-
Journal of Nuclear Medicine : Official... Nov 2022Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy movement disorder that can be imaged by the F-labeled tau PET tracer... (Observational Study)
Observational Study
Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy movement disorder that can be imaged by the F-labeled tau PET tracer 2-(2-([F]fluoro)pyridin-4-yl)-9-pyrrolo[2,3-:4,5-']dipyridine (F-PI-2620). The in vivo diagnosis is currently established on clinical grounds and supported by midbrain atrophy estimation in structural MRI. Here, we investigate whether F-PI-2620 tau PET has the potential to improve the imaging diagnosis of PSP. In this multicenter observational study, dynamic (0-60 min after injection) F-PI-2620 PET and structural MRI data for 36 patients with PSP, 22 with PSP-Richardson syndrome, and 14 with a clinical phenotype other than Richardson syndrome (i.e., variant PSP) were analyzed along with data for 10 age-matched healthy controls (HCs). The PET data underwent kinetic modeling, which resulted in distribution volume ratio (DVR) images. These and the MR images were visually assessed by 3 masked experts for typical PSP signs. Furthermore, established midbrain atrophy parameters were measured in structural MR images, and regional DVRs were measured in typical tau-in-PSP target regions in the PET data. Visual assessments discriminated PSP patients and HCs with an accuracy of 63% for MRI and 80% for the combination of MRI and F-PI-2620 PET. As compared with patients of the PSP-Richardson syndrome subgroup, those of the variant PSP subgroup profited more in terms of sensitivity from the addition of the visual F-PI-2620 PET to the visual MRI information (35% vs. 22%). In quantitative image evaluation, midbrain-to-pons area ratio and globus pallidus DVRs discriminated best between the PSP patients and HCs, with sensitivities and specificities of 83% and 90%, respectively, for MRI and 94% and 100%, respectively, for the combination of MRI and F-PI-2620 PET. The gain of sensitivity by adding F-PI-2620 PET to MRI data was more marked in clinically less affected patients than in more affected patients (37% vs. 19% for visual, and 16% vs. 12% for quantitative image evaluation). These results provide evidence for an improved imaging-based PSP diagnosis by adding F-PI-2620 tau PET to structural MRI. This approach seems to be particularly promising at earlier disease stages and could be of value both for improving early clinical PSP diagnosis and for enriching PSP cohorts for trials of disease-modifying drugs.
Topics: Humans; Supranuclear Palsy, Progressive; tau Proteins; Magnetic Resonance Imaging; Atrophy
PubMed: 35422444
DOI: 10.2967/jnumed.121.262854 -
Viruses Nov 2021Herpes simplex virus type 1, or HSV-1, is a widespread human pathogen that replicates in epithelial cells of the body surface and then establishes latent infection in... (Review)
Review
Herpes simplex virus type 1, or HSV-1, is a widespread human pathogen that replicates in epithelial cells of the body surface and then establishes latent infection in peripheral neurons. When HSV-1 replicates, viral progeny must be efficiently released to spread infection to new target cells. Viral spread occurs via two major routes. In cell-cell spread, progeny virions are delivered directly to cellular junctions, where they infect adjacent cells. In cell-free release, progeny virions are released into the extracellular milieu, potentially allowing the infection of distant cells. Cell-cell spread of HSV-1 has been well studied and is known to be important for in vivo infection and pathogenesis. In contrast, HSV-1 cell-free release has received less attention, and its significance to viral biology is unclear. Here, I review the mechanisms and regulation of HSV-1 cell-free virion release. Based on knowledge accrued in other herpesviral systems, I argue that HSV-1 cell-free release is likely to be tightly regulated in vivo. Specifically, I hypothesize that this process is generally suppressed as the virus replicates within the body, but activated to high levels at sites of viral reactivation, such as the oral mucosa and skin, in order to promote efficient transmission of HSV-1 to new human hosts.
Topics: Animals; Cell Line; Cell-Free System; Herpes Simplex; Herpesvirus 1, Human; Humans; Virion; Virus Release
PubMed: 34960664
DOI: 10.3390/v13122395 -
Frontiers in Immunology 2022The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed...
The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed class I molecule with strong associations between disease resistance and MHC haplotype. For Marek's disease virus (MDV) infections of chickens, the MHC haplotype is one of the major determinants of genetic resistance and susceptibility. VALO specific pathogen free (SPF) chickens are widely used in biomedical research and vaccine production. While valuable findings originate from MDV infections of VALO SPF chickens, their MHC haplotypes and associated disease resistance remained elusive. In this study, we used several typing systems to show that VALO SPF chickens possess MHC haplotypes that include B9, B9:02, B15, B19 and B21 at various frequencies. Moreover, we associate the MHC haplotypes to MDV-induced disease and lymphoma formation and found that B15 homozygotes had the lowest tumor incidence while B21 homozygotes had the lowest number of organs with tumors. Finally, we found transmission at variable levels to all contact birds except B15/B21 heterozygotes. These data have immediate implications for the use of VALO SPF chickens and eggs in the life sciences and add another piece to the puzzle of the chicken MHC complex and its role in infections with this oncogenic herpesvirus.
Topics: Animals; Carcinogenesis; Chickens; Disease Resistance; Haplotypes; Herpesvirus 2, Gallid; Histocompatibility Antigens; Major Histocompatibility Complex; Marek Disease
PubMed: 35693787
DOI: 10.3389/fimmu.2022.908305 -
Alzheimer's Research & Therapy Oct 2023Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly...
BACKGROUND
Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer's disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected.
METHODS
We examined 237 men ages 45-74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates.
RESULTS
There were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL (p = 0.94, 95% C.I. = [- 0.033, 0.025]), PRO-UE (p = 0.40, 95% C.I. = [- 0.010, 0.029]), COL-UE (p = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning.
CONCLUSIONS
Cognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications.
TRIAL REGISTRATION
NCT02798185.
Topics: Male; Humans; Chronic Traumatic Encephalopathy; Football; Neurodegenerative Diseases; Alzheimer Disease; Cognitive Dysfunction; Amyloid beta-Peptides; Amyloid; Cognition; Positron-Emission Tomography
PubMed: 37798671
DOI: 10.1186/s13195-023-01315-5 -
Movement Disorders Clinical Practice Jun 2023Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD).
BACKGROUND
Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD).
OBJECTIVES
We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD.
METHODS
PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut-offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine-123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system-related biomarkers and CI, including persistent impairment.
RESULTS
Demographic and clinical variables associated with CI were higher age, male sex, lower education, non-White race, higher depression and anxiety scores and higher MDS-UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values ( range 0.003-0.005) and higher LEDD over time ( range <0.001-0.01) were significantly associated with increased risk for CI.
CONCLUSIONS
Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically-relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course.
TRIAL REGISTRATION
Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023).
PubMed: 37332638
DOI: 10.1002/mdc3.13751 -
International Journal of Molecular... Mar 2021MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression post-transcriptionally by targeting either the 3' untranslated or coding regions of genes.... (Review)
Review
MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression post-transcriptionally by targeting either the 3' untranslated or coding regions of genes. They have been reported to play key roles in a wide range of biological processes. The recent remarkable developments of transcriptomics technologies, especially next-generation sequencing technologies and advanced bioinformatics tools, allow more in-depth exploration of messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), including miRNAs. These technologies have offered great opportunities for a deeper exploration of miRNA involvement in farm animal diseases, as well as livestock productivity and welfare. In this review, we provide an overview of the current knowledge of miRNA roles in major farm animal diseases with a particular focus on diseases of economic importance. In addition, we discuss the steps and future perspectives of using miRNAs as biomarkers and molecular therapy for livestock disease management as well as the challenges and opportunities for understanding the regulatory mechanisms of miRNAs related to disease pathogenesis.
Topics: Animal Diseases; Animals; Animals, Domestic; Biomarkers; Gene Expression Regulation; Humans; Livestock; MicroRNAs
PubMed: 33802936
DOI: 10.3390/ijms22063080 -
Poultry Science Aug 2021The reticuloendotheliosis virus (REV) and the Marek's disease virus (MDV) cause reticuloendotheliosis (RE) and Marek's disease (MD) in poultry, respectively. According...
The reticuloendotheliosis virus (REV) and the Marek's disease virus (MDV) cause reticuloendotheliosis (RE) and Marek's disease (MD) in poultry, respectively. According to epidemiological results obtained in our laboratory from 2010 to 2017, the positive rates of REV and MDV co-infection remained at low levels. In the present study, during the period of October 2018 to July 2020, 4 clinical cases with high morbidity (5%-20%) and mortality (2%-10%), caused by the co-infection of REV and vv+ MDV-like strains, were diagnosed and analyzed by histopathological observation, cell cultures and detection with ELISA and IFA, and the PCR and by sequencing of the isolates' genes. Sequencing and the sequence analysis on the complete genomes of the REV strains and the meq genes of the MDV strains were performed. The results, based on the complete genome, LTR, gag, pol, and env genes' nucleotide sequences of the REV strains, showed that the REV isolates and 68.0 % (17/25) of the reference strains were in a same branch, and all had a high sequence similarity (>99.0%). The similarities between the four isolates and a vv+MDV strain GX18NNM4 were very high, up to 99.3-99.8%. Also, the amino acid residuals at locations 71, 77, 80, 115, 139, 176, and 217 were all the same as A, E, Y, A, A, R, and A, respectively, in the meq gene of the four MDV isolates. In addition, the substitutes at P176R and P217A interrupted the stretches of the proline-rich repeat PPPP, indicating that these strains belonged to the vv+ MDV-like category. Our findings indicated that the more recent and frequent reemergence of REV and the subsequent co-infection with vv+ MDV-like strain has become one of the causes of the clinical outbreaks of tumors and is undoubtedly a threat to the poultry industry in southern China.
Topics: Animals; Chickens; China; Coinfection; Herpesvirus 2, Gallid; Marek Disease; Poultry Diseases; Reticuloendotheliosis virus
PubMed: 34174570
DOI: 10.1016/j.psj.2021.101099 -
Alzheimer's Research & Therapy Jan 2023Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the...
BACKGROUND
Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players.
METHODS
One hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests.
RESULTS
Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent.
CONCLUSIONS
In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.
Topics: Male; Humans; Football; Brain Concussion; Cognitive Dysfunction; Memory, Short-Term; Neuropsychological Tests
PubMed: 36597138
DOI: 10.1186/s13195-022-01147-9 -
Journal of Virology Jan 2020Viruses may hijack glycolysis, glutaminolysis, or fatty acid β-oxidation of host cells to provide the energy and macromolecules required for efficient viral...
Viruses may hijack glycolysis, glutaminolysis, or fatty acid β-oxidation of host cells to provide the energy and macromolecules required for efficient viral replication. Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens and modulates metabolism of host cells. Metabolic analysis of MDV-infected chicken embryonic fibroblasts (CEFs) identified elevated levels of metabolites involved in glutamine catabolism, such as glutamic acid, alanine, glycine, pyrimidine, and creatine. In addition, our results demonstrate that glutamine uptake is elevated by MDV-infected cells Although glutamine, but not glucose, deprivation significantly reduced cell viability in MDV-infected cells, both glutamine and glucose were required for virus replication and spread. In the presence of minimum glutamine requirements based on optimal cell viability, virus replication was partially rescued by the addition of the tricarboxylic acid (TCA) cycle intermediate, α-ketoglutarate, suggesting that exogenous glutamine is an essential carbon source for the TCA cycle to generate energy and macromolecules required for virus replication. Surprisingly, the inhibition of carnitine palmitoyltransferase 1a (CPT1a), which is elevated in MDV-infected cells, by chemical (etomoxir) or physiological (malonyl-CoA) inhibitors, did not reduce MDV replication, indicating that MDV replication does not require fatty acid β-oxidation. Taken together, our results demonstrate that MDV infection activates anaplerotic substrate from glucose to glutamine to provide energy and macromolecules required for MDV replication, and optimal MDV replication occurs when the cells do not depend on mitochondrial β-oxidation. Viruses can manipulate host cellular metabolism to provide energy and essential biosynthetic requirements for efficient replication. Marek's disease virus (MDV), an avian alphaherpesvirus, causes a deadly lymphoma in chickens and hijacks host cell metabolism. This study provides evidence for the importance of glycolysis and glutaminolysis, but not fatty acid β-oxidation, as an essential energy source for the replication and spread of MDV. Moreover, it suggests that in MDV infection, as in many tumor cells, glutamine is used for generation of energetic and biosynthetic requirements of the MDV infection, while glucose is used biosynthetically.
Topics: Alphaherpesvirinae; Animals; Chick Embryo; Chickens; Glucose; Glutamine; Glycolysis; Herpesvirus 2, Gallid; Mardivirus; Marek Disease; Viral Proteins; Virus Replication
PubMed: 31748393
DOI: 10.1128/JVI.01680-19 -
Open Veterinary Journal 2021Duck viral enteritis, commonly known as duck plague (DP), is an acute and contagious fatal disease in ducks, geese, and swans caused by the DP virus (DPV). It poses a...
BACKGROUND
Duck viral enteritis, commonly known as duck plague (DP), is an acute and contagious fatal disease in ducks, geese, and swans caused by the DP virus (DPV). It poses a serious threat to the growth of duck farming in the Haor (wetland) areas of Bangladesh.
AIM
This study aimed to detect the circulating DPV by molecular characterization, followed by phylogenetic analysis, targeting the gene in infected ducks from five Haor districts in Bangladesh and to observe the variation in the genome sequence between the field virus and vaccine strain of DPV.
METHODS
A total of 150 samples (liver, 50; intestine, 50; and oropharyngeal tissue, 50) were collected from DP-suspected sick/dead ducks from 50 affected farms in Kishoreganj, Netrokona, B. Baria, Habiganj, and Sunamganj districts in Bangladesh. For the identification of DPV in collected samples, polymerase chain reaction (PCR) was utilized. Nucleotide sequences of the amplified gene were compared with those of other DPV strains available in GenBank.
RESULTS
Of the 150 samples, 90 (60%) were found to be positive for DPV, as confirmed by PCR. Organ-wise prevalence was higher in the liver (72%), followed by the intestine (64%) and oropharyngeal tissue (44%). Regarding areas, the highest and lowest prevalence in the liver and intestine was observed in Habiganj and B. Baria, respectively, whereas the highest and lowest prevalence in the oropharyngeal tissue was observed in B. Baria and Habiganj, respectively. Two isolates, BAU/KA/DPV(B1)/2014 from Kishoreganj and BAU/KA/DPV(B4)/2014 from Sunamganj were sequenced, and phylogenetic analysis revealed that these isolates are evolutionarily closely related to Chinese isolates of DPV. Additionally, the isolates of DPV BAU/KA/DPV(B1)/2014 and BAU/KA/DPV(B4)/2014 showed the highest (98%) similarity to each other. The nucleotide sequence of the isolate BAU/KA/DPV(B1)/2014 exhibited higher nucleotide variability (246 nucleotides) than that of the vaccine strain (accession no. EU082088), which may affect protein function and additional drug sensitivity.
CONCLUSION
Based on the findings of the molecular study, it can be assumed that the Bangladeshi isolates and all Chinese isolates of DPV may have a common ancestry.
Topics: Animals; Bangladesh; Base Sequence; DNA-Directed DNA Polymerase; Ducks; Mardivirus; Marek Disease; Phylogeny; Polymerase Chain Reaction; Poultry Diseases; Prevalence; Viral Proteins
PubMed: 33898283
DOI: 10.4314/ovj.v11i1.8