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Topical delivery to paranasal sinuses through sustained-release stents is one of the new horizons in treating chronic rhinosinusitis (CRS). This study aims to introduce and evaluate sustained co-release of encapsulated ciprofloxacin (CIP) and dexamethasone (DEX) in polyvinyl alcohol-based carriers within the maxillary sinus of rabbit animals. DEX and CIP were loaded in a tyramine-substituted polyvinyl alcohol microparticle (PVATyr MP). The mechanical stability, degradability, and sustained-release patterns of both drugs as well as cellular cytocompatibility were assessed in vitro. The PVATyr MPs were then injected into the maxillary sinus of rabbits and they were monitored weekly for 21 days. Nasal endoscopy, MRI imaging, and tissue microscopy were used to follow the changes and compared them with the control condition. Also, the concentrations of drugs were evaluated in the maxillary sinus and blood samples over the study period. Produced PVA-based MPs possessed a relatively narrow particle size distribution (CV 7.7%) with proper physical stability until 30 days of incubation. The uniform-sized PVATyr MPs and their surrounding hydrogel showed sustained-release profiles for DEX and CIP for up to 32 days in vitro. The injected drugs-loaded hydrogel showed complete clearance from the maxillary sinus of rabbits within 28 days. The concentrations of DEX and CIP in mucosal remained within the therapeutic window when measured on days 7, 14, and 21, which were well above the plasma concentrations without any pathological changes in endoscopy, MRI imaging, and histological examinations. DEX/CIP loaded PVATyr MPs provided an effective, controlled, and safe sustained-drug delivery in both in vitro and in vivo analyses at therapeutic concentrations with minimal systemic absorption, suggesting a promising treatment approach for CRS. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including “positive regulation of intracellular signal transduction”, “arachidonic acid metabolic process”, “spermatogenesis” and “negative regulation of cellular protein metabolic process”. Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders. Methods: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set. Results: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients. Conclusion: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies. [ABSTRACT FROM AUTHOR]

Recent studies have established the possible role of microbiota in developing various diseases. In this regard, attention has shifted to the evaluation of microbiota changes in the paranasal sinuses and its relationship to chronic rhinosinusitis (CRS), especially CRS with nasal polyposis (CRSwNP). This study aimed to examine the bacterial communities of the sphenoidal sinus in Iranian patients with and without CRS. The investigation included 36 subjects, including 18 patients with CRSwNP who underwent Functional Endoscopic Sinus Surgery (FESS) and 18 non-CRS patients who underwent Endoscopic Endonasal Approach (EEA) for pituitary adenoma. The surgeries were performed under general anesthesia, and the sphenoidal sinus was sampled using sterile rayon-tipped swabs coated with a sheet. TaqMan quantitative real-time polymerase chain reaction (qPCR) method (the 16S rDNA gene from bacteria) was used for detection of bacterial communities in different samples. Staphylococcus haemolyticus and Pseudomonas aeruginosa were significantly more prevalent in CRS patients than non-CRS patients (P value ≤ 0.05). However, no significant difference in the frequency of Corynebacterium spp. and Staphylococcus aureus was observed between the two groups, and no Streptococcus pneumoniae or Haemophilus influenza species were isolated from any of the samples. The current study’s findings indicated a significant difference in the frequency of certain bacterial species in patients with CRS vs. non-CRS patients. By establishing a link between microbial burden and CRS, it is possible to develop effective treatments or even prevent disorders in this body area. [ABSTRACT FROM AUTHOR]

Non-functioning pituitary adenomas (NFPAs) are typical pituitary macroadenomas in adults associated with increased mortality and morbidity. Although pituitary adenomas are commonly considered slow-growing benign brain tumors, numerous of them possess an invasive nature. Such tumors destroy sella turcica and invade the adjacent tissues such as the cavernous sinus and sphenoid sinus. In these cases, the most critical obstacle for complete surgical removal is the high risk of damaging adjacent vital structures. Therefore, the development of novel therapeutic strategies for either early diagnosis through biomarkers or medical therapies to reduce the recurrence rate of NFPAs is imperative. Identification of gene interactions has paved the way for decoding complex molecular mechanisms, including disease-related pathways, and identifying the most momentous genes involved in a specific disease. Currently, our knowledge of the invasion of the pituitary adenoma at the molecular level is not sufficient. The current study aimed to identify critical biomarkers and biological pathways associated with invasiveness in the NFPAs using a three-way interaction model for the first time. In the current study, the Liquid association method was applied to capture the statistically significant triplets involved in NFPAs invasiveness. Subsequently, Random Forest analysis was applied to select the most important switch genes. Finally, gene set enrichment (GSE) and gene regulatory network (GRN) analyses were applied to trace the biological relevance of the statistically significant triplets. The results of this study suggest that "mRNA processing" and "spindle organization" biological processes are important in NFAPs invasiveness. Specifically, our results suggest Nkx3-1 and Fech as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology. [ABSTRACT FROM AUTHOR]

Post-traumatic olfactory dysfunction (PTOD) is associated with a significant decrease in quality of life. The present study aimed to explore whether PTOD is associated with depression and changes in sexuality. There were two groups in this case–control study. The patient group consisted of patients with PTOD (n = 55), and the control group comprised healthy individuals without the olfactory disorder (n = 115). Olfactory function, depression, partnership, and sexual satisfaction were assessed using the Iranian version of the Sniffin' Sticks test (Ir-SST), Beck Depression Inventory (BDI), Enrich Couple Scale (ECS) and Sexual Satisfaction Scale for Women (SSSW). The BDI scores were higher in the patient group than in the control group (p < 0.001). The SSSW score was lower in the patient group than in controls (p < 0.01), although the ECS score was not significantly different between patients and controls. Also, there was no significant difference in the severity of trauma between marital satisfaction and sexual satisfaction. However, the analysis showed a statistically significant difference in depression scores in connection with the head trauma severity. In the PTOD group, depression was increased and sexual satisfaction declined. Understanding the association of olfactory dysfunction with depression and sexuality allows patients and doctors to deal with less notable consequences of this disorder. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. Objective: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. Methods: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. Results: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). Conclusions: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) have potent immunomodulatory abilities to regulate most of the immune cells. Not only the tissue origin of MSCs can affect their functions, but also their microenvironment can strongly influence their biology, particularly through toll-like receptors (TLR)/ligands interaction. In the present study, we compared MSCs derived from two different sources, i.e. human olfactory ecto-mesenchymal stem cells (OE-MSCs) and adipose tissue (AT-MSCs), in terms of their immunosuppressive effects before and after TLR3 and TLR4 stimulation through low-level and short-term TLR-priming protocol. After isolation and characterization of OE-MSCs and AT-MSCs, flow cytometry analyses were used to assess the expression of TLR3, TLR4 by MSCs. Secretion and expression levels of immune-related genes were analyzed using ELISA and RT-qPCR techniques. Based on the results, the proliferation potential of OE-MSCs was significantly higher than that of AT-MSCs. The gene expression and also protein levels of both TLR3 and TLR4 were significantly higher in OE-MSCs, compared to AT-MSCs. Among the examined cytokines and chemokines, OE-MSCs exhibited significantly higher levels of CCL5, IL-8, and TGF-β production, in comparison with AT-MSCs. However, IL-6 secretion by AT-MSCs was considerably more than that by OE-MSCs. OE-MSCs were only affected by the TLR4 ligand, and IL-8 and IL-6 production levels increased after LPS treatment. However, only IL-8 significantly increased after adding LPS or Poly (I:C) to the AT-MSC media. According to the obtained data, OE-MSCs exhibited a higher proliferative potential and greater expression levels of TLR3 and TLR4 genes, compared to AT-MSCs. However, unlike AT-MSCs, the expression of TLR3 by OE-MSCs was nonfunctional. Finally, based on our findings, OE-MSCs have a stronger secretion of immunosuppressive cytokines both before and after LPS or PIC treatment, compared to AT-MSCs. [ABSTRACT FROM AUTHOR]

To evaluate the impact of nasoseptal flap (NSF) elevation on sinonasal quality of life (QOL) in patients with pituitary adenomas who underwent endoscopic endonasal trans-sphenoidal approach (EETSA), the data of 106 eligible patients were included from February 2011 to December 2014. The scores of Sinonasal Outcome Test (SNOT-22) Questionnaire were assessed in case (that received reconstruction with NSF) and control groups preoperatively as well as 1, 3, 6, and more than 12 months postoperatively. Nine most related sinonasal questions were evaluated separately (9Q). There were no significant inter-group differences in the mean SNOT-22, 9Q, and sense of taste/smell scores in preoperative and all postoperative assessments. Within each group, a significant improvement of SNOT-22 and 9Q scores were noted after 12 months of surgery compared to preoperative data. In the NSF group, comparison of the pre- and first postoperative evaluation revealed a significant deterioration in 9Q score ( p = 0.007) and 'sense of taste/smell' ( p < 0.001) which both returned to baseline in the 3rd month. Patients who used nasal paper mask for more than 100 'hour-days' showed a better SNOT-22 scores at 1st ( p = 0.04) and 3rd ( p < 0.001) months after surgery. Patients with adrenocorticotropic hormone (ACTH) secretory adenomas showed significantly higher scores of SNOT-22 in all postoperative assessments compared to the others. Although nasal symptoms deteriorated at first postoperative month (compare to preoperative data) in the NSF group, no negative impacts on the sinonasal QOL was showed comparing to the control group. ACTH-secreting adenomas could be assumed as a risk factor for poorer sinonasal QOL in EETSA. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is a common sleep disorder affecting quality of life. The aim of this study was to evaluate the perception of Quality of Life (QOL) in patients with OSA by means of World Health Organization Quality of Life (WHOQOL-BREF) instrument. This study was conducted on adult patients with sleep problems referred to Noor Sleep Lab for an overnight sleep study. Subjects were assessed for QOL using WHOQOL-BREF questionnaire. The Epworth sleepiness scale (ESS) was also employed to assess excessive daytime sleepiness (EDS). Baseline characteristics, ESS, and measured QOL are reported and their correlations with QOL were examined. Out of 502 patients included in the study, 62.7 % had moderate to severe OSA. The mean score of QOL in physical domain was significantly lower compared with normative population data. While AHI did not show any correlation with quality of life, mean O was weakly correlated with physical domain. Among the baseline characteristics, BMI and ESS were negatively correlated with physical and mental domains. Findings of this study show the impairment in quality of life related to physical functioning in patients with obstructive sleep apnea. Our study further supports the lack of association between AHI and QOL. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-00431-2, published online 22 October 2021 In the original version of this Article, Maryam Jalessi was omitted as a corresponding author. The original article can be found online at https://doi.org/10.1038/s41598-021-00431-2. [Extracted from the article]