Parkinson’s disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, ...bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel
p
-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.
Abstract Background The eight-item Patient Health Questionnaire depression scale (PHQ-8) is established as a valid diagnostic and severity measure for depressive disorders in large clinical studies. ...Our objectives were to assess the PHQ-8 as a depression measure in a large, epidemiological population-based study, and to determine the comparability of depression as defined by the PHQ-8 diagnostic algorithm vs. a PHQ-8 cutpoint ≥ 10. Methods Random-digit-dialed telephone survey of 198,678 participants in the 2006 Behavioral Risk Factor Surveillance Survey (BRFSS), a population-based survey in the United States. Current depression as defined by either the DSM-IV based diagnostic algorithm (i.e., major depressive or other depressive disorder) of the PHQ-8 or a PHQ-8 score ≥ 10; respondent sociodemographic characteristics; number of days of impairment in the past 30 days in multiple domains of health-related quality of life (HRQoL). Results The prevalence of current depression was similar whether defined by the diagnostic algorithm or a PHQ-8 score ≥ 10 (9.1% vs. 8.6%). Depressed patients had substantially more days of impairment across multiple domains of HRQoL, and the impairment was nearly identical in depressed groups defined by either method. Of the 17,040 respondents with a PHQ-8 score ≥ 10, major depressive disorder was present in 49.7%, other depressive disorder in 23.9%, depressed mood or anhedonia in another 22.8%, and no evidence of depressive disorder or depressive symptoms in only 3.5%. Limitations The PHQ-8 diagnostic algorithm rather than an independent structured psychiatric interview was used as the criterion standard. Conclusions The PHQ-8 is a useful depression measure for population-based studies, and either its diagnostic algorithm or a cutpoint ≥ 10 can be used for defining current depression.
Since the mid-1990s, the popular perception of the militia movement in the United States has associated it with racism and far-right expressions of Christianity. There are good reasons for this ...assessment, though the movement is more complex than such generalizations suggest. In this article, I describe how Oath Keepers mobilized the image of a “good militia” seeking broader legitimacy and how their efforts have often been damaged by troubling and even criminal elements in their organization, which included militant efforts to keep Trump in power by attempting to subvert the 2020 election. I further argue that public revelations of the group’s racialized discourses and activities, allegations of domestic abuse against its founder, and the recent convictions related to 6 January, including seditious conspiracy, further challenge this effort at legitimization and have thrown the organization into disarray. Moreover, I argue though broader legitimacy may be now out of reach for this fragmented and isolated organization, they may yet find legitimacy among Christian nationalists who have come to conclude that political violence is potentially necessary to save America.
A genetic analysis of plant characters associated with lodging resistance, yield and other agronomic traits was made on two doubled haploid winter wheat populations grown at two UK locations in the ...2004/2005, 2005/2006 and 2006/2007 seasons. Wide genetic variation was found for traits that affect lodging, including plant height, components of stem strength (stem diameter, wall width and material strength), components of anchorage strength (spread and depth of the root plate), ear area and shoot number per plant. Heritabilities were estimated for each of the key lodging traits, with plant height having the highest heritability and anchorage traits the lowest values. Six quantitative trait loci (QTL) controlling plant height had individual height effects (2 × the additive effect) of 3–9 cm and taken together, could potentially increase plant height by up to 34 cm. Three of the height QTL were also associated with greater yield or greater thousand grain weight, and three were associated with components of stem strength or anchorage strength. QTL were also identified for each of the measured lodging traits, which were unrelated to height. Individual QTL with the largest estimated effects on lodging resistance were for height, stem diameter, stem material strength, stem failure moment, root plate spread and root plate depth. Diagnostic genetic markers for the most important QTL regions are now required to enable breeders to efficiently combine multiple traits together in a single variety that will increase lodging resistance and yield simultaneously.
Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has ...proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients.
Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018.
Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome.
This study describes the natural history of classic galactosemia based on the hitherto largest data set.
Significant motivations and incentives exist for young-adult students to seek a diagnosis of attention-deficit/hyperactivity disorder (ADHD). With ADHD information readily accessible on the Internet, ...today's students are likely to be symptom educated prior to evaluation. This may result in false-positive diagnoses, particularly when students are motivated to convey symptoms. We evaluated the utility of ADHD symptom checklists, neurocognitive tests, and measures initially developed to detect feigned neurocognitive or psychiatric dysfunction (symptom validity tests SVTs). The performance of 31 undergraduates financially motivated and coached about ADHD via Internet-derived information was compared to that of 29 ADHD undergraduates following medication washout and 14 students not endorsing symptomatology. Results indicated malingerers readily produced ADHD-consistent profiles. Symptom checklists, including the ADHD Rating Scale and Conners's Adult ADHD Rating Scale-Self-Rating Form: Long, were particularly susceptible to faking. Conners's Continuous Performance Test-II findings appeared more related to motivation than condition. Promising results were seen with all cognitive SVTs (Test of Memory Malingering TOMM, Digit Memory Test, Letter Memory Test, and Nonverbal-Medical Symptom Validity Test), particularly TOMM Trial 1 when scored using Trial 2 criteria. All SVTs demonstrated very high specificity for the ADHD condition and moderate sensitivity to faking, which translated into high positive predictive values at rising base rates of feigning. Combining 2 or more failures resulted in only modest declines in sensitivity but robust specificity. Results point to the need for a thorough evaluation of history, cognitive and emotional functioning, and the consideration of exaggerated symptomatology in the diagnosis of ADHD.
The metabolite acetyl-coenzyme A (acetyl-CoA) is the required acetyl donor for lysine acetylation and thereby links metabolism, signaling, and epigenetics. Nutrient availability alters acetyl-CoA ...levels in cancer cells, correlating with changes in global histone acetylation and gene expression. However, the specific molecular mechanisms through which acetyl-CoA production impacts gene expression and its functional roles in promoting malignant phenotypes are poorly understood. Here, using histone H3 Lys27 acetylation (H3K27ac) ChIP-seq (chromatin immunoprecipitation ChIP coupled with next-generation sequencing) with normalization to an exogenous reference genome (ChIP-Rx), we found that changes in acetyl-CoA abundance trigger site-specific regulation of H3K27ac, correlating with gene expression as opposed to uniformly modulating this mark at all genes. Genes involved in integrin signaling and cell adhesion were identified as acetyl-CoA-responsive in glioblastoma cells, and we demonstrate that ATP citrate lyase (ACLY)-dependent acetyl-CoA production promotes cell migration and adhesion to the extracellular matrix. Mechanistically, the transcription factor NFAT1 (nuclear factor of activated T cells 1) was found to mediate acetyl-CoA-dependent gene regulation and cell adhesion. This occurs through modulation of Ca2+ signals, triggering NFAT1 nuclear translocation when acetyl-CoA is abundant. The findings of this study thus establish that acetyl-CoA impacts H3K27ac at specific loci, correlating with gene expression, and that expression of cell adhesion genes are driven by acetyl-CoA in part through activation of Ca2+-NFAT signaling.
Non-melanoma skin cancers are cutaneous malignancies representing the most common form of cancer in the United States. They are comprised predominantly of basal cell carcinomas and squamous cell ...carcinomas (cSCC). The incidence of cSCC is increasing, resulting in substantial morbidity and ever higher treatment costs; currently in excess of one billion dollars, per annum. Here, we review research defining the molecular basis and development of cSCC that aims to provide new insights into pathogenesis and drive the development of novel, cost and morbidity saving therapies.
The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a worldwide epidemic. African American (AA) individuals are disproportionately more likely to become diabetic than other ...ethnic groups. Over the long-term, metabolic complications related to diabetes result in significant alterations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited exercise-related studies in the area of gene expression changes with disease progression, the objective of this study was to examine differences in exercise-induced gene expression related to the GH and IGF-1 pathways in peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals.
Ten subjects 5 PD (age = 35±9.3 yr, BMI = 32.1±4.0, FBG = 101.8±1.3 mg/dl) and 5 CON (age = 31±9.4 yr, BMI = 29.4±5.2, FBG = 82.8±9.7 mg/dl) had blood drawn for RNA isolation prior to exercise (Pre), immediately following acute moderate intensity exercise on a treadmill (Post-1), 6-hours post (Post-6), and 24-hours post (Post-24). Isolation of mRNA from PBMCs was performed using ficoll separation, while the profiling of mRNA expression was performed using Illumina beadchip arrays with standard protocols. Scan results were statistically analyzed for a specific list of genes related to GH and IGF-1. GH and IGF-1 protein levels were also assessed in each sample. To address issues of normality, all GH and IGF-1 data were log-transformed prior to analysis. Statistical significance was set at p<0.05.
Group differences for GH2 variant 2 (p = 0.070) and GH2 variant 3 (p = 0.059) were coupled with significant alterations in IGF-1 mRNA over time (p = 0.024). A significant interaction between group and time was observed for GHRH mRNA (p = 0.008). No group differences were observed in GH AUC (p = 0.649), ΔGH (p = 0.331), GHrec (p = 0.294), or IGF-1 AUC (p = 0.865), representing a similar exercise-induced GH and IGF-1 response for both groups.
Analysis of GH and IGF-1 related-gene expression indicates that mild elevations in fasting blood glucose and exercise-induced alterations in gene expression are impacted by the prediabetic state.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present meta-analysis provides the first meta-analysis of research on stand-alone neurocognitive feigning tests since publication of the preceding paper by Vickery, Berry, Inman, Harris & Orey ...(2001). Studies of dedicated neurocognitive feigning test performances in adults appearing in published or unpublished (theses and dissertations) sources through October 2010 were reviewed and subjected to stringent inclusion criteria to maximize the validity of results. Neurocognitive feigning tests were included only if at least three contrasts of criterion-supported honest patient groups and feigners were available. Tests that met criteria for review included the Victoria Symptom Validity Test, used as an anchor to compare Vickery and colleagues' results; Test of Memory Malingering, Word Memory Test, Letter Memory Test, and Medical Symptom Validity Test. Effect sizes and test parameters at published cut scores were compiled and compared. Results reflected large effect sizes for all measures (mean d = 1.55, 95% confidence interval CI = 1.48-1.63). Mean specificity was 0.90 (95% CI = 0.85-0.94). Mean sensitivity was 0.69 (95% CI = 0.63-0.75). Several moderators of effect size were identified, with certain manipulations resulting in a weakening of effect size. Unexpectedly, warning simulators to feign believably increased effect sizes.
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