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Journal of Parkinson's Disease Mar 2024During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The... (Review)
Review
During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The most important among them are REM sleep behavior disorder (RBD) and olfactory dysfunction. RBD is a parasomnia characterized by the loss of REM sleep muscle atonia and dream-enacting behaviors. Olfactory dysfunction in individuals with prodromal PD is usually described as hyposmia (reduced sense of smell) or anosmia (complete loss of olfactory function). These symptoms can precede the full expression of motor symptoms by decades. A close comprehension of these symptoms and the underlying mechanisms may enable early screening as well as interventions to improve patients' quality of life. Therefore, these symptoms have unmatched potential for identifying PD patients in prodromal stages, not only allowing early diagnosis but potentially opening a window for early, possibly disease-modifying intervention. However, they come with certain challenges. This review addresses some of the key opportunities and pitfalls of both RBD and olfactory dysfunction as early markers of PD.
PubMed: 38517805
DOI: 10.3233/JPD-230348 -
PloS One 2024SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and... (Observational Study)
Observational Study
COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.4/5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history.
BACKGROUND
SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC).
METHODS
In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10. We compared participant-reported symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 or BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR cycle threshold (Ct) as a proxy for viral load using Chi-squared (χ2) and Wilcoxon tests.
RESULTS
563 infection episodes were reported among 491 participants. Across infection episodes, there was little variation in symptom burden (4 [IQR 3-5] symptoms) and duration (8 [IQR 6-11] days). Whilst symptom profiles differed among infections caused by Delta compared to Omicron sub-variants, symptom profiles were similar between Omicron sub-variants. Anosmia was reported more frequently in Delta infections after 2 doses compared with Omicron sub-variant infections after 3 doses, for example: 42% (25/60) of participants with Delta infection compared to 9% (6/67) with Omicron BA.4/5 (χ2 P < 0.001; OR 7.3 [95% CI 2.7-19.4]). Fever was less common with Delta (20/60 participants; 33%) than Omicron BA.4/5 (39/67; 58%; χ2 P = 0.008; OR 0.4 [CI 0.2-0.7]). Amongst infections with an Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. PCR Ct values were negatively associated with time since vaccination in participants infected with BA.1 (β = -0.05 (CI -0.10-0.01); P = 0.031); however, this trend was not observed in BA.2 or BA.4/5 infections.
CONCLUSION
Our study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults.
TRIAL REGISTRATION
NCT04750356.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Prospective Studies; Vaccination
PubMed: 38512960
DOI: 10.1371/journal.pone.0294897 -
Frontiers in Aging Neuroscience 2024Olfactory dysfunction in Parkinson's disease (PD) is associated with more severe phenotypes, but trajectories of cognitive function, disease severity, and subdomains of...
BACKGROUND
Olfactory dysfunction in Parkinson's disease (PD) is associated with more severe phenotypes, but trajectories of cognitive function, disease severity, and subdomains of quality-of-life measurements in patients with distinct olfactory profiles remain underexplored.
OBJECTIVE
To analyze the influence of olfaction on trajectories of clinical parameters in patients with PD.
DESIGN
Retrospective cohort study.
SUBJECTS
From October 2016 to May 2021, the study tracked 58 participants over 3 years. Participants completed follow-up assessments using tools including the Chinese version of the University of Pennsylvania's Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, and the Chinese translation of the 39-item Parkinson's Disease Questionnaire (PDQ-39).
METHODS
Participants were divided into anosmia (UPSIT < 19) and non-anosmia (UPSIT ≥ 19) groups based on initial scores. Generalized estimating equations and repeated measures correlations were used to examine longitudinal associations and correlations between olfaction and clinical parameters.
RESULTS
Divergent cognitive trajectories were observed between groups. The anosmia group exhibited a faster cognitive decline (adjusted B [beta coefficient] = -1.8, = 0.012) according to the interaction effect of olfaction and time on the MoCA score. The anosmia group exhibited no longitudinal correlation between cognition and olfactory function but showed correlations with age ( [coefficient of repeated measures correlation] = -0.464, = 0.004) and disease duration ( = -0.457, = 0.005). The non-anosmia group's UPSIT scores decreased over time ( = -2.3, = 0.005) alongside a significant correlation with motor function ( = -0.479, = 0.006).
CONCLUSION
The anosmia group's accelerated cognitive decline correlated with age and disease duration, but not olfactory function, suggesting a poor cognitive outcome in this population despite the lack of longitudinal correlation between cognition and olfaction. The non-anosmia group exhibited progressive olfactory degradation and notable correlations between motor function and UPSIT scores, implying pathological accumulation in the olfactory structure and basal ganglia.
PubMed: 38501060
DOI: 10.3389/fnagi.2024.1329551 -
Health Expectations : An International... Apr 2024Sudden smell loss is one of the early symptoms of COVID-19. Although it is stated that the loss of smell and taste following COVID-19 improves within a few weeks, there...
OBJECTIVES
Sudden smell loss is one of the early symptoms of COVID-19. Although it is stated that the loss of smell and taste following COVID-19 improves within a few weeks, there are also cases that do not improve for a long time. The aim of this study is to reveal long-term smell loss experiences after COVID-19.
METHODS
A qualitative approach was adopted. We conducted semistructured interviews with 11 participants who had smell loss for at least 3 months. Interviews were recorded, transcribed and evaluated using a thematic analysis for qualitative data.
RESULTS
Nutrition and appetite, personal hygiene, threats to safety and emotional changes were the main themes created by the authors and were the areas where participant expressions focused. The participants used oral/nasal corticosteroid therapy for smell loss and received short-term olfactory training, but could not find a solution.
CONCLUSIONS
Long-term smell loss problems, which were neglected during the pandemic period, should be carefully evaluated due to their negative effects. Understanding and focusing on the negative effects of loss of smell may contribute to the solution of long-term smell loss problems.
PATIENT AND PUBLIC CONTRIBUTION
Eleven participants who experienced long-term loss of smell following COVID-19 contributed to the study. They enriched the study by describing the effects of their experiences. There was no other participation or contribution from the public to the research.
Topics: Humans; COVID-19; Anosmia; SARS-CoV-2; Olfaction Disorders; Smell
PubMed: 38494992
DOI: 10.1111/hex.14018 -
Current Allergy and Asthma Reports Apr 2024Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic... (Review)
Review
PURPOSE OF REVIEW
Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases.
RECENT FINDINGS
Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons. The interaction between olfactory stem cells and immune system might critically underlie ongoing loss of smell in type 2 and non-type 2 inflammatory upper airway diseases. In this review, we describe the neurobiology of olfaction and the olfactory alterations in type 2 and non-type 2 inflammatory upper airway diseases, highlighting the role of immune response attenuating olfactory neurogenesis, as a possibly mechanism for the lack of loss of smell recovery.
Topics: Humans; Smell; Anosmia; Inflammation; Olfactory Mucosa; Sinusitis; Olfaction Disorders; Chronic Disease; Rhinitis
PubMed: 38492160
DOI: 10.1007/s11882-024-01137-x -
European Archives of... Jul 2024Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PURPOSE
Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.
METHODS
After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T) and 6 months (T) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia.
RESULTS
The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated.
CONCLUSIONS
umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.
Topics: Humans; Female; COVID-19; Male; Middle Aged; Olfaction Disorders; Thioctic Acid; Ethanolamines; Palmitic Acids; Amides; Adult; SARS-CoV-2; Treatment Outcome; Aged; Anosmia; Smell; Combined Modality Therapy; Olfactory Training
PubMed: 38492007
DOI: 10.1007/s00405-024-08548-6 -
Physiology & Behavior May 2024Major functions of the olfactory system include guiding ingestion and avoidance of environmental hazards. People with anosmia report reliance on others, for example to...
Major functions of the olfactory system include guiding ingestion and avoidance of environmental hazards. People with anosmia report reliance on others, for example to check the edibility of food, as their primary coping strategy. Facial expressions are a major source of non-verbal social information that can be used to guide approach and avoidance behaviour. Thus, it is of interest to explore whether a life-long absence of the sense of smell heightens sensitivity to others' facial emotions, particularly those depicting threat. In the present, online study 28 people with congenital anosmia (mean age 43.46) and 24 people reporting no olfactory dysfunction (mean age 42.75) completed a facial emotion recognition task whereby emotionally neutral faces (6 different identities) morphed, over 40 stages, to express one of 5 basic emotions: anger, disgust, fear, happiness, or sadness. Results showed that, while the groups did not differ in their ability to identify the final, full-strength emotional expressions, nor in the accuracy of their first response, the congenital anosmia group successfully identified the emotions at significantly lower intensity (i.e. an earlier stage of the morph) than the control group. Exploratory analysis showed this main effect was primarily driven by an advantage in detecting anger and disgust. These findings indicate the absence of a functioning sense of smell during development leads to compensatory changes in visual, social cognition. Future work should explore the neural and behavioural basis for this advantage.
Topics: Humans; Adult; Facial Recognition; Emotions; Fear; Anger; Facial Expression; Happiness; Olfaction Disorders
PubMed: 38490365
DOI: 10.1016/j.physbeh.2024.114519 -
Glia Jun 2024Barrier-forming olfactory glia cells, termed sustentacular cells, play important roles for immune defense of the olfactory mucosa, for example as entry sites for...
Barrier-forming olfactory glia cells, termed sustentacular cells, play important roles for immune defense of the olfactory mucosa, for example as entry sites for SARS-CoV-2 and subsequent development of inflammation-induced smell loss. Here we demonstrate that sustentacular cells express ACKR3, a chemokine receptor that functions both as a scavenger of the chemokine CXCL12 and as an activator of alternative signaling pathways. Differential gene expression analysis of bulk RNA sequencing data obtained from WT and ACKR3 conditional knockout mice revealed upregulation of genes involved in immune defense. To map the regulated genes to the different cell types of the olfactory mucosa, we employed biocomputational methods utilizing a single-cell reference atlas. Transcriptome analysis, PCR and immunofluorescence identified up-regulation of NF-κB-related genes, known to amplify inflammatory signaling and to facilitate leukocyte transmigration, in the gliogenic lineage. Accordingly, we found a marked increase in leukocyte-expressed genes and confirmed leukocyte infiltration into the olfactory mucosa. In addition, lack of ACKR3 led to enhanced expression and secretion of early mediators of immune defense by Bowman's glands. As a result, the number of apoptotic cells in the epithelium was decreased. In conclusion, our research underlines the importance of sustentacular cells in immune defense of the olfactory mucosa. Moreover, it identifies ACKR3, a druggable G protein-coupled receptor, as a promising target for modulation of inflammation-associated anosmia.
Topics: Animals; Mice; Chemokine CXCL12; Gene Expression Profiling; Inflammation; Neuroglia; Olfactory Mucosa
PubMed: 38477581
DOI: 10.1002/glia.24527 -
Acta Neuropathologica Mar 2024Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis,...
Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research-L-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan aptamer precipitation assay, and liquid chromatography-mass spectrometry proteomics. We discovered that hundreds of proteins were upregulated in the CSF, blood, or urine of PD patients, prodromal PD patients with DAT deficit and REM sleep behavior disorder or anosmia, and non-manifesting genetic carriers of LRRK2 and GBA mutations. We nominate multiple novel hits across our analyses as promising markers of early PD, including DOPA decarboxylase (DDC), also known as L-aromatic acid decarboxylase (AADC), sulfatase-modifying factor 1 (SUMF1), dipeptidyl peptidase 2/7 (DPP7), glutamyl aminopeptidase (ENPEP), WAP four-disulfide core domain 2 (WFDC2), and others. DDC, which catalyzes the final step in dopamine synthesis, particularly stands out as a novel hit with a compelling mechanistic link to PD pathogenesis. DDC is consistently upregulated in the CSF and urine of treatment-naïve PD, prodromal PD, and GBA or LRRK2 carrier participants by all three proteomics methods. We show that CSF DDC levels correlate with clinical symptom severity in treatment-naïve PD patients and can be used to accurately diagnose PD and prodromal PD. This suggests that urine and CSF DDC could be a promising diagnostic and prognostic marker with utility in both clinical care and translational research.
Topics: Humans; Parkinson Disease; Dopa Decarboxylase; Proteomics; Biomarkers; Plasma; Oxidoreductases Acting on Sulfur Group Donors; Aromatic-L-Amino-Acid Decarboxylases
PubMed: 38467937
DOI: 10.1007/s00401-024-02706-0 -
Chirurgia (Bucharest, Romania : 1990) Feb 2024Odontogenic sinusitis is a frequent disease of the maxillary sinus, resulting from a dental inflammatory condition or a foreign body migrated in the sinus cavity. We...
Odontogenic sinusitis is a frequent disease of the maxillary sinus, resulting from a dental inflammatory condition or a foreign body migrated in the sinus cavity. We performed a clinical retrospective study aimed to review the two surgical endoscopic approaches for odontogenic maxillary sinusitis middle and inferior meatotomy, in terms of realistic indications, efficacy, outcomes, and possible complications. In our study, we included a number of 400 patients with odontogenic maxillary sinusitis divided into two groups, treated in our hospital over five years, from January 2019 to December 2023. The patients included in this research were over 18 years old, diagnosed with odontogenic maxillary sinusitis, and underwent either middle meatal antrostomy or inferior meatotomy. We examined the medical records of 400 patients. The vast majority of patients had a history of dental interventions, and the most affected tooth was the first maxillary molar. The symptoms at admission were typical for sinusitis: nasal obstruction, anterior or posterior rhinorrhea, hyposmia to anosmia, cacosmia, and pain or facial pressure. 80% of the patients in the study underwent middle meatal antrostomy, while 20% underwent inferior meatotomy. There were no significant differences between these two approaches in terms of efficacy, complication rates, recovery, or relapses. The complications that occurred after the surgical treatment were minor and with a very low frequency. The most reported were middle meatus synechiae and the persistence of the meatotomy ostium, with mucus recirculation (in patients with inferior meatotomy). Endoscopic surgical treatment of odontogenic maxillary sinusitis can be done as middle or inferior meatotomy, each having specific indications. The maxillary antrostomy is preferred in the majority of cases, as it is a procedure in which the natural ostium of the maxillary sinus is enlarged, thereby maintaining the natural drainage pathway of the sinus. However, the inferior meatotomy is preferred in the case of foreign bodies or maxillary sinus retention cysts localized at the level of the sinus floor or in the alveolar or lateral recesses, or as part of a combined approach (inferior and middle meatotomy), when the ablation of a "fungus ball" is required.
Topics: Humans; Maxillary Sinusitis; Neoplasm Recurrence, Local; Retrospective Studies; Sinus Floor Augmentation; Sinusitis; Treatment Outcome; Adult
PubMed: 38465718
DOI: 10.21614/chirurgia.2024.v.119.i.1.p.76