Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected ...to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches.
Due to the high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD), routine cognitive screening is important for the optimal management of patients with PD. The ...Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting MCI and dementia in patients without PD, but its validity in PD has not been established.
A representative sample of 132 patients with PD at 2 movement disorders centers was administered the MoCA, MMSE, and a neuropsychological battery with operationalized criteria for deficits. MCI and PD dementia (PDD) criteria were applied by an investigator blinded to the MoCA and MMSE results. The discriminant validity of the MoCA and MMSE as screening and diagnostic instruments was ascertained.
Approximately one third of the sample met diagnostic criteria for a cognitive disorder (12.9% PDD and 17.4% MCI). Mean (SD) MoCA and MMSE scores were 25.0 (3.8) and 28.1 (2.0). The overall discriminant validity for detection of any cognitive disorder was similar for the MoCA and the MMSE (receiver operating characteristic area under the curve 95% confidence interval): MoCA (0.79 0.72, 0.87) and MMSE (0.76 0.67, 0.85), but as a screening instrument the MoCA (optimal cutoff point = 26/27, 64% correctly diagnosed, lack of ceiling effect) was superior to the MMSE (optimal cutoff point = 29/30, 54% correctly diagnosed, presence of ceiling effect).
The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, has adequate psychometric properties as a screening instrument for the detection of mild cognitive impairment or dementia in Parkinson disease. However, a positive screen using either instrument requires additional assessment due to suboptimal specificity at the recommended screening cutoff point.
Chloroplast RNA metabolism Stern, David B; Goldschmidt-Clermont, Michel; Hanson, Maureen R
Annual review of plant biology,
01/2010, Volume:
61
Journal Article
Peer reviewed
The chloroplast genome encodes proteins required for photosynthesis, gene expression, and other essential organellar functions. Derived from a cyanobacterial ancestor, the chloroplast combines ...prokaryotic and eukaryotic features of gene expression and is regulated by many nucleus-encoded proteins. This review covers four major chloroplast posttranscriptional processes: RNA processing, editing, splicing, and turnover. RNA processing includes the generation of transcript 5' and 3' termini, as well as the cleavage of polycistronic transcripts. Editing converts specific C residues to U and often changes the amino acid that is specified by the edited codon. Chloroplasts feature introns of groups I and II, which undergo protein-facilitated cis- or trans-splicing in vivo. Each of these RNA-based processes involves proteins of the pentatricopeptide motif-containing family, which does not occur in prokaryotes. Plant-specific RNA-binding proteins may underpin the adaptation of the chloroplast to the eukaryotic context.
"Prevailing perspectives on ancient Jewish life have been shaped largely by the voices of intellectual and social elites, preserved in the writings of Philo and Josephus and the rabbinic texts of the ...Mishnah and Talmud. Commissioned art, architecture, and formal inscriptions displayed on tombs and synagogues equally reflect the sensibilities of their influential patrons. The perspectives and sentiments of nonelite Jews, by contrast, have mostly disappeared from the historical record. Focusing on these forgotten Jews of antiquity, 'Writing on the Wall' takes an unprecedented look at the vernacular inscriptions and drawings they left behind and sheds new light on the richness of their quotidian lives. Just like their neighbors throughout the eastern and southern Mediterranean, Mesopotamia, Arabia, and Egypt, ancient Jews scribbled and drew graffiti everyplace--in and around markets, hippodromes, theaters, pagan temples, open cliffs, sanctuaries, and even inside burial caves and synagogues. Karen Stern reveals what these markings tell us about the men and women who made them, people whose lives, beliefs, and behaviors eluded commemoration in grand literary and architectural works. Making compelling analogies with modern graffiti practices, she documents the overlooked connections between Jews and their neighbors, showing how popular Jewish practices of prayer, mortuary commemoration, commerce, and civic engagement regularly crossed ethnic and religious boundaries."
Summary Background Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first ...prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis. Methods We recruited participants with probable multiple system atrophy—of either the parkinsonism subtype (MSA-P) or the cerebellar ataxia subtype (MSA-C)—at 12 neurology centres in the USA specialising in movement or autonomic disorders. We followed up patients every 6 months for 5 years and assessed them with the Unified Multiple System Atrophy Rating Scale part I (UMSARS I; a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status). We assessed potential predictors of outcome. We used Cox proportional hazards models to calculate univariate hazard ratios for shorter survival using age at disease onset as a continuous variable and sex, clinical phenotype, and early development of neurological and autonomic manifestations as categorical variables. Findings We recruited 175 participants. Mean age at study entry was 63·4 years (SD 8·6). Median survival from symptom onset was 9·8 years (95% CI 8·8–10·7) and median survival from enrolment was 1·8 years (0·9–2·7). Participants with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence, or both) at diagnosis (n=62) had a worse prognosis than those without severe disease (n=113; median survival 8·0 years, 95% CI 6·5–9·5 vs 10·3 years, 9·3–11·4; p=0·021). At baseline, patients with MSA-P (n=126) and MSA-C (n=49) had much the same symptoms and functional status: mean UMSARS I 25·2 (SD 8·08) versus 24·6 (8·34; p=0·835); mean UMSARS II 26·4 (8·8) versus 25·4 (10·5; p=0·764); COMPASS-select 43·5 (18·7) versus 42·8 (19·6; p=0·835). Progression over 5 years, assessed by change in UMSARS I, UMSARS II, and COMPASS-select, was modest. Interpretation Probable multiple system atrophy is a late-stage disease with short survival. The natural histories of MSA-P and MSA-C are similar and severe symptomatic autonomic failure at diagnosis is associated with worse prognosis. Funding US National Institutes of Health, Mayo Clinic, and Kathy Shih Memorial Foundation.
The mitochondrial genomes of seed plants are unusually large and vary in size by at least an order of magnitude. Much of this variation occurs within a single family, the Cucurbitaceae, whose genomes ...range from an estimated 390 to 2,900 kb in size. We sequenced the mitochondrial genomes of Citrullus lanatus (watermelon: 379,236 nt) and Cucurbita pepo (zucchini: 982,833 nt)--the two smallest characterized cucurbit mitochondrial genomes--and determined their RNA editing content. The relatively compact Citrullus mitochondrial genome actually contains more and longer genes and introns, longer segmental duplications, and more discernibly nuclear-derived DNA. The large size of the Cucurbita mitochondrial genome reflects the accumulation of unprecedented amounts of both chloroplast sequences (>113 kb) and short repeated sequences (>370 kb). A low mutation rate has been hypothesized to underlie increases in both genome size and RNA editing frequency in plant mitochondria. However, despite its much larger genome, Cucurbita has a significantly higher synonymous substitution rate (and presumably mutation rate) than Citrullus but comparable levels of RNA editing. The evolution of mutation rate, genome size, and RNA editing are apparently decoupled in Cucurbitaceae, reflecting either simple stochastic variation or governance by different factors.
We study GRB 221009A, the brightest gamma-ray burst in the history of observations, using Fermi data. To calibrate them for large inclination angles, we use the Vela X gamma-ray source. Light curves ...in different spectral ranges demonstrate a 300 s overlap of afterglow and delayed episodes of soft prompt emission. We demonstrate that a relatively weak burst precursor that occurs 3 min before the main episode has its own afterglow, i.e., presumably, its own external shock. This is the first observation of such phenomenon which rules out some theoretical models of GRB precursors. The main afterglow is the brightest one, includes a photon with an energy of 400 GeV 9 h after the burst, we show that it is visible in the LAT data for up to two days.
Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously ...shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.
We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.
The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.
The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
To evaluate the effectiveness of a coparenting intervention on exclusive breastfeeding among primiparous mothers and fathers.
A randomized controlled trial was conducted in a large teaching hospital ...in Toronto, Canada. Couples were randomized to receive either usual care (n = 107) or a coparenting breastfeeding support intervention (n = 107). Follow-up of exclusive breastfeeding and diverse secondary outcomes was conducted at 6 and 12 weeks postpartum.
Significantly more mothers in the intervention group than in the control group continued to breastfeed at 12 weeks postpartum (96.2% vs 87.6%, P = .02). Although proportionately more mothers in the intervention group were exclusively breastfeeding at 6 and 12 weeks, these differences were not significant. Fathers in the intervention group had a significantly greater increase in breastfeeding self-efficacy scores from baseline to 6 weeks postpartum compared with fathers in the control group (P = .03). In addition, significantly more mothers in the intervention group than in the control group reported that their partners provided them with breastfeeding help in the first 6 weeks (71% vs 52%, P = .02) and that they were satisfied with their partners' involvement with breastfeeding (89% vs 78.1%, P = .04). Mothers in the intervention group were also more satisfied with the breastfeeding information they received (81% vs 62.5%, P < .001).
The significant improvements in breastfeeding duration, paternal breastfeeding self-efficacy, and maternal perceptions of paternal involvement and assistance with breastfeeding suggest that a coparenting intervention involving fathers warrants additional investigation.
This article addresses the meaning of the term brand means by presenting a method of historical analysis and construct definition based on information in the Oxford English Dictionary. The method's ...use is demonstrated in an analysis of the original meanings that underlie the term's usage both as a single word and in compounds such as brand competition, brand personality, brand reputation, and so forth. Literal (denotative) definitions and metaphoric (connotative) associations are examined to explain the use of brand to refer to a physical entity and/or a mental representation. The method is also theoretically grounded in the disciplines of philology (the history of words), poetics, rhetoric, and the philosophy of science. The historical-analysis method is applied to the meanings of brand, starting with its original usage about 1,500 years ago and culminating with the definitions used by authors in this special issue. PUBLICATION ABSTRACT
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