•White matter disruption occurs in Parkinson's disease across several brain regions.•DTI properties could identify clinically distinct subtypes of Parkinson's disease.•Structural neural disruption ...can predict clinical outcomes in Parkinson's disease.
Objectives: Investigating biomarkers to demonstrate progression of Parkinson's disease (PD) is of high priority. We investigated the association of brain structural properties with progression of clinical outcomes and their ability to differentiate clinical subtypes of PD.
Methods: A comprehensive set of clinical features was evaluated at baseline and 4.5-year follow-up for 144 de-novo PD patients from the Parkinson's Progression Markers Initiative. We created a global composite outcome (GCO) by combining z-scores of non-motor and motor symptoms, motor signs, overall activities of daily living and global cognition, as a single numeric indicator of prognosis. We classified patients into three subtypes based on multi-domain clinical criteria: ‘mild motor-predominant’, ‘intermediate’ and ‘diffuse-malignant’. We analyzed diffusion-weighted scans at the early drug-naïve stage and extracted fractional anisotropy and mean diffusivity (MD) of basal ganglia and cortical sub-regions. Then, we employed graph theory to calculate network properties and used network-based statistic to investigate our primary hypothesis.
Results: Baseline MD of globus pallidus was associated with worsening of motor severity, cognition, and GCO after 4.5 years of follow-up. Connectivity disruption at baseline was correlated with decline in cognition, and increase in GCO. Baseline MD of nucleus accumbens, globus pallidus and basal-ganglia were linked to clinical subtypes at 4.5-year of follow-up. Disruption in sub-cortical networks associated with being subtyped as ‘diffuse-malignant’ versus ‘mild motor-predominant’ after 4.5 years.
Conclusions: Diffusion imaging analysis at the early de-novo stage of PD was able to differentiate clinical sub-types of PD after 4.5 years and was highly associated with future clinical outcomes of PD.
Self-care education can play an important role in improving the quality of life in hemodialysis patients.
The purpose of this study was to determine the effect of self-care education with teach back ...method on the quality of life in hemodialysis patients.
In this pre- and post-test clinical trial, 45 patients with end-stage renal disease undergoing hemodialysis at Sina hospital in Tehran were included. Patient education was done with teach back method. The duration of training were 3 sessions and the time of each session lasted from 45 minutes to one hour. To collect data from patients, a demographic questionnaire was used and to assess the quality of life of patients, kidney disease quality of life-short form before and after education was used. A significant level of 5% was determined.
The mean age of patients was 58.49±9.97 years. Among the dimensions of quality of life before education, the highest score was for physical role (64.24±7.68) and the lowest was related to job status (28.33±11.06). After training, the most score was related to emotional role (71.15±2.84) and the least was related to job status (43.87±11.54). A significant difference between the quality of life at before and after education was seen (P=0.000).
This study showed that self-care education through teach back method improves the quality of life in hemodialysis patients. Therefore, it is recommended that nurses in the hemodialysis unit implement self-care education through teach back method as an important task.
Today, changes in political and economic conditions, epidemiological and sociological developments, and the advancement of science and technology have necessitated the health and medical education ...systems to change. Therefore, we conducted a study entitled "Global perspectives on trends in higher education in healthcare," to improve the quality of healthcare so that it can be used as a model for predicting future events related to medical education. This futures study applied the social, technological, economical, ecological, political, values (STEEPV) model to identify and analyze the trends that affect medical education at different levels. To collect and analyze the data, a scoping review of the articles published from the year 2000 was conducted on the World Health Organization (WHO), Web of Science, Scopus, PubMed/MEDLINE, EMBASE, Science Direct, Google Scholar, EBSCO, and Cochrane databases. The review process was performed in five stages: 1- Determining the research question, 2- Identifying relevant studies, 3- Selecting the studies, 4- Charting the data, and 5- Analyzing data. The preferred reporting item for systematic review and meta-analysis (PRISMA) statement was used in the selection and screening of articles. A total of 213 articles were included in the study for qualitative synthesis. A total of 154 trends were identified using the STEEPV model at seven levels of health behaviors and patients, diseases and health problems, healthcare system, medical education system, medical education institutions, medical curricula, and teaching and learning. Considering the results of this study, it is possible to formulate proper and efficient future scenarios for the higher health education system. Also, it will be helpful for medical education policymaking.
Parkinson's disease varies in severity and age of onset. One source of this variability is sex. Males are twice as likely as females to develop Parkinson's disease, and tend to have more severe ...symptoms and greater speed of progression. However, to date, there is little information in large cohorts on sex differences in the patterns of neurodegeneration. Here we used MRI and clinical information from the Parkinson Progression Markers Initiative to measure structural brain differences between sexes in Parkinson's disease after regressing out the expected effect of age and sex. We derived atrophy maps from deformation-based morphometry of T1-weighted MRI and connectivity from diffusion-weighted MRI in de novo Parkinson's disease patients (149 males: 83 females) with comparable clinical severity, and healthy control participants (78 males: 39 females). Overall, even though the two patient groups were matched for disease duration and severity, males demonstrated generally greater brain atrophy and disrupted connectivity. Males with Parkinson's disease had significantly greater tissue loss than females in 11 cortical regions including bilateral frontal and left insular lobe, right postcentral gyrus, left inferior temporal and cingulate gyrus and left thalamus, while females had greater atrophy in six cortical regions, including regions in the left frontal lobe, right parietal lobe, left insular gyrus and right occipital cortex. Local efficiency of white matter connectivity showed greater disruption in males in multiple regions such as basal ganglia, hippocampus, amygdala and thalamus. These findings support the idea that development of Parkinson's disease may involve different pathological mechanisms and yield distinct prognosis in males and females, which may have implications for research into neuroprotection, and stratification for clinical trials.
Humans have a unique ability to use language for social communication. The neural architecture for language comprehension and production may have prominently emerged in the brain areas that were ...originally involved in social cognition. Here, we directly tested the fundamental link between language and social processing using functional magnetic resonance data (MRI) data from over 1,000 human subjects. Cortical activations in language and social tasks showed a striking similarity with a complementary hemispheric lateralization. Within core language areas, left-lateralized activations in the language task were mirrored by right-lateralized activations in the social task. Outside these areas, the activations were left lateralized in both tasks, perhaps indicating multimodal integration of social and semantic information. Our findings could have important implications in understanding neurocognitive mechanisms of social disorders such as autism.
Display omitted
•Cortical activation maps in language and social tasks show a striking similarity•Language and social activations are lateralized to left and right brain, respectively•Homologs of language areas in the right hemisphere are involved in social processing•Outside the language network, a left-hemisphere dominance is seen in both tasks
Rajimehr et al. demonstrate a relationship between language and social processing in the brain. While language areas are typically found in the left hemisphere, their homologs in the right hemisphere are involved in social processing. The results have implications for understanding how the cortical language network has evolved in humans.
Recent studies have shown that the histone deacetylase-8 (HDAC8), as one of the HDACs, regulates the expression and activity of various genes involved in cancer initiation and progression. The HDAC8 ...plays an epigenetic role to dysregulate expressions or to interact with transcription factors. Most researchers had focused on the HDAC 1–3 and 6, but today the HDAC8 isotype is a promising target in cancer therapy. Different studies, on breast cancer (BC) cells, have recently shown the HDAC8 overexpression and suggested its oncogenic potential.
It seems that the HDAC8 could be a novel and promising target in breast cancer treatment. Some studies on BC demonstrated therapeutic properties of the inhibitors of HDAC8 such as suberoylanilide hydroxamic acid (SAHA), Trichostatin A, valproic acid, sodium butyrate, 1,3,4 oxadiazole with alanine hybrid (R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl) methyl) propanamide (10b), N-(2-Hydroxyphenyl)-2propylpentanamide (compound 2) and PCI-34051. In this review, we highlight the role and existing inhibitors of HDAC8 in BC pathogenesis and therapy.
Parkinson's disease is a progressive neurodegenerative disorder characterized by the intracellular accumulation of insoluble alpha-synuclein aggregates into Lewy bodies and neurites. Increasing ...evidence indicates that Parkinson's disease progression results from the spread of pathologic alpha-synuclein through neuronal networks. However, the exact mechanisms underlying the propagation of abnormal proteins in the brain are only partially understood. The objective of this study was first to describe the long-term spatiotemporal distributions of Lewy-related pathology in mice injected with alpha-synuclein preformed fibrils and then to recreate these patterns using a computational model that simulates in silico the spread of pathologic alpha-synuclein. In this study, 87 2-3-month-old non-transgenic mice were injected with alpha-synuclein preformed fibrils to generate a comprehensive post-mortem dataset representing the long-term spatiotemporal distributions of hyperphosphorylated alpha-synuclein, an established marker of Lewy pathology, across the 426 regions of the Allen Mouse Brain Atlas. The mice were injected into either the caudoputamen, nucleus accumbens or hippocampus, and followed over 24 months with pathologic alpha-synuclein quantified at seven intermediate time points. The pathologic patterns observed at each time point in this high-resolution dataset were then compared to those generated using a Susceptible-Infected-Removed (SIR) computational model, an agent-based model that simulates the spread of pathologic alpha-synuclein for every brain region taking simultaneously into account the effect of regional brain connectivity and Snca gene expression. Our histopathological findings showed that differentially targeted seeding of pathological alpha-synuclein resulted in unique propagation patterns over 24 months and that most brain regions were permissive to pathology. We found that the SIR model recreated the observed distributions of pathology over 24 months for each injection site. Null models showed that both Snca gene expression and connectivity had a significant influence on model fit. In sum, our study demonstrates that the combination of normal alpha-synuclein concentration and brain connectomics contributes to making brain regions more vulnerable to the pathological process, providing support for a prion-like spread of pathologic alpha-synuclein. We propose that this rich dataset and the related computational model will help test new hypotheses regarding mechanisms that may alter the spread of pathologic alpha-synuclein in the brain.
PDF
