Exposure to urban particulate matter alters responses of olfactory mucosal cells to SARS-CoV-2 infection.

Respiratory viruses have a significant impact on health, as highlighted by the COVID-19 pandemic. Exposure to air pollution can contribute to viral susceptibility and be associated with severe outcomes, as suggested by recent epidemiological studies. Furthermore, exposure to particulate matter (PM), an important constituent of air pollution, is linked to adverse effects on the brain, including cognitive decline and Alzheimer's disease (AD). The olfactory mucosa (OM), a tissue located at the rooftop of the nasal cavity, is directly exposed to inhaled air and in direct contact with the brain. Increasing evidence of OM dysfunction related to neuropathogenesis and viral infection demonstrates the importance of elucidating the interplay between viruses and air pollutants at the OM. This study examined the effects of subacute exposure to urban PM 0.2 and PM 10-2.5 on SARS-CoV-2 infection using primary human OM cells obtained from cognitively healthy individuals and individuals diagnosed with AD. OM cells were exposed to PM and subsequently infected with the SARS-CoV-2 virus in the presence of pollutants. SARS-CoV-2 entry receptors and replication, toxicological endpoints, cytokine release, oxidative stress markers, and amyloid beta levels were measured. Exposure to PM did not enhance the expression of viral entry receptors or cellular viral load in human OM cells. However, PM-exposed and SARS-CoV-2-infected cells showed alterations in cellular and immune responses when compared to cells infected only with the virus or pollutants. These changes are highly pronounced in AD OM cells. These results suggest that exposure of human OM cells to PM does not increase susceptibility to SARS-CoV-2 infection in vitro, but it can alter cellular immune responses to the virus, particularly in AD. Understanding the interplay of air pollutants and COVID-19 can provide important insight for the development of public health policies and interventions to reduce the negative influences of air pollution exposure.

Human-derived air-liquid interface cultures decipher Alzheimer's disease-SARS-CoV-2 crosstalk in the olfactory mucosa.

BACKGROUND: The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD. METHODS: To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the air-liquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing. RESULTS: Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation. CONCLUSIONS: The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection.

Finnish Version of the Eating Assessment Tool (F-EAT-10): A Valid and Reliable Patient-reported Outcome Measure for Dysphagia Evaluation.

Our aim was to validate a Finnish version of the Eating Assessment Tool (F-EAT-10) for clinical use and to test its reliability and validity in a multicenter nationwide study. Normative data were acquired from 180 non-dysphagic participants (median age 57.0 years, 62.2% female). Dysphagia patients (n = 117, median age 69.7 years, 53.0% female) referred to fiberoptic endoscopic evaluation of swallowing (FEES) completed F-EAT-10 before the examination and after 2 weeks. Patients underwent the 100-ml water swallow test (WST) and FEES was evaluated using the following three scales: the Yale Pharyngeal Residue Severity Rating Scale, Penetration-Aspiration Scale, and the Dysphagia Outcome Severity Scale. An operative cohort of 19 patients (median age 75.8 years, 57.9% female) underwent an endoscopic operation on Zenker's diverticulum, tight cricopharyngeal muscle diagnosed in videofluorography, or both. Patients completed the F-EAT-10 preoperatively and 3 months postoperatively. The cut-off score for controls was < 3 (sensitivity 94.0%, specificity 96.1%) suggesting that ≥ 3 is abnormal. Re-questionnaires for test-retest reliability analysis were available from 92 FEES patients and 123 controls. The intraclass correlation coefficient was excellent for the total F-EAT-10 score (0.93, 95% confidence interval 0.91-0.95). Pearson correlation coefficients were strong (p < 0.001) for each of the questions and the total score. Internal consistency as assessed by Cronbach's alpha was excellent (0.95). Some correlations between findings in FEES and 100-ml WST with F-EAT-10 were observed. The change in subjective symptoms of operative patients paralleled the change in F-EAT-10. F-EAT-10 is a reliable, valid, and symptom-specific patient-reported outcome measure for assessing dysphagia among Finnish speakers.

Biometal Dyshomeostasis in Olfactory Mucosa of Alzheimer's Disease Patients.

Olfactory function, orchestrated by the cells of the olfactory mucosa at the rooftop of the nasal cavity, is disturbed early in the pathogenesis of Alzheimer's disease (AD). Biometals including zinc and calcium are known to be important for sense of smell and to be altered in the brains of AD patients. Little is known about elemental homeostasis in the AD patient olfactory mucosa. Here we aimed to assess whether the disease-related alterations to biometal homeostasis observed in the brain are also reflected in the olfactory mucosa. We applied RNA sequencing to discover gene expression changes related to metals in olfactory mucosal cells of cognitively healthy controls, individuals with mild cognitive impairment and AD patients, and performed analysis of the elemental content to determine metal levels. Results demonstrate that the levels of zinc, calcium and sodium are increased in the AD olfactory mucosa concomitantly with alterations to 17 genes related to metal-ion binding or metal-related function of the protein product. A significant elevation in alpha-2-macroglobulin, a known metal-binding biomarker correlated with brain disease burden, was observed on the gene and protein levels in the olfactory mucosa cells of AD patients. These data demonstrate that the olfactory mucosa cells derived from AD patients recapitulate certain impairments of biometal homeostasis observed in the brains of patients.

Perceptual Assessment and Acoustic Voice Analysis as Screening Tests for Vocal Fold Paresis After Thyroid or Parathyroid Surgery.

BACKGROUND: The aim of this study was to evaluate the reliability of clinician-based perceptual assessment of voice and computerized acoustic voice analysis as screening tests for vocal fold paresis or paralysis (VFP) after thyroid and parathyroid surgery. METHODS: This was a prospective study of 181 patients undergoing thyroid or parathyroid procedure with pre and postoperative laryngoscopic vocal fold inspection, perceptual voice assessment using grade, roughness, breathiness, asthenia, and strain (GRBAS) scale and acoustic voice analysis using the multi-dimensional voice program (MDVP). Patients were divided into 2 groups for comparison; those with new postoperative VFP and those without. Potential screening tools were evaluated using the receiving operating characteristic (ROC) analysis. RESULTS: Fourteen (6.6%) patients had a new postoperative VFP. Postoperative GRBAS scores were significantly (P < 0.05) higher in patients with VFP compared to those without. However, there were no statistically significant differences in MDVP values between the groups. Postoperative GRBAS grade score (cut off > 0) had the best sensitivity, 93%, for predicting VFP, but the specificity was only 50%. Postoperative jitter (cut off > 1.60) in MDVP had a good specificity, 90%, but only 50% sensitivity. Combining all the GRBAS and MDVP variables with P < 0.05 in the ROC analysis yielded a test with 100% sensitivity and 55% specificity. CONCLUSIONS: Physician-based perceptual voice assessment has a high sensitivity for detecting postoperative VFP, but the specificity is poor. The risk of VFP is low in patients with completely normal voice at discharge. However, routine laryngoscopy after thyroid and parathyroid surgery is still the most reliable exam for VFP screening.

Nasal saline irrigation: prescribing habits and attitudes of physicians and pharmacists.

OBJECTIVES: To explore the opinions, the usage and the patient education given on nasal saline irrigation by physicians and pharmaceutical personnel working in Finland. DESIGN: An internet-based survey with predetermined, multiple-choice answers. SETTING: Primary care centres, occupational health centres and private care centres in Eastern Finland as well as pharmacies in Finland. MAIN OUTCOME MEASURES: Healthcare professionals views, practice and general knowledge of nasal irrigation for sinonasal symptoms and conditions. RESULTS: We received 595 completed surveys (110 physicians, 485 pharmacists). The majority of the respondents recommended nasal saline irrigation for their patients either as a symptomatic treatment (98.0%) or to treat a specific condition (97.5%) such as acute rhinosinusitis, chronic rhinosinusitis and allergic rhinitis. Nasal saline irrigation was also often recommended as a prophylaxis for airway-infections (71.9%) and to enhance the health of the nasal mucosa (58.2%). In general, the possible adverse effects were recognised poorly by both professions. There was a clear difference between the two professions, as physicians were more conservative in recommending nasal saline irrigation and recognised possible adverse effects, such as epistaxis, pain, and dryness of the nose, better (75% vs. 59%, p = 0.002). CONCLUSIONS: Nasal saline irrigation seems to be a popular treatment recommended by many health care professionals in Finland. Physicians and pharmaceutical personnel had variable opinions on the indications, utility and risks of nasal saline irrigation. There are also clear differences between physicians and pharmaceutical personnel's practices. There is a need to better educate professionals about nasal saline irrigation and to further study whether nasal saline irrigation is efficient and safe option for the different common sinonasal conditions.KEY POINTSLittle information is available on how physicians and pharmacists recommend nasal saline irrigation as a symptomatic treatment.Physicians and pharmacists seem to have variable opinions about the indications, utility and safety of nasal saline irrigation.The patient education given is in general very heterogenous.Both professions require more education to ensure that the usage remains as safe as possible for the patient.

Translation, cross-cultural adaptation, and validation of the sino-nasal outcome test (snot)-22 for Finnish patients.

PURPOSE: The Sino-Nasal Outcome Test-22 (SNOT-22) is the most commonly used disease-specific quality of life questionnaire in rhinology. The purpose of this prospective study was to translate and validate SNOT-22 into Finnish. METHODS: The validation process followed the guidelines proposed for cross-cultural adaptation of health-related measures of quality of life. The study consisted of three groups: rhinologic out-patients (N = 96), FESS patients (N = 49) and healthy controls (N = 79). Out-patient and FESS groups completed the questionnaire twice (answers A and B), out-patients after two weeks and FESS patients after 3 months. Validity, reliability and responsiveness were evaluated. RESULTS: The mean SNOT-22 sum score of the out-patient questionnaires were 35.3 points (answer A) and 32.4 points (answer B). ICC in out-patient group was 0.879. For the FESS patients, the mean pre- and postoperative (answer A and B) SNOT-22 sum scores were 46.8 and 21.9 points, respectively (p < 0.0001). The mean SNOT-22 of healthy controls was 8.9 points. The out-patients (answer A) and healthy controls had statistically significant difference in SNOT-22 scores (p < 0.0001). CONCLUSIONS: The results of our study show that the validated Finnish version of the SNOT-22 questionnaire demonstrates good validity, reliability and responsiveness.

Eosinophilia, asthma, NERD and the use of oral corticosteroids predict uncontrolled chronic rhinosinusitis with nasal polyps after surgery.

BACKGROUND: Severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging condition to treat. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) has the following criteria when considering biological therapy for severe uncontrolled CRSwNP: eosinophilia, need for oral corticosteroids (OCS), symptom score, loss of sense of smell and co-morbid asthma. OBJECTIVE: This study aimed at finding associations of baseline factors with uncontrolled CRSwNP after endoscopic sinus surgery (ESS). METHODS: Electronic health record data of CRSwNP patients (N = 137) undergoing ESS in 2002-17 were used. Endpoints of uncontrolled CRSwNP were revision ESS, purchased OCS and antibiotic courses during follow up. Baseline factors were chosen based on EPOS2020 and the data available: nasal polyp (NP) eosinophilia, peripheral blood eosinophilia, co-existing asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD), need for OCS during the previous year, previous ESS, endoscopic NP score, and Lund-Mackay score of sinus computed tomography scans. RESULTS: During the follow-up of 10.1 ± 3.1 (mean ± standard deviation) years, 35 (25.5%) individuals underwent revision ESS. The best predictive model was obtained by a sum of baseline (1) blood eosinophilia ≥ 250 cells/≥l and/or NP eosinophilia ≥ 30% (Eos), (2) asthma/NERD, and (3) ≥ 1 OCS/year. It was significantly associated with revision ESS, purchased doctor-prescribed OCS and antibiotic courses during follow-up. CONCLUSIONS: We identified similar predictive variables for uncontrolled CRSwNP that are used in the EPOS2020 indications of biological therapy, thus suggesting that these estimates are usable in clinical practice.

Incidence, Risk Factors, and Natural Outcome of Vocal Fold Paresis in 920 Thyroid Operations with Routine Pre- and Postoperative Laryngoscopic Evaluation.

BACKGROUND: The aim of this study was to determine the incidence, risk factors, and spontaneous recovery rate of vocal fold paresis (VFP) with routine laryngoscopy before and after thyroid surgery. METHODS: All consecutive patients undergoing primary or redo thyroid surgery between years 2011-2016 were prospectively registered in an electronic database, and scheduled for pre- and postoperative laryngoscopic vocal fold inspection by otolaryngologists independently of the surgical team. RESULTS: A total of 920 thyroid operations with 1296 nerves at risk were performed in 866 patients. Pre- and postoperative laryngoscopy was done in 95% and 98%, respectively. Preoperative VFP was detected in 24 (2.8%) patients. New postoperative VFP was found in 53 of 920 operations (5.8%) and in 55 of 1296 nerves at risk (4.2%). After 12 months, 14 had recovered full vocal fold function and eight had near-complete recovery. VFP was permanent after 29 operations (3.2%); two patients were lost to follow-up with uncertain outcome. Of the 1296 nerves at risk, injury was permanent in 30 (2.3%). In multivariate analysis, patients operated for recurrent goiter had nearly nine times higher risk of new VFP (23% rate), whereas patients with malignant histology had three times higher risk of postoperative VFP (up to 22% rate). CONCLUSION: VFP continues to be a serious complication of thyroid surgery, especially in operations for redo goiter and thyroid malignancy. The incidence of VFP may be underestimated unless laryngoscopic examinations are performed routinely.

Sleep of professional athletes: Underexploited potential to improve health and performance.

Sleep disorders have become increasingly prevalent affecting health and working ability. Restorative sleep may be considered important for athletes' successful recovery and performance. However, some athletes seem to experience major problems in sleeping. Thus far, there is limited scientific information about their sleep. This study aimed to evaluate the quality of sleep and the prevalence of sleep disorders as well as the impact of a structured sleep counselling protocol in professional athletes. A total of 107 professional ice hockey players participated in the study. The exploratory observational 1-year follow-up study consisted of questionnaire-based sleep assessment followed by general sleep counselling and, when needed, polysomnography and an individual treatment plan. One in every four players was found to have a significant problem in sleeping. All athletes considered sleep essential for their health and three in every four players considered that counselling would improve their performance. Counselling and individual treatment were found to improve significantly the quality of sleep with the mean alteration of 0.6 (95% CI 0.2-1.0, P = 0.004) in a scale from 0 to 10. Our results support that sleep problems are common in professional athletes. However, systematic examination, counselling and individual treatment planning can improve the quality of their sleep.

Traffic-related ultrafine particles impair mitochondrial functions in human olfactory mucosa cells - Implications for Alzheimer's disease.

Constituents of air pollution, the ultrafine particles (UFP) with a diameter of ≤0.1 µm, are considerably related to traffic emissions. Several studies link air pollution to Alzheimer's disease (AD), yet the exact relationship between the two remains poorly understood. Mitochondria are known targets of environmental toxicants, and their dysfunction is associated with neurodegenerative diseases. The olfactory mucosa (OM), located at the rooftop of the nasal cavity, is directly exposed to the environment and in contact with the brain. Mounting evidence suggests that the UFPs can impact the brain directly through the olfactory tract. By using primary human OM cultures established from nasal biopsies of cognitively healthy controls and individuals diagnosed with AD, we aimed to decipher the effects of traffic-related UFPs on mitochondria. The UFP samples were collected from the exhausts of a modern heavy-duty diesel engine (HDE) without aftertreatment systems, run with renewable diesel (A0) and petroleum diesel (A20), and from an engine of a 2019 model diesel passenger car (DI-E6d) equipped with state-of-the-art aftertreatment devices and run with renewable diesel (Euro6). OM cells were exposed to three different UFPs for 24-h and 72-h, after which cellular processes were assessed on the functional and transcriptomic levels. Our results show that UFPs impair mitochondrial functions in primary human OM cells by hampering oxidative phosphorylation (OXPHOS) and redox balance, and the responses of AD cells differ from cognitively healthy controls. RNA-Seq and IPA® revealed inhibition of OXPHOS and mitochondrial dysfunction in response to UFPs A0 and A20. Functional validation confirmed that A0 and A20 impair cellular respiration, decrease ATP levels, and disturb redox balance by altering NAD and glutathione metabolism, leading to increased ROS and oxidative stress. RNA-Seq and functional assessment revealed the presence of AD-related alterations in human OM cells and that different fuels and engine technologies elicit differential effects.

Development of Lyophilised Eudragit® Retard Nanoparticles for the Sustained Release of Clozapine via Intranasal Administration.

Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the i.m. route is often painful, with low patient compliance and requiring specialised personnel. Moreover, CZP has a very low aqueous solubility. This study proposes the intranasal route as an alternative route of administration for CZP, through its encapsulation in polymeric nanoparticles (NPs) based on Eudragit® RS100 and RL100 copolymers. Slow-release polymeric NPs with dimensions around 400-500 nm were formulated to reside and release CZP in the nasal cavity, where it can be absorbed through the nasal mucosa and reach the systemic circulation. CZP-EUD-NPs showed a controlled release of CZP for up to 8 h. Furthermore, to reduce mucociliary clearance and increase the residence time of NPs in the nasal cavity to improve drug bioavailability, mucoadhesive NPs were formulated. This study shows that the NPs already exhibited strong electrostatic interactions with mucin at time zero due to the presence of the positive charge of the used copolymers. Furthermore, to improve the solubility, diffusion and adsorption of CZPs and the storage stability of the formulation, it was lyophilised using 5% (w/v) HP-ß-CD as a cryoprotectant. It ensured the preservation of the NPs' size, PDI and charge upon reconstitution. Moreover, physicochemical characterisation studies of solid-state NPs were performed. Finally, toxicity studies were performed in vitro on MDCKII cells and primary human olfactory mucosa cells and in vivo on the nasal mucosa of CD-1 mice. The latter showed non-toxicity of B-EUD-NPs and mild CZP-EUD-NP-induced tissue abnormalities.

Emissions from modern engines induce distinct effects in human olfactory mucosa cells, depending on fuel and aftertreatment.

Ultrafine particles (UFP) with a diameter of ≤0.1 µm, are contributors to ambient air pollution and derived mainly from traffic emissions, yet their health effects remain poorly characterized. The olfactory mucosa (OM) is located at the rooftop of the nasal cavity and directly exposed to both the environment and the brain. Mounting evidence suggests that pollutant particles affect the brain through the olfactory tract, however, the exact cellular mechanisms of how the OM responds to air pollutants remain poorly known. Here we show that the responses of primary human OM cells are altered upon exposure to UFPs and that different fuels and engines elicit different adverse effects. We used UFPs collected from exhausts of a heavy-duty-engine run with renewable diesel (A0) and fossil diesel (A20), and from a modern diesel vehicle run with renewable diesel (Euro6) and compared their health effects on the OM cells by assessing cellular processes on the functional and transcriptomic levels. Quantification revealed all samples as UFPs with the majority of particles being ≤0.1 µm by an aerodynamic diameter. Exposure to A0 and A20 induced substantial alterations in processes associated with inflammatory response, xenobiotic metabolism, olfactory signaling, and epithelial integrity. Euro6 caused only negligible changes, demonstrating the efficacy of aftertreatment devices. Furthermore, when compared to A20, A0 elicited less pronounced effects on OM cells, suggesting renewable diesel induces less adverse effects in OM cells. Prior studies and these results suggest that PAHs may disturb the inflammatory process and xenobiotic metabolism in the OM and that UFPs might mediate harmful effects on the brain through the olfactory route. This study provides important information on the adverse effects of UFPs in a human-based in vitro model, therefore providing new insight to form the basis for mitigation and preventive actions against the possible toxicological impairments caused by UFP exposure.

Position-dependent pressure pneumocephalus after transsphenoidal surgery: illustrative case.

BACKGROUND: Intracranial air may become trapped inside the cranial vault after cranial surgery, causing tension pneumocephalus with a variety of possible neurological symptoms. The authors reported a unique case in which position-dependent tension pneumocephalus developed after standard pituitary adenoma resection, causing severe intermittent visual symptoms. OBSERVATIONS: A tiny hole in the sellar floor after transsphenoidal surgery created a valve mechanism, allowing pressurized air accumulation inside the tumor capsule that periodically compressed the optic chiasm. This caused acute visual field defects only when the patient was in an upright position. Symptoms resolved when the patient lay down because pressurized air was allowed to escape from the cranial vault and compression of the optic chiasm was relieved. This phenomenon was verified with consecutive magnetic resonance imaging sequences demonstrating the relaxation of suprasellar space, after the intracranial air had escaped in a horizontal imaging position. LESSONS: Imperfect sealing of the sellar floor after transsphenoidal surgery is not uncommon. Even a tiny defect may in rare cases work in a valve-like manner, leading to intermittent air accumulation in the suprasellar space and causing corresponding visual symptoms. Pressure pneumocephalus inside an empty tumor capsule should be kept in mind as a possible rare complication after transsphenoidal surgery.

An Alzheimer's Disease Patient-Derived Olfactory Stem Cell Model Identifies Gene Expression Changes Associated with Cognition.

An early symptom of Alzheimer's disease (AD) is an impaired sense of smell, for which the molecular basis remains elusive. Here, we generated human olfactory neurosphere-derived (ONS) cells from people with AD and mild cognitive impairment (MCI), and performed global RNA sequencing to determine gene expression changes. ONS cells expressed markers of neuroglial differentiation, providing a unique cellular model to explore changes of early AD-associated pathways. Our transcriptomics data from ONS cells revealed differentially expressed genes (DEGs) associated with cognitive processes in AD cells compared to MCI, or matched healthy controls (HC). A-Kinase Anchoring Protein 6 (AKAP6) was the most significantly altered gene in AD compared to both MCI and HC, and has been linked to cognitive function. The greatest change in gene expression of all DEGs occurred between AD and MCI. Gene pathway analysis revealed defects in multiple cellular processes with aging, intellectual deficiency and alternative splicing being the most significantly dysregulated in AD ONS cells. Our results demonstrate that ONS cells can provide a cellular model for AD that recapitulates disease-associated differences. We have revealed potential novel genes, including AKAP6 that may have a role in AD, particularly MCI to AD transition, and should be further examined.

Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients.

Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. Olfactory dysfunction manifests early in several neurodegenerative disorders including Alzheimer's disease, however, disease-related alterations to the olfactory mucosal cells remain poorly described. The aim of this study was to evaluate the olfactory mucosa differences between cognitively healthy individuals and Alzheimer's disease patients. We report increased amyloid-beta secretion in Alzheimer's disease olfactory mucosal cells and detail cell-type-specific gene expression patterns, unveiling 240 differentially expressed disease-associated genes compared to the cognitively healthy controls, and five distinct cell populations. Overall, alterations of RNA and protein metabolism, inflammatory processes, and signal transduction were observed in multiple cell populations, suggesting their role in Alzheimer's disease-related olfactory mucosa pathophysiology. Furthermore, the single-cell RNA-sequencing proposed alterations in gene expression of mitochondrially located genes in AD OM cells, which were verified by functional assays, demonstrating altered mitochondrial respiration and a reduction of ATP production. Our results reveal disease-related changes of olfactory mucosal cells in Alzheimer's disease and demonstrate the utility of single-cell RNA sequencing data for investigating molecular and cellular mechanisms associated with the disease.

Patient Self-Assessment and Acoustic Voice Analysis in Screening of Postoperative Vocal Fold Paresis and Paralysis.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the utility of two items in vocal fold paresis and paralysis screening after thyroid and parathyroid surgery: patient self-assessment of voice using the Voice Handicap Index and computer-based acoustic voice analysis using the Multi-Dimensional Voice Program. METHODS: This was a prospective study of 181 patients who underwent thyroid or parathyroid surgery over a 1-year study period (2017). Preoperatively, all patients underwent laryngoscopic vocal fold inspection and acoustic voice analysis, and they completed the Voice Handicap Index questionnaire. Postoperatively, all patients underwent laryngoscopy prior to hospital discharge; 2 weeks after the surgery, they completed the Voice Handicap Index questionnaire a second time. Two weeks postoperatively, patients with vocal fold paresis or paralysis and 20 randomly selected controls without vocal fold paresis or paralysis underwent a follow-up acoustic voice analysis. RESULTS: Fourteen patients had a new postoperative vocal fold paresis or paralysis. Postoperatively, the total Voice Handicap Index score was significantly higher (p = 0.040) and the change between preoperative and postoperative scores was greater (p = 0.028) in vocal fold paresis or paralysis patients. A total postoperative Voice Handicap Index score > 30 had 55% sensitivity, and 90% specificity, for vocal fold paresis or paralysis. In the postoperative Multi-Dimensional Voice Program analysis, vocal fold paresis or paralysis patients had significantly more jitter (p = 0.044). Postoperative jitter > 1.33 corresponded to 55% sensitivity, and 95% specificity, for vocal fold paresis or paralysis. CONCLUSIONS: In identifying postoperative vocal fold paresis or paralysis, patient self-assessment and jitter in acoustic voice analysis have high specificity but poor sensitivity. Without routine laryngoscopy, approximately half of the patients with postoperative vocal fold paresis or paralysis could be overlooked. However, if the patient has no complaints of voice disturbance 2 weeks after thyroid or parathyroid surgery, the likelihood of vocal fold paresis or paralysis is low.

Satisfaction of young ENT surgeons with their work. A Finnish national study.

The objective was to investigate work satisfaction among recently graduated otorhinolaryngologist - head and neck surgeons - (ENT surgeons). An electronic questionnaire was sent to all ENT surgeons graduated in Finland during a ten-year period. Answers about work satisfaction were analyzed in detail with regards to age, gender, university of specialist training, experience, place of work and further education.Altogether 125/129 (96.9%) responded. The majority (87.8%) of the respondents enjoyed their current main occupation. The older age group (≥40 vs <40 years) was more satisfied (93.7% vs. 81.7%; p=0.042). Consultation opportunities and workplace atmosphere were reported as good by 85.6% and 90.4% of the respondents, respectively. Training opportunities were considered good by 82.4%, albeit by only 60% of the private physicians (p=0.047). Private sector practitioners were also less satisfied with the versatility of their work (p<0.001). Work at a university hospital was considered more strenuous (p<0.001). Over half (54.8%) felt insecure about continuation of their employment status. Most of the recently graduated Finnish ENT surgeons are satisfied with their current occupation, consultation opportunities and workplace atmosphere. However, work at university hospitals in particular was considered often strenuous and over half of the respondents felt insecure about the continuity of their employment.

Employment status of young otorhinolaryngologists in Finland during a 10-year period.

We determined the employment status of recently graduated otorhinolaryngologist-head and neck surgeons (ENT doctors) in Finland during the past 10 years. We also investigated the job vacancy rate of the Departments of Otorhinolaryngology-Head and Neck Surgery (Department of ORL-HNS). An electronic questionnaire was sent to all ENT doctors who had graduated during 2007-2017 and to chief physicians of all Departments of ORL-HNS. Chi-square and Fisher's test were used in the analyses. Altogether 129 ENT doctors had graduated and 125 (96.9%) responded. Thirty (24%) physicians had been employed in a position that did not correspond to their ENT doctor training. All 30 chief physicians responded and a total of 306 physicians were working at their departments (215 ENT doctors, 91 residents). However, there were only 241 available positions (197 for ENT doctors, 44 for residents). It was estimated that 65 ENT doctors would retire within 10 years. At the moment there does not seem to be a significant shortage of ENT doctors in Finland. The current national volume of resident intake in the ENT training programme is twofold in comparison with the estimated retirement rate in the public sector.