Surgical correction of nasal obstruction in obstructive sleep apnea improves CPAP outcomes and compliance.

BACKGROUND: Although continuous positive airway pressure (CPAP) therapy curtails most of the negative impacts of obstructive sleep apnea (OSA), its efficacy is limited by its low long-term adherence. Nasal obstruction contributes to OSA pathophysiology and necessitates high CPAP titration pressures which reduce CPAP compliance. AIM: This study aims at elucidating the outcomes of surgical correction of nasal obstruction in patients intolerant to CPAP therapy. METHODS: Forty-nine patients with severe OSA intolerant to CPAP secondary to surgically correctable nasal obstruction were operated upon. Patients were evaluated preoperatively and at least 3 months after the surgical intervention. Subjective assessment entailed the Nasal Obstruction Symptom Evaluation score (NOSE) and the Epworth Sleepiness Scale (ESS). Objectively the patients were assessed by acoustic rhinometry and standard polysomnography. RESULTS: Nasal surgical intervention resulted in an a statistically significant decrease in the mean NOSE score, ESS and optimal CPAP titration pressure. In addition, the minimal cross-sectional area (MCA1&2) increased significantly postoperatively. There was a positive correlation between the improvement in NOSE score as well as the MCA1& 2 and the postoperative decrease in CPAP titration pressure. Surgical correction of nasal obstruction improved CPAP outcomes and compliance in all patients. CONCLUSIONS: Nasal surgery in OSA objectively assessed by acoustic rhinometry improved nasal obstruction with a resultant decrease in the CPAP pressure requirements. Given that lower CPAP pressures improve adherence to CPAP therapy, surgical alleviation of nasal obstruction should be considered a crucial intervention in the management armamentarium of OSA.

Nasal Reactivity After Radiofrequency Ablation of Peripheral Branches of Posterior Nasal Nerve.

Objective: Transection or ablation of the posterior nasal nerve (TRPN) has been described as an adjunctive tool to reduce the symptoms of intractable allergic rhinitis (AR). The procedure, however, requires surgical skill and carries the risk of bleeding from the sphenopalatine artery. The aim of the present study is to describe radiofrequency ablation of the peripheral branches of the posterior nasal nerves within the inferior turbinates (RAPN) as an effective easier alternative to TRPN. Methods: The procedure was performed on 24 patients with intractable AR. Nasal reactivity was tested by cold dry air (CDA) provocation before and 12 months after the radiofrequency procedure. Visual analog scale and acoustic rhinometry were used to measure the changes in nasal reactivity subjectively and objectively. Results: Worsening of nasal symptoms following CDA provocation had significantly decreased after the RAPN procedure. Likewise, postoperative decrease in nasal volumes and minimal cross-sectional areas after CDA provocation were significantly less than the corresponding preoperative values. Conclusion: RAPN effectively reduces nasal reactivity in patients with AR. The procedure is simple, minimally invasive, and can be performed under local or general anesthesia.

Development of Fe3O4 core-TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization.

BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe3O4 core-TiO2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe3O4 core-TiO2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe3O4@TiO2 as potential radiosensitizers for neuroblastoma in vitro. RESULTS: The uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs. CONCLUSIONS: The intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization - use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12645-021-00081-z.

Quitting smoking reverses nasal mucosal changes.

BACKGROUND: Smoking, whether active or passive, has proven deleterious effects on the nasal mucosa. There is also a link between smoking and development and/or maintenance of chronic rhinosinusitis (CRS). Reversal of smoking-induced mucosal changes after quitting smoking is still unconfirmed and controversial. The present study investigated the possibility of reversal of smoking-related nasal mucosal changes back to normal after completely quitting smoking. METHODS: The study was performed on 32 smokers whose nasal mucosa was previously biopsied for electron microscopic examination and then they completely quit smoking. Smoking history of the participants and duration of cessation of smoking were recorded. A tiny 1-mm3 biopsy was taken from the inferior turbinate 1 cm behind its anterior end and processed for electron microscopy. The specimens were processed for electron microscopy and the sections were examined by a pathologist who was blinded to the identity and smoking status of the participant. The results of electron microscopic examination of the nasal mucosa before and after quitting smoking were compared. RESULTS: The mean duration of quitting smoking was 30.75 months (± 8.26). Examination of the electron microscopic sections before quitting smoking showed variable degrees of loss of cilia and columnar cells, edema between the epithelial cells, few goblet cells, hyperplasia of seromucinous acini, and vascular congestion. The pathologic changes correlated positively with the smoking index of the participant. On the other hand, the sections after quitting smoking showed variable degrees of regeneration of the ciliated cells and decreased vascular congestion. Numerous goblet cells and seromucinous acini were seen. Less pathologic changes were observed with longer durations of cessation of smoking. CONCLUSIONS: The present study showed an association between smoking and the nasal mucosa. Smoking has several injurious effects on the nasal mucosa. However, the nasal mucosa has excellent regeneration potentials and quitting smoking for sufficient periods of time may reverse these deleterious changes. Considering the established link between smoking and CRS, quitting smoking may help smokers to overcome their recalcitrant disease. This should be further investigated.

Extramucosal pyriplasty without stenting for management of pyriform aperture stenosis.

PURPOSE: The current management options of congenital pyriform aperture stenosis (CNPAS) are either conservative measures awaiting further growth of the bony nasal framework or surgical intervention that focuses on bone removal from the margin of the pyriform aperture (PA) without exposure of the nasolacrimal duct (NLD) followed by stenting. Recently, CT measurements of the nasal cavity in CNPAS have shed light that the site of maximal bony obstruction corresponds to the bony buttress encasing the NLD rather than the margin of the PA as initially thought. Herein, we present an extramucosal pyriplasty technique that can be used without stenting to enlarge the PA and achieve immediate and sustained relief of nasal obstruction. METHODS: Retrospective chart review of 4 patients with radiologically confirmed CNPAS who had undergone extramucosal pyriplasty without stenting during the period from 2012 to 2016. RESULTS: Three patients were full term without any clinically detectable congenital anomaly. The fourth patient was preterm infant who needed ICU management. On computerized tomography scan, the PA width ranged from 5.8 to 7.1 mm with a mean of 6.4 mm while site of maximal stenosis ranged from 5.4 to 6.8 with a mean of 6 mm. Extramucosal pyriplasty relieved nasal obstruction and restored normal oral feeding in all patients. Postoperative follow-up endoscopy revealed an adequately patent airway with no scarring, granulation or restenosis. CONCLUSIONS: Extramucosal pyriplasty with decompression of the NLD without stenting is a treatment modality for CNPAS that provides prompt sustainable relief of nasal obstruction and avoids the drawbacks of stenting and shortcomings of the current conservative methods.

Intracellular in situ labeling of TiO2 nanoparticles for fluorescence microscopy detection.

Titanium dioxide (TiO2) nanoparticles are produced for many different purposes, including development of therapeutic and diagnostic nanoparticles for cancer detection and treatment, drug delivery, induction of DNA double-strand breaks, and imaging of specific cells and subcellular structures. Currently, the use of optical microscopy, an imaging technique most accessible to biology and medical pathology, to detect TiO2 nanoparticles in cells and tissues ex vivo is limited with low detection limits, while more sensitive imaging methods (transmission electron microscopy, X-ray fluorescence microscopy, etc.) have low throughput and technical and operational complications. Herein, we describe two in situ post-treatment labeling approaches to stain TiO2 nanoparticles taken up by the cells. The first approach utilizes fluorescent biotin and fluorescent streptavidin to label the nanoparticles before and after cellular uptake; the second approach is based on the copper-catalyzed azide-alkyne cycloaddition, the so-called Click chemistry, for labeling and detection of azide-conjugated TiO2 nanoparticles with alkyne-conjugated fluorescent dyes such as Alexa Fluor 488. To confirm that optical fluorescence signals of these nanoparticles match the distribution of the Ti element, we used synchrotron X-ray fluorescence microscopy (XFM) at the Advanced Photon Source at Argonne National Laboratory. Titanium-specific XFM showed excellent overlap with the location of optical fluorescence detected by confocal microscopy. Therefore, future experiments with TiO2 nanoparticles may safely rely on confocal microscopy after in situ nanoparticle labeling using approaches described here.

Cancer active targeting by nanoparticles: a comprehensive review of literature.

PURPOSE: Cancer is one of the leading causes of death, and thus, the scientific community has but great efforts to improve cancer management. Among the major challenges in cancer management is development of agents that can be used for early diagnosis and effective therapy. Conventional cancer management frequently lacks accurate tools for detection of early tumors and has an associated risk of serious side effects of chemotherapeutics. The need to optimize therapeutic ratio as the difference with which a treatment affects cancer cells versus healthy tissues lead to idea that it is needful to have a treatment that could act a the "magic bullet"-recognize cancer cells only. Nanoparticle platforms offer a variety of potentially efficient solutions for development of targeted agents that can be exploited for cancer diagnosis and treatment. There are two ways by which targeting of nanoparticles can be achieved, namely passive and active targeting. Passive targeting allows for the efficient localization of nanoparticles within the tumor microenvironment. Active targeting facilitates the active uptake of nanoparticles by the tumor cells themselves. METHODS: Relevant English electronic databases and scientifically published original articles and reviews were systematically searched for the purpose of this review. RESULTS: In this report, we present a comprehensive review of literatures focusing on the active targeting of nanoparticles to cancer cells, including antibody and antibody fragment-based targeting, antigen-based targeting, aptamer-based targeting, as well as ligand-based targeting. CONCLUSION: To date, the optimum targeting strategy has not yet been announced, each has its own advantages and disadvantages even though a number of them have found their way for clinical application. Perhaps, a combination of strategies can be employed to improve the precision of drug delivery, paving the way for a more effective personalized therapy.

Passive targeting of nanoparticles to cancer: A comprehensive review of the literature.

Cancer remains the one of the most common causes of mortality in humans; thus, cancer treatment is currently a major focus of investigation. Researchers worldwide have been searching for the optimal treatment (the 'magic bullet') that will selectively target cancer, without afflicting significant morbidity. Recent advances in cancer nanotechnology have raised exciting opportunities for specific drug delivery by an emerging class of nanotherapeutics that may be targeted to neoplastic cells, thereby offering a major advantage over conventional chemotherapeutic agents. There are two ways by which targeting of nanoparticles may be achieved, namely passive and active targeting. The aim of this study was to provide a comprehensive review of the literature focusing on passive targeting.

Cytotoxicity and DNA cleavage with core-shell nanocomposites functionalized by a KH domain DNA binding peptide.

A nanoconjugate was composed of metal oxide nanoparticles decorated with peptides and fluorescent dye and tested for DNA cleavage following UV light activation. The peptide design was based on a DNA binding domain, the so called KH domain of the hnRNPK protein. This "KH peptide" enabled cellular uptake of nanoconjugates and their entry into cell nuclei. The control nanoconjugate carried no peptide; it consisted only of the metal oxide nanoparticle prepared as Fe3O4@TiO2 nanocomposite and the fluorescent dye alizarin red S. These components of either construct are responsible for nanoconjugate activation by UV light and the resultant production of reactive oxygen species (ROS). Production of ROS at different subcellular locations causes damage to different components of cells: only nanoconjugates inside cell nuclei can be expected to cause DNA cleavage. Degradation of cellular DNA with KH peptide decorated nanoconjugates exceeded the DNA damage obtained from control, no-peptide nanoconjugate counterparts. Moreover, caspase activation and cell death were more extensive in the same cells.