Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception.

A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the "gain-of-editing" variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the "loss-of-editing" (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors-both Unc80 deficient (Unc80+/-) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80's neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity.

Olfactory stimulus as environmental enrichment for shelter dogs: a pilot study / Estímulo olfativo como enriquecimento ambiental para cães de abrigo: um estudo piloto

Environmental enrichment techniques include olfactory stimuli for improving animal welfare. This study aimed to analyze the reactions of 41 shelter dogs exposed to odorous stimuli, such as the method used in another study on wild canids. The focal animal method analyzed the dogs' reactions, with all behaviors recorded. Behavioral responses were classified as positive (P+), negative (N-), or other (Ot). Independent variables were all dogs and the size of the packs. The behavior between the basal (without stimulus), exposure, and after-stimulus withdrawal was analyzed. For all dogs, olfactory stimuli significantly increased P+ (P=0.001) and N- (P=0.004), contrasting with the decrement of Ot behaviors (P=0.001) from the basal to the exposure phase. After the withdrawal of the stimuli, P+, N-, and Ot behaviors returned to basal levels (P>0.05). There were no significant differences (P>0.05) in the conduct of small or large packs exposed to stimuli. Dogs are sensitive to olfactory stimuli, but arousal is generalized to P+ and N-. It is undesirable to an N- increase for improvement of animal welfare. Contrary to what was observed in a study with wild canids, the method failed in shelter dogs because N- was increased. The introduction of sudden novelty (olfactory stimulus) in an impoverished shelter environment may have caused excitement in the dogs. It is suggested that changes in the method, such as stimuli exposition to each dog in an isolated room, are necessary to increase sheltered dog well-being.(AU)

As técnicas de enriquecimento ambiental incluem estímulos olfativos para aumentar o bem-estar animal. O objetivo deste estudo foi analisar as reações de 41 cães de abrigo expostos a estímulos odoríferos, como o método utilizado em outro estudo com canídeos selvagens. As reações dos cães foram analisadas pelo método animal focal, com todos os comportamentos registrados. As respostas comportamentais foram classificadas como positivas (P+), negativas (N-) ou outras (Ot). As variáveis independentes foram todos os cães e o tamanho das matilhas. Foi analisado o comportamento entre o basal (sem estímulo), exposição e após a retirada do estímulo. Para todos os cães, os estímulos olfativos aumentaram significativamente P+ (P=0,001) e N- (P=0,004), contrastando com a diminuição dos comportamentos Ot (P=0,001) da fase basal para a de exposição. Após a retirada dos estímulos, os comportamentos P+, N- e Ot retornaram aos níveis basais (P>0,05). Não houve diferenças significativas (P>0,05) no comportamento de matilhas pequenas ou grandes expostas a estímulos. Os cães são sensíveis a estímulos olfativos, mas a excitação parece ser generalizada para ambos, P+ e N-. É indesejável um aumento de N- para melhoria do bem-estar animal. Ao contrário do que foi observado em um estudo com canídeos selvagens, o método falhou em abrigar cães porque o N- foi aumentado. A introdução de uma novidade repentina (estímulo olfativo) em um ambiente de abrigo empobrecido, pode ter causado excitação exagerada nos cães. Sugere-se alterações no método, como a exposição de estímulos a cada cão em uma sala isolada necessária para aumentar o bem-estar do cão abrigado.(AU)

Evaluación del olfato en pacientes operados por adenoma hipofisario con acceso transesfenoidal en el Instituto de Neurocirugía Dr. Asenjo / Olfactory evaluation in patients operated for pituitary adenoma with transsphenoidal access at the Instituto de Neurocirugía Dr. Asenjo

Introducción: El olfato tiene una gran importancia en la calidad de vida. Los accesos quirúrgicos selares pueden realizarse por vía transcraneal, transeptal y transnasal, y pueden generar hiposmia al incluir resecciones que afectan a la mucosa olfatoria. Objetivo: Determinar la existencia de alteración persistente en el olfato ocasionado por los accesos quirúrgicos transeptal y transnasal en pacientes operados por adenoma hipofisiario en el Instituto de Neurocirugía Dr. Asenjo. Material y Método: Estudio prospectivo de cohorte con comparación de resultados olfatorios ("sniffin' sticks" versión extendida) y encuesta SNOT-22 pre y poscirugía por adenoma hipofisiario por vía transeptal o transnasal. Se utilizaron medidas estadísticas de comparación de pruebas pareadas paramétricas y no paramétricas según las características de las variables evaluadas. Resultados: Se reclutaron 60 pacientes, completando el seguimiento 39. En 21 se realizó acceso transeptal y en 18 transnasal. Al analizar el total de pacientes y por cada técnica quirúrgica, no hubo diferencias significativas en los puntajes del "sniffin' sticks" versión extendida y tampoco en SNOT-22. Conclusión: La literatura describe incidencia de hiposmia posoperatoria muy variable, entre 0% y 88%, con mediciones subjetivas y objetivas. Existe una predilección por la técnica endoscópica a nivel internacional, por lo que cuenta con estudios de mejor calidad. A nivel nacional existen dos estudios previos que han encontrado tasas de hiposmia posoperatoria de 10% y 14%. En este estudio no hubo diferencias significativas en los puntajes obtenidos en la prueba de olfato entre el pre y posoperatorio.

Introduction: Olfaction is of great importance in quality of life. Surgical accesses to the sellar region can be performed by transcranial, transseptal, and transnasal routes, which can generate hyposmia when including resections that affect the olfactory mucosa. Aim: To determine the existence of persistent alteration in olfaction caused by transseptal and transnasal surgical accesses in patients operated for pituitary adenoma at the Instituto de Neurocirugía Dr. Asenjo. Material and Method: Prospective cohort study with comparison of olfactory results ("sniffin' sticks" extended version) and SNOT-22 survey pre and post transseptal or transnasal surgery for pituitary adenoma. Parametric and non-parametric paired test comparison statistics were used according to the characteristics of the variables evaluated. Results: 60 patients were recruited and 39 completed follow-up. 21 patients underwent transseptal access and 18 underwent transnasal access. When analyzing the total number of patients and for each surgical technique, there were no significant differences in the scores obtained in the "sniffin' sticks" extended version and neither for the SNOT-22. Conclusion: The literature describes a highly variable incidence of postoperative hyposmia, between 0% and 88%, with subjective and objective measurements. There is a predilection for the endoscopic technique at an international level, which is why it has better quality studies. At the national level there are two previous studies that have found postoperative hyposmia rates of 10% and 14%. In this study there were no significant differences in the scores obtained between pre and postoperative olfaction test.

Polyphenism in Antennal Sensilla Among Different Adult Morphs of Nonhost-Alternating, Holocyclic Sitobion avenae (Hemiptera: Aphididae).

Aphids, mainly distributed in temperate zones, exhibit seasonal generation-alternating phenomena. Across the life cycle, different morphs are produced. Sitobion avenae (Fabricius 1775) is a major pest of wheat worldwide. To elucidate olfactory perception of morph-specific behavior across their life cycle, we investigated antennal sensilla among seven morphs using scanning electron microscopy. Trichoid, placoid, coeloconic, and campaniform sensilla were identified. Trichoid sensilla, big multiporous placoid sensilla (primary rhinarium), a group of sensilla (primary rhinaria), and campaniform sensilla showed similar distribution and resemblance among morphs, whereas small multiporous placoid sensilla (secondary rhinaria) exhibited obvious differences. Compared to apterous morphs, alate morphs possessed a greater abundance of secondary rhinaria, with the greatest found in males on antennal segments III-V. Alate virginoparae and alate sexuparae ranged from six to fourteen rhinaria on antennal segment III. Fundatrices, apterous virginoparae and apterous sexuparae only had one or two secondary rhinaria on antennal segment III while they disappeared in oviparae. Secondary rhinaria, lying in a cuticle cavity, are convex or concave in their central part. In males, both forms were present, with a greater proportion of convex form than that of the concave form. Fundatrices and virginoparae had the convex form while sexuparae had the concave form. Polyphenism of secondary rhinaria might suggest their association with the olfactory functions of morph-specific behavior. These results have improved our understanding of the adaptive evolution of the antennal sensilla in nonhost-alternating, holocyclic aphids.

Olfactory function testing before and after anesthesia.

This study aimed to determine whether anesthesia would affect olfactory function. Patients who were admitted for surgical intervention that did not include the nasal cavity and paranasal sinuses were included in this prospective cohort study. Structured medical history was taken from the patients, including the following: age, sex, smoking history, alcohol intake, current medications, and sleep deficits prior to surgery. Before surgery, patients were asked for a self-rating of their olfactory function. Olfactory function was also measured using Sniffin' Sticks comprising measures of odor threshold, discrimination, and identification. The mean interval between olfactory tests was 6 days (range 3-12 days). Seventy-three patients were included in the study, 34 men and 39 women. Olfactory scores were consistent before and after surgery as indicated by correlative analyses (p < 0.05). Odor thresholds, discrimination, identification, and composite TDI scores did not change significantly, whereas odor identification scores increased (p = 0.011) after surgery. In conclusion, post-operative olfactory scores remained stable. However, identification scores exhibited a slight increase which can be attributed to a retest effect. Overall, the present results indicate that surgery outside of the nasal and paranasal sinus region performed in general anesthesia has no major effect on the sense of smell.

Integrating pheromonal and spatial information in the amygdalo-hippocampal network.

Vomeronasal information is critical in mice for territorial behavior. Consequently, learning the territorial spatial structure should incorporate the vomeronasal signals indicating individual identity into the hippocampal cognitive map. In this work we show in mice that navigating a virtual environment induces synchronic activity, with causality in both directionalities, between the vomeronasal amygdala and the dorsal CA1 of the hippocampus in the theta frequency range. The detection of urine stimuli induces synaptic plasticity in the vomeronasal pathway and the dorsal hippocampus, even in animals with experimentally induced anosmia. In the dorsal hippocampus, this plasticity is associated with the overexpression of pAKT and pGSK3ß. An amygdalo-entorhino-hippocampal circuit likely underlies this effect of pheromonal information on hippocampal learning. This circuit likely constitutes the neural substrate of territorial behavior in mice, and it allows the integration of social and spatial information.

Disgusting odours affect the characteristics of the Adaptive Force in contrast to neutral and pleasant odours.

The olfactomotor system is especially investigated by examining the sniffing in reaction to olfactory stimuli. The motor output of respiratory-independent muscles was seldomly considered regarding possible influences of smells. The Adaptive Force (AF) characterizes the capability of the neuromuscular system to adapt to external forces in a holding manner and was suggested to be more vulnerable to possible interfering stimuli due to the underlying complex control processes. The aim of this pilot study was to measure the effects of olfactory inputs on the AF of the hip and elbow flexors, respectively. The AF of 10 subjects was examined manually by experienced testers while smelling at sniffing sticks with neutral, pleasant or disgusting odours. The reaction force and the limb position were recorded by a handheld device. The results show, inter alia, a significantly lower maximal isometric AF and a significantly higher AF at the onset of oscillations by perceiving disgusting odours compared to pleasant or neutral odours (p < 0.001). The adaptive holding capacity seems to reflect the functionality of the neuromuscular control, which can be impaired by disgusting olfactory inputs. An undisturbed functioning neuromuscular system appears to be characterized by a proper length tension control and by an earlier onset of mutual oscillations during an external force increase. This highlights the strong connection of olfaction and motor control also regarding respiratory-independent muscles.

Sniffer dogs can identify lung cancer patients from breath and urine samples.

BACKGROUND: Lung cancer is the most common oncological cause of death in the Western world. Early diagnosis is critical for successful treatment. However, no effective screening methods exist. A promising approach could be the use of volatile organic compounds as diagnostic biomarkers. To date there are several studies, in which dogs were trained to discriminate cancer samples from controls. In this study we evaluated the abilities of specifically trained dogs to distinguish samples derived from lung cancer patients of various tumor stages from matched healthy controls. METHODS: This single center, double-blind clinical trial was approved by the local ethics committee, project no FF20/2016. The dog was conditioned with urine and breath samples of 36 cancer patients and 150 controls; afterwards, further 246 patients were included: 41 lung cancer patients comprising all stages and 205 healthy controls. From each patient two breath and urine samples were collected and shock frozen. Only samples from new subjects were presented to the dog during study phase randomized, double-blinded. This resulted in a specific conditioned reaction pointing to the cancer sample. RESULTS: Using a combination of urine and breath samples, the dog correctly predicted 40 out of 41 cancer samples, corresponding to an overall detection rate of cancer samples of 97.6% (95% CI [87.1, 99.9%]). Using urine samples only the dog achieved a detection rate of 87.8% (95% CI [73.8, 95.9%]). With breath samples, the dog correctly identified cancer in 32 of 41 samples, resulting in a detection rate of 78% (95% CI [62.4, 89.4%]). CONCLUSIONS: It is known from current literature that breath and urine samples carry VOCs pointing to cancer growth. We conclude that olfactory detection of lung cancer by specifically trained dogs is highly suggestive to be a simple and non-invasive tool to detect lung cancer. To translate this approach into practice further target compounds need to be identified.

Gene therapy rescues olfactory perception in a clinically relevant ciliopathy model of Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a hereditary genetic disorder that results in numerous clinical manifestations including olfactory dysfunction. Of at least 21 BBS-related genes that can carry multiple mutations, a pathogenic mutation, BBS1M390R, is the single most common mutation of clinically diagnosed BBS outcomes. While the deletion of BBS-related genes in mice can cause variable penetrance in different organ systems, the impact of the Bbs1M390R mutation in the olfactory system remains unclear. Using a clinically relevant knock-in mouse model homozygous for Bbs1M390R, we investigated the impact of the mutation on the olfactory system and tested the potential of viral-mediated, wildtype gene replacement therapy to rescue smell loss. The cilia of olfactory sensory neurons (OSNs) in Bbs1M390R/M390R mice were significantly shorter and fewer than those of wild-type mice. Also, both peripheral cellular odor detection and synaptic-dependent activity in the olfactory bulb were significantly decreased in the mutant mice. Furthermore, to gain insight into the degree to which perceptual features are impaired in the mutant mice, we used whole-body plethysmography to quantitatively measure odor-evoked sniffing. The Bbs1M390R/M390R mice showed significantly higher odor detection thresholds (reduced odor sensitivity) compared to wild-type mice; however, their odor discrimination acuity was still well maintained. Importantly, adenoviral expression of Bbs1 in OSNs restored cilia length and re-established both peripheral odorant detection and odor perception. Together, our findings further expand our understanding for the development of gene therapeutic treatment for congenital ciliopathies in the olfactory system.

Olfactory sensory evaluation in newborn children of women infected with COVID-19 during pregnancy / Avaliação sensorial olfativa em crianças recémnascidas de mulheres infectadas com COVID-19 durante a gravidez

INTRODUCTION: In adults, olfactory loss is one of the earliest and most frequent acute clinical manifestations of SARS-CoV-2 infection. The number of children infected with SARS-CoV-2 is relatively small, perhaps due to the lower expression of Angiotensin Converting Enzyme 2 (ACE2) in children compared to adults. Little is known about foetal impairment in mothers infected with SARS-CoV-2. This paper describes an ongoing scientific project on smell perception in infantsOBJECTIVE: The goal of the study is to develop and validate a behavioural evaluative scale of olfactory perception in healthy newborns and to apply this scale to newborn children of women infected with COVID-19 during pregnancy comparing to newborn children of women without COVID-19 infection history, in order to compare these groupsMETHODS: This is a retrospective comparative analytical cohort study of 300 newborns exposed and unexposed to COVID-19 during pregnancy. The data collection will follow the experimental procedure in a previous study that explored odours of the maternal breastmilk, vanilla (sweet) and distilled water (neutral). A coffee smell was implemented as an addition to this previous study in order to include acid/bitterness category to the categories of stimuliDISCUSSION: It is feasible to argue the hypothesis of the involvement of the foetus' olfactory bulb as one of the indelible pathophysiological manifestations to the clinical diagnosis of COVID-19 with neurosensory olfactory deficit in foetuses and newborns affected by intrauterine infection. This study aims to investigate if newborn children of women infected with COVID-19 during pregnancy have olfactory sensory changes. The clinical trial was registered in the Brazilian Registry of Clinical Trials (ReBEC- RBR-65qxs2

INTRODUÇÃO: Em adultos, a perda olfativa é uma das manifestações clínicas agudas mais precoces e frequentes da infecção por SARS-CoV-2. O número de crianças infectadas com SARS-CoV-2 é pequeno, talvez devido à menor expressão da Enzima Conversora da Angiotensina 2 (ACE2) em crianças em comparação com adultos. Pouco se sabe sobre o comprometimento fetal em mães infectadas com SARS-CoV-2. Este artigo descreve um projeto em andamento sobre a percepção olfativa em bebês recém-nascidosOBJETIVO: o objetivo do presente estudo é desenvolver e validar uma escala de avaliação comportamental da percepção olfativa em recém-nascidos saudáveis e aplicá-la a recém-nascidos de mulheres infectadas com COVID-19 durante a gravidez e comparar a recém-nascidos de mulheres sem histórico de infecção por COVID-19MÉTODO: Este é um estudo de coorte analítico comparativo retrospectivo de 300 recém-nascidos expostos e não expostos ao COVID-19 durante a gravidez. A coleta de dados seguirá o procedimento experimental de estudo anterior que explorou odores do leite materno, baunilha (doce) e água destilada (neutro). Um cheiro de café foi implementado como um complemento a este estudo anterior, a fim de incluir a categoria ácido / amargo nas categorias de estímulosDISCUSSÃO: É possível argumentar a hipótese do envolvimento do bulbo olfatório do feto durante a vida intrauterina como uma das manifestações fisiopatológicas indeléveis para o diagnóstico clínico de COVID-19 com déficit olfatório neurossensorial em fetos e recém-nascidos afetados por infecção intrauterina. Este estudo tem como objetivo investigar se filhos recém-nascidos de mulheres infectadas com COVID-19 durante a gravidez apresentam alterações sensoriais olfativas. O ensaio clínico foi registrado no Registro Brasileiro de Ensaios Clínicos (ReBEC- RBR-65qxs2

Enzyme-assisted Solvent Extraction of High-yield Paeonia suffruticosa Andr. Seed Oil and Fatty Acid Composition and Anti-Alzheimer's Disease Activity.

Enzyme-assisted solvent extraction (EASE) of Paeonia suffruticosa Andr. seed oil (PSO) was optimized by response surface methodology (RSM). The fatty acid composition and anti-Alzheimer's disease (AD) activity of PSO were analyzed. An enzyme mixture composed of cellulase and hemicellulase (1:1, w/w) was most effective in determining the extraction yield of PSO. The ideal extraction conditions were a pH value of 5.1, an enzymolysis time of 68 min, and a temperature of 50℃. The average extraction yield of PSO was 38.2 mL/100 g, 37.4% higher than that of untreated peony seed (27.8 mL/100 g). The fatty acid composition of PSO under optimal conditions for EASE was analyzed by gas chromatography-mass spectrometry (GC-MS). The predominant unsaturated fatty acids of PSO were determined to be more than 90.00%, including n-3 α-linolenic acid (43.33%), n-6 linoleic acid (23.40%) and oleic acid (23.59%). In this experiment, the anti-AD effect of PSO was also analyzed by performing learning and memory ability tests with Drosophila. PSO retarded the decrease in climbing ability in AD Drosophila. The 1% and 5% PSO groups were significantly different from the model group (b p < 0.05). The smell short-term memory ability test revealed the number of Drosophila in barrier and barrier-free centrifuge tubes in each group. PSO feeding improved learning and memory in AD Drosophila, with the highest number entering the barrierfree centrifuge tube. The performance index (PI) measured by the Pavlov olfactory avoidance conditioning test also demonstrated the effect of PSO on the learning and memory abilities of Drosophila. The PI of the PSO group was significantly increased compared to that of the model group. HE-stained brain tissue sections of AD Drosophila showed higher neurodegenerative changes, while PSO significantly reduced neurodegenerative damage. These results indicated that PSO can significantly improve the cognitive function of AD Drosophila and may help to prevent AD.

Adenosine A2A receptor neurons in the olfactory bulb mediate odor-guided behaviors in mice.

Depression, rapid eye movement (REM) sleep behavior disorder, and altered olfaction are often present in Parkinson's disease. Our previous studies demonstrated the role of the olfactory bulb (OB) in causing REM sleep disturbances in depression. Furthermore, adenosine A2A receptors (A2AR) which are richly expressed in the OB, play an important role in the regulation of REM sleep. Caffeine, an adenosine A1 receptors and A2AR antagonist, and other A2AR antagonists were reported to improve olfactory function and restore age-related olfactory deficits. Therefore, we hypothesized that the A2AR neurons in the OB may regulate olfaction or odor-guided behaviors in mice. In the present study, we employed chemogenetics to specifically activate or inhibit neuronal activity. Then, buried food test and olfactory habituation/dishabituation test were performed to measure the changes in the mice's olfactory ability. We demonstrated that activation of OB neurons or OB A2AR neurons shortened the latency of buried food test and enhanced olfactory habituation to the same odors and dishabituation to different odors; inhibition of these neurons showed the opposite effects. Photostimulation of ChR2-expressing OB A2AR neuron terminals evoked inward current in the olfactory tubercle (OT) and the piriform cortex (Pir), which was blocked by glutamate receptor antagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7nitroquinoxaline-2,3-dione. Collectively, these results suggest that the OB mediates olfaction via A2AR neurons in mice. Moreover, the excitatory glutamatergic release from OB neurons to the OT and the Pir were found responsible for the olfaction-mediated effects of OB A2AR neurons.

Investigating Olfactory Gene Variation and Odour Identification in Older Adults.

Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour identification. In this study, we sought to find olfactory gene family variants associated with individual and overall odour identification and to examine the relationships between polygenic risk scores (PRS) for olfactory-related phenotypes and olfaction. Participants were Caucasian older adults from the Sydney Memory and Ageing Study and the Older Australian Twins Study with genome-wide genotyping data (n = 1395, mean age = 75.52 ± 6.45). The Brief-Smell Identification Test (BSIT) was administered in both cohorts. PRS were calculated from independent GWAS summary statistics for Alzheimer's disease (AD), white matter hyperintensities (WMH), Parkinson's disease (PD), hippocampal volume and smoking. Associations with olfactory receptor genes (n = 967), previously identified candidate olfaction-related SNPs (n = 36) and different PRS with BSIT scores (total and individual smells) were examined. All of the relationships were analysed using generalised linear mixed models (GLMM), adjusted for age and sex. Genes with suggestive evidence for odour identification were found for 8 of the 12 BSIT items. Thirteen out of 36 candidate SNPs previously identified from the literature were suggestively associated with several individual BSIT items but not total score. PRS for smoking, WMH and PD were negatively associated with chocolate identification. This is the first study to conduct genetic analyses with individual odorant identification, which found suggestive olfactory-related genes and genetic variants for multiple individual BSIT odours. Replication in independent and larger cohorts is needed.

Caenorhabditis elegans as a Diagnostic Aid for Pancreatic Cancer.

OBJECTIVES: Early detection of pancreatic cancer is notoriously difficult. A novel cancer diagnostic method using the ability of nematodes to detect odor of urine samples has been developed (N-NOSE). This method has a high sensitivity and specificity for various cancers; however, it has not yet been verified in pancreatic cancer. We examined the usefulness of this method to aid early diagnosis of pancreatic cancer in a cancer center. METHODS: We collected urine samples and clinical data from patients hospitalized in our division, between July 2017 and February 2019. We excluded patients with a known current or past history of other cancers. We investigated the relationship between the results of N-NOSE and the presence of pancreatic cancer. RESULTS: There were 95 noncancer cases and 104 pancreatic cancer cases. The sensitivity and specificity of N-NOSE for pancreatic cancer were 84.6% (88/104) and 60% (57/95), respectively. N-NOSE was able to detect stages 0 to I pancreatic cancer and had a higher correlation with early-stage pancreatic cancer than advanced stage. CONCLUSIONS: N-NOSE has sufficient sensitivity and specificity for use in clinical practice, and it holds great potential as a diagnostic aid for pancreatic cancer, especially for early-stage pancreatic cancer.

Unusual visual and olfactory perceptions during radiotherapy sessions: an investigation of the organs responsible.

During radiotherapy sessions to treat brain tumors or head-and-neck cancers, some patients experience unusual visual and/or olfactory perceptions. This prospective study sought to answer two questions: (i) what proportion of patients experience these unpleasant sensations?, and (ii) which organs are responsible? Eligible patients had brain or near-orbital tumors treated by helical tomotherapy. All were aged 10 years or older, able to communicate, and interviewed by a radiation oncologist at least once weekly during radiation therapy. If they had experienced such sensations, they were encouraged to join the second phase of the study. The patients were asked to indicate, using a button, when a sensation commenced and ended. The recorded data were collated with the treatment log. Thirty-eight consecutive patients were eligible. Twenty-six experienced visual and 13 olfactory sensations. The radiation doses to the organs related to the visual or olfactory sensations did not differ between patients who reported sensations and those who did not. Seventeen patients were enrolled in the second phase of the study. All 14 with visual sensations reported that the sensations occurred when the X-rays passed at eye level. Olfactory sensations were reported by eight out of nine patients when the X-rays passed through the olfactory epithelium and/or ethmoid sinus level. In conclusion, 68% of patients experienced visual sensations caused by X-rays passing through the level of the eyes, and 34% complained of olfactory sensations. With the exception of one patient, olfactory sensations occurred when the X-rays passed through the levels of the olfactory epithelium and/or ethmoid sinus.

Developmental Profile of Brain Neprilysin Expression Correlates with Olfactory Behaviour of Rats.

A neuropeptidase, neprilysin (NEP), is a major amyloid (Aß)-degrading enzyme involved in the pathogenesis of Alzheimer's disease (AD). The olfactory system is affected early in AD with characteristic Aß accumulation, but data on the dynamics of NEP expression in the olfactory system are absent. Our study demonstrates that NEP mRNA expression in rat olfactory bulbs (OB), entorhinal cortex (ECx), hippocampus (Hip), parietal cortex (PCx) and striatum (Str) increases during the first postnatal month being the highest in the OB and Str. By 3 months, NEP mRNA levels sharply decrease in the ECx, Hip and PCx and by 9 months in the OB, but not in the Str, which correlates with declining olfaction in aged rats tested in the food search paradigm. One-month-old rats subjected to prenatal hypoxia on E14 had lower NEP mRNA levels in the ECx, Hip and PCx (but not in the OB and Str) compared with the control offspring and demonstrated impaired olfaction in the odour preference and food search paradigms. Administration to these rats of a histone deacetylase inhibitor, sodium valproate, restored NEP expression in the ECx, Hip and PCx and improved olfaction. Our data support NEP involvement in olfactory function.

Medial Amygdala Arginine Vasopressin Neurons Regulate Innate Aversion to Cat Odors in Male Mice.

Aversion to environmental cues of predators is an integral part of defensive behaviors in many prey animals. It enhances their survival and probability of future reproduction. At the same time, animals cannot be maximally defended because imperatives of defense usually trade-off with behaviors required for sexual reproduction like display of dominance and production of sexual pheromones. Here, we approach this trade-off through the lens of arginine vasopressin (AVP) neurons within the posterodorsal medial amygdala (MePD) of mice. This neuronal population is known to be involved in sexual behaviors like approach to sexually salient cues. We show that chemogenetic partial ablation of this neuronal population increases aversion to predator odors. Moreover, overexpression of AVP within this population is sufficient to reduce aversion to predator odors. The loss of fear of the predator odor occurs in parallel with increased recruitment of AVP neurons within the MePD. These observations suggest that AVP neurons in the medial aspect of the extended amygdala are a proximate locus for the reduction in innate fear during life stages dominated by reproductive efforts.

Poor Sleep Quality Is Associated with Altered Taste Perception in Chinese Adults.

BACKGROUND: Small clinical studies have suggested that individuals with insufficient sleep could experience taste dysfunction. However, this notion has not been examined in a large-scale, population-based study. OBJECTIVE: This study aimed to examine whether overall sleep quality, as assessed by insomnia, daytime sleepiness, snoring, and sleep duration, was associated with the odds of having altered taste perception in a large population-based study. DESIGN: This was a cross-sectional study that used data from a subcohort of the Kailuan study, an ongoing multicenter cohort study that began in 2006 in Tangshan City, China. PARTICIPANTS/SETTING: The participants were 11,030 adults aged 25 years or older (mean age 53.7 ± 10.7 years), who were free of neurodegenerative diseases. All the participants had undergone questionnaire assessments and medical examinations at Kailuan General Hospital from June 2012 to October 2013. MAIN OUTCOME MEASURES: Altered taste and olfactory perception were assessed via a questionnaire with two questions regarding whether participants had any problems with sense of taste or smell for ≥3 months. STATISTICAL ANALYSES PERFORMED: The association between sleep quality and altered taste/olfactory perception was examined using a logistic regression model, adjusting for age, sex, lifestyle factors (eg, obesity, smoking, alcohol intake, and physical activity) and health status (eg, lipid profiles, blood pressure, modification use, and presence of chronic diseases). RESULTS: Poor overall sleep quality was associated with a higher risk of having altered taste perception (adjusted odds ratio for low vs high sleep quality 2.03, 95% CI 1.42 to 2.91; P < 0.001). Specifically, insomnia, daytime sleepiness, and short sleep duration, but not prolonged sleep duration and snoring, were significantly associated with altered taste perception. A significant association between overall sleep quality and the risk of having altered olfactory perception was also observed (adjusted odds ratio for low vs high sleep quality 2.17, 95% CI 1.68 to 2.80; P < 0.001). CONCLUSIONS: In this population-based study, poor sleep quality was associated with a high likelihood of altered taste perception.

Electrical stimulation of the medial orbitofrontal cortex in humans elicits pleasant olfactory perceptions.

BACKGROUND: Olfactory hallucinations can be part of epileptic seizures of orbitofrontal origin. Olfactory hallucinations, however, are rare and therefore the semiology, localization and lateralization characteristics are underdetermined. In addition, many discrepancies are found in the literature regarding olfactory processing and orbitofrontal (OF) functions and olfactory function. Particularly, the questions of laterality and affective component in coding of odors in the OF cortex remain controversial. AIMS: This study explored whether cortical electrical stimulation of the OF and mesiotemporal brain can trigger olfactory hallucinations with special focus on olfactory percepts in terms of laterality and hedonics. MATERIALS AND METHODS: Eight patients with temporal lobe epilepsy participated in the study, at the time of invasive exploration of their epilepsy. The most distal contact of the OF and anterior hippocampus depth electrodes were stimulated (50 Hz, 0.2 ms biphasic pulse; maximal stimulation 4 mA). Patients were instructed to report any kind of sensation they might experience. Intracranial depth electrodes were localized (iElectrodes): subject-specific brain mask, subcortical segmentation and cortical parcellation based on the Destrieux atlas (FreeSurfer) were superposed to the coregistered T1-weighted MRI and CT images (SPM). The center of mass of each electrode-artifact cluster determined the electrode localization. The electrode labeling was done in patient space. To obtain the electrode coordinates in Montreal Neurological Institute (MNI) space, the images obtained previously in the patient space were first segmented and normalized (SPM). Then, the localization procedure (iElectrodes) was run again with these new normalized images in MNI space. RESULTS: No hallucination was evoked by stimulation, neither of the right nor the left hippocampus (8/8 patients). Pleasant olfactory hallucinations were evoked by OF stimulation in 5/8 patients in either hemisphere. Patients named the percept as the smell of lemon or coffee for example. Among those 5 patients, electrodes were localized in the cortex of the olfactory sulcus, medial orbital sulcus or medial OF gyrus. Increasing stimulation amplitude changed the olfactory percept identification in 3 out of those 5 patients. No affective judgement or change in perceived odor intensity was reported by the patients. No hallucination was evoked by the stimulation of the white matter of the medial OF brain in 3/8 patients independently of the hemisphere stimulated. CONCLUSIONS: This study demonstrated that stimulation of the cortex of the medial OF brain and not of its white matter elicits specific pleasant olfactory hallucinations independently of the hemisphere stimulated, supporting one symmetrical olfactory processing in human.

Percepção olfativa e gustativa na doença de Parkinson / Olfative and taste perception in Parkinson's disease

RESUMO Objetivo Analisar a percepção e discriminação olfativa e gustativa e a autopercepção do olfato e paladar em pessoas com Doença de Parkinson, comparando-as com indivíduos hígidos. Método Estudo observacional, analítico, transversal e quantitativo. Verificou-se a percepção e a discriminação olfativa e gustativa em indivíduos com Doença de Parkinson, comparados a um grupo controle, pareado por sexo e idade, por meio dos Testes de Percepção Olfativa e de Tiras Gustativas, respectivamente, após limpeza nasal e escovação oral. A autopercepção foi avaliada pela Escala Visual Analógica antes e após os testes específicos de percepção e discriminação. Resultados Foram incluídos indivíduos de ambos os sexos, sendo 35 com Doença de Parkinson e 20 designados ao grupo controle, pareados pela média de idade. A autopercepção olfativa do grupo com Doença de Parkinson melhorou após o teste olfativo. Não houve diferença na autopercepção gustativa no grupo Doença de Parkinson antes e após o teste gustativo. No teste de avaliação da percepção olfativa, o grupo Doença de Parkinson discriminou menos essências que o grupo controle. Ambos os grupos apresentaram semelhante percepção e discriminação gustativa. Conclusão A percepção olfativa das pessoas com Doença de Parkinson foi menor, comparativamente ao grupo de indivíduos hígidos e a autopercepção da eficácia olfativa melhorou após o teste, em ambos os grupos. Quanto ao paladar, não houve diferença na percepção e discriminação entre os grupos, o sabor azedo foi o mais identificado e houve melhora na autopercepção da eficácia gustativa somente no grupo sem a doença de Parkinson, após o teste.

ABSTRACT Purpose To analyze the olfactory and gustatory perception and discrimination and self-perception of smell and taste in people with Parkinson's disease, comparing them with healthy nodes. Methods Observational, analytical, cross-sectional, and quantitative study. Olfactory and gustatory perception and discrimination were verified following Parkinson's disease, compared to a control group, matched by sex and age, using the Olfactory Perception and Taste Strips Tests, respectively, after nasal cleaning and oral brushing. Self-perception was assessed by the Visual Analogue Scale before and after specific tests of perception and discrimination. Results We included individuals of both sexes, 35 with Parkinson's Disease and 20 assigned to the control group, matched for mean age. The olfactory self-perception of the group with Parkinson's disease improved after the olfactory test. There was no difference in taste self-perception in the Parkinson's disease group before and after the taste test. In the olfactory perception assessment test, the Parkinson's disease group discriminated fewer essences than the control group. Both groups have similar generation and taste discrimination. Conclusion The olfactory perception of people with Parkinson's disease was lower, compared to the group of healthy desires, and the self-perception of olfactory efficacy improved after the test, in both groups. As for taste, there was no difference in perception and discrimination between groups, the sour taste was the most identified and there was an improvement in self-perception of taste efficiency in the group without Parkinson's disease after the test.