Altered cholinergic innervation in De Novo Parkinson's disease with and without cognitive impairment

BACKGROUND: Altered cholinergic innervation plays a putative role in cognitive impairment in Parkinson's disease (PD) at least in advanced stages. Identification of the relationship between cognitive impairment and cholinergic innervation early in the disease will provide better insight into disease prognosis and possible early intervention. OBJECTIVE: The aim was to assess regional cholinergic innervation status in de novo patients with PD, with and without cognitive impairment. METHODS: Fifty-seven newly diagnosed, treatment-naive, PD patients (32 men, mean age 64.6 ± 8.2 years) and 10 healthy controls (5 men, mean age 54.6 ± 6.0 years) were included. All participants underwent cholinergic [18 F]fluoroethoxybenzovesamicol positron emission tomography and detailed neuropsychological assessment. PD patients were classified as either cognitively normal (PD-NC) or mild cognitive impairment (PD-MCI). Whole brain voxel-based group comparisons were performed. RESULTS: Results show bidirectional cholinergic innervation changes in PD. Both PD-NC and PD-MCI groups showed significant cortical cholinergic denervation compared to controls (P < 0.05, false discovery rate corrected), primarily in the posterior cortical regions. Higher-than-normal binding was most prominent in PD-NC in both cortical and subcortical regions, including the cerebellum, cingulate cortex, putamen, gyrus rectus, hippocampus, and amygdala. CONCLUSION: Altered cholinergic innervation is already present in de novo patients with PD. Posterior cortical cholinergic losses were present in all patients independent of cognitive status. Higher-than-normal binding in cerebellar, frontal, and subcortical regions in cognitively intact patients may reflect compensatory cholinergic upregulation in early-stage PD. Limited or failing cholinergic upregulation may play an important role in early, clinically evident cognitive impairment in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Stellar Lyman-alpha Emission Lines in the Hubble Space Telescope Archive: Intrinsic Line Fluxes and Absorption from the Heliosphere and Astrospheres

We search the Hubble Space Telescope (HST) archive for previously unanalyzed observations of stellar H I Lyman-alpha emission lines, our primary purpose being to look for new detections of Lyman-alpha absorption from the outer heliosphere, and to also search for analogous absorption from the astrospheres surrounding the observed stars. The astrospheric absorption is of particular interest because it can be used to study solar-like stellar winds that are otherwise undetectable. We find and analyze 33 HST Lyman-alpha spectra in the archive. All the spectra were taken with the E140M grating of the Space Telescope Imaging Spectrograph (STIS) instrument on board HST. The HST/STIS spectra yield 4 new detections of heliospheric absorption (70 Oph, Xi Boo, 61 Vir, and HD 165185) and 7 new detections of astrospheric absorption (EV Lac, 70 Oph, Xi Boo, 61 Vir, Delta Eri, HD 128987, and DK UMa), doubling the previous number of heliospheric and astrospheric detections. When combined with previous results, 10 of 17 lines of sight within 10 pc yield detections of astrospheric absorption. This high detection fraction implies that most of the ISM within 10 pc must be at least partially neutral, since the presence of H I within the ISM surrounding the observed star is necessary for an astrospheric detection. In contrast, the detection percentage is only 9.7% (3 out of 31) for stars beyond 10 pc. Our Lyman-alpha analyses provide measurements of ISM H I and D I column densities for all 33 lines of sight, and we discuss some implications of these results. Finally, we measure chromospheric Lyman-alpha fluxes from the observed stars. We use these fluxes to determine how Lyman-alpha flux correlates with coronal X-ray and chromospheric Mg II emission, and we also study how Lyman-alpha emission depends on stellar rotation.Comment: 56 pages, 15 figures; AASTEX v5.0 plus EPSF extensions in mkfig.sty; accepted by ApJ

A conditional-phase switch at the single-photon level

We present an experimental realization of a two-photon conditional-phase switch, related to the ``$c$-$\phi$'' gate of quantum computation. This gate relies on quantum interference between photon pairs, generating entanglement between two optical modes through the process of spontaneous parametric down-conversion (SPDC). The interference effect serves to enhance the effective nonlinearity by many orders of magnitude, so it is significant at the quantum (single-photon) level. By adjusting the relative optical phase between the classical pump for SPDC and the pair of input modes, one can impress a large phase shift on one beam which depends on the presence or absence of a single photon in a control mode.Comment: 8 pages, 4 figure

Unknown Quantum States: The Quantum de Finetti Representation

We present an elementary proof of the quantum de Finetti representation theorem, a quantum analogue of de Finetti's classical theorem on exchangeable probability assignments. This contrasts with the original proof of Hudson and Moody [Z. Wahrschein. verw. Geb. 33, 343 (1976)], which relies on advanced mathematics and does not share the same potential for generalization. The classical de Finetti theorem provides an operational definition of the concept of an unknown probability in Bayesian probability theory, where probabilities are taken to be degrees of belief instead of objective states of nature. The quantum de Finetti theorem, in a closely analogous fashion, deals with exchangeable density-operator assignments and provides an operational definition of the concept of an ``unknown quantum state'' in quantum-state tomography. This result is especially important for information-based interpretations of quantum mechanics, where quantum states, like probabilities, are taken to be states of knowledge rather than states of nature. We further demonstrate that the theorem fails for real Hilbert spaces and discuss the significance of this point.Comment: 30 pages, 2 figure

In-hospital costs associated with new percutaneous coronary devices

To determine the relative economic impact of alternative methods of coronary revascularization, in-hospital patient accounts were reviewed in 149 patients undergoing elective coronary angioplasty (n = 50), coronary atherectomy (n = 72) or intracoronary stent placement (n = 27) over an 18-month period. Clinical and angiographic features were similar in the 3 groups, except that prior restenosis was seen more often in patients undergoing intracoronary stent placement. Procedural success, obtained in &gt;90% of patients, was independent of the treatment strategy. Total in-hospital stay was significantly longer in patients undergoing intracoronary stent placement than in patients undergoing coronary angioplasty and directional atherectomy (4.9 +/- 2.4 days vs 1.5 +/- 1.3 and 2.2 +/- 3.9 days, respectively; p &lt; 0.0001). Furthermore, the total in-hospital charges were significantly higher in patients undergoing intracoronary stent placement ($12,574 +/-$4,564 vs $6,220 +/-$5,716; p &lt; 0.001) and directional atherectomy ($8,329 +/-$8,588 vs $6,220 +/-$5,716; p &lt; 0.01) than in patients undergoing coronary angioplasty, reflecting overall differences in room costs, laboratory fees and pharmacy fees. The longer in-hospital stay in the intracoronary stent group was primarily attributed to the time required for anticoagulation with coumadin. It is concluded that a 102 and 34% increase in early hospital charges resulted with stenting or directional atherectomy, respectively, compared with coronary angioplasty. These increased in-hospital charges were chiefly due to the prolonged hospitalization time, device cost, laboratory fees and, in patients with intracoronary stents, the prolonged time needed to achieve systemic anticoagulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29116/1/0000155.pd

Measured Mass Loss Rates of Solar-like Stars as a Function of Age and Activity

Collisions between the winds of solar-like stars and the local ISM result in a population of hot hydrogen gas surrounding these stars. Absorption from this hot H I can be detected in high resolution Lyman-alpha spectra of these stars from the Hubble Space Telescope. The amount of absorption can be used as a diagnostic for the stellar mass loss rate. We present new mass loss rate measurements derived in this fashion for four stars (Epsilon Eri, 61 Cyg A, 36 Oph AB, and 40 Eri A). Combining these measurements with others, we study how mass loss varies with stellar activity. We find that for the solar-like GK dwarfs, the mass loss per unit surface area is correlated with X-ray surface flux. Fitting a power law to this relation yields Mdot ~ Fx^(1.15+/-0.20). The active M dwarf Proxima Cen and the very active RS CVn system Lambda And appear to be inconsistent with this relation. Since activity is known to decrease with age, the above power law relation for solar-like stars suggests that mass loss decreases with time. We infer a power law relation of Mdot ~ t^(-2.00+/-0.52). This suggests that the solar wind may have been as much as 1000 times more massive in the distant past, which may have had important ramifications for the history of planetary atmospheres in our solar system, that of Mars in particular.Comment: 34 pages, 9 figures; AASTEX v5.0 plus EPSF extensions in mkfig.sty; accepted by Ap

Lack of macrolide resistance in Mycoplasma genitalium infections in a cohort of pregnant women in South Africa

No abstract available.http://sti.bmj.comhj2022Medical Microbiolog

Mesoscopic organization reveals the constraints governing C. elegans nervous system

One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations, such as optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis, we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.Comment: Published version, Minor modifications, 16 pages, 9 figure

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface

Plasma concentrations of biologically active vitamin D (1,25- (OH)2D) are tightly controlled via feedback regulation of renal 1-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)2D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitaminDderegulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface