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Revista de Neurologia Feb 2024Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the strongest prodromal markers of alpha-synucleinopathies. We aimed to investigate...
INTRODUCTION
Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the strongest prodromal markers of alpha-synucleinopathies. We aimed to investigate non-invasive clinical and quantitative predictors of phenoconversion from iRBD to parkinsonism.
PATIENTS AND METHODS
We prospectively followed-up a total of 45 patients (57.8% men) for eight years. Clinical assessments, Sniffin' Sticks Odor Identification Test, Farnsworth-Munsell 100 Hue Color Vision test, Beck Depression Inventory and Rome III Criteria for constipation were performed. Polysomnographic parameters, sleep spindles, electroencephalographic (EEG) spectral analysis, heart rate variability (HRV) were analyzed.
RESULTS
Eight patients (17.8%) showed phenoconversion to parkinsonism after a mean duration of 3.2 ± 1 years. Odds ratio for predicting phenoconversion was highest for patients =60 years of age with anosmia and constipation -44.8 (4.5-445.7); kappa = 4.291-. Duration, frequency or density of sleep spindles failed to demonstrate significant correlations. In EEG spectral analysis, lower alpha power in occipital region during wakefulness and REM sleep was significantly correlated with phenoconversion. Slowing in EEG spectrum power, together with age =60 years, anosmia and constipation, resulted in the highest odds ratio -122.5 (9.7-1543.8); kappa = 3.051-.
CONCLUSIONS
It is of great importance to have a world-wide perspective of phenoconversion rates from iRBD to overt neurodegeneration, since racial and geographical factors may play important modifying roles. Relatively younger age and shorter disease duration may also be confounding factors for lower rate in our study. Neurophysiological biomarkers seem to be important predictors of phenoconversion, though more research is needed to establish subtypes of iRBD with different probabilities of evolution to overt synucleinopathy.
Topics: Male; Humans; Middle Aged; Female; REM Sleep Behavior Disorder; Follow-Up Studies; Turkey; Anosmia; Constipation; Parkinsonian Disorders; Risk Assessment
PubMed: 38289245
DOI: 10.33588/rn.7803.2023181 -
Scientific Reports Jan 2024Limited studies explore the use of AI for COVID-19 prognostication. This study investigates the relationship between AI-aided radiographic parameters, clinical and...
Derivation and validation of novel integrated inpatient mortality prediction score for COVID-19 (IMPACT) using clinical, laboratory, and AI-processed radiological parameter upon admission: a multicentre study.
Limited studies explore the use of AI for COVID-19 prognostication. This study investigates the relationship between AI-aided radiographic parameters, clinical and laboratory data, and mortality in hospitalized COVID-19 patients. We conducted a multicentre retrospective study. The derivation and validation cohort comprised of 512 and 137 confirmed COVID-19 patients, respectively. Variable selection for constructing an in-hospital mortality scoring model was performed using the least absolute shrinkage and selection operator, followed by logistic regression. The accuracy of the scoring model was assessed using the area under the receiver operating characteristic curve. The final model included eight variables: anosmia (OR: 0.280; 95%CI 0.095-0.826), dyspnoea (OR: 1.684; 95%CI 1.049-2.705), loss of consciousness (OR: 4.593; 95%CI 1.702-12.396), mean arterial pressure (OR: 0.928; 95%CI 0.900-0.957), peripheral oxygen saturation (OR: 0.981; 95%CI 0.967-0.996), neutrophil % (OR: 1.034; 95%CI 1.013-1.055), serum urea (OR: 1.018; 95%CI 1.010-1.026), affected lung area score (OR: 1.026; 95%CI 1.014-1.038). The Integrated Inpatient Mortality Prediction Score for COVID-19 (IMPACT) demonstrated a predictive value of 0.815 (95% CI 0.774-0.856) in the derivation cohort. Internal validation resulted in an AUROC of 0.770 (95% CI 0.661-0.879). Our study provides valuable evidence of the real-world application of AI in clinical settings. However, it is imperative to conduct prospective validation of our findings, preferably utilizing a control group and extending the application to broader populations.
Topics: Humans; COVID-19; Retrospective Studies; Inpatients; Logistic Models; Arterial Pressure; ROC Curve
PubMed: 38272920
DOI: 10.1038/s41598-023-50564-9 -
PLoS Biology Jan 2024In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction...
In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs themselves by regulating their cell type-specific gene expression, such as that of olfactory marker protein (omp) involved in odor-evoked signal transduction. In line with this, response to bile acids, odors detected by OMP-positive OSNs, was significantly diminished in foxj1 mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of immotile olfactory cilia, as well as for the development of the OSNs.
Topics: Animals; Humans; Mice; Zebrafish; Cilia; Forkhead Transcription Factors; Olfactory Receptor Neurons; Olfactory Mucosa
PubMed: 38271330
DOI: 10.1371/journal.pbio.3002468 -
Frontiers in Public Health 2023There have been reports of otolaryngological adverse event following immunization (AEFI) such as instances of olfactory and gustatory dysfunction following COVID-19...
BACKGROUND
There have been reports of otolaryngological adverse event following immunization (AEFI) such as instances of olfactory and gustatory dysfunction following COVID-19 vaccination. This study aimed to analyze otolaryngological AEFIs following COVID-19 vaccination.
METHODS
This study was conducted with a secondary data analysis that the Vaccine Adverse Events Reporting System (VAERS) and the COVID-19 Data Tracker, which are both administered by the Centers for Disease Control and Prevention in the US. Using Medical Dictionary for Regulatory Activities (MedDRA) concepts, AEFIs included: Considering the overall frequency and similarity of symptoms in the first 153 PTs, they were grouped into major 19 AEFIs groups. The incidence rates (IRs) of AEFIs per 100,000 were calculated on individual and cumulative AEFIs levels, involving people who received complete primary series and an updated bivalent booster dose with one of the available COVID-19 vaccines in the US. The proportions of AEFIs by age, sex, and vaccine manufacturer were reported. We also calculated the proportional reporting ratio (PRR) of AEFIs.
RESULTS
We identified 106,653 otorhinolaryngologic AEFIs from the VAERS database, and a total of 226,593,618 people who received complete primary series in the US. Overall, the IR of total Otorhinolaryngologic AEFIs was 47.068 of CPS (completed primary series) and 7.237 UBB (updated bivalent booster) per 100,000. For most symptoms, being female was associated with statistically significant higher AEFIs. Upon examining the impact of different vaccine manufacturers, the researchers found that Janssen's vaccine exhibited higher IRs for hearing loss (5.871), tinnitus (19.182), ear infection (0.709), dizziness (121.202), sinusitis (2.088), epistaxis (4.251), anosmia (5.264), snoring (0.734), allergies (5.555), and pharyngitis (5.428). The highest PRRs were for Anosmia (3.617), Laryngopharyngeal Reflux - Acid Reflux (2.632), and Tinnitus -Ringing in the ears (2.343), in that order, with these three significantly incidence than other background noises.
CONCLUSION
This study, utilizing an extensive sample sizes, represents a significant step toward comprehensively characterizing the otolaryngological AEFIs associated with COVID-19 vaccinations. This large-scale analysis aims to move beyond isolated case reports and anecdotal evidence, providing a robust and detailed portrait of the otolaryngological AEFIs landscape in response to COVID-19 vaccinations.
Topics: Female; Humans; Male; Adverse Drug Reaction Reporting Systems; Anosmia; COVID-19; COVID-19 Vaccines; Tinnitus; United States; Vaccination
PubMed: 38269374
DOI: 10.3389/fpubh.2023.1338862 -
BMC Infectious Diseases Jan 2024To evaluate the frequency, duration and patterns of long-term coronavirus disease 2019 (COVID-19) symptoms and to analyse risk factors for long-lasting COVID-19 sequelae...
PURPOSE
To evaluate the frequency, duration and patterns of long-term coronavirus disease 2019 (COVID-19) symptoms and to analyse risk factors for long-lasting COVID-19 sequelae among a cohort of hospital employees (HEs).
METHODS
We conducted a survey regarding persistent COVID-19 related symptoms with all HEs from three medical centres in Cologne, Germany, who were tested SARS-CoV-2 PCR positive from March 2020 until May 2021. Duration of symptoms and possible risk factors for protracted COVID-19 course were analysed.
RESULTS
Of 221 included HEs, a number of 104 HEs (47.1%) reported at least one persisting symptom for more than 90 days after initial SARS-CoV-2 detection. Each one cycle higher initial Ct value significantly increased the chances of overcoming symptoms (odds ratio [OR] 1.05; 95% confidence interval (95%CI) 1.01-1.09; p = 0.019). The occurrence of breathlessness within the first ten days (OR 7.89; 95%CI 1.87-41.43; p = 0.008), an initial Ct value under 30 (OR 3.36; 95%CI 1.22-9.94; p = 0.022) as well as the occurrence of anosmia or ageusia within the first ten days (OR 3.01; 95%CI 1.10-8.84; p = 0.037) showed a statistically significant association with increased odds of illness duration over 90 days.
CONCLUSION
About half of the HEs suffered from long lasting symptoms over 90 days after almost entirely mild acute COVID-19. Predictive factors could possibly be used for early treatment to prevent development of long-term symptoms after COVID-19 in future.
Topics: Humans; COVID-19; SARS-CoV-2; Personnel, Hospital; Ageusia; Hospitals
PubMed: 38262969
DOI: 10.1186/s12879-023-08710-1 -
Medicina (Kaunas, Lithuania) Jan 2024COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a... (Review)
Review
COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49-83.87%), GI bleeding/hemorrhage (IR: 0.47-10.6%), hepatic ischemia (IR: 1.0-7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5-90.9%), anosmia (IR: 4.9-79.6%), dysgeusia (IR: 2.8-83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19-35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5-68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2-55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9-16.7%), and coagulopathy/venous thromboembolism (IR: 19-34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications.
Topics: Humans; COVID-19; Ischemic Stroke; Acute Kidney Injury; Brain Diseases; Ischemia
PubMed: 38256424
DOI: 10.3390/medicina60010164 -
Epidemiology and Infection Jan 2024To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected...
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
Topics: Humans; Ageusia; Anosmia; COVID-19; COVID-19 Testing; COVID-19 Vaccines; Longitudinal Studies; SARS-CoV-2; Clinical Trials, Phase III as Topic
PubMed: 38250791
DOI: 10.1017/S0950268824000037 -
Journal of the Association of Medical... Jan 2024Delays in COVID-19 testing may increase the risk of secondary household and community transmission. Little is known about what patient characteristics and symptom...
BACKGROUND
Delays in COVID-19 testing may increase the risk of secondary household and community transmission. Little is known about what patient characteristics and symptom profiles are associated with delays in test seeking.
METHODS
We conducted a retrospective cohort study of all symptomatic patients diagnosed with COVID-19 and assessed in a COVID Expansion to Outpatients (COVIDEO) virtual care program between March 2020 and June 2021. The primary outcome was later test seeking more than 3 days from symptom onset. Multivariable logistic regression was used to examine predictors of later testing including patient characteristics and symptoms (30 individual symptoms or 7 symptom clusters).
RESULTS
Of 5,363 COVIDEO patients, 4,607 were eligible and 2,155/4,607 (46.8%) underwent later testing. Older age was associated with increased odds of late testing (adjusted odds ratio [aOR] 1.007/year; 95% CI 1.00 to 1.01), as was history of recent travel (aOR 1.4; 95% CI 1.01 to 1.95). Health care workers had lower odds of late testing (aOR 0.50; 95% CI 0.39 to 0.62). Late testing was associated with symptoms in the cardiorespiratory (aOR 1.2; 95% CI 1.05, 1.36), gastrointestinal (aOR = 1.2; 95% CI 1.04, 1.4), neurological (aOR 1.1; 95% CI 1.003, 1.3) and psychiatric (aOR 1.3; 95% CI 1.1, 1.5) symptom clusters. Among individual symptoms, dyspnea, anosmia, dysgeusia, sputum, and anorexia were associated with late testing; pharyngitis, myalgia, and headache were associated with early testing.
CONCLUSION
Certain patient characteristics and symptoms are associated with later testing, and warrant further efforts to encourage earlier testing to minimize transmission.
PubMed: 38250614
DOI: 10.3138/jammi-2023-0007 -
PloS One 2024Alzheimer's disease (AD) is a complex neurodegenerative disorder with both genetic and non-genetic causes. Animal research models are available for a multitude of...
Alzheimer's disease (AD) is a complex neurodegenerative disorder with both genetic and non-genetic causes. Animal research models are available for a multitude of diseases and conditions affecting the central nervous system (CNS), and large-scale CNS gene expression data exist for many of these. Although there are several models specifically for AD, each recapitulates different aspects of the human disease. In this study we evaluate over 500 animal models to identify those with CNS gene expression patterns matching human AD datasets. Approaches included a hypergeometric based scoring system that rewards congruent gene expression patterns but penalizes discordant gene expression patterns. The top two models identified were APP/PS1 transgenic mice expressing mutant APP and PSEN1, and mice carrying a GFAP mutation that is causative of Alexander disease, a primary disorder of astrocytes in the CNS. The APP/PS1 and GFAP models both matched over 500 genes moving in the same direction as in human AD, and both had elevated GFAP expression and were highly congruent with one another. Also scoring highly were the 5XFAD model (with five mutations in APP and PSEN1) and mice carrying CK-p25, APP, and MAPT mutations. Animals with the APOE3 and 4 mutations combined with traumatic brain injury ranked highly. Bulbectomized rats scored high, suggesting anosmia could be causative of AD-like gene expression. Other matching models included the SOD1G93A strain and knockouts for SNORD116 (Prader-Willi mutation), GRID2, INSM1, XBP1, and CSTB. Many top models demonstrated increased expression of GFAP, and results were similar across multiple human AD datasets. Heatmap and Uniform Manifold Approximation Plot results were consistent with hypergeometric ranking. Finally, some gene manipulation models, including for TYROBP and ATG7, were identified with reversed AD patterns, suggesting possible neuroprotective effects. This study provides insight for the pathobiology of AD and the potential utility of available animal models.
Topics: Animals; Humans; Mice; Rats; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Disease Models, Animal; Gene Expression; Mice, Transgenic; Mutation; Presenilin-1; Repressor Proteins
PubMed: 38236817
DOI: 10.1371/journal.pone.0291995 -
Saudi Medical Journal Jan 2024To develop a reliable version of the Saudi Arabian-University of Pennsylvania smell identification test (SA-UPSIT) and to establish normative values for both genders.
OBJECTIVES
To develop a reliable version of the Saudi Arabian-University of Pennsylvania smell identification test (SA-UPSIT) and to establish normative values for both genders.
METHODS
This cross-sectional study was carried out on voluntarily recruited normal participants in King Saud University Medical City, Riyadh, Saudi Arabia, from April 2018 to May 2023. Culture-familiar odors were chosen and the kit was translated into Arabic for the study. The test was modified 3 times in 4 versions. Following this, a random sample was collected to carry out a re-test after 6 weeks.
RESULTS
A total of 288 subjects participated in the development of the SA-UPSIT across all versions, including 146 females and 142 males. The average age of the participants was 28.4±9.9 years. In the final version, 111 participants scored an average of 34.5±2.5 for the total score, 35±2.3 for females, and 34.1±2.6 for males. The test-retest reliability coefficient was 0.73, indicating acceptable reliability.
CONCLUSION
The new changes carried out to the SA-UPSIT increased the average scores and demonstrated good reliability, making it clinically applicable for diagnosing and monitoring olfactory dysfunction.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Smell; Saudi Arabia; Olfaction Disorders; Cross-Cultural Comparison; Cross-Sectional Studies; Reproducibility of Results
PubMed: 38220245
DOI: 10.15537/smj.2024.45.1.20230422