Search Results (224)

Background: Olfactory recovery plays an important role in improving the quality of life in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP), and Dupilumab therapy shows promising results. The Nasal Polyp Score (NPS), Visual Analog Scale (VAS) for olfactory disorders (ODs), and the Sniffin’ Sticks 16-item identification test (SS-I) are three of the main indices of efficacy in CRSwNP treatment. Although mechanical obstruction appears to be a major cause of olfactory disorders in this condition, the three indices can often vary with different trends. Aim: The aim is to assess whether there is a correlation between the sense of smell recovery and the volumetric reduction in polyps and to assess how the reduction in NPS affects the improvement in olfactory symptoms. Methods: An observational monocentric retrospective cohort study was conducted on a sample of 50 patients, enrolled in treatment with Dupilumab for 12 months at the ENT Unit of Rodolico Hospital. We investigated the relationship between NPS changes and olfactory recovery using the Sniffin’ Stick 16-item identification test and the VAS for ODs at baseline and follow-up endpoints (1-, 3-, 6-, 9-, and 12-month assessments). Results: During the follow-up, according to the data in the literature, the patients showed a faster improvement in terms of SS-I and VAS for ODs than expressed in terms of NPS variation. Conclusions: This study shows that, in patients treated with Dupilumab, there is no strong correlation between the reduction in NPS and the recovery of the sense of smell evaluated by an improvement in the SS-I and VAS for ODs in the 12 months of follow-up, suggesting that, in patients with CRSwNP, the improvement in olfactory symptoms following treatment with Dupilumab is mainly related to its anti-inflammatory effects and not to the reduction in mechanical obstruction caused by nasal polyps. Full article

Background: Parkinson’s disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota–nose–brain axis might be involved in the pathogenesis of PD. However relative studies are rare. Methods: By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP. Results: 16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology. Conclusions: We present evidence supporting the microbiota–nose–brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain. Full article

Obstructive sleep apnea (OSA) is increasingly recognized as a chronic condition that is closely interrelated to olfactory disorders, with a significant contribution to quality of health and overall quality of life. This narrative review aims to provide a thorough overview of the emerging evidence that now integrates these two previously considered distinct physiologic systems. Studies published recently have reported a significantly higher frequency of olfactory dysfunction among OSA patients compared to the general population, which raises the possibility of a causal relationship. We explore the postulated mechanisms behind this association, namely, the chronic intermittent hypoxia, local inflammatory effect, and neuroanatomical changes attributed to OSA. The review further explores the clinical impacts of this relationship through proposing the potential for an olfactory assessment to be used as a diagnostic modality for OSA and the effects of OSA treatment on olfactory function. Thus, we explore the difficulties in treating patients who experience both and suggest future areas for research. This review attempts to bridge the gap between the existing literature and impending investigation necessary for a better management of the interaction of sleep apnea and the human sense of smell. Full article

In restricted regions of the rodent brain, neurogenesis persists throughout life, hinting that perhaps similar phenomena may exist in humans. Neural stem cells (NSCs) that reside within the ventricular-subventricular zone (V-SVZ) continually produce functional cells, including neurons that integrate into the olfactory bulb circuitry. The ability to achieve this feat is based on genetically encoded transcriptional programs that are controlled by environmentally regulated post-transcriptional signaling pathways. One such pathway that molds V-SVZ neurogenesis is the mTOR pathway. This pathway integrates nutrient sufficiency with growth factor signaling to control distinct steps of neurogenesis. Alterations in mTOR pathway signaling occur in numerous neurodevelopmental disorders. Here, we provide a narrative review for the role of the mTOR pathway in this process and discuss the use of this region to study the mTOR pathway in both health and disease. Full article

Background/Objectives: Autism is a complex neurodevelopmental disorder characterized by restricted behaviors and impaired social and communication skills. The exact cause of autism remains unknown. One promising animal model for studying autism is the valproic acid rat model. Due to a 1 to 4 bias for males in autism occurrence, most animal model studies investigate only males and neglect females. However, female autism often appears different from that observed in males. Females are said to be less regularly diagnosed because they can “mask” their symptoms. Female autism is as necessary to investigate as male autism. Methods: Fertile adult female Sprague-Dawley rats were impregnated and injected with valproic acid on gestational day 13. Male and female offspring were subjected to behavioral tests to investigate autistic symptoms. Tests included novel object recognition, balance-beam, Y-maze, hole-board, three-chamber, marble burying, olfactory, light/dark and hot plate tests. Results: The tests revealed that VPA-exposed rats had increased anxiety-like behaviors, hyperactivity, and impaired non-verbal communication. However, they did not display repetitive behaviors or cognitive impairments. Notably, male and female rats showed different autism-like traits, with both showing hyperactivity, and males (but not females) additionally showing impaired sociability and increased anxiety. Conclusions: The findings suggest that prenatal exposure to VPA induces autism-like behaviors in both male and female Sprague-Dawley rat offspring. However, males appear more impacted by VPA exposure as evinced by their display of more autism-like symptoms relative to females. This study provides support for including both sexes in all studies modelling autism, as outcomes are seemingly impacted by the sex being observed. Full article

Air pollution plays a key role in sleep disorders and neurodegeneration. Alzheimer’s disease (AD), Parkinson’s disease (PD), and/or transactive response DNA-binding protein TDP-43 neuropathology have been documented in children and young adult forensic autopsies in the metropolitan area of Mexico City (MMC), along with sleep disorders, cognitive deficits, and MRI brain atrophy in seemingly healthy young populations. Ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs) reach urbanites’ brains through nasal/olfactory, lung, gastrointestinal tract, and placental barriers. We documented Fe UFPM/NPs in neurovascular units, as well as lateral hypothalamic nucleus orexinergic neurons, thalamus, medullary, pontine, and mesencephalic reticular formation, and in pinealocytes. We quantified ferromagnetic materials in sleep and arousal brain hubs and examined their motion behavior to low magnetic fields in MMC brain autopsy samples from nine children and 25 adults with AD, PD, and TDP-43 neuropathology. Saturated isothermal remanent magnetization curves at 50–300 mT were associated with UFPM/NP accumulation in sleep/awake hubs and their motion associated with 30–50 µT (DC magnetic fields) exposure. Brain samples exposed to anthropogenic PM pollution were found to be sensitive to low magnetic fields, with motion behaviors that were potentially linked to the early development and progression of fatal neurodegenerative diseases and sleep disorders. Single-domain magnetic UFPM/NPs in the orexin system, as well as arousal, sleep, and autonomic regions, are key to neurodegeneration, behavioral and cognitive impairment, and sleep disorders. We need to identify children at higher risk and monitor environmental UFPM and NP emissions and exposures to magnetic fields. Ubiquitous ferrimagnetic particles and low magnetic field exposures are a threat to global brain health. Full article

Background: Pain is prevalent in almost all populations and may often hinder visual, auditory, tactile, olfactory, and taste perception as it alters brain neural processing. The quantitative methods emerging to define pain and assess its effects on neural functions and perception are important. Identifying pain biomarkers is one of the initial stages in developing such models and interventions. The existing literature has explored chronic and experimentally induced pain, leveraging electroencephalograms (EEGs) to identify biomarkers and employing various qualitative and quantitative approaches to measure pain. Objectives: This systematic review examines the methods, participant characteristics, types of pain states, associated pain biomarkers of the brain’s electrical activity, and limitations of current pain studies. The review identifies what experimental methods researchers implement to study human pain states compared to human control pain-free states, as well as the limitations in the current techniques of studying human pain states and future directions for research. Methods: The research questions were formed using the Population, Intervention, Comparison, Outcome (PICO) framework. A literature search was conducted using PubMed, PsycINFO, Embase, the Cochrane Library, IEEE Explore, Medline, Scopus, and Web of Science until December 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to obtain relevant studies. The inclusion criteria included studies that focused on pain states and EEG data reporting. The exclusion criteria included studies that used only MEG or fMRI neuroimaging techniques and those that did not focus on the evaluation or assessment of neural markers. Bias risk was determined by the Newcastle–Ottawa Scale. Target data were compared between studies to organize the findings among the reported results. Results: The initial search resulted in 592 articles. After exclusions, 24 studies were included in the review, 6 of which focused on chronic pain populations. Experimentally induced pain methods were identified as techniques that centered on tactile perception: thermal, electrical, mechanical, and chemical. Across both chronic and stimulated pain studies, pain was associated with decreased or slowing peak alpha frequency (PAF). In the chronic pain studies, beta power increases were seen with pain intensity. The functional connectivity and pain networks of chronic pain patients differ from those of healthy controls; this includes the processing of experimental pain. Reportedly small sample sizes, participant comorbidities such as neuropsychiatric disorders and peripheral nerve damage, and uncontrolled studies were the common drawbacks of the studies. Standardizing methods and establishing collaborations to collect open-access comprehensive longitudinal data were identified as necessary future directions to generalize neuro markers of pain. Conclusions: This review presents a variety of experimental setups, participant populations, pain stimulation methods, lack of standardized data analysis methods, supporting and contradicting study findings, limitations, and future directions. Comprehensive studies are needed to understand the pain and brain relationship deeper in order to confirm or disregard the existing findings and to generalize biomarkers across chronic and experimentally induced pain studies. This requires the implementation of larger, diverse cohorts in longitudinal study designs, establishment of procedural standards, and creation of repositories. Additional techniques include the utilization of machine learning and analyzing data from long-term wearable EEG systems. The review protocol is registered on INPLASY (# 202520040). Full article

Sickle cell disease (SCD) is a severe inherited blood disorder characterized by abnormal hemoglobin (HbS) that leads to varying degrees of severity, including chronic hemolysis, episodic vaso-occlusion, and damage to multiple organs, causing significant morbidity and mortality. While SCD is a monogenic disease, its complications are influenced by polygenic factors. SCD prevalence is notably high in regions including the Middle East, with Saudi Arabia reporting significant cases, particularly in the Eastern Province. Most genetic factors associated with SCD outcomes have been identified in populations predominantly from Africa or of African ancestry. This study aims to identify genetic variants that characterize Saudi SCD patients with the potential to influence disease outcomes in this population. A multicenter case-control genome-wide association study (GWAS) was conducted involving 350 adult Saudi SCD patients and 202 healthy controls. Participants were genotyped using the Affymetrix Axiom array, covering 683,030 markers. Rigorous quality control measures were applied to ensure data integrity. Fisher’s exact was used to identify genetic variants with a significant difference in allele frequency (p < 5 × 10⁻⁸). Functional annotations and regulatory functions of variants were determined using the Ensembl Variant Effect Predictor (VEP) and RegulomeDB databases. The GWAS identified numerous significant genetic variants characterizing SCD cases in the Saudi population. These variants, distributed across multiple chromosomes, were found in genes with known functional consequences. A substantial proportion of the markers were detected in the olfactory receptor cluster, TRIM family, and HBB locus genes. Many of the identified genes were reported in previous studies showing significant associations with various SCD outcomes, including hemoglobin regulation, inflammation, immune response, and vascular function. The findings highlight the genetic complexity underlying SCD and its clinical manifestations. The identified variants suggest potential molecular biomarkers and therapeutic targets, enhancing our understanding of the molecular basis of SCD in the Saudi population. This is the first genetic analysis characterizing SCD patients compared to healthy individuals, uncovering genetic markers that could serve as diagnostic biomarkers and therapeutic targets. Given the known molecular mechanisms of the detected genetic loci, these provide a foundation for precision medicine in SCD management, highlighting the need for further studies to validate these results and explore their clinical implications. Full article

Alpha-synuclein has been associated with neurodegeneration, especially in Parkinson’s disease (PD). This study aimed to review clinical, biochemical, and neuroimaging markers and management of prodromal synucleinopathies. The prodromal state of synucleinopathies can be better understood with PD pathophysiology, and it can be separated into premotor and pre-diagnostic phases. The incidence of PD in patients with prodromal phase symptoms ranges from 0.07 to 14.30, and the most frequently studied pathology is the REM behavioral disorder (RBD). Neuroimaging markers are related to dopamine denervation, brain perfusion changes, gross anatomy changes, and peripheral abnormalities. α-synuclein assays (SAA) in CSF revealed high sensitivity (up to 97%) and high specificity (up to 92%); in the last decade, there was the development of other matrices (blood, skin, and olfactory mucosa) for obtaining quantitative and qualitative α-synuclein. Other biomarkers are neurofilament light chain, DOPA decarboxylase, and multiplexed mass spectrometry assay. Regarding genetic counseling in α-synucleinopathies, it is an important topic in clinical practice to discuss with patients with high-risk individuals and should involve basic principles of autonomy, beneficence, and non-maleficence. Some of the themes that should be reviewed are the involvement of physical activity, diet (including alcohol, coffee, and vitamin supplementation), smoking, sleep, and stress in the pathophysiology of synucleinopathies. The number of trials related to prodromal symptoms is still scarce, and the number of studies evaluating intervention is even lower. Full article

An abnormal accumulation of misfolded proteins is a common feature shared by most neurodegenerative disorders. Olfactory dysfunction (OD) is common in the elderly population and is present in 90% of patients with Alzheimer’s or Parkinson’s disease, usually preceding the cognitive and motor symptoms onset by several years. Early Aβ, tau, and α-synuclein protein aggregates deposit in brain structures involved in odor processing (olfactory bulb and tract, piriform cortex, amygdala, entorhinal cortex, and hippocampus) and seem to underly OD. The glymphatic system is a glial-associated fluid transport system that facilitates the movement of brain fluids and removes brain waste during specific sleep stages. Notably, the glymphatic system became less functional in aging and it is impaired in several conditions, including neurodegenerative diseases. As the nasal pathway has been recently described as the main outflow exit of cerebrospinal fluid and solutes, we hypothesized that OD may indeed be a clinical marker of early glymphatic dysfunction through abnormal accumulation of pathological proteins in olfactory structures. This effect may be more pronounced in peri- and postmenopausal women due to the well-documented impact of estrogen loss on the locus coeruleus, which may disrupt multiple mechanisms involved in glymphatic clearance. If this hypothesis is confirmed, olfactory dysfunction might be considered as a clinical proxy of glymphatic failure in neurodegenerative diseases. Full article

Parkinson’s disease (PD) is a neurological disorder characterized by heterogeneous symptomatology, in which the classical motor features of Parkinsonism are associated with clinically significant non-motor symptoms. Olfactory alteration, as a manifestation of PD’s premotor or prodromal phase, is well known. These impairments can lead to malnutrition, decreased appetite, and depression, thereby worsening patients’ quality of life. However, only a few studies clarify the mechanisms, characteristics, and clinical diagnostic and therapeutic implications of impaired taste perception. Moreover, unlike most motor features of PD, non-motor symptoms often have limited treatment options or responses. The purpose of this review is to collate and describe all relevant studies on taste and smell alterations in patients with PD and how these alterations could affect nutritional status. Our search aimed to identify English-language research articles and reviews published in peer-reviewed journals over the past two decades (2004–2024), while also including older foundational studies when relevant. Several studies show that hyposmia in PD worsens over time, potentially linked to structural changes in the brain’s basal ganglia and piriform cortex. Severe hyposmia is also associated with a higher risk of dementia in PD patients and can negatively influence quality of life, affecting social interactions and nutrition. Regarding taste perception, recent studies have suggested that hypogeusia may occur even in the prodromal stage of PD, such as in patients with REM sleep disorder, although the exact mechanisms remain unclear. Additionally, research has explored the role of bitter taste receptors and their possible involvement in inflammation and α-synuclein misfolding, suggesting a link between taste dysfunction and immune system changes in PD. Attention was then focused on the gut microbiota’s link to the central nervous system and its contribution to gustatory dysfunctions, as well as how the nasal microbiome influences PD progression by altering the olfactory system. Nowadays, the primary role of a correct diet in the overall treatment of PD patients is becoming increasingly important for practitioners. Diet should be included among the available aids to counteract some aspects of the pathology itself. For all these reasons, it is also crucial to determine whether these chemosensory impairments could serve as disease markers, helping to better understand the underlying mechanisms of the disease. Full article

Objective: To explore recent findings on how nutritional, gastrointestinal, social, and epigenetic factors interact in autism spectrum disorder, highlighting their implications for clinical management and intervention strategies that could improve development and quality of life of affected children. Sources: Studies published from 2000 to 2024 in the PubMed, Web of Science, Scopus, Scielo, Lilacs, and Google Scholar databases were collected. The process for the review adhered to the Search, Appraisal, Synthesis, and Analysis framework. Summary of the findings: Children with autism spectrum disorder have restrictive eating habits and often exhibit food selectivity with either hyper- or hypo-sensory characteristics. This review provides an overview of the literature on diagnosis and intervention strategies for selectivity in autism spectrum disorder, including the involvement of family members in meals, sharing a healthy diet and positive relationship with food, and the importance of exploring visual, olfactory, and tactile experiences of food and introducing new foods through play activities to expand the food repertoire. Modifications in the microbiota and gastrointestinal disorders may also be present in autism spectrum disorder and are presented due to their frequent nutritional repercussions. The medium and long-term implications of food preferences and behavior issues for nutritional status are also discussed, given the tendency for children with autism spectrum disorder to consume low-quality and energy-dense foods, leading to nutritional problems. Conclusions: Children with autism spectrum disorder have feeding difficulties, especially selectivity, gastrointestinal problems, changes in the microbiota and can evolve with micronutrient deficiencies, malnutrition and obesity. This review describes the evidence for possible targets for interventions aiming to improve nutritional health for children with autism spectrum disorder. Full article

Objectives: Evidence for the usefulness of biomarkers that aid in diagnosis, assessment of severity, and prediction of prognosis in patients with long COVID is limited. The aim of this study was to clarify the characteristics of brain natriuretic peptide (BNP) in long COVID. Methods: We conducted a retrospective observational study of patients who visited the COVID-19 aftercare outpatient clinic at Okayama University Hospital from February 2021 to April 2024. Results: A total of 428 patients were enrolled in this study, and the patients were divided into a group with normal BNP (n = 314, ≤18.4 pg/mL) and a group with increased BNP (n = 114, >18.4 pg/mL). The long COVID group with increased BNP had a higher proportion of females (44.3% vs. 73.7%, p < 0.01) and an older median age (38 vs. 51 years, p < 0.01). Fatigue and brain fog were commonly manifested in both groups, while dyspnea was a more frequent complaint in the group with increased BNP. Various symptoms including fatigue, palpitations, and taste and/or olfactory disorders were associated with elevated BNP (23 to 24 pg/mL). Memory impairment was also linked to higher BNP (OR: 2.36, p = 0.05). In long COVID patients, plasma BNP elevation appears to be more pronounced in females and is often related to cardiogenic factors, in which inflammatory responses are also involved. Conclusions: Plasma BNP measurement may be useful for evaluating the severity of long COVID, especially in female patients and those with respiratory symptoms and/or memory impairment. Full article

The International Classification of Diseases (ICD) has been developed and edited by the World Health Organisation and represents the global standard for recording health information and causes of death. The ICD-11 is the eleventh revision and came into effect on 1 January 2022. Perceptual disturbances refer to abnormalities in the way sensory information is interpreted by the brain, leading to distortions in the perception of reality. These can manifest as distorted perceptions or as phantom perceptions and can occur in all sensory modalities as visual, auditory, olfactory, gustatory tactile, vestibular, proprioceptory or interoceptory disturbances. There are similar brain mechanisms involved in the generation of these analogous perceptual disturbances and disorders, and they are treated with similar approaches. Perceptual disturbances are highly prevalent, with large variations across the different sensory modalities. They can be associated with significant suffering and cause a high socioeconomic burden. Perceptual disturbances can be symptoms of another disease or disease entities on their own. In the context of pain, this is reflected by the distinction between secondary pain (pain as a symptom of another underlying condition) and primary pain (a disease in its own right, rather than being a symptom of another underlying condition) in the ICD-11. Such a clear distinction is not found in an entirely consistent way across the various sensory modalities. By using the example of auditory phantom perceptions, we propose a framework for the classification of sensory disorders in alignment with the classification of pain in the ICD-11. The descriptions of the sensory disturbances should include (1) a causal aspect (primary versus secondary), (2) a temporal aspect (acute vs. chronic and persistent vs. intermittent), (3) a cognitive, emotional and autonomic interpretation aspect (=suffering) and (4) a social aspect (=disability). If the latter two aspects are present, we propose that the sensory disturbance is called a sensory disorder. Full article

Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear. We harvested the secretome from human mucosal OECs and characterized its protein content, identifying 709 proteins in the human OEC secretome from three donors in two passages. Thirty-nine proteins, including neurological-related proteins, such as profilin-1, and antioxidants, such as peroxiredoxin-1 and glutathione S-transferase, were shared between the six samples. The secretome consistently demonstrated potential effects such as antioxidant activity, neuronal differentiation, and quiescence exit of neural stem cells (NSCs). The total secretome produced by OECs protects NSCs from H₂O₂-induced reactive oxygen species accumulation. During induction of neuronal differentiation, secretomes promoted neurite outgrowth, axon elongation, and expression of neuronal markers. The secretome ameliorated bone morphogenetic protein 4- and fibroblast growth factor 2-induced quiescence of NSCs. The human OEC secretome triggers NSCs to exit prime quiescence, which is related to increased phosphoribosomal protein S6 expression and RNA synthesis. The human OEC secretome has beneficial effects on NSCs and may be applied in neurological disease studies. Full article