Disruption of exploratory behavior and olfactory memory in cockroaches exposed to sublethal doses of the neonicotinoid Thiamethoxam.

Neonicotinoid insecticides (NNI) are agonists of insect nicotinic acetylcholine receptors (nAChR) that induce non-elucidate mechanisms of abnormal behavior in insects. In this work, we investigated the effects of sublethal doses of the neonicotinoid thiamethoxam (TMX) on neurochemical and physiological parameters in cockroaches. Sublethal doses of TMX (0.01-10 ng.g-1 body mass) caused significant alterations in most of the neurophysiological parameters evaluated. TMX reduced sustained locomotor activity by 19.9-25.8 %, depending on the dose. Leg grooming activity increased by 124.5 ± 3.4 %, 158.7 ± 3.5 %, 168.3 ± 3.4 %, and 160.4 ± 3.4 % (mean ± SEM) with TMX doses of 0.01, 0.1, 1, and 10 ng.g-1, respectively. Exploratory activity was significantly reduced only at the lowest TMX dose (0.01 ng.g-1) - the time spent immobile increased from 30 % to ∼45 %, whereas none of the doses affected the walking speed. Treatment with TMX (0.01 ng.g-1) markedly reduced the olfactory sensitivity of the cockroaches and also reduced the mechanosensory action potential amplitude, rise time and decay time by 61.2 ± 19 %, 50 ± 4 %, and 76.8 ± 9.5 %, respectively. In semi-isolated heart preparations, TMX caused positive chronotropism (increases of 34.7 ± 15.9 %, 26.8 ± 7.8 %, 43.0 ± 16.5 %, and 19.0 ± 13.7 % for 0.01, 0.1, 1, and 10 ng of TMX, respectively). TMX attenuated the activity of glutathione-S-transferase by 35.1 ± 6.4 % at the highest dose tested (10 ng.g-1). TMX caused alterations in the metal ion content of cockroach brains that varied with the dose tested and the ion examined. These findings indicate that sublethal doses of TMX can interfere with normal neurological function in cockroaches and disrupt brain metal ion homeostasis.

Dose-dependent responses: a preliminary investigation into the olfactory effects of essential oil concentrations on canine behavior.

The positive impact of essential oils (EOs) on stress release has been demonstrated in both humans and dogs. Among the EOs known for their anxiety-reducing properties, including Cananga odorata, Citrus aurantium, Cupressus sempervirens, Lavandula angustifolia, and Litsea citrata, there is a lack of consensus on the optimal concentration for efficacy. This exploratory study sought to investigate the effects of olfactory enrichment with a blend of these EOs on dogs introduced to an unfamiliar environment. The authors sought to determine the minimum concentration required to achieve increased relaxation. In a randomized controlled crossover study design, 54 dogs were exposed to 0, 1, 5, and 10 drops of the EO blend applied to their collars before entering an unfamiliar room with their owners. Behavioral observations were employed to quantify the total duration of activity and relaxation related behaviours for each dog under each treatment condition. A significant difference in panting was identified among the treatments (χ2(3) = 9.88; p = 0.020). Dunn-Bonferroni post-hoc tests revealed a significant reduction in panting during the 10 drops treatment compared to the control treatment (p = 0.047). No significant differences were observed for other behaviors. To provide a comprehensive overview of behavioral tendencies in this canine population, owners also completed the Canine Behavioral Assessment and Research Questionnaire (C-BARQ), revealing low scores for anxiety in the study group. These preliminary findings suggest that a concentration of 10 drops of the EO blend on a dog's collar induces increased relaxation, specifically reflected in decreased panting behavior. Lower concentrations did not exhibit a significant relationship with the observed behaviors. These initial findings underscore the importance of exposing dogs to an appropriate concentration of EOs when exploring their potential benefits on welfare among dogs with low anxiety levels. Further research in this area is crucial for a comprehensive understanding of the potential benefits of EOs for canine welfare.

Screening olfaction under dupilumab in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently leads to olfactory dysfunction. This study aimed to assess the impact of dupilumab on CRSwNP patients, focusing on olfactory outcomes and potential correlations with other clinical factors. METHODS: CRSwNP patients eligible for dupilumab therapy received subcutaneous Dupixent® injections every two weeks (300mg/2ml dupilumab). The 12-item Sniffin' Sticks Test (SST-12), fractional exhaled nitric oxide (FeNO) and Nasal Polyp Score (NPS) were assessed at baseline and after one, three, and six months. Patients also completed the Sino-Nasal Outcome Test (SNOT-22) weekly. RESULTS: 26 CRSwNP patients were included. After one month, dupilumab led to substantial reductions in FeNO, SNOT scores, andNPS, whereas SST-12 scores improved significantly only after three months. A shift toward normosmia occurred, with 81% achieving normosmia after six months, and a drop in anosmia prevalence to 9.5%. Significant negative correlations between olfaction (SST-12) and polyp severity (NPS) at baseline and after six months were found, while no significant correlations were observed between SST-12 and FeNO or SNOT scores. Age did not correlate with olfaction. CONCLUSIONS: Dupilumab demonstrated efficacy in restoring olfaction in CRSwNP patients. Reaching normosmia in over 80% ofpatients after six months of treatment underscores the drug's effectiveness in managing this challenging symptom.

Steroid responsiveness predicts olfactory function recovery in dupilumab treated CRSwNP.

BACKGROUND: There is no known predictor for olfactory function recovery with dupilumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP). This study assessed whether patient-reported recovery of olfactory function on oral corticosteroids (OCS) is a prognostic factor. METHODS: Retrospective analysis of pre-biological OCS-responsiveness on olfactory functioning (OCS-responsive or OCS-unresponsive; OCS-r and OCR-u, respectively) as predictor for olfactory functioning after 6 months of dupilumab therapy for severe CRSwNP. RESULTS: 212 CRSwNP patients treated with dupilumab were divided between OCS-r (reported improvement of olfactory function with OCS before dupilumab treatment, n = 152), and OCS-u (OCS-unresponsive; no such improvement, n = 60). Olfactory function was tested with Sniffin's Sticks Identification Test (12 pens; SSIT-12). At baseline, both groups had a median SSIT-12 score of 3 / 12 indicating anosmia. Hyposmia and normosmia rates were also comparable (5.9% and 3.3% in OCS-r, respectively; 5.0% and 1.7% in OCS-u, respectively). After 6 months of dupilumab treatment, OCS-r showed higher olfactory scores (median SSIT-12: 8/12; 52.6% hyposmia and 17.8% normosmia) than OCS-u (median SSIT-12: 5/12; 31.7% hyposmia and 3.3% normosmia). The positive predictive value of OCS-responsiveness on scoring <7 (normosmia/hyposmia) on the SSIT-12 after 6 months of dupilumab treatment was 70.4%. Conversely, the negative predictive value of OCS-unresponsiveness on scoring <7 (anosmia) on the SSIT-12 after 6 months of dupilumab treatment was 65.0%. CONCLUSION: Patients who report olfactory function improvement on OCS have a higher chance of recovery of olfactory function during the first six months of treatment with dupilumab than patients who do not.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Intranasal insulin for COVID-19-related smell loss.

BACKGROUND: Quantitative (hyposmia and anosmia) and qualitative (phantosmia and parosmia) olfactory disorders are common consequences of COVID-19 infection found in more than 38% of patients even months after resolution of acute disease. SARS-CoV-2 has tropism for angiotensin-converting enzyme 2 (ACE2) in the respiratory system, suggesting that it is the mechanism of damage to the olfactory neuroepithelium and of involvement at the central nervous system. The olfactory bulb is the organ with the highest insulin uptake in the central nervous system. Insulin increases the production of Growth Factors (GF); therefore, in this study, the administration of intranasal insulin is proposed as a viable treatment for olfactory disturbances. The aim of this study was to obtain improvement in olfaction after 4 weeks of intranasal insulin administration in a group of patients presenting chronic olfactory disturbances secondary to COVID-19 infection, quantified using the Threshold, Discrimination, and Identification (TDI) score based on the Sniffin Sticks®. METHODS: Experimental, longitudinal, prolective and prospective study of patients with a previous diagnosis of COVID-19 in the last 3-18 months and who persisted with anosmia or hyposmia. The sample size was calculated with "satulator". The intervention was performed from January to May 2022. Throughout four appointments, a baseline olfactory measurement was obtained using the TDI score based on the Sniffin Sticks® test. In the first three appointments, Gelfoam® cottonoids soaked in 40 IU of NPH insulin were placed on the nasal roof of each nostril for 15 min. Descriptive statistics, student's paired t test and a multiple linear regression were utilized to ascertain statistical significance of the outcome on the TDI score obtained on the fourth and final appointment. RESULTS: 27 patients were included in the study. Table 1 summarizes the sample characteristics. The results exhibit that 93% of the sample had an improvement. The initial mean TDI score was 67% (63-71) compared to the final mean of 83% (80-86, p < 0.01). TDI subsection analysis is shown in Table 2. There was no significant difference in pre-intervention and post-intervention glucose measurements after the intranasal insulin administration. CONCLUSIONS: The administration of intranasal insulin has promising results, pointing towards an alternative of treatment for chronic olfactory disturbances secondary to neuroepithelial damage caused by upper respiratory tract infections. Furthermore, this is the first study to use a three-point assessment of olfaction in post-COVID-19 patients, while using the Sniffin Sticks® TDI score adapted to Latin Spanish.

In healthy subjects nasal nitric oxide does not correlate with olfactory sensitivity, trigeminal sensitivity, and nasal airflow.

OBJECTIVE: The aim of the study was to determine the relationship between nasal nitric oxide (nNO) and olfactory sensitivity, trigeminal sensitivity and nasal airflow in healthy subjects. STUDY DESIGN: This is a correlational study. SETTING: This study was carried out in a tertiary referral centre. PARTICIPANTS: Forty healthy participants were recruited. MAIN OUTCOME MEASURES: nNO was measured using a chemiluminescence analyser (Niox Vero® , Circassia AB, Uppsala, Sweden), olfactory sensitivity was determined using phenyl ethyl alcohol odour thresholds using the 'Sniffin' Sticks', trigeminal sensitivity was assessed with carbon dioxide delivered by an automated device, and nasal airflow was measured using the peak nasal inspiratory flow (PNIF). RESULTS: The median nNO was 518 ppb (IQR =333) in the right nostril, and it was 567 ppb (IQR = 314) in the left nostril. The median odour threshold was 7.1 (IQR = 4.4), the median CO2 threshold was 919 ms (IQR = 1297) and the mean PNIF was 108 L/min (SEM = 4.9). nNO did not correlate significantly with odour threshold, CO2 threshold or PNIF (Spearman's |ρ|  <0.15, p > .18). CONCLUSION: In healthy subjects, nNO does not appear to be associated with olfactory sensitivity, trigeminal sensitivity and PNIF.

The efficacy of systemic administration of lipopolysaccharide in modelling pre-motor Parkinson's disease in C57BL/6 mice.

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterised by the loss of dopaminergic neurons in the substantia nigra. Mounting evidence indicates a crucial role of inflammation and concomitant oxidative stress in the disease progression. Therefore, the aim of this study was to investigate the ability of systemically administered lipopolysaccharide (LPS) to induce motor and non-motor symptoms of PD, inflammation, oxidative stress and major neuropathological hallmarks of the disease in regions postulated to be affected, including the olfactory bulb, hippocampus, midbrain and cerebellum. Twenty-one male C57BL/6 mice, approximately 20 weeks old, received a dose of 0.3 mg/kg/day of LPS systemically on 4 consecutive days and behavioural testing was conducted on days 14-18 post-treatment, followed by tissue collection. Systemically administered LPS increased latency time in the buried food seeking test (indicative of olfactory impairment), and decreased time spent in central zone of the open field (anxiety-like behaviour). However, there was no change in latency time in the rotarod test or the expression of tyrosine hydroxylase (TH) in the midbrain. Systemically administered LPS induced increased glial markers GFAP and Iba-1 and oxidative stress marker 3-nitrotyrosine (3-NT) in the olfactory bulb, hippocampus, midbrain and cerebellum, and there were region specific changes in the expression of NFκB, IL-1ß, α-synuclein, TH and BDNF proteins. The model could be useful to further elucidate early non-motor aspects of PD and the possible mechanisms contributing to the non-motor deficits.

ALTERTASTE: improving food pleasure and intake of oncology patients receiving chemotherapy.

ALTERTASTE is a prospective study to evaluate changes in taste/flavor perception and food preferences in patients treated with adjuvant or neoadjuvant chemotherapy for breast or colorectal cancer. The study adopts a longitudinal approach. Taste and odor responsiveness, food preferences and habits, emotions elicited by foods, and quality of life will be measured at six-time points: before chemotherapy (T0), after two cycles (T1, after around 1 month), after four cycles (T2, after around 2 months), after six cycles (T3, after around 4 months), at the end of chemotherapy (T4, after around 6 months) and 3 months after the conclusion of the therapy (T5). In addition, patients will be characterized for oral responsiveness and their psychological traits and attitudes toward food. The ALTERTASTE trial is expected to improve the understanding of the impact of chemotherapy on taste and smell and the repercussions of these alterations on food behaviors. Furthermore, the trial aims to develop an easy and reliable procedure to test smell, taste and food behavior alterations to allow a routine measure with patients. Clinical trial registration: NCT04495387 (ClinicalTrials.gov).

Lay abstract Malnutrition (under- or over-nutrition) is highly prevalent in cancer patients receiving chemotherapy and is an important predictor of morbidity, mortality, treatment response and toxicity. Alterations in taste and smell are frequently reported as side effects of chemotherapy and may contribute strongly to malnutrition through an impact on eating behaviors and to a worse quality of life. ALTERTASTE is a prospective longitudinal study to evaluate changes in taste/flavor perception and food preferences in patients treated with chemotherapy for breast, colon or rectal cancer. Taste and odor responsiveness, food preferences and habits, emotions elicited by foods, and quality of life will be measured at six-time points: before chemotherapy (T0), after two cycles (T1, after around 1 month), after four cycles (T2, after around 2 months), after six cycles (T3, after around 4 months), at the end of chemotherapy (T4, after around 6 months) and 3 months after the conclusion of the therapy (T5). In addition, patients will be characterized for oral responsiveness and psychological traits and attitudes toward food. The ALTERTASTE trial is expected to improve the understanding of the impact of chemotherapy on taste and smell and the repercussions of these alterations on food behaviors.

The odorant metabolizing enzyme UGT2A1: Immunolocalization and impact of the modulation of its activity on the olfactory response.

Odorant metabolizing enzymes (OMEs) are expressed in the olfactory epithelium (OE) where they play a significant role in the peripheral olfactory process by catalyzing the fast biotransformation of odorants leading either to their elimination or to the synthesis of new odorant stimuli. The large family of OMEs gathers different classes which interact with a myriad of odorants alike and complementary to olfactory receptors. Thus, it is necessary to increase our knowledge on OMEs to better understand their function in the physiological process of olfaction. This study focused on a major olfactory UDP-glucuronosyltransferase (UGT): UGT2A1. Immunohistochemistry and immunogold electronic microscopy allowed to localize its expression in the apical part of the sustentacular cells and originally at the plasma membrane of the olfactory cilia of the olfactory sensory neurons, both locations in close vicinity with olfactory receptors. Moreover, using electroolfactogram, we showed that a treatment of the OE with beta-glucuronidase, an enzyme which counterbalance the UGTs activity, increased the response to eugenol which is a strong odorant UGT substrate. Altogether, the results supported the function of the olfactory UGTs in the vertebrate olfactory perireceptor process.

Chemotherapy-induced taste and smell changes influence food perception in cancer patients.

PURPOSE: Chemotherapy-induced taste and smell alterations may have a negative impact on the quality of life and nutritional status. A prominent issue when dealing with taste and smell alterations and their consequences on food behavior and well-being lies in the variation arising from individual differences in chemosensory perceptions. The main aim of this study was to examine the effect of individuals' variation in the severity of taste and smell alterations relative to the stage of chemotherapy on self-reported food behavior and food perception. METHODS: Eighty-nine cancer patients completed a questionnaire subdivided into two parts: a chemosensory part that allowed classification of patients in three groups ("no alterations," "moderate alterations," and "severe alterations") and a food behavior part. RESULTS: The results highlighted a negative impact of chemosensory alterations on food perception. Compared with patients without taste and smell alterations, patients with severe chemosensory alterations reported significantly more frequent food perception problems, including modification of the perceived taste of food, finding bad taste in all food, and being unable to perceive food taste. Whereas 72% of patients with severe alterations were in late stage, only 37% of patients were in late stage in the no alterations group, indicating an effect of the treatment stage on taste and smell alterations. CONCLUSION: Our results underlie the importance of providing specific attention to the severity of chemotherapy-induced taste and smell alterations and considering the individual differences among patients for a better nutritional management.

The effect of chemotherapy on olfactory function and mucociliary clearance.

OBJECTIVES: Olfactory sensory neurons and the olfactory mucosa are both important for optimal olfactory function. The potential nasal mucosal toxicity of chemotherapy regimens has not been assessed yet. The aim of this study was to objectively investigate the effect of chemotherapy on mucociliary clearance and olfactory function and to evaluate whether this effect differs between different chemotherapy regimens and age groups. PATIENTS AND METHODS: The study included consecutive patients admitted for the treatment of a variety of primary tumors (except head and neck and brain malignancies). Patients were evaluated for olfaction and mucociliary clearance before and immediately after completing the last session of chemotherapy cycles, according to the therapeutic protocol. For objective evaluation, the saccharine test was used for mucociliary clearance and the Sniffin' Sticks test for olfactory function. Of the 46 initial patients, 30 completed the study. Groups were formed according to the chemotherapy regimen (four groups: CA (doxorubicin + cyclophosphamide), Folfox (oxaliplatin +5-FU + folinic acid), DCF (docetaxel + cisplatin +5-FU), and GC (gemcitabine + cisplatin)) and according to age (two groups: < 55 years and > 55 years). RESULTS: In the overall analyses, significant deterioration was noted in both mucociliary clearance time and smell scores (olfactory threshold (OT), olfactory discrimination (OD), olfactory identification (OI), and the composite threshold-discrimination-identification (TDI) score). The changes in these scores showed no significant differences between chemotherapy groups. The decrease in OT and global TDI scores was more severe in the younger age group. CONCLUSIONS: Chemotherapy impairs both the mucociliary clearance and olfactory function in cancer patients. This might reflect the collective negative effect of chemotherapy on olfactory function, not only through the neurocytotoxic effect but also the cytotoxic effect on the nasal mucosa. In addition, the reduction in olfactory threshold and total olfactory function scores was seen to be more profound in younger patients, which could have been due to higher initial scores.

Floral tea polyphenols can improve honey bee memory retention and olfactory sensitivity.

Animal-pollinated plants face a common problem, how their defensive anti-herbivore compounds may impair or alter pollinator behavior. Evolution has tailored multiple solutions, which largely involve pollinator tolerance or manipulation, to the benefit of the plant, not the removal of these compounds from pollen or nectar. The tea plant, Camilla sinensis, is famous for the caffeine and tea polyphenols (TP) that it produces in its leaves. However, these compounds are also found in its nectar, which honey bees readily collect. We examined the effects of these compounds on bee foraging choices, learning, memory, and olfactory sensitivity. Foragers preferred a sucrose feeder with 100 µg or 10 µg TP/ml over a control feeder. Caffeine, but not TP, weakly increased honey bee learning. Both caffeine and TP significantly increased memory retention, even when tested 7 d after the last learning trial. In addition, TP generally elevated EAG responsiveness to alarm pheromone odors. These results demonstrate that other secondary plant compounds, not only caffeine, can attract pollinators and influence their learning and memory.

Letter to the editor: Study Summary - Randomized Control Trial of Omega-3 Fatty Acid Supplementation for the Treatment of COVID-19 Related Olfactory Dysfunction.

OBJECTIVES: To evaluate a therapeutic role for omega-3 fatty acid supplementation in the treatment of olfactory dysfunction associated with COVID-19 infection TRIAL DESIGN: Randomized, double-blinded, placebo-controlled trial PARTICIPANTS: Eligible patients are adults with self-reported new-onset olfactory dysfunction of any duration associated with laboratory-confirmed or clinically suspected COVID-19 patients. Exclusion criteria include patients with pre-existing olfactory dysfunction, history of chronic rhinosinusitis or history of sinus surgery, current use of nasal steroid sprays or omega-3 supplementation, fish allergy, or inability to provide informed consent for any reason. The trial is conducted at Mount Sinai Hospital INTERVENTION AND COMPARATOR: The intervention group will receive 2000 mg daily of omega-3 supplementation in the form of two "Fish Oil, Ultra Omega-3" capsules (product of Pharmavite®) daily. The comparator group will take 2 placebo capsules of identical size, shape, and odor daily for 6 weeks. MAIN OUTCOMES: Each subject will take a Brief Smell Identification Test at study enrolment and completion after 6 weeks. The primary outcome will be change in Brief Smell Identification Test over the 6-week period. RANDOMISATION: Patients will be randomized by the Investigational Drug Pharmacy at the Icahn School of Medicine at Sinai via a computer-generated sequence in a 1:1 allocation to treatment or control arms. BLINDING (MASKING): Both participants and researchers will be blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): There will be 88 participants randomized to each group. A total of 176 participants will be randomized. TRIAL STATUS: Protocol Version 1, 8/3/2020 Recruitment is ongoing, started 8/5/2020 with estimated completion 11/30/2020. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov with Protocol Identifier: NCT04495816 . TRIAL REGISTRATION: ClinicalTrials.gov, NCT04495816 . Registered 3 August 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).

Genomic approach to explore altered signaling networks of olfaction in response to diesel exhaust particles in mice.

Airborne pollutants have detrimental effect on the human body and the environment. Diesel exhaust particles (DEPs) are known to be major component of particulate matter (PM) and cause respiratory diseases and neurotoxicity. However, the effects of air pollutants on the sensory nervous system, especially on the olfactory sense, have not been well studied. Herein, we aimed to explore DEP-induced changes in the olfactory perception process. Olfactory sensitivity test was performed after DEP inhalation in mice. Microarray was conducted to determine the differentially expressed genes, which were then utilized to build a network focused on neurotoxicity. Exposure to DEPs significantly reduced sniffing in mice, indicating a disturbance in the olfactory perception process. Through network analysis, we proposed five genes (Cfap69, Cyp26b1, Il1b, Il6, and Synpr) as biomarker candidates for DEP-mediated olfactory dysfunction. Changes in their expression might provoke malfunction of sensory transduction by inhibiting olfactory receptors, neurite outgrowth, and axonal guidance as well as lead to failure of recovery from neuroinflammatory damage through inhibition of nerve regeneration. Thus, we suggest the potential mechanism underlying DEPs-mediated olfactory disorders using genomic approach. Our study will be helpful to future researchers to assess an individual's olfactory vulnerability following exposure to inhalational environmental hazards.

Short exposure to cadmium disrupts the olfactory system of zebrafish (Danio rerio) - Relating altered gene expression in the olfactory organ to behavioral deficits.

Fish strongly rely on olfaction as a variety of essential behaviors such as foraging and predator avoidance are mediated by the olfactory system. Cadmium (Cd) is known to impair olfaction and accumulate in the olfactory epithelium (OE) and bulb (OB) of fishes. In the present study, the acute toxicity of Cd on olfaction in zebrafish (Danio rerio) was characterized on the molecular and behavioral level. To this end, quantitative real-time PCR was performed in order to analyze the expression of selected genes in both the OE and OB. Moreover, the response of zebrafish to an alarm cue was investigated. Following 24 h of exposure to Cd, the expression of genes associated with olfactory sensory neurons was reduced in the OE. Furthermore, the antioxidant genes peroxiredoxin 1 (prdx1) and heme oxygenase 1 (hmox1), as well as the metallothionein 2 gene (mt2) were upregulated in the OE, whereas hmox1 and the stress-inducible heat shock protein 70 gene (hsp70) were upregulated in the OB upon exposure to Cd. Following stimulation with a conspecific skin extract, zebrafish displayed a considerable disruption of the antipredator behavior with increasing Cd concentration. Taken together, Cd impaired olfaction in zebrafish, thereby disrupting the antipredator response, which is crucial for the survival of individuals. Cellular stress followed by disruption of olfactory sensory neurons may have contributed to the observed behavioral deficits.

Taste alterations in patients with breast cancer following chemotherapy: a cohort study.

BACKGROUND: Chemotherapy-induced taste and smell alterations in cancer patients are associated with multiple adverse effects, namely, malnutrition, weight loss, and a diminished quality of life. The aim of this prospective study was to identify the incidence of taste alterations following epirubicin and cyclophosphamide (EC) chemotherapy in patients with breast cancer without previous history of cancer or chemotherapy. METHODS: Forty-one patients undergoing EC chemotherapy for breast cancer at Tokai University Hospital were included. A subjective (questionnaire) and an objective (filter paper disk method) assessment for 5 basic tastes were administered on day 4 post-chemotherapy and immediately before the subsequent cycle of chemotherapy for each cycle, in addition to an olfactory evaluation and oral examination. The correlation between subjective and objective taste alterations and factors influencing these alterations were analyzed by statistical means. RESULTS: The mean incidence of subjective taste alteration on the 4th day after chemotherapy was 53%. In each of the 4 cycles, taste alterations decreased to about 9.0% immediately before the next cycle. A significant correlation between subjective and objective assessments was seen only for salty taste, suggesting important differences in subjective versus objective assessment outcomes. A multivariate analysis indicated that age and body surface area influenced taste alterations. CONCLUSIONS: EC chemotherapy induced taste alterations in more than 50% of patients, which decreased to less than 10% immediately before the next chemotherapy cycle. A combination of objective and subjective assessments is essential to evaluate taste alterations induced by EC chemotherapy. These could be used in routine clinical practice.

[Short term olfactory memory and olfactory function after inhalation anesthetic agents: a randomized clinical trial]. / Memória olfativa de curta duração e função olfativa após anestésicos inalatórios: estudo clínico randomizado.

BACKGROUND AND OBJECTIVES: This clinical trial aimed to evaluate the effects of two different inhalation anesthetic agents on postoperative olfactory memory and olfactory function in patients who underwent micro laryngeal surgery. METHODS: This randomized prospective controlled study consisted of 102 consecutive patients with a voice disorder. The patients underwent micro laryngeal surgery for voice disorders under general anesthesia. Patients who did not meet inclusion criteria and/or declined to participate (n=34) were excluded from the study. Patients were divided into two groups. Four patients from Group 1 and four patients from Group 2 were lost to follow-up. Group 1 (n=30) received sevoflurane, and Group 2 (n=30) received desflurane during anesthesia. We compared the results by performing the pre-op and post-op Connecticut Chemosensory Clinical Research Center Olfactory test. RESULTS: Thirty-three patients (55%) were male and 27 (45%) were female. The mean age was 48.18±13.88 years (range: 19-70 years). Preoperative and postoperative olfactory functions did not show a significant difference within the groups postoperatively (p> 0.05). Preoperative and postoperative olfactory memory showed a significant decrease 3hours after the surgery (p <0.05). CONCLUSIONS: Olfactory functions and memory were not affected by desflurane in the early postoperative period. Although sevoflurane did not affect olfactory functions, it had a temporary negative effect on olfactory memory in the early postoperative period.

Associations between Cadmium Exposure and Taste and Smell Dysfunction: Results from the National Health and Nutrition Examination Survey (NHANES), 2011-2014.

BACKGROUND: Cadmium is a ubiquitous environmental pollutant and has been associated with many adverse health outcomes. However, little is known about the effect of cadmium exposure on taste and smell dysfunction. METHODS: We used the National Health and Nutrition Examination Survey (NHANES) 2011-2014 to investigate the associations between blood cadmium and taste and smell dysfunction among 5038 adults aged 40-80 years old. Taste and smell dysfunction were defined by questionnaires, examinations, or both criteria. RESULTS: In survey weighted logistic regression models adjusting for age, gender, race/ethnicity, income-to-poverty ratio (IPR), and education, individuals with a blood cadmium level in the highest tertiles had significantly higher odds of having perceived smell dysfunction (odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.08, 1.84), perceived taste dysfunction (OR = 1.48, 95% CI: 1.16, 1.89), and taste dysfunction defined by both self-reported and objectively measured data (OR = 1.46, 95% CI: 1.03, 2.07). After further adjusting for body mass index (BMI), cigarette smoking, and alcohol drinking, consistent results were observed for perceived taste dysfunction (OR = 1.49, 95% CI: 1.10, 2.00), and no significant associations were found between cadmium exposure and other outcomes. CONCLUSIONS: Our findings suggest that cadmium exposure is associated with perceived taste dysfunction.

Short term olfactory memory and olfactory function after inhalation anesthetic agents: a randomized clinical trial / Memória olfativa de curta duração e função olfativa após anestésicos inalatórios: estudo clínico randomizado

Abstract Background and objectives: This clinical trial aimed to evaluate the effects of two different inhalation anesthetic agents on postoperative olfactory memory and olfactory function in patients who underwent micro laryngeal surgery. Methods: This randomized prospective controlled study consisted of 102 consecutive patients with a voice disorder. The patients underwent micro laryngeal surgery for voice disorders under general anesthesia. Patients who did not meet inclusion criteria and/or declined to participate (n = 34) were excluded from the study. Patients were divided into two groups. Four patients from Group 1 and four patients from Group 2 were lost to follow-up. Group 1 (n = 30) received sevoflurane, and Group 2 (n = 30) received desflurane during anesthesia. We compared the results by performing the pre-op and post-op Connecticut Chemosensory Clinical Research Center Olfactory test. Results: Thirty-three patients (55%) were male and 27 (45%) were female. The mean age was 48.18 ± 13.88 years (range: 19‒70 years). Preoperative and postoperative olfactory functions did not show a significant difference within the groups postoperatively (p > 0.05). Preoperative and postoperative olfactory memory showed a significant decrease 3 hours after the surgery (p < 0.05). Conclusions: Olfactory functions and memory were not affected by desflurane in the early postoperative period. Although sevoflurane did not affect olfactory functions, it had a temporary negative effect on olfactory memory in the early postoperative period.

Resumo Introdução e objetivos: O estudo avaliou o efeito pós-operatório de dois agentes anestésicos inalatórios distintos na memória olfativa de curta duração e na função olfativa em pacientes submetidos à microcirurgia de laringe. Método: O estudo prospectivo controlado randomizado avaliou, consecutivamente, 102 pacientes com alteração vocal submetidos à microcirurgia de laringe sob anestesia geral. Trinta e quatro pacientes não obedeceram aos critérios de inclusão e/ou não aceitaram participar do estudo e foram excluídos. Os pacientes foram divididos em dois grupos. Quatro pacientes do Grupo 1 e quatro do Grupo 2 foram perdidos durante o seguimento. O Grupo 1 (n = 30) recebeu sevoflurano durante a anestesia e o Grupo 2 (n = 30), desflurano. Comparamos resultados pré e pós-operatórios de memória olfativa e funções olfativas, realizando o Connecticut Chemosensory Clinical Research Center Olfactory test. Resultados: Foram incluídos um total de 33 (55%) homens e 27 (45%) mulheres. A idade média foi 48,18 ± 13,88 anos (variação: 19-70 anos). As funções olfativas pré e pós-operatórias não apresentaram diferença estatisticamente significante dentro dos grupos no pós-operatório (p > 0,05). A memória olfativa pré e pós-operatória não mostrou diminuição estatisticamente significante quando avaliada três horas após a cirurgia (p< 0,05). Conclusões: Memória e funções olfativas não foram alteradas pelo desflurano no pós-operatório imediato. Embora o sevoflurano não tenha alterado as funções olfativas, causou efeito temporário negativo na memória olfativa no pós-operatório imediato.