive route to the central nervous system while bypassing first-pass metabolism. This study aims to extend previous work by systematically investigating the impact of different preparation methods (spray drying vs. lyophilization) and the incorporation of hydroxypropyl methylcellulose (HPMC) and mannitol/lecithin microparticles (MLMPs) on the physicochemical characteristics, structural properties, and in vitro diffusion behavior of HPβCD-based nasal powder formulations of Que. Thermal behavior and stability were analyzed using TGA, while morphology and particle distribution were assessed via Scanning Electron Microscopy. In vitro diffusion studies using Franz cells and regenerated cellulose membranes were conducted under simulated nasal conditions. Among all tested formulations, the spray-dried HPβCD/Que powder (F4) showed the highest permeation (0.11 ± 0.01 mg/cm² at 120 min). The inclusion of HPMC improved thermal stability but reduced Que diffusion, likely due to increased viscosity and matrix formation. Blending with MLMPs enhanced powder flow and dose placement, although it modestly reduced diffusion efficiency. Overall, this study highlights the potential of HPβCD-based spray-dried powders for nasal Que delivery and demonstrates how HPMC and MLMPs can be strategically employed to tailor performance characteristics. Full article

Background/Objectives: Mometasone furoate (MF) is a topical corticosteroid used to reduce allergic and inflammation symptoms. In this study, MF was incorporated into the hydrophobic cavities of γ-cyclodextrin metal-organic frameworks (CD-MOFs) to prepare MF@MOF powders for nasal delivery. Methods: MF@MOF particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetry. A transparent biomimetic model of the human nasal cavity was produced by 3D printing and used to evaluate intra-nasal depositions patterns. Results: Drug loading was optimized by incubating MF with a CD-MOF at a ratio of 4% for 1 h at 40 °C, and the cubic morphology and particle size of the nanoparticles were not altered using an incubation method. PXRD and FTIR analyses confirmed the successful loading of MF into the CD-MOF. Using a 3D biomimetic nasal cavity model, a 30° administration angle was found to result in reduced drug accumulation in the nasal vestibule and enhanced deposition in the respiratory and olfactory regions, compared with administration at 45°. Approximately 51% of the drug reached the respiratory zone in the model of the nasal cavity from male subjects, while almost 60% of the drug reached this zone in the model associated with female subjects. Compared with nasal sprays, nasal powder sprays had less deposition in the nasal vestibule and more deposits in the middle and inferior nasal concha. Conclusions: MF@MOF is suitable for intranasal administration. Delivery of MF as a nasal powder shows potential in the treatment of chronic rhinosinusitis. Full article

Background/Objectives: The limited permeability of the blood–brain barrier (BBB) to biotherapeutics is a major challenge in the treatment of brain tumors. The nose-to-brain (N2B) delivery approach, which bypasses the BBB, offers a promising alternative way to treat these tumors. The aim of this work was to develop PLGA nanoparticles for N2B delivery of biodrugs using trastuzumab (TZB) as a paradigm. Methods: An in vitro model was used to evaluate the ability of PLGA nanoparticles to enhance passage through the nasal epithelium. We also compared the passage of loaded TZB versus unencapsulated TZB across an in vitro BBB model simulating systemic administration of TZB. TZB-loaded PLGA nanoparticles (NP-TZBs) were prepared using a double emulsion method followed by solvent evaporation and characterized for various properties, including particle size, polydispersity index, zeta potential, morphology, encapsulation efficiency, and drug loading capacity and release kinetics. TZB functionality was assessed after release from NP or passage through an in vitro barrier model. The permeability of TZB and NP-TZBs through in vitro models of nasal epithelium and BBB was investigated. Results: NP-TZBs exhibited an average size of about 200 nm with a polydispersity index of less than 20%, neutral charge, and a loading efficiency of 67%. Transmission electron microscopy revealed spherical nanoparticles with a smooth surface. Importantly, the TZB released from the nanoparticles retained all of its physicochemical properties and functionality. We observed that the NP-TZB formulation results in at least a nine-fold increase in TZB permeability across the nasal epithelium 24 h post-exposure, depending on the exposure conditions, but shows no significant improvement across the BBB model. The TZB released in the basal compartment is fully functional and able to recognize HER2 expressed on the surface of breast tumor BT474 cells. Conclusions: Using compounds already validated for clinical use, we were able to develop a formulation that allowed efficient passage of TZB across an in vitro nasal epithelial model. In contrast, no passage was observed across the BBB, supporting the notion of the superiority of the nose–brain route over systemic injection for in vivo delivery of TZB to the central nervous system. Full article

Objectives: This study investigates the canine fossa (CF) topography relative to the maxillary sinus and nasal fossa and examines its association with facial types, focusing on side and gender. Methods: One hundred CBCT scans were analysed bilaterally at the first (PM1) and second (PM2) premolar levels. The CF was classified according to its anatomical relationship with adjacent structures: type 1, where the CF lies predominantly lateral to the maxillary sinus; type 2, where it is lateral to the nasal fossa; and type 3, where the CF is positioned lateral to the nasal fossa inferiorly and to the maxillary sinus superiorly. Facial measurements (height and width) were used to calculate the facial index, classifying individuals into five facial types: hypereuroprosopic, euryprosopic, mesoprosopic, leptoprosopic, and hyperleptoprosopic. A statistical analysis assessed the correlation between CF types and facial morphology. Results: Types 1 and 3 were the most prevalent CF types, while type 2 was observed only at the PM1 site. The PM2 level showed a predominance of type 1, indicating a consistent anatomical association of the CF with the maxillary sinus. In contrast, the PM1 level demonstrated a higher prevalence of type 3, reflecting the presence of the CF in the walls of both the nasal fossa and maxillary sinus. Leptoprosopic facial type was strongly associated with type 3, while no significant associations of CF types were found for other facial types. The sample lacked hypereuroprosopic individuals (facial index < 79.9), while hyperleptoprosopic faces (facial index > 95) were present in 23% of cases. Conclusions: The CF topography varies significantly by premolar site and is influenced by facial proportions. Type-3 CFs correlate strongly with elongated (leptoprosopic) facial configurations; broader facial types were underrepresented in this sample. Full article

Background/Objectives: The combination of nanomedicine with nasal administration is of paramount importance in current research and development. Polymeric micelles coated with hyaluronic acid may be a suitable solution to enhance drug release and permeation whilst properly adhering to the nasal mucosa, increasing residence time. Methods: Solid state characterization included morphology and laser diffraction-based size analysis and X-ray powder diffraction. The characterization of dispersed polymeric micelles in aqueous media was performed based on dynamic light scattering and determining the solubility enhancement related factors such as encapsulation efficiency and thermodynamic solubility. In vitro nasal drug release and permeability studies were also conducted to characterize the different hyaluronic acid-modified polymeric micelles. Quantitative measurements were carried out via liquid chromatography. Results: Concentration dependence on hyaluronic acid was found during all measurements, with one formulation candidate overcoming the others. With a high yield above 80%, monodispersed particles were formulated with an approximately 4 µm particle size in uniform distribution and spherical morphology. The small micelle size (107.3 nm) in uniform manner led to a high encapsulation efficiency above 80% and released the drug amount above 70% in 15 min. High drug permeation was also achieved compared with the initial active substance by itself. Conclusions: A value-added polymeric micelle formulation was developed with rapid drug release and permeation kinetics alongside its high mucoadhesion. Full article

Background/Objectives: We aimed to evaluate the effectiveness of a 0.1% cyclosporin A cationic emulsion (CsA-CE) for dry eye disease (DED) post-cataract surgery using the DED index measured with a Placido tear film analyzer. Methods: We retrospectively reviewed the medical records of patients who underwent simple cataract surgery. All patients used 0.5% moxifloxacin and 1% prednisolone acetate eye drops four times daily postoperatively. They were divided into the CsA-CE and control groups based on whether they had used CsA-CE 1 week after surgery. Subjective and objective assessments were performed at the baseline and 1 month postoperation. The non-invasive tear meniscus height, non-invasive tear break-up time, conjunctival redness, meibomian gland morphology, and lipid layer thickness were assessed using the Keratograph 5M (Oculus). Results: No differences were observed in the preoperative dry eye parameters between the groups. The ocular surface disease index decreased from 19.26 to 14.58 (p = 0.046) at 1 month postoperation for the CsA-CE group, and the average non-invasive tear break-up time significantly increased from 10.97 to 13.00 s (p = 0.002). No such differences were observed for the control group. Nasal bulbar conjunctival hyperemia increased (p < 0.001) for the control group. Nasal limbal hyperemia and overall limbal hyperemia increased for both groups (CsA-CE, p = 0.005, 0.017; control, p = 0.001, 0.012). The lipid layer thickness increased from 70.29 to 86.41 nm for the CsA-CE group (p < 0.001), whereas no significant change was noted for the control group. Conclusions: CsA-CE (0.1%) is effective for treating DED after cataract surgery and improves the tear lipid layer. Full article

We describe a new species of snake of the genus Tachymenoides using molecular and morphological evidence. The description is based on 21 specimens (4 females, 17 males) obtained in the regions of Pasco, Junín, and Puno between 2190 and 3050 m elevation. A maximum likelihood phylogenetic tree based on two mitochondrial (12S and cyt-b) genes and one nuclear (c-mos) gene shows that the new species is the sister taxon of T. affinis and distinct from Galvarinus tarmensis, which we transfer back to Tachymenis. The new species has smooth dorsal scales without apical pits usually in 19/17/15 series, 1 preocular, 2 postoculars, 1 loreal undivided nasal scale, 8 supralabials (4th and 5th in contact with the eye), 9 infralabials, 1–2+2–3 temporals, 139–157 ventrals, 52–67 subcaudals, and a divided cloacal scale. The longest specimen, a male, had a total length of 559 mm. Two females contained six and five eggs with small embryos. In life, the dorsum and flanks are olive brown to pale grayish brown with scattered black and cream flecks and no longitudinal stripes. Ventral coloration is highly variable, nearly uniformly black, mottled gray and dark-gray, mottled pale gray and tan, or pale grayish tan. Usually, three irregularly shaped, narrow, longitudinal ventral stripes are present. The iris is brown with a distinct yellowish-tan ringlet. Full article

Respiratory diseases have presented a remarkable challenge during modern history, contributing to important pandemics. The scientific community has focused its efforts on developing vaccines and blocking the transmission of viruses through the respiratory tract. In this study, we propose the use of stable silver nanoparticles (AgNPs) functionalized with tannic acid (TA) and sodium citrate (SC) as a nasal spray disinfectant (NSD). The non-ionic ethoxylated surfactant Tween 80 (T80) was added to enhance the wetting effect on nasal and oral tissues following spray application. We analyzed the physicochemical properties of the AgNPs and the NSD, including zeta potential, polarity, morphology, composition, particle size, and distribution. The results indicated spherical AgNPs ranging from 3 to 5 nm, stabilized by TA-SC. The addition of T80 resulted in particles with negative polarity, high stability, and improved coverage area. Furthermore, the colloidal stability was monitored over one year, showing no signs of degradation or precipitation. Interestingly, the interaction between the capped AgNP complex, the spike protein, and ACE2 was studied by molecular docking, indicating a strong and thermodynamically favorable complex interaction. These findings hold promise for the development of potential inhibitors, antagonist receptors, Ag-complex agonists (as observed here), and drug development for viral protection. Full article

Background/Objectives: This study investigates differences in craniofacial morphology including skull thickness, sella turcica morphology, nasal bone length, and posterior cranial fossa dimensions, as well as differences in head posture and deviations in upper spine morphology, in adult OSA patients compared to healthy controls with neutral occlusion. Methods: 51 OSA patients (34 men, 17 women, mean age 51.9 ± 11.3 years) and 74 healthy controls (19 men, 55 women, mean age 38.7 years ± 14.0 years) with neutral occlusion were included. Craniofacial morphology and head posture were investigated using cephalometric measurements on lateral cephalograms and morphological deviations in sella turcica and upper spine were assessed through visual description of lateral cephalograms. Results: OSA patients had significantly more retrognathic maxilla (p = 0.02) and mandible (p = 0.032 and p = 0.009), significantly larger beta-angle (p = 0.006), and significantly smaller jaw angle (p = 0.045) compared to controls. OSA patients had significantly larger length (p = 0.003, p = 0.001, p = 0.044) and depth of the posterior cranial fossa (p < 0.001) compared to controls. OSA patients had a significantly more extended (p < 0.001) and forward-inclined head posture (p < 0.001) and morphological deviations in the upper spine occurred significantly more often in OSA patients compared to controls (p = 0.05). No significant differences in skull thickness, nasal bone length, and morphological deviations in the sella turcica (p = 0.235) were found between the groups. Conclusions: Significant deviations were found in craniofacial morphology, head posture, and morphological deviations in the upper spine. The results may prove valuable in the diagnostics of OSA patients and in considerations regarding etiology and the phenotypic differentiation of OSA patients. Full article

Background/Objectives: Congenital heart disease (CHD) is the most common birth defect, an important cause of morbidity and mortality, with a reported prevalence of 5–12 per 1000 live births. The aim of our study was to identify the role of fetal morphological ultrasound examination in the first and second trimester of pregnancy in the detection of fetal congenital cardiac anomalies in a low-risk population. Methods: We performed a retrospective study in a tertiary fetal medicine center in Emergency Hospital Craiova, Romania. The longitudinal analysis combined first- and second-trimester screening using improved ultrasound protocols. Our study evaluated 8944 pregnant women with singleton pregnancies in a 6-year period between January 2018 and December 2023. All ultrasound examinations were performed using a standard extended protocol according to the main guidelines’ recommendations for the detection of fetal anomalies. Results: In the first trimester of pregnancy, 37 cases with cardiac anomalies were diagnosed. Thirteen of these cases were associated with genetic anomalies (Down syndrome—eight cases, Edwards syndrome—four cases, Turner syndrome—one case). Some of these pregnancies were associated with at least one of the minor ultrasound markers (inverted ductus venosus, abnormal flow in the tricuspid valve, presence of choroid plexus cysts, absent/hypoplastic nasal bone). In the second trimester of pregnancy, 17 cases of cardiac anomalies were diagnosed. From these cases, one was associated with genetic anomalies (DiGeorge Syndrome), and one case developed hydrops and delivered prematurely in the early third trimester. Conclusions: Ultrasound screening for the detection of congenital heart disease is feasible early in pregnancy, but some anomalies would be obvious later in pregnancy. An early diagnosis using an extended ultrasound protocol, genetic testing, and a multidisciplinary evaluation would improve the prognosis and the overall survival rate by delivering in a tertiary center that allows for rapid cardiac surgery in dedicated cases. Full article

Background: The nasal septal swell body (NSB) is a thickened area of the nasal septum with erectile tissues, located above the nasal floor. We hypothesized that the presence of the NSB in this space exerts favorable effects to generate laminar nasal airflow by developing its morphology as adjusted to nasal septal deviation (NSD). Patients and Methods: We objectively measured the NSB morphology in 152 patients by computed tomography (CT) and assessed its relationship with the width of the inferior turbinate (IT), the severity of NSD, and the patency of the nasal airflow passage (NAP). Results: In the patients with moderate or severe NSD, the mean widths of the NSB, IT, and NAP were significantly narrower at the convex side compared to the paired concave side, with the degree being more prominent in the severe-NSD group. A positive correlation was observed between the degree of the NSD angles and the difference in the widths of the NSB (r = 0.805) and IT (r = 0.609). Conclusions: These results imply novel roles of the NSB in the maintenance of physiological nasal airflow to generate a laminar airflow from the nostrils toward the middle nasal meatus at a constant rate. Full article

Background/Objectives: The effect of rapid maxillary expansion (RME) on the nasal and pharyngeal airways in children remains uncertain. This retrospective study utilized computational fluid dynamics (CFD) to assess the changes in ventilation parameters caused by RME in children. Methods: Pre- and post-RME cone beam computed tomography (CBCT) images of 20 patients (4 males, mean age 13 ± 2 years) treated with RME for maxillary transverse insufficiency were evaluated. The RME treatment was conducted using two distinct techniques: tooth-borne and tooth-bone-borne. CFD simulations were used to investigate the airflow conditions (pressure and velocity) in the whole upper airway, nasal airway, and maxillary sinus. Morphological alterations and variations in ventilation parameters before and after RME treatment were statistically compared. The extent of changes in the morphological and ventilatory characteristics of the upper airway, depending on the type of RME, was assessed. Additionally, changes in the ventilation conditions of the upper airway, nasal airway, and maxillary sinus after RME treatment were statistically analyzed. Statistical analyses using IBM SPSS v22 (New York, USA) software included paired t-tests, Mann–Whitney U tests, Wilcoxon matched-pairs signed-rank tests, intraclass correlation coefficients, and coefficients of variation (p < 0.05). Results: The CFD study revealed a notable reduction in both air flow velocity and pressure after the RME treatment (p < 0.05). A statistically significant increase was seen in the parameters used to assess the morphological changes following RME treatment, including nasal width, anterior and posterior nasal cross-sectional area, intermaxillary and intermandibulary molar width, and oropharyngeal airway width (p < 0.05). Regarding the change in airway ventilation, there was no statistically significant difference between tooth-borne and tooth-bone-borne RME treatments (p > 0.05). Conclusions: RME not only treats orthodontic issues in childhood but also increases airflow, which enhances ventilation. CDF is an effective method for the detection of ventilation improvement. Full article

Although embryological studies of squamates have a long history, most groups in this large clade remain poorly studied. One such group is the family Scincidae, which consists of morphologically and ecologically diverse lizards. In this study, we describe several stages of embryonic development based on cleared and stained specimens of Heremites auratus and Heremites vittatus. Our analysis indicates that the pterygoid and frontal are the first bones to be ossified at stage 34 in the skull of H. auratus. At stage 37, which was examined in both studied species, the ossified bones include the nasal, maxilla, parietal, prefrontal, premaxilla, postorbital, postfrontal, jugal, squamosal, quadrate, vomer, palatine and all mandible bones. In both species, the skull roof is relatively poorly ossified at stage 37. However, in H. auratus, the frontal and parietal bones ossify at their lateral edges at stage 37, while in H. vittatus, the frontal bones begin to ossify towards the midline. This suggests that ossification occurs later in H. auratus compared to H. vittatus, indicating a heterochronic pattern in ossification between these species. Additionally, pigmentation on the dorsal side of the body and scaling, which covered the entire body by stage 37 in H. vittatus, occur earlier compared to H. auratus. Compared to other scincid species, ossification in these lizards begins at a later stage but is completed earlier. Full article