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1.
Proc Natl Acad Sci U S A ; 121(39): e2406479121, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39284050

RESUMEN

Parkinson's disease (PD) is typically a sporadic late-onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA, which encodes alpha-Synuclein (α-Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock-in mice bearing the G51D SNCA mutation. After establishing that their motor symptoms begin at 9 mo of age, we then sought earlier pathologies. We assessed the phosphorylation at Serine 129 of α-Syn in different tissues and detected phospho-α-Syn in the olfactory bulb and enteric nervous system at 3 mo of age. Olfactory deficit and impaired gut transit followed at 6 mo, preceding motor symptoms. The SncaG51D mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies.


Asunto(s)
Modelos Animales de Enfermedad , Técnicas de Sustitución del Gen , Enfermedad de Parkinson , alfa-Sinucleína , Animales , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Ratones , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/patología , Ratones Transgénicos , Fosforilación , Trastornos del Olfato/genética , Trastornos del Olfato/metabolismo , Trastornos del Olfato/fisiopatología , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/patología , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/patología , Sistema Nervioso Entérico/metabolismo , Sistema Nervioso Entérico/fisiopatología , Humanos , Masculino
2.
Sci Rep ; 14(1): 20951, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251830

RESUMEN

COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis. Psychophysical validated tests were applied on a sub-population of 50 patients. Qualitative chemosensory symptoms as well as nasal and oral chemesthesis were evaluated through anamnestic interview and the quality of life through the SF-36 questionnaire. Chemosensory symptoms evolution and olfactory training's outcome were assessed through phone-call interviews. Out of 1187 patients (female, N = 630), 550 (47%) presented NSc-PCS, with a lower risk for older age and monoclonal antibodies treatment, and a higher risk in females (p < 0.001). Out of the 50 patients evaluated with psychophysical tests, 66% showed smell reduction with a qualitative alteration in 50% of hyposmic and 35% of normosmic patients. Hypogeusia was present in 14 (28%) of the patients assessed, with 56% showing a qualitative alteration; 53% of normogeusic patients presented qualitative disorders. NSc-PCS has a complex, fluctuating, multifaceted presentation. Quantifying and characterizing COVID-19-related chemosensory impairment is key to understand underlying mechanisms and to develop preventive and therapeutic treatment.


Asunto(s)
COVID-19 , Trastornos del Olfato , Calidad de Vida , Humanos , Femenino , COVID-19/psicología , COVID-19/epidemiología , Masculino , Persona de Mediana Edad , Trastornos del Olfato/etiología , Trastornos del Olfato/virología , Trastornos del Olfato/fisiopatología , Anciano , Adulto , SARS-CoV-2/aislamiento & purificación , Anosmia/etiología , Factores de Riesgo , Encuestas y Cuestionarios , Olfato/fisiología , Síndrome Post Agudo de COVID-19
4.
Ageing Res Rev ; 100: 102453, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39127444

RESUMEN

Olfactory functioning involves multiple cognitive processes and the coordinated actions of various neural systems. Any disruption at any stage of this process may result in olfactory dysfunction, which is consequently widely used to predict the onset and progression of diseases, such as Alzheimer's Disease (AD). Although the underlying mechanisms have not yet been fully unraveled, apparent changes were observed in olfactory brain areas form patients who suffer from AD by means of medical imaging and electroencephalography (EEG). Olfactory dysfunction holds significant promise in detecting AD during the preclinical stage preceding mild cognitive impairment (MCI). Owing to the strong specificity, olfactory tests are prevalently applied for screening in community cohorts. And combining olfactory tests with other biomarkers may further establish an optimal model for AD prediction in studies of specific olfactory dysfunctions and improve the sensitivity and specificity of early AD diagnosis.


Asunto(s)
Enfermedad de Alzheimer , Trastornos del Olfato , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Humanos , Trastornos del Olfato/etiología , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/diagnóstico , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Olfato/fisiología , Electroencefalografía/métodos
5.
Life Sci ; 355: 122967, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39142504

RESUMEN

Olfactory dysfunction, influenced by factors such as aging and environmental stress, is linked to various neurological disorders. The olfactory bulb's connections to brain areas like the hypothalamus, piriform cortex, entorhinal cortex, and limbic system make olfactory dysfunction a contributor to a range of neuropathological conditions. Recent research has underscored that olfactory deficits are prevalent in individuals with both metabolic syndrome and dementia. These systemic metabolic alterations correlate with olfactory impairments, potentially affecting brain regions associated with the olfactory bulb. In cases of metabolic syndrome, phenomena such as insulin resistance and disrupted glucose metabolism may result in compromised olfactory function, leading to multiple neurological issues. This review synthesizes key findings on the interplay between metabolic-induced olfactory dysfunction and neuropathology. It emphasizes the critical role of olfactory assessment in diagnosing and managing neurological diseases related to metabolic syndrome.


Asunto(s)
Síndrome Metabólico , Bulbo Olfatorio , Humanos , Síndrome Metabólico/metabolismo , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/patología , Trastornos del Olfato/metabolismo , Trastornos del Olfato/etiología , Trastornos del Olfato/fisiopatología , Animales , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/patología
7.
Int J Pediatr Otorhinolaryngol ; 184: 112081, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39208514

RESUMEN

AIM: Smell and taste are senses that contribute to a child's overall well-being. Disorders affecting these senses can impact a child's daily life from enjoying meals to detecting potential dangers through scent. The aim of this study is to describe patient characteristics and etiological causes of olfactory (OD) and/or gustatory disorders (GD) in children referred to a smell and taste clinic. Secondly, we aim to suggest a clinical work up. METHODS: Retrospective study where data were collected from 57 children who were referred consecutively to the University Clinic for Flavour, Balance, and Sleep; Department of Otorhinolaryngology (ORL), Head and Neck Surgery; Goedstrup Hospital, Denmark, for assessment due to OD/GD from January 2017 to May 2023. RESULTS: Most of the children had anosmia (60 %), whereas sensation of the basic tastes was intact in all but eight children (16 %). The lowest TDI scores were in children with congenital OD. The underlying etiology was congenital followed by postinfectious mostly related to Covid-19. Picky eating including anorectic traits were seen in 16 % of patients. CONCLUSION: The focus on smell loss in pediatric population is low, and probably does not adequately reflect either underlying prevalence in this group or the possible consequences on a child's well-being. Moreover, increased awareness of children's smell and taste loss is needed, as it may be associated with eating disturbances.


Asunto(s)
COVID-19 , Trastornos del Olfato , Trastornos del Gusto , Humanos , Femenino , Masculino , Estudios Retrospectivos , Niño , Trastornos del Gusto/diagnóstico , Trastornos del Gusto/etiología , Trastornos del Gusto/epidemiología , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/epidemiología , Preescolar , COVID-19/epidemiología , COVID-19/complicaciones , Adolescente , Dinamarca/epidemiología , Lactante , SARS-CoV-2
8.
Brain Res ; 1844: 149150, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39127119

RESUMEN

Olfactory dysfunction is a common non-motor symptom of Parkinson's disease(PD) and may hold valuable insights into the disease's underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients' right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD's pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions.


Asunto(s)
Anosmia , Corteza Cerebral , Imagen por Resonancia Magnética , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Corteza Cerebral/patología , Corteza Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Anosmia/patología , Trastornos del Olfato/patología , Trastornos del Olfato/etiología , Trastornos del Olfato/diagnóstico por imagen , Trastornos del Olfato/fisiopatología
9.
Artículo en Inglés | MEDLINE | ID: mdl-39173992

RESUMEN

BACKGROUND: Borderline personality disorder (BPD) is a serious disorder with a lifetime prevalence of 2.7-5.9% and is thought to correlate with altered neuroplasticity. The aim of the present study is to investigate possible associations of BPD (-severity) and alterations in neurological soft signs (NSS) and olfactory function. METHODS: For the monocentric observational study, 39 female subjects with a BPD diagnosis and 19 female healthy control subjects were recruited. The groups were matched by age. Olfactory functions were examined using Sniffin' Sticks. NSS were assessed by a standardized test with 50 items. RESULTS: BPD subjects have higher NSS scores in group comparison. By contrast, there are no alterations in the total score of olfactory function, while the BPD subjects scored higher in smell identification. Within the BPD group, the total NSS score was discovered to have a negative correlation with olfactory function. BPD subjects taking antipsychotics show more NSS than those without. We found no significant influence of posttraumatic stress disorder on the NSS or olfactory function. The BPD-severity correlates with NSS. LIMITATIONS: Due to the cross-sectional design, we did not have a follow up examination. The sample size was small, and all patients had psychiatric comorbidities. Additionally, we did not perform MRI to connect our findings with possible structural abnormalities. CONCLUSIONS: Our study confirmed altered NSS in BPD patients, whereas no impairment in the olfactory function was found. Further research is required to establish NSS and smell tests as clinical screening tools in BPD patients and to uncover the disorder's impact on neuroplasticity.


Asunto(s)
Trastorno de Personalidad Limítrofe , Trastornos del Olfato , Humanos , Trastorno de Personalidad Limítrofe/fisiopatología , Trastorno de Personalidad Limítrofe/complicaciones , Femenino , Adulto , Trastornos del Olfato/fisiopatología , Estudios Transversales , Adulto Joven , Antipsicóticos/uso terapéutico
10.
Theranostics ; 14(11): 4499-4518, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39113792

RESUMEN

Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.


Asunto(s)
Ventrículos Laterales , Ratones Noqueados , Células-Madre Neurales , Neurogénesis , Enfermedad de Parkinson , Proteínas de Unión al ARN , Receptor Notch1 , Transducción de Señal , Animales , Masculino , Ratones , Proliferación Celular , Modelos Animales de Enfermedad , Ventrículos Laterales/metabolismo , Ratones Endogámicos C57BL , Células-Madre Neurales/metabolismo , Trastornos del Olfato/metabolismo , Trastornos del Olfato/genética , Trastornos del Olfato/fisiopatología , Bulbo Olfatorio/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Receptor Notch1/metabolismo , Receptor Notch1/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética
12.
Vestn Otorinolaringol ; 89(3): 36-40, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-39104271

RESUMEN

The psychophysical Sniffin' Sticks test, which includes an odor identification test, is the gold standard for assessing the sense of smell in clinical and scientific practice. A necessary requirement for the odor identification test is a close familiarity with the odors used by the inhabitants of the region in which it is used. We studied 77 healthy volunteers and 51 patients with olfactory dysfunction and we found that Russians are not familiar with the three smells from the test (licorice, turpentine and anise) and are completely unfamiliar with the one proposed alternative answer (chives). Moreover, four odors demonstrated very low recognition (less than 75%). The test has been adapted for the use In Russia. In the booklet, licorice is replaced by cough syrup, turpentine by paint thinner, and chives by bay leaf. For odors with low recognition (lemon, apple, pineapple), the alternative fruity odors in the booklet were replaced with more contrasting ones. Based on the data obtained, we are going to develop a domestic version of the odor identification test.


Asunto(s)
Odorantes , Trastornos del Olfato , Olfato , Humanos , Federación de Rusia , Odorantes/análisis , Masculino , Femenino , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/etiología , Olfato/fisiología , Adulto , Umbral Sensorial/fisiología , Persona de Mediana Edad , Reproducibilidad de los Resultados
13.
Vestn Otorinolaringol ; 89(3): 41-47, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-39104272

RESUMEN

Olfactory disorders is one of the first symptoms of diseases from various departments of medicine (otorhinolaryngology, psychology, neurology, etc.). Based on international clinical recommendations, olfactory tests are the gold standard for the diagnosis of olfactory disorders. There are many different psychophysical tests: UPSIT (USA, Pennsylvania), Sniffin' Sticks test (Germany), BAST-24 (Spain), etc. Currently, there is an acute shortage of olfactory tests available for clinical practice In Russia. This problem is related to the fact that there are no olfactory tests registered as medical devices on the territory of the Russian Federation. Also, a significant limitation is the unrecognizability of odors by the population of our country, which include foreign analogues (licorice, anise, turpentine, etc.). OBJECTIVE: To develop and validate the national olfactory test on healthy volunteers. MATERIAL AND METHODS: The development and validation of the olfactory test included several stages. First, the development of an olfactory test was carried out, the selection of aromas to assess the threshold and identification ability of olfaction. 25 dilutions of n-butanol were used for the assessment of the threshold olfactory ability. For the stage of assessing the identification ability of the sense of smell, in our previous study, an assessment of the recognition of odor names in the territory of the Russian Federation was carried out. A total of 3.000 people from 8 federal districts of the Russian Federation were interviewed. During the development of the test, 20 names of flavors with the highest rating were used. By the 8th, the selection of monocomponent substances was carried out. Commercially available certified food and perfume flavorings have been used for fragrances whose equivalent in the test cannot be a monocomponent substance. A group of 25 healthy volunteers selected a flavor or a monocomponent for each of the 20 positions. To carry out the identification stage of testing, a booklet was developed with answer options for each fragrance, including 80 images associated with the smell. A methodology for conducting diagnostics has been created. Next, the validation of the developed olfactory test was carried out on 150 healthy volunteers. The study included an assessment of the threshold and identification ability of the sense of smell using the developed test and conducting a comparative analysis with a set of flavors and descriptors corresponding to the Sniffin' Sticks test. RESULTS: The developed test includes: 2 panels - panel 1 to assess the threshold ability of smell, panel 2 to assess the identification ability of smell, a booklet with 80 images and captions to them. The norms of threshold and identification olfactory abilities were also determined in the developed test. The domestic test was validated against the relative foreign Sniffin' Sticks test. Spearman's correlation between the accuracy values of the domestic test (17-20; 85.00-100.00%) and the values of the foreign test (11-16; 68.75-100.00%) did not reveal statistically significant differences (rs=0.065, p=0.432), which confirms the equally effective assessment of olfactory ability by the domestic olfactory test in comparison with its foreign counterpart. CONCLUSION: In this work, a methodology for the use of Russian olfactory test was developed and validated on healthy volunteers. The features of the developed test are an assessment of the threshold and identification ability of smell, an adapted set of odors for the Russian population, the use of paper blotters when applying flavor and visual images of descriptors. Despite the wide variety of psychophysical tests, this problem requires further study and comparative analysis of olfactory tests available In Russia and foreign analogues in order to obtain a universal and effective diagnostic method for the populations of our country.This work was supported by the Russian Foundation for Basic Research (Project No. 24-25-00415).


Asunto(s)
Trastornos del Olfato , Olfato , Humanos , Federación de Rusia , Trastornos del Olfato/diagnóstico , Adulto , Femenino , Masculino , Olfato/fisiología , Reproducibilidad de los Resultados , Odorantes/análisis , Umbral Sensorial/fisiología
14.
Braz J Otorhinolaryngol ; 90(5): 101451, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38972284

RESUMEN

OBJECTIVES: The new corona virus infection, has a wide range of clinical manifestations. Fever and cough are the most common symptoms. The olfactory function may be also affected with COVID-19. In this randomized clinical trial, we wanted to evaluate the therapeutic effect of olfactory training with and without oral vitamin A for COVID-19-related olfactory dysfunction. METHODS: Patients answered to the standard Persian version of anosmia reporting tool and performed the quick smell test before and after 12 weeks and at the end of the 12 months follow up. The patients were randomly allocated to three groups; Group A treatment with olfactory training, Group B treatment with oral vitamin A and olfactory training, and Group C as control group which only underwent nasal irrigation twice a day. Patients were treated for 3 months and followed up for 12 months. RESULTS: Totally 90 patients were included in three groups. After interventions, 76.9% of patients in Group A, 86.7% of patients in Group B, and 26.7% of patients in Group C completely improved. The average intervention time was statistically significant in relationship with the final olfactory status of the patients in the 12 months follow-up. The olfactory training has significantly improved the smell alteration at the end of 3- and 12- months follow-up in A and B groups. CONCLUSION: A three-months olfactory training is effective for improvement of COVID-19-related olfactory dysfunction. Adding daily oral vitamin A to olfactory training did not lead to better results in improving olfactory dysfunction. LEVEL OF EVIDENCE: Step 2 (Level 2*): Randomized trial.


Asunto(s)
COVID-19 , Trastornos del Olfato , Vitamina A , Humanos , Vitamina A/uso terapéutico , Vitamina A/administración & dosificación , COVID-19/complicaciones , Masculino , Femenino , Método Doble Ciego , Trastornos del Olfato/etiología , Trastornos del Olfato/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Vitaminas/uso terapéutico , Vitaminas/administración & dosificación , Entrenamiento Olfativo
15.
Braz J Otorhinolaryngol ; 90(5): 101461, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38991402

RESUMEN

OBJECTIVE: This study aimed to investigate the prevalence and factors associated with olfactory dysfunction in individuals exposed to Isotretinoin (ISO) for the treatment of acne, using the University of Pennsylvania Smell Identification Test (UPSIT®). METHODS: This cross-sectional study enrolled age and sex-matched patients with acne who were current users of oral ISO and unexposed controls without olfactory complaints. UPSIT® and a validated questionnaire (Nasal Obstruction Symptom Evaluation) were administered to evaluate nasal obstruction in patients exposed to ISO. RESULTS: A total of seventy patients were recruited, with 35 in the exposed group and 35 in the unexposed group, consisting of 18 males and 17 females in each group, aged from 17 to 47 years. The prevalence of olfactory dysfunction was higher in the exposed group compared to the non-exposed group (62.9% vs. 17.1%), yielding a Prevalence Ratio (PR) of 3.7 (95% CI 1.9-7.1). However, no participants were categorized as anosmia or severe hyposmia and the majority of dysfunction was mild hyposmia compared to moderate hyposmia (51.5% vs. 11.4%). Among the exposed individuals, gasoline, orange, coffee, and wood exhibited the highest rates of identification errors (≥54%). Olfactory function demonstrated a negative correlation with treatment duration (p = 0.01), cumulative dose (p = 0.02), and nasal obstruction (p = 0.02). CONCLUSIONS: Olfactory dysfunction was more prevalent among ISO users, despite the patients being unaware of the disorder. Olfactory changes were correlated with treatment duration, cumulative dose, and nasal obstruction. LEVEL OF EVIDENCE: Level 4.


Asunto(s)
Acné Vulgar , Fármacos Dermatológicos , Isotretinoína , Trastornos del Olfato , Humanos , Masculino , Isotretinoína/efectos adversos , Isotretinoína/administración & dosificación , Estudios Transversales , Femenino , Acné Vulgar/tratamiento farmacológico , Adulto , Adolescente , Trastornos del Olfato/inducido químicamente , Trastornos del Olfato/epidemiología , Adulto Joven , Prevalencia , Persona de Mediana Edad , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/administración & dosificación , Estudios de Casos y Controles , Encuestas y Cuestionarios , Administración Oral , Factores de Riesgo , Índice de Severidad de la Enfermedad
16.
J Neurol ; 271(9): 6102-6113, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39043904

RESUMEN

BACKGROUND: Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. METHODS: Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2-4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. RESULTS: Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3 years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. CONCLUSIONS: The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries.


Asunto(s)
Progresión de la Enfermedad , Enfermedad de Parkinson , Tomografía de Emisión de Positrones , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/patología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Trastornos del Olfato/etiología , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/diagnóstico por imagen , Pruebas Neuropsicológicas , Estudios Longitudinales
17.
Arq Neuropsiquiatr ; 82(9): 1-7, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39025107

RESUMEN

BACKGROUND: Olfactory dysfunction (OD) represents a frequent manifestation of the coronavirus disease 2019 (COVID-19). Apolipoprotein E (APOE) is a protein that interacts with the angiotensin-converting enzyme receptor, essential for viral entry into the cell. Previous publications have suggested a possible role of APOE in COVID-19 severity. As far as we know, no publications found significant associations between this disease's severity, OD, and APOE polymorphisms (E2, E3, and E4). OBJECTIVE: To analyze the epidemiology of OD and its relationship with APOE polymorphisms in a cohort of Long-COVID patients. METHODS: We conducted a prospective cohort study with patients followed in a post-COVID neurological outpatient clinic, with OD being defined as a subjective reduction of olfactory function after infection, and persistent OD being defined when the complaint lasted more than 3 months after the COVID-19 infection resolution. This cross-sectional study is part of a large research with previously reported data focusing on the cognitive performance of our sample. RESULTS: The final sample comprised 221 patients, among whom 186 collected blood samples for APOE genotyping. The persistent OD group was younger and had a lower hospitalization rate during the acute phase of the disease (p < 0.001). Furthermore, the APOE variant E4 allele frequency was lower in this group (p = 0.035). This study evaluated OD in an outpatient population with COVID-19. In the current literature on this disease, anosmia is associated with better clinical outcomes and the E4 allele is associated with worse outcomes. CONCLUSION: Our study provides new information to these correlations, suggesting APOE E4 as a protective factor for OD.


ANTECEDENTES: A disfunção olfatória (DO) é uma manifestação frequente da doença do coronavírus 2019 (COVID-19). A apolipoproteína E (APOE) é uma proteína que interage com o receptor da enzima conversora de angiotensina, essencial para a entrada viral na célula. Publicações anteriores sugeriram um possível papel da APOE na gravidade da COVID-19. Até onde sabemos, nenhuma publicação encontrou associações significativas entre a gravidade dessa doença, DO e polimorfismos da APOE (E2, E3 e E4). OBJETIVO: Analisar a epidemiologia da DO e sua relação com os polimorfismos do gene APOE em uma coorte de pacientes com COVID longa. MéTODOS: Um estudo de coorte prospectiva com pacientes acompanhados em ambulatório neurológico pós-COVID, com DO sendo definida como uma redução subjetiva da função olfativa após a infecção e a DO persistente sendo definida quando a queixa durou mais de 3 meses após a resolução da infecção por COVID-19. Este estudo transversal é parte de uma pesquisa maior com dados anteriormente relatados, focando na performance cognitiva dos pacientes. RESULTADOS: Foram selecionados 221 pacientes para esse estudo, dos quais 186 haviam coletado amostras de sangue para genotipagem APOE. O grupo DO persistente foi mais jovem e apresentou menor taxa de internação na fase aguda da doença (p < 0,001). Além disso, a frequência do alelo E4 da APOE foi menor nesse grupo (p = 0,035). Este estudo avaliou a DO em uma população com COVID longa. Na literatura atual sobre essa doença, a anosmia está associada a melhores desfechos clínicos e o alelo E4 está associado a piores desfechos. CONCLUSãO: Nosso estudo acrescenta novas informações a essas correlações, sugerindo a APOE E4 como um fator de proteção para DO.


Asunto(s)
Alelos , COVID-19 , Trastornos del Olfato , Humanos , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Trastornos del Olfato/genética , Estudios Transversales , Apolipoproteína E4/genética , Anciano , Adulto , Factores Protectores , Apolipoproteínas E/genética , Polimorfismo Genético , SARS-CoV-2 , Genotipo , Síndrome Post Agudo de COVID-19
18.
Anal Biochem ; 694: 115614, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38996899

RESUMEN

Nasal ions environment plays a crucial role in maintaining nasal physiology and supports olfactory transmission. Addressing the limited research on nasal ion levels and their association with olfactory function, paper-based sensors were developed for determination of sodium, potassium, calcium and chloride in the nasal mucus of healthy volunteers and patients with olfactory dysfunction. Multi-walled carbon nanotubes and carbon quantum dots from beetroot were incorporated into paper substrate where sensors were designed with ion association complexes for sodium, potassium, calcium and chloride enhancing the recognition sensing capabilities. The sensors composition was optimized, including ion-exchange materials and plasticizers, to enhance sensitivity and selectivity. The performance of the sensors is evaluated based on Nernstian slope, dynamic range, detection limit and response time. Selectivity of the sensors was tested and the results demonstrated high selectivity for the target ions. The sensors were successfully determined sodium, potassium, calcium and chloride levels in nasal mucus of healthy volunteers and patients with olfactory dysfunction. The results revealed elevated calcium levels in patients with olfactory dysfunction, highlighting associated diagnostic implications. This suggests that the proposed sensors could serve as a diagnostic tool for olfactory evaluation, particularly in resource-constrained settings where access to advanced diagnostic tools is limited.


Asunto(s)
Calcio , Papel , Humanos , Calcio/análisis , Calcio/metabolismo , Trastornos del Olfato/diagnóstico , Nanotubos de Carbono/química , Sodio/análisis , Sodio/metabolismo , Potasio/análisis , Iones/análisis , Puntos Cuánticos/química , Olfato , Cloruros/análisis , Mucosa Nasal/metabolismo , Masculino , Adulto
19.
Multisens Res ; 37(4-5): 299-316, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39043376

RESUMEN

Approximately 30-60% of people suffer from olfactory dysfunction (OD) such as hyposmia or anosmia after being diagnosed with COVID-19; 15-20% of these cases last beyond resolution of the acute phase. Previous studies have shown that olfactory training can be beneficial for patients affected by OD caused by viral infections of the upper respiratory tract. The aim of the study is to evaluate whether a multisensory olfactory training involving simultaneously tasting and seeing congruent stimuli is more effective than the classical olfactory training. We recruited 68 participants with persistent OD for two months or more after COVID-19 infection; they were divided into three groups. One group received olfactory training which involved smelling four odorants (strawberry, cheese, coffee, lemon; classical olfactory training). The other group received the same olfactory stimuli but presented retronasally (i.e., as droplets on their tongue); while simultaneous and congruent gustatory (i.e., sweet, salty, bitter, sour) and visual (corresponding images) stimuli were presented (multisensory olfactory training). The third group received odorless propylene glycol in four bottles (control group). Training was carried out twice daily for 12 weeks. We assessed olfactory function and olfactory specific quality of life before and after the intervention. Both intervention groups showed a similar significant improvement of olfactory function, although there was no difference in the assessment of quality of life. Both multisensory and classical training can be beneficial for OD following a viral infection; however, only the classical olfactory training paradigm leads to an improvement that was significantly stronger than the control group.


Asunto(s)
COVID-19 , Trastornos del Olfato , Olfato , Humanos , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Trastornos del Olfato/rehabilitación , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/etiología , Trastornos del Olfato/virología , Trastornos del Olfato/terapia , Adulto , Olfato/fisiología , SARS-CoV-2 , Calidad de Vida , Anciano , Percepción Olfatoria/fisiología , Entrenamiento Olfativo
20.
Acta Psychol (Amst) ; 248: 104422, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39059244

RESUMEN

INTRODUCTION: Coronavirus disease 19 (COVID-19) affected the health-related quality of life (HRQoL), and its impact on well-being is not sufficiently understood yet. The worsening of HRQoL and symptoms such as fatigue, anxiety, depression, chronic Headache, Myalgia, ageusia, olfactory disorders, and cognitive impairment can be seen in people of different ages and genders after COVID-19 infection, even mild infections without hospitalization. These issues generate a disease burden that can reduce work skills and cause social, psychological, and neuropsychiatric challenges. OBJECTIVE: To evaluate the HRQoL of patients affected by COVID-19, the domains most affected, and their relationship with fatigue, anxiety, depression, chronic Headache and Myalgia, ageusia, olfactory disorders, and cognitive impairment. METHODS: An analytical transverse was conducted with 143 patients after COVID-19 infection. The patient-reported outcomes measures (PROMS) were collected by the 36-item Short Form survey (SF-36), Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), Mini-Mental State Examination-2 (MMSE-2), Symbol Digit Modalities Test (SDMT), and a questionnaire regarding symptoms such as chronic Headache, myalgia, and olfactory disorders. Spearman's correlation test was used to correlate the performance of the patients on different PROMS. RESULTS: Fatigue, depression, and anxiety were negatively correlated with all the SF-36 domains, and patients with subjective cognitive complaints had low scores in all SF-36 domains. Furthermore, those with chronic Headaches had low scores in physical functioning, role-physical functioning, and vitality. Regarding myalgia complaints, the worst scores were observed in the physical functioning and vitality domains. Patients with ageusia had low scores in general health perceptions, and those with olfactory dysfunction had low scores in the vitality and mental health domains. CONCLUSIONS: Although the acute phase of COVID-19 has resolved, knowledge about HRQoL after this period is essential since many individual and collective changes have been taking place until today-patients with neuropsychiatric manifestations that persisted after the acute phase showed lower overall quality of life.


Asunto(s)
COVID-19 , Depresión , Fatiga , Calidad de Vida , Humanos , COVID-19/psicología , Calidad de Vida/psicología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Ansiedad/psicología , Disfunción Cognitiva/fisiopatología , Anciano , Mialgia , Medición de Resultados Informados por el Paciente , Ageusia , Trastornos del Olfato , SARS-CoV-2 , Cefalea
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