Nasal Drug Delivery and Nose-to-Brain Delivery Technology Development Status and Trend Analysis: Based on Questionnaire Survey and Patent Analysis.

Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990-2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology.

The influence of processing methods on polyphenol profiling of tea leaves from the same large-leaf cultivar (Camellia sinensis var. assamica cv. Yunkang-10): nontargeted/targeted polyphenomics and electronic sensory analysis.

Tea polyphenols transform under processing methods, but a systematic study on their changes in the same large-leaf tea cultivar is lacking. Here, Camellia sinensis var. assamica cv. Yunkang-10 leaves underwent six processing methods and were assessed using optimized nontargeted (UHPLC-Q-Exactive Orbitrap-MS) and targeted (UHPLC-QqQ-MS) polyphenomics, along with molecular networking analysis. 903 and 52 polyphenolic compounds (catechins, flavones and flavonols, and phenolic acids) were respectively relatively and absolutely quantified for the first time. Dark and black teas, with the lowest polyphenol content, differed from the other four tea types, although variations existed among these four teas. However, some flavonol and flavone aglycones (e.g. kaempferol, apigenin), as well as some phenolic acids (e.g. ellagic acid, gallic acid), exhibited higher levels in dark and black teas. Correlations between polyphenolic composition and electronic sensory characteristics were observed using E-tongue and E-eye. This study enriches understanding of polyphenol profiles in Chinese teas post diverse processing.

Real time detection and identification of fish quality using low-power multimodal artificial olfaction system.

Single gas quantification and mixed gas identification have been the major challenges in the field of gas detection. To address the shortcomings of chemo-resistive gas sensors, sensor arrays have been the subject of recent research. In this work, the research focused on both optimization of gas-sensing materials and further analysis of pattern recognition algorithms. Four bimetallic oxide-based gas sensors capable of operating at room temperature were first developed by introducing different modulating techniques on the sensing layer, including constructing surface oxygen defects, polymerizing conducting polymers, modifying Nano-metal, and compositing flexible substrates. The signals derived from the gas sensor array were then processed to eliminate noise and reduce dimension with the feature engineering. The gases of were qualitatively identified by support vector machine (SVM) model with an accuracy of 98.86 %. Meanwhile, a combined model of convolutional neural network and long short-term memory network (CNN-LSTM) was established to remove the interference samples and quantitatively estimate the concentration of the target gases. The combined model based on deep learning, which avoids the overfitting with local optimal solutions, effectively boosts the performance of concentration recognition with the lowest root mean square error (RMSE) of 2.3. Finally, a low-power artificial olfactory system was established by merging the multi-sensor data and applied for real-time and accurate judgment of the food freshness.

Characterization of volatile profile from different coriander (Coriandrum sativum L.) varieties via HS-SPME/GC-MS combined with E-nose analyzed by chemometrics.

Headspace-solid phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) and electronic nose (E-nose) technologies were implemented to characterize the volatile profile of aerial part from 40 coriander varieties. A total of 207 volatile compounds were identified and quantified, including aldehydes, alcohols, terpenes, hydrocarbons, esters, ketones, acids, furans, phenols and others. E-nose results showed that W5S and W2W were representative sensors responding to coriander odor. Among all varieties, the number (21-30 species) and content (449.94-1050.55 µg/g) of aldehydes were the highest, and the most abundant analytes were (Z)-9-hexadecenal or (E)-2-tetratecenal, which accounted for approximately one-third of the total content. In addition, 37 components were determined the characteristic constituents with odor activity values (OAVs) ≥ 1, mainly presenting citrusy, fatty, soapy and floral smells. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) could effectively distinguish different varieties. This study provided a crucial theoretical basis for flavor evaluation and quality improvement of coriander germplasm resources.

Sigmoid sinus diverticulum without pulsatile tinnitus occurring concurrently with chronic otitis media mucosal type.

Sigmoid sinus diverticulum is a rare vascular anomaly often associated with pulsatile tinnitus. It can occur in cases of chronic otitis media squamous type (unsafe type) due to dehiscence of the sigmoid sinus plate caused by cholesteatoma. The presentation of which is that of pulsatile tinnitus. However, we present an unusual case of sigmoid sinus diverticulum occurring concurrently with chronic otitis media mucosal type (safe type) but in the absence of pulsatile tinnitus. This case report highlights the diagnostic challenges and management of this rare clinical scenario.

Retained foreign body in nose following eye injury.

A man in his 60s presented with diminution of vision of the left eye with nasal bleeding after accidental fall. On examination his left upper eyelid was lacerated and left temporal sclera was punctured which was repaired under local anaesthesia after which he was discharged by ophthalmologists but continued to complain of pain and left nasal obstruction. A non-contrast CT of paranasal sinuses revealed fracture of medial wall of left orbit, left ethmoid haemosinus and a metallic foreign body (FB) in the septum and anterior face of sphenoid. Diagnostic nasal endoscopy performed to remove the metallic FB showed plastic splinters embedded in the mucosa of nasal cavity which was unexpected. Hence, the FB was removed in two sittings because of diagnostic dilemma.

Vulvar Dermatofibrosarcoma protuberance in Iran and a narrative review of literature: A first case report.

Background: Pott's Puffy tumor (PPT) is a complicated frontal sinusitis that is also described as frontal bone osteomyelitis and a localized sub periosteal abscess. Early diagnosis and immediate active treatment are necessary to prevent severe neurologic sequelae. Case Presentation: Here, we report on a case of Pott's puffy tumor in a previously healthy 13-year-old girl with a worsening headache and swelling of the frontal bone accompanied by vomiting and fever. Magnetic resonance imaging revealed osteomyelitis of the frontal bone. A foreign body was discovered and removed via endoscopy which was then followed by 6 weeks of parenteral and enteral antibiotic therapy, resulting in resolution of all symptoms. Conclusion: A complete history in terms of trauma and insect bite or foreign body in the nose is paramount for a correct diagnosis, and performing a full examination of ear, nose and throat (ENT) to rule out a foreign body is advised.

Correlation between physicochemical properties, flavor characteristics and microbial community structure in Dushan shrimp sour paste.

Dushan shrimp sour paste (DSSP), a traditional Guizhou condiment, and its unique flavor is determined by the fermentation microbiota. However, the relationship between the microbiota structure and its flavor remains unclear. This study identified 116 volatile flavor compounds using electronic nose and headspace solid-phase microextraction-gas chromatography mass spectrometry (HS-SPME-GC-MS) techniques, of which 19 were considered as key flavor compounds, mainly consisting of 13 esters and 1 alcohol. High-throughput sequencing technique, the bacterial community structure of nine groups of DSSPs was determined. Further analysis revealed Vagococcus, Lactococcus, and Tepidimicrobium as key bacteria involved in flavor formation. This study contributes to our understanding of the relationship between bacterial communities and the flavor formation, and provides guidance for screening starter culture that enhance the flavor of DSSP in industrial production.

Promising brain biodistribution of insulin via intranasal dry powder for nose-to-brain delivery.

Nose-to-brain delivery (NTBD) offering potential benefits for treating Alzheimer's disease. In previous research, insulin dry powder (IDP) formulation for NTBD was developed, exhibiting favorable stability. This study aims to conduct in vitro and ex vivo assessment of release, permeation, mucoadhesion and histopathology, as well as an in vivo biodistribution study to produce IDP for NTBD and evaluate brain biodistribution. Spray-freeze-dried IDP formulations with varying weight ratios of trehalose-to-inulin were produced and analyzed. The release study was carried out in PBS with a pH of 5.8 stirred at 50 rpm and maintained at 37 °C ± 0.5 °C. Goat nasal mucosa was used for ex vivo permeation and mucoadhesion testing under similar conditions. An ex vivo histopathological examination and an in vivo study using enzyme-linked immunosorbent assay, were also performed. The IDP dissolution study demonstrated complete release of all IDPs within 120 min. The permeation study indicated that steady-state conditions were observed between 30 and 240 min. The mucoadhesion study unveiled that IDP F5 exhibited the fastest mucoadhesion time and the least force required within the fastest time of 43.60 ± 2.57 s. The histopathological study confirmed that none of the tested IDPs induced irritation in the nasal mucosa. Furthermore, the biodistribution study demonstrated the absence of detectable insulin in the plasma, while IDP F3 exhibited the highest deposited concentration of insulin within both the olfactory bulb and the whole brain. The extensive evaluation of the IDP formulations through in vitro, ex vivo, and in vivo studies implies their strength non-invasive NTBD. IDP F3, with a 1:1 wt ratio of trehalose to inulin, exhibited favorable brain biodistribution outcomes and was recommended for further investigation and development in the context of NTBD.

Effects of Nasal Packing on Patients' Post-operative Vital Signs.

Background Since bilateral nasal packing entails nasal and airway obstruction, this practice consequently leads to oral breathing. The resulting hypoxemia may then negatively impact vital signs, including blood pressure (BP), blood oxygen saturation (SpO2), and heart rate (HR). These systemic effects have a detrimental effect on patients. Objective The objective of this study is to observe the effects of bilateral nasal packing on patients' post-operative vital signs. Materials and methods This prospective study was conducted in the department of otolaryngology - head and neck surgery over a six-month period. The study included 83 post-operative patients with nasal surgery, in which bilateral merocele nasal packing was performed. The patients' pulse oximetry, systolic and diastolic BP, and HR were recorded four times the night before and after surgery. A statistical analysis was performed, and the mean values, standard deviation, and range were calculated. A paired sample t-test was also applied. The results are presented in figures and tables. Results The mean age of the participants was 27.65 ± 10.72 years, and 56 (67.5%) were male. Septoplasty was the most common surgery performed, with 63 participants having undergone this procedure (75.9%). When the pre-operative mean values of systolic and diastolic BP, SpO2, and HR were compared with the post-operative mean values, when a bilateral nasal pack was in place, a significant increase was found in all, with a p-value of <0.001 in each. Conclusion Bilateral nasal packing affects patients' vital signs by significantly increasing diastolic and systolic BP and decreasing SpO2. The HR is also significantly increased when packing is in place.

Development and analysis of an artificial olfactory bulb.

This article presents the development of an artificial olfactory bulb (OB) using an electronic nose with thermally modulated metal-oxide sensors. Inspired by animal OBs, our approach employs thermal modulation to replicate the spatial encoding patterns of glomeruli clusters and subclusters. This new approach enhances the classification capabilities of traditional electronic noses and offers new insights for biomimetic olfaction. Molecular receptive range (MRR) analysis confirms that our artificial OB effectively mimics the glomerular distribution of animal OBs. Additionally, the incorporation of a short axon cell (SAC) network, inspired by the animal olfactory system, significantly improves lifetime sparseness and qualitative ability of the artificial OB through extensive lateral inhibition, providing a theoretical framework for enhanced olfactory performance.

Laryngeal schwannoma masquerading as malignancy.

Laryngeal schwannoma is a rare type of neurogenous tumour with a non-specific presentation. We present a case of a middle-aged man with issues of hoarseness, globus sensation and intermittent episodes of throat pain. The Hopkins examination showed right vocal fold irregularity with fullness in the right ventricle. The contrast-enhanced CT neck revealed an ill-defined lesion with contrast uptake extending into the paraglottic region with no neck node involvement. Considering the clinical presentation of hoarseness, throat pain and globus with imaging revealing contrast enhancement of lesion, direct laryngoscopy and biopsy were planned to rule out malignancy. Intraoperatively, a well-defined submucosal capsulated swelling became apparent after incision and dissection of the mucosa over the right vocal fold. A complete excision of the swelling was done with microlaryngeal instruments without tracheostomy. The histopathological report was suggestive of schwannoma. The literature review discusses clinical presentation, location, imaging features and management strategy.

Kimchi Lactic Acid Bacteria Starter Culture: Impact on Fermented Malt Beverage Volatile Profile, Sensory Analysis, and Physicochemical Traits.

Starter cultures used during the fermentation of malt wort can increase the sensory characteristics of the resulting beverages. This study aimed to explore the aroma composition and flavor recognition of malt wort beverages fermented with lactic acid bacteria (Levilactobacillus brevis WiKim0194) isolated from kimchi, using metabolomic profiling and electronic tongue and nose technologies. Four sugars and five organic acids were detected using high-performance liquid chromatography, with maltose and lactic acid present in the highest amounts. Additionally, etongue measurements showed a significant increase in the sourness (AHS), sweetness (ANS), and umami (NMS) sensors, whereas bitterness (SCS) significantly decreased. Furthermore, 20 key aroma compounds were identified using gas chromatography-mass spectrometry and 15 key aroma flavors were detected using an electronic nose. Vanillin, citronellol, and ß-damascenone exhibited significant differences in the flavor profile of the beverage fermented by WiKim0194, which correlated with floral, fruity, and sweet notes. Therefore, we suggest that an appropriate starter culture can improve sensory characteristics and predict flavor development in malt wort beverages.

Internal mucosal resection and LLC suspension: a new method to establish a stable tip rotation angle and reduce the nasal bridge length.

Background/aim: Herein, we describe a new technique to obtain both the appropriate degree of rotation angle and the ideal nasal bridge length. The aim of this study is to investigate the long-term results of this new technique with regard to these two variables. Materials and methods: A total of 76 (27 males, 49 females) patients were operated in accordance with the presented technique. Internal caudal mucosal excision and lower lateral cartilage (LLC) suspension were applied to all the patients included in this prospective study. Preoperative, immediate postoperative, and postoperative 1st-year photographs were taken. NOSE scores were obtained in the postoperative 1st year. Results: The mean nasolabial angle values of the patients preoperatively, at the end of the surgery (immediate postoperative), and at the end of the first year were 94.13° ± 5.1, 113.1° ± 5.3, and 109.6° ± 5.2, respectively. The patients had an average gain of 19° at the nasolabial angle at the end of the surgery and experienced a 3.5° (3.1%) loss at the end of the first year. For the nasal bridge length (n-prn) values; the preoperative, immediate postoperative, and first year mean values were 5.1 ± 0.55 cm, 3.98 ± 0.41 cm, and 4.29 ± 0.39 cm, respectively. The noses of the patients were shortened by 1.11 cm on average at the end of the surgery. Conclusion: Internal caudal mucosal resection with a suspension of the LLC to the caudal edge of the upper lateral cartilages (ULC) offers a reliable method to control the nasal tip rotation and shorten the long noses. This technique's effect is more obvious in long noses compared to the short ones.

Microbiota diversity and anti-Pseudogymnoascus destructans bacteria isolated from Myotis pilosus skin during late hibernation.

Symbiotic microorganisms that reside on the host skin serve as the primary defense against pathogens in vertebrates. Specifically, the skin microbiome of bats may play a crucial role in providing resistance against Pseudogymnoascus destructans (Pd), the pathogen causing white-nose syndrome. However, the epidermis symbiotic microbiome and its specific role in resisting Pd in highly resistant bats in Asia are still not well understood. In this study, we collected and characterized skin microbiota samples of 19 Myotis pilosus in China and explored the differences between Pd-positive and negative individuals. We identified inhibitory effects of these bacteria through cultivation methods. Our results revealed that the Simpson diversity index of the skin microbiota for positive individuals was significantly lower than that of negative individuals, and the relative abundance of Pseudomonas was significantly higher in positive bats. Regardless of whether individuals were positive or negative for Pd, the relative abundance of potentially antifungal genera in skin microbiota was high. Moreover, we successfully isolated 165 microbes from bat skin and 41 isolates from positive individuals able to inhibit Pd growth compared to only 12 isolates from negative individuals. A total of 10 genera of Pd-inhibiting bacteria were screened, among which the genera Algoriella, Glutamicibacter, and Psychrobacter were newly discovered as Pd-inhibiting genera. These Pd-inhibiting bacteria metabolized a variety of volatile compounds, including dimethyl trisulfide, dimethyl disulfide, propylene sulfide, 2-undecanone, and 2-nonanone, which were able to completely inhibit Pd growth at low concentrations.IMPORTANCERecently, white-nose syndrome has caused the deaths of millions of hibernating bats, even threatening some with regional extinction. Bats in China with high resistance to Pseudogymnoascus destructans can provide a powerful reference for studying the management of white-nose syndrome and understanding the bats against the pathogen's intrinsic mechanisms. This study sheds light on the crucial role of host symbiotic skin microorganisms in resistance to pathogenic fungi and highlights the potential for harnessing natural defense mechanisms for the prevention and treatment of white-nose syndrome. In addition, this may also provide promising candidates for the development of bioinsecticides and fungicides that offer new avenues for addressing fungal diseases in wildlife and agricultural environments.

Effect of jujube powder addition on the aroma profile of quinoa snacks (QS).

Quinoa is a full-nutrition food; however, its poor flavor and small size make it not the best food option for direct consumption. In this study, a quinoa snack (QS, a cake) was developed, and the aroma profile of the products was improved by adding jujube fruit powder (made from dried jujube fruits, from 5% to 30%). Gas chromatography mass spectrum (GC-MS) combined with electronic nose (e-nose) was applied for characterizing the aroma profiles of QS samples. Results showed a total of 26 aroma compounds were identified in QS samples by GC-MS, and 3-methylbutanol (from 1525 µg/kg in QS-30 to 3487 µg/kg in QS-0), ethanol (from 1126 µg/kg in QS-0 to 3581 µg/kg in QS-30), hexanal (from 125.6 µg/kg in QS-30 to 984.1 µg/kg in QS-0), and acetaldehyde (from 531.9 µg/kg in QS-30 to 191.1 µg/kg in QS-0) were common. The e-nose response of W1S (sensitive to methane, from 17.50 of QS-0 to 93.85 of QS-30) and W1W (sensitive to sulfur-organic compounds of e-nose, from 15.57 of QS-0 to 39.50 of QS-30) were significantly higher, and significant differences were presented among QS samples. In conclusion, the aroma profile of the QS sample was significantly (p < .05) enhanced by the addition of jujube powder, and QS-30 with the highest jujube content (30%) presented the strongest aroma profile. Moreover, QS samples with different additions of jujube powders could be well distinguished by principal component analysis (PCA), and the combination of e-nose and GC-MS was effective in the volatile profile analysis of QS samples.

Nonsurgical Rhinoplasty: Results from a Retrospective Study of Rino-4-Puntos Technique with Hyaluronic Acid.

BACKGROUND: Nonsurgical rhinoplasty (NSR) utilizing hyaluronic acid (HA) filler injections is increasingly used to address nose shape issues. While refinements have been proposed, the technique lacks standardization. OBJECTIVES: Our study aimed to evaluate the aesthetic outcome, longevity of results, safety, and patient satisfaction with the novel Rino-4-Puntos (R4P) NSR technique. METHODS: This is a retrospective study of consecutive individuals treated with R4P between January 2021 and July 2023. All participants had one of the four indications: rectification of the dorsum (21%), triangulation of the tip (32%), projection (25%), and strengthening of the columella (22%). Each patient received two hyaluronic acid (HA) fillers: one with intermediate G prime (G') at Points 1-3 and another with high G' at Point 4, which is further divided into Points 4.1, 4.2, 4.3, and 4.4. The injection points were as follows: P1 (radix, 0.05-0.15 mL, supraperiosteal), P2 (supratip, 0.025 mL, suprachondrial), P3 (tip, 0.15 mL, deep fat), P4 (columella, 0.30 mL, supraperiosteal [4.1], or deep fat [4.2, 4.3, and 4.4]). RESULTS: Four hundred individuals (n = 284 [71%] females) are included. The mean filler volume used was 0.65 ± 0.17 mL. Injecting small boluses (≤ 0.05 mL) in the midline at deep planes minimized the risk of adverse effects, as no vascular complications occurred. Ninety-three percent of participants considered the overall outcome at least satisfactory ("good," "very good," or "excellent"). The treatment effect was maintained for a median of 11 months. CONCLUSIONS: The R4P technique refines NSR by combining enhanced aesthetic outcome, longevity, and safety. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Neck lump evaluation and pseudoaneurysm.

Pseudoaneurysm is the formation of a sac due to damage in the continuity of the arterial wall. Iatrogenic carotid artery aneurysm is a rare, life-threatening complication following fine needle aspiration (FNA). We are presenting here a case of pseudoaneurysm following FNA with a literature review.

Silent threat of isolated sphenoid sinus tuberculosis resulting in blindness and ophthalmoplegia.

A diabetic woman in her fifties presented with a sudden onset of failing vision and diplopia involving the right eye for two days, along with fever and headache. Radiological investigations revealed right sphenoid sinusitis along with inflammation around the right orbital apex and optic nerve. Functional endoscopic sinus surgery, with orbital and optic nerve decompression improved the ocular movements, but not the visual acuity. Histopathology was suggestive of a granulomatous inflammatory lesion, and high-resolution computed tommography (HRCT) of the thorax revealed lung lesions suggestive of an old tubercular infection, and antitubercular treatment (ATT) was then initiated.At the end of two months of ATT, there was complete resolution of ophthalmoplegia, relative afferent pupillary defect, direct and consensual light reflex however, failure of improvement in her visual acuity, indicated damage to the optic nerve.Extrapulmonary tuberculosis involving an isolated sphenoid sinus is rare and elusive. Prompt radiological investigations, followed by orbital decompression and ATT, provide the best possible outcomes.

[Occupational diseases related to otorhinolaryngology]. / Berufskrankheiten mit Bezug zur HNO-Heilkunde.

In the German Ordinance on Occupational Diseases (BKV), there are currently 82 occupational diseases listed, of which 18 partially or completely fall within the field of ENT medicine due to the associated health disorders. Noise-induced hearing loss is usually the focus of attention for the ENT specialist, but it has long since ceased to be the only occupational disease. In order to help uncover possible causalities between occupational noxious substances and diseases, it is important that physicians report their own observations and new scientific findings regarding suspected cases to the German Social Accident Insurance, especially in situations where cancer may be linked to occupational influences.