α-Synuclein Conformations in Plasma Distinguish Parkinson's Disease from Dementia with Lewy Bodies.

Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Evidence exists for aSyn "strains" - conformations with distinct biological properties. However, biomarkers for PD vs.

α-Synuclein Conformations in Plasma Distinguish Parkinson's Disease from Dementia with Lewy Bodies.

Spread and aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). While evidence exists for multiple aSyn protein conformations, often termed "strains" for their distinct biological properties, it is unclear whether PD and DLB result from aSyn strain differences, and biomarkers that differentiate PD and DLB are lacking. Moreover, while pathological forms of aSyn have been detected outside the brain ( in skin, gut, blood), the functional significance of these peripheral aSyn species is unclear.

Public perceptions of air pollution and its impacts on fertility desire: a nationwide study in China.

Over the past few years, there has been a significant focus on air pollution due to its various detrimental effects on human health. However, its influence on people's tendency to have children remains uncertain, as only a few studies have examined the correlation between public perception of air pollution and the desire to start a family. This article introduces a theoretical framework utilizing a two-stage interval iteration model to explore the connection between children's relative utility and the perception of air pollution.

Is air pollution detrimental to regional innovation? An empirical heterogeneity test based on Chinese cities.

Nowadays, innovation seems to be the inevitable choice to achieve stable economic growth. However, the negative impact of air pollution on health and economy makes air pollution an important factor in regional innovation, which deserves our discussion. The overall regional innovation level from 2014 to 2019 has an upward trend, while the overall air pollution has a downward trend during the period, which provides foundation for our research.

Novel THAP1 missense variant with incomplete penetrance in a case of generalized young onset dystonia showing good response to deep brain stimulation.

We describe a case of young onset generalized dystonia, harboring a previously unreported likely pathogenic THAP1 missense variant (c.109 G > A; p.Glu37Lys) that was inherited from her unaffected father.

Novel bi-allelic FBXO7 variants in a family with early-onset typical Parkinson's disease.

Bi-allelic mutations in FBXO7 are classically associated with a complex phenotype, known as parkinsonian-pyramidal syndrome. We describe two brothers affected by typical early onset Parkinson's disease (EOPD), who carry novel compound heterozygous variants in FBXO7. Our report highlights that typical EOPD can be part of an expanding FBXO7-related phenotype.

Whole Clinic Research Enrollment in Parkinson's Disease: The Molecular Integration in Neurological Diagnosis (MIND) Study.

Background: Observational studies in Parkinson's disease (PD) have focused on relatively small numbers of research participants who are studied extensively. The Molecular Integration in Neurological Diagnosis Initiative at the University of Pennsylvania aims to characterize molecular and clinical features of PD in every patient in a large academic center.

Objective: To determine the feasibility and interest in a global-capture biomarker research protocol.

Design of fractional evolutionary processing for reactive power planning with FACTS devices.

Reactive power dispatch is a vital problem in the operation, planning and control of power system for obtaining a fixed economic load expedition. An optimal dispatch reduces the grid congestion through the minimization of the active power loss. This strategy involves adjusting the transformer tap settings, generator voltages and reactive power sources, such as flexible alternating current transmission systems (FACTS).

Subjective Cognitive Complaint in Parkinson's Disease Patients With Normal Cognition: Canary in the Coal Mine?

Objective: The objective of this study was to determine the frequency and impact of subjective cognitive complaint (SCC) in Parkinson's disease (PD) patients with normal cognition.

Methods: Patients with PD with expert consensus-determined normal cognition at baseline were asked a single question regarding the presence of SCC. Baseline (N = 153) and longitudinal (up to 4 follow-up visits during a 5-year period; N = 121) between-group differences in patients with PD with (+SCC) and without (-SCC) cognitive complaint were examined, including cognitive test performance and self-rated and informant-rated functional abilities.

Using scalp EEG and intracranial EEG signals for predicting epileptic seizures: Review of available methodologies.

Patients suffering from epileptic seizures are usually treated with medication and/or surgical procedures. However, in more than 30% of cases, medication or surgery does not effectively control seizure activity. A method that predicts the onset of a seizure before it occurs may prove useful as patients might be alerted to make themselves safe or seizures could be prevented with therapeutic interventions just before they occur.

Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders.

Objective: To use digital histology in a large autopsy cohort of Lewy body disorder (LBD) patients with dementia to test the hypotheses that co-occurring Alzheimer disease (AD) pathology impacts the anatomic distribution of α-synuclein (SYN) pathology and that co-occurring neocortical tau pathology in LBDs associates with worse cognitive performance and occurs in a pattern differing from AD.

Methods: Fifty-five autopsy-confirmed LBD (Parkinson disease with dementia, n = 36; dementia with Lewy bodies, n = 19) patients and 25 AD patients were studied. LBD patients were categorized as having moderate/severe AD copathology (SYN + AD = 20) or little/no AD copathology (SYN-AD = 35).

Measurements of auto-antibodies to α-synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease.

Biomarkers for α-synuclein are needed for diagnosis and prognosis in Parkinson's disease (PD). Endogenous auto-antibodies to α-synuclein could serve as biomarkers for underlying synucleinopathy, but previous assessments of auto-antibodies have shown variability and inconsistent clinical correlations. We hypothesized that auto-antibodies to α-synuclein could be diagnostic for PD and explain its clinical heterogeneity.

CSF tau and β-amyloid predict cerebral synucleinopathy in autopsied Lewy body disorders.

Objective: To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD).

Methods: Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN - AD = 14).

Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients.

Hyponatraemia: Epidemiology and aetiology in a tertiary care centre in Pakistan.

Objective: To determine the incidence, aetiology and epidemiology of hospitalized patients with hyponatraemia.

Methods: Subjects were identified through hospital information system for two consecutive low sodium values (< 130 mEq/L) and charts were reviewed retrospectively. Possible etiologic factors were identified and co-morbidities documented.

Amyloid-Beta Positron Emission Tomography Imaging of Alzheimer's Pathology in Parkinson's Disease Dementia.

Background: Neuronal loss and α-synuclein (α-syn) pathology are diagnostic of PD in the appropriate clinical context. However, some PD patients have co-morbid Alzheimer's disease (AD) pathology on autopsy, including amyloid-β (Aβ) plaques and neurofibrillary tangles. Florbetapir(F) is a PET ligand that detects Aβ pathology.

Diagnostic Accuracy of Anti-Endomysial Antibody in Celiac Disease.

The objective of the study was to determine the diagnostic accuracy of anti-EMA antibody in comparison to histopathological findings in patients suspected of CD. This cross-sectional study was conducted at Gastroenterology Department, Fatima Memorial Hospital, Lahore, from March to October 2014. One hundred and twenty-one patients aged between 5 - 60 years of either gender were recruited in the study.

Longitudinal study of normal cognition in Parkinson disease.

Objective: To report the rates and predictors of progression from normal cognition to either mild cognitive impairment (MCI) or dementia using standardized neuropsychological methods.

Methods: A prospective cohort of patients diagnosed with Parkinson disease (PD) and baseline normal cognition was assessed for cognitive decline, performance, and function for a minimum of 2 years, and up to 6. A panel of movement disorders experts classified patients as having normal cognition, MCI, or dementia, with 55/68 (80.

New concepts in the early and preclinical detection of Parkinson's disease: therapeutic implications.

Parkinson's disease is a chronic neurodegenerative disorder leading to progressive motor impairment for which there is no cure. Currently, the diagnosis is made by the presence of cardinal motor features and several associated non-motor symptoms. However, at this point, the underlying neuropathological changes are already underway, and efforts in basic and clinical research have converged to suggest that Parkinson's disease actually begins well before symptom onset.

Cytoplasmic p53 and activated Bax regulate p53-dependent, transcription-independent neural precursor cell apoptosis.

The prodeath effects of p53 are typically mediated via its transcriptional upregulation of proapoptotic Bcl-2 family members, including PUMA, Noxa, and/or Bax. We previously reported that staurosporine (STS), a broad-spectrum kinase inhibitor and prototypical apoptosis-inducing agent, produced p53-dependent, Bax-dependent, neural precursor cell (NPC) apoptosis, but that this effect occurred independently of new gene transcription and PUMA expression. To further characterize the mechanism by which p53 regulates NPC death, we used primary cerebellar NPCs derived from wild-type, p53-deficient, and Bax-deficient neonatal mice and the mouse cerebellar neural stem cell line, C17.

Loss of BH3-only protein Bim inhibits apoptosis of hemopoietic cells in the fetal liver and male germ cells but not neuronal cells in bcl-x-deficient mice.

Members of the Bcl-2 family include pro- and antiapoptotic proteins that regulate programmed cell death of developing tissues and death in response to cellular damage. In developing mice, the antiapoptotic Bcl-x(L) is necessary for survival of neural and hematopoietic cells, and consequently, bcl-x-deficient mice die around Day 13.5 of embryogenesis.

Immunohistochemical detection with quantum dots.

Quantum dot (QD) conjugates have many immunohistochemical applications. The optical, excitation/emission, and photostable properties of QDs offer several advantages over the use of chromogens or organic fluorophores in these applications. Here, we describe the use of QD conjugates to detect primary antibody binding in fixed tissue sections.

p53 transcription-dependent and -independent regulation of cerebellar neural precursor cell apoptosis.

Regulation of cerebellar neural precursor cell (NPC) death is important for both normal brain development and prevention of brain tumor formation. The tumor suppressor p53 is an important regulator of NPC apoptosis, but the precise mechanism of p53-regulated cerebellar NPC death remains largely unknown. Here, by using primary cerebellar NPCs and a mouse cerebellar NPC line, we compared the molecular regulation of cerebellar NPC death produced by staurosporine (STS), a broad-spectrum kinase inhibitor, with that caused by genotoxic agents.