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Movement Disorders : Official Journal... Apr 2024Rapid eye movement (REM) sleep behavior disorder (RBD) is an early feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Damaging coding variants in...
BACKGROUND
Rapid eye movement (REM) sleep behavior disorder (RBD) is an early feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Damaging coding variants in Glucocerebrosidase (GBA1) are a genetic risk factor for RBD. Recently, a population-specific non-coding risk variant (rs3115534) was found to be associated with PD risk and earlier onset in individuals of African ancestry.
OBJECTIVES
We aimed to investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD in persons with PD.
METHODS
We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. All DNA samples were genotyped and imputed, and the GBA1 rs3115534 risk variant was extracted. The RBD screening questionnaire (RBDSQ) was used to assess symptoms of possible RBD.
RESULTS
RBD was present in 200 PD (28.2%) and 51 (6.6%) controls. We identified that the non-coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (β, 0.3640; standard error [SE], 0.103, P = 4.093e-04), as well as in all samples after adjusting for PD status (β, 0.2542; SE, 0.108; P = 0.019) suggesting that although non-coding, this variant may have the same downstream consequences as GBA1 coding variants.
CONCLUSIONS
Our results indicate that the non-coding GBA1 rs3115534 risk variant is associated with an increasing number of RBD symptoms in persons with PD of Nigerian origin. Further research is needed to assess if this variant is also associated with polysomnography-defined RBD and with RBD symptoms in DLB. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Genetic Predisposition to Disease; Genotype; Glucosylceramidase; Nigeria; Parkinson Disease; Polymorphism, Single Nucleotide; REM Sleep Behavior Disorder; West African People; Young Adult; Adult
PubMed: 38390630
DOI: 10.1002/mds.29753 -
Innere Medizin (Heidelberg, Germany) Mar 2024Due to the availability of disease-modifying anti-asthmatic drugs (DMAADs), especially inhaled steroids (alone or in combination with long-acting bronchodilators),... (Review)
Review
Due to the availability of disease-modifying anti-asthmatic drugs (DMAADs), especially inhaled steroids (alone or in combination with long-acting bronchodilators), biologics and modern allergen immunotherapy, the treatment of asthma has fundamentally changed. The aims of modern asthma precision medicine are prevention of symptoms and the induction and maintenance of asthma remission (long-term asthma control, freedom from exacerbations and stable lung function without the use of systemic steroids). A treat to target approach is used as for other chronic inflammatory diseases in internal medicine: the aim is to achieve remission by an individually tailored treatment with DMAADs; however, the prerequisite for modern asthma precision medicine is asthma phenotyping, including a detailed medical history, lung function testing, allergological diagnostics and measurement of type 2 markers (blood eosinophils and, if available, exhaled nitric oxide, FeNO).
Topics: Humans; Precision Medicine; Asthma; Anti-Asthmatic Agents; Bronchodilator Agents; Steroids
PubMed: 38360901
DOI: 10.1007/s00108-024-01666-7 -
Journal of Neuroinflammation Feb 2024Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature...
BACKGROUND
Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals.
METHODS
Our cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES.
RESULTS
CSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations.
CONCLUSION
Specific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.
Topics: Humans; Aged; Middle Aged; Chronic Traumatic Encephalopathy; Football; Interleukin-6; Brain Injuries, Traumatic; Biomarkers
PubMed: 38336728
DOI: 10.1186/s12974-024-03034-6 -
Avian Pathology : Journal of the W.V.P.A Aug 2024Marek's disease (MD) is a neoplastic disease that significantly affects the poultry industry. Long non-coding RNAs (lncRNAs) are crucial regulatory factors in various...
Marek's disease (MD) is a neoplastic disease that significantly affects the poultry industry. Long non-coding RNAs (lncRNAs) are crucial regulatory factors in various biological processes, including tumourigenesis. However, the involvement of novel lncRNAs in the course of MD virus (MDV) infection is still underexplored. Here, we present the first comprehensive characterization of differentially expressed lncRNAs in chicken spleen at different stages of MDV infection. A series of differentially expressed lncRNAs was identified at each stage of MDV infection through screening. Notably, our investigation revealed a novel lncRNA, lncRNA 803, which exhibited significant differential expression at different stages of MDV infection and was likely to be associated with the p53 pathway. Further analyses demonstrated that the overexpression of lncRNA 803 positively regulated the expression of p53 and TP53BP1 in DF-1 cells, leading to the inhibition of apoptosis. This is the first study to focus on the lncRNA expression profiles in chicken spleens during MDV pathogenesis. Our findings highlight the potential role of the p53-related novel lncRNA 803 in MD pathogenesis and provide valuable insights for decoding the molecular mechanism of MD pathogenesis involving non-coding RNA. Differentially expressed lncRNAs in spleens of chickens infected with Marek's disease virus at different stages were identified for the first time.The effects of novel lncRNA 803 on p53 pathway and apoptosis of DF-1 cells were reported for the first time.
Topics: Animals; RNA, Long Noncoding; Marek Disease; Chickens; Apoptosis; Spleen; Poultry Diseases; Tumor Suppressor Protein p53; Cell Line; Herpesvirus 2, Gallid
PubMed: 38323582
DOI: 10.1080/03079457.2024.2316817 -
Neurology Feb 2024In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid...
BACKGROUND AND OBJECTIVES
In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ), phosphorylated tau 181 (p-tau), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ. First, we describe longitudinal trajectories of biofluid markers in PD. Second, we modified the AD β-amyloid/tau/neurodegeneration (ATN) framework for application in PD (ATN) using CSF Aβ (A), p-tau (T), and serum NfL (N) and tested ATN prediction of longitudinal cognitive decline in PD.
METHODS
Participants were selected from the Parkinson's Progression Markers Initiative cohort, clinically diagnosed with sporadic PD or as controls, and followed up annually for 5 years. Linear mixed-effects models (LMEMs) tested the interaction of diagnosis with longitudinal trajectories of analytes (log transformed, false discovery rate [FDR] corrected). In patients with PD, LMEMs tested how baseline ATN status (AD [A+T+N±] vs not) predicted clinical outcomes, including Montreal Cognitive Assessment (MoCA; rank transformed, FDR corrected).
RESULTS
Participants were 364 patients with PD and 168 controls, with comparable baseline mean (±SD) age (patients with PD = 62 ± 10 years; controls = 61 ± 11 years]; Mann-Whitney Wilcoxon: = 0.4) and sex distribution (patients with PD = 231 male individuals [63%]; controls = 107 male individuals [64%]; χ: = 1). Patients with PD had overall lower CSF p-tau (β = -0.16, 95% CI -0.23 to -0.092, = 2.2e-05) and t-tau than controls (β = -0.13, 95% CI -0.19 to -0.065, = 4e-04), but not Aβ ( = 0.061) or NfL ( = 0.32). Over time, patients with PD had greater increases in serum NfL than controls (β = 0.035, 95% CI 0.022 to 0.048, = 9.8e-07); slopes of patients with PD did not differ from those of controls for CSF Aβ ( = 0.18), p-tau ( = 1), or t-tau ( = 0.96). Using ATN, PD classified as A+T+N± (n = 32; 9%) had worse cognitive decline on global MoCA (β = -73, 95% CI -110 to -37, = 0.00077) than all other ATN statuses including A+ alone (A+T-N-; n = 75; 21%).
DISCUSSION
In patients with early PD, CSF p-tau and t-tau were low compared with those in controls and did not increase over 5 years of follow-up. Our study shows that classification using modified ATN (incorporating CSF Aβ, CSF p-tau, and serum NfL) can identify biologically relevant subgroups of PD to improve prediction of cognitive decline in early PD.
Topics: Humans; Male; Middle Aged; Aged; Parkinson Disease; tau Proteins; Alzheimer Disease; Amyloid beta-Peptides; Cognitive Dysfunction; Prognosis; Biomarkers
PubMed: 38306599
DOI: 10.1212/WNL.0000000000208033 -
Avian Diseases Jan 2024The poultry industry is the largest source of meat and eggs for the growing human population worldwide. Key concerns in poultry farming are nutrition, management, flock... (Review)
Review
The poultry industry is the largest source of meat and eggs for the growing human population worldwide. Key concerns in poultry farming are nutrition, management, flock health, and biosecurity measures. As part of the flock health, use of live viral vaccines plays a vital role in the prevention of economically important and common viral diseases. This includes diseases and production losses caused by Newcastle disease virus, infectious bronchitis virus, infectious laryngotracheitis virus, infectious bursal disease virus, Marek's disease virus, chicken infectious anemia virus, avian encephalomyelitis virus, fowlpox virus, and avian metapneumovirus. These viruses cause direct and indirect harms, such as financial losses worth millions of dollars, loss of protein sources, and threats to animal welfare. Flock losses vary by type of poultry, age of affected animals, co-infections, immune status, and environmental factors. Losses in broiler birds can consist of high mortality, poor body weight gain, high feed conversion ratio, and increased carcass condemnation. In commercial layers and breeder flocks, losses include higher than normal mortality rate, poor flock uniformity, drops in egg production and quality, poor hatchability, and poor day-old-chick quality. Despite the emergence of technology-based vaccines, such as inactivated, subunit, vector-based, DNA or RNA, and others, the attenuated live vaccines remain as important as before. Live vaccines are preferred in the global veterinary vaccine market, accounting for 24.3% of the global market share in 2022. The remaining 75% includes inactivated, DNA, subunit, conjugate, recombinant, and toxoid vaccines. The main reason for this is that live vaccines can induce innate, mucosal, cellular, and humoral immunities by single or multiple applications. Some live vaccine combinations provide higher and broader protection against several diseases or strains of viruses. This review aimed to explore insights on the pros and cons of attenuated live vaccines commonly used against major viral infections of the global chicken industry, and the future road map for improvement.
Topics: Humans; Animals; Chickens; Viral Vaccines; Poultry Diseases; Vaccines, Attenuated; DNA
PubMed: 38300660
DOI: 10.1637/aviandiseases-D-23-99998 -
Veterinary Sciences Jan 2024Marek's disease virus (MDV) causes malignant lymphoma (Marek's disease; MD) in chickens. The Meq protein is essential for tumorigenesis since it regulates the expression...
Marek's disease virus (MDV) causes malignant lymphoma (Marek's disease; MD) in chickens. The Meq protein is essential for tumorigenesis since it regulates the expression of host and viral genes. Previously, we reported that the deletion of the short isoform of Meq (S-Meq) decreases the pathogenicity of MDV. Recently, we identified a further short isoform of Meq (very short isoform of Meq, VS-Meq) in chickens with MD in Japan. A 64-amino-acid deletion was confirmed at the C-terminus of VS-Meq. We measured the transcriptional regulation by VS-Meq in three gene promoters to investigate the effect of VS-Meq on protein function. Wild-type VS-Meq decreased the transrepression of the pp38 promoter but did not alter the transactivation activity of the Meq and Bcl-2 promoters. The deletion in VS-Meq did not affect the activity of the pp38 promoter but enhanced the transactivation activities of the Meq and Bcl-2 promoters. Collectively, the deletion of VS-Meq potentially enhanced the activity of the Meq promoter, while other amino acid sequences in wild-type VS-Meq seemed to affect the weak transrepression of the pp38 promoter. Further investigation is required to clarify the effects of these changes on pathogenicity.
PubMed: 38275925
DOI: 10.3390/vetsci11010043 -
The Lancet. Neurology Feb 2024Parkinson's disease and dementia with Lewy bodies are currently defined by their clinical features, with α-synuclein pathology as the gold standard to establish the... (Review)
Review
Parkinson's disease and dementia with Lewy bodies are currently defined by their clinical features, with α-synuclein pathology as the gold standard to establish the definitive diagnosis. We propose that, given biomarker advances enabling accurate detection of pathological α-synuclein (ie, misfolded and aggregated) in CSF using the seed amplification assay, it is time to redefine Parkinson's disease and dementia with Lewy bodies as neuronal α-synuclein disease rather than as clinical syndromes. This major shift from a clinical to a biological definition of Parkinson's disease and dementia with Lewy bodies takes advantage of the availability of tools to assess the gold standard for diagnosis of neuronal α-synuclein (n-αsyn) in human beings during life. Neuronal α-synuclein disease is defined by the presence of pathological n-αsyn species detected in vivo (S; the first biological anchor) regardless of the presence of any specific clinical syndrome. On the basis of this definition, we propose that individuals with pathological n-αsyn aggregates are at risk for dopaminergic neuronal dysfunction (D; the second biological anchor). Our biological definition establishes a staging system, the neuronal α-synuclein disease integrated staging system (NSD-ISS), rooted in the biological anchors (S and D) and the degree of functional impairment caused by clinical signs or symptoms. Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B). The presence of clinical manifestations marks the transition to stage 2 and beyond. Stage 2 is characterised by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment. A biological definition of neuronal α-synuclein disease and an NSD-ISS research framework are essential to enable interventional trials at early disease stages. The NSD-ISS will evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated. Presently, the NSD-ISS is intended for research use only; its application in the clinical setting is premature and inappropriate.
Topics: Humans; alpha-Synuclein; Parkinson Disease; Lewy Body Disease; Synucleinopathies; Lewy Bodies; Syndrome
PubMed: 38267190
DOI: 10.1016/S1474-4422(23)00405-2 -
The Lancet. Neurology Feb 2024
Topics: Humans; Parkinson Disease; Carbamates; Quinuclidines
PubMed: 38267178
DOI: 10.1016/S1474-4422(23)00470-2 -
Animals : An Open Access Journal From... Jan 2024Marek's disease (MD), caused by (GaAHV-2), also known as MD virus (MDV), is a lymphoproliferative disease that primarily affects chickens. Recently, MDV has been...
Marek's disease (MD), caused by (GaAHV-2), also known as MD virus (MDV), is a lymphoproliferative disease that primarily affects chickens. Recently, MDV has been detected in lymphomatous tumors in turkeys in various countries. Between 2021 and 2023, three cases ranging from no to severe clinical disorders (depression, lameness, and increased mortality) occurred in commercial turkey flocks in Slovenia. In all cases, MDV was detected by PCR in DNA samples extracted from organs developing tumor infiltrations. Sequencing and phylogenetic analysis of the gene revealed that the GaAHV-2 detected has molecular features of a very virulent pathotype and genetic similarity with GaAHV-2 detected in chickens in Tunisia. This is the first report of MDV in commercial turkeys in Slovenia.
PubMed: 38254418
DOI: 10.3390/ani14020250