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INTRODUCTION: Alzheimer's disease is associated with sleep disturbances and accumulation of cerebral amyloid beta. The objective was to examine whether actigraphy‐detected sleep parameters might be biomarkers for early amyloid burden. METHODS: Participants underwent a week of actigraphy and an amyloid positron emission tomography (PET) scan. Sleep duration and continuity disruption (sleep fragmentation and nocturnal awakenings) were extracted and compared between amyloid‐positive and amyloid‐negative participants. Then multiple linear regressions were used between mean or night‐to‐night intra‐individual variability (standard deviation) of sleep parameters and brain amyloid burden in a voxel‐wise analysis. RESULTS: Eighty‐six subjects were included (80.3 ± 5.4 years; 48.8% of women). Amyloid‐positive participants had a higher variability of sleep fragmentation compared to amyloid‐negative participants. This parameter was associated with a higher amyloid burden in the frontal and parietal regions, and in the precuneus, in the whole sample. DISCUSSION: This study highlights the relevance of using variability in sleep continuity as a potential biomarker of early amyloid pathogenesis. [ABSTRACT FROM AUTHOR]

N‐glycosylation is an important post‐translational modification of proteins that has been highly conserved during evolution and is found in Eukaryota, Bacteria and Archaea. In eukaryotes, N‐glycan processing is sequential, involving multiple specific steps within the secretory pathway as proteins travel through the endoplasmic reticulum and the Golgi apparatus. In this review, we first summarize the different steps of the N‐glycan processing and further describe recent findings regarding the diversity of N‐glycan structures in eukaryotic clades. This comparison allows us to explore the different regulation mechanisms of N‐glycan processing among eukaryotic clades. Recent findings regarding the regulation of protein N‐glycosylation are highlighted, especially the regulation of the biosynthesis of complex‐type N‐glycans through manganese and calcium homeostasis and the specific role of transmembrane protein 165 (TMEM165) for which homologous sequences have been identified in several eukaryotic clades. Further research will be required to characterize the function of TMEM165 homologous sequences in different eukaryotic clades. [ABSTRACT FROM AUTHOR]

Rhythmic eye movements performed during eye movement desensitization and reprocessing (EMDR) therapy have been shown to evoke a physiological de‐arousal pattern. Objectives: Here, we examined whether the efficacy of a virtual reality exposure therapy (VRET) paradigm for phobic patients could be improved by adding rhythmic eye movements. Design: Spider‐phobic patients (N = 53) were randomly assigned to either a group performing rhythmic eye movements or a control group undergoing exposure without such eye movements. Methods: During the VRET session, heart rate, electrodermal activity, eye movements, and subjective fear ratings were recorded. Participants underwent behavioural avoidance tests before and after treatment as well as a follow‐up 10–14 days later. Questionnaire data were assessed before exposure and at follow‐up. Results: There were clear treatment effects in both groups with almost no group differences (i.e., the subjective fear ratings and the skin conductance response). Conclusions: Contrary to our expectation, the implementation of rhythmic eye movements during virtual exposure did not enhance the effectiveness of the treatment. However, the eye movement group did show a significantly lower heart rate during exposure compared with the control group which might indicate a less stressful treatment. Practitioner points: One‐session Virtual Reality Exposure Therapy reduced fear of spiders effectively.Performing rhythmic eye movements during exposure did not enhance therapy effects.Rhythmic eye movements during exposure resulted in lower heart rate than standard exposure. [ABSTRACT FROM AUTHOR]

Background: Accurate and detailed records of children's speech are a critical component of competent service delivery in speech–language pathology/speech and language therapy (SLP/SLT). Previous research has shown that during speech‐sound acquisition, children gradually learn to produce sounds in adult‐like manners. Continuous rating scales are a way to track this gradual learning. Aims: To examine whether clinical experience affects the ability and willingness to rate children's speech production using continuous rating scales. Methods & Procedures: An online survey was administered to 81 US‐based SLPs/SLTs, binned into more‐ and less‐experienced groups, and 20 non‐SLPs/SLTs. The survey included a speech‐sound rating task in which participants rated the production of place of articulation in children's productions of word‐initial /θ/, /s/, /ʃ/, /d/, /ɡ/, /t/ and /k/ on a nine‐point equally appearing interval scale. We examined the extent to which these were accurate (i.e., the extent to which they matched laboratory measures of production characteristics) and the extent to which the ratings were gradual (i.e., they used the entire rating scales, rather than just the endpoints). Main Contribution: There were no consistent differences between non‐SLPs/SLTs, less‐experienced SLPs/SLTs and more‐experienced SLPs/SLTs in a measure of the accuracy of responses. More consistent differences were found in the extent to which listeners used the endpoints of the scale: greater experience was associated with greater use of the endpoint values. Conclusions & Implications: More‐experienced SLPs/SLTs are less likely to use the entire range of continuous rating scales to rate children's speech accuracy than less‐experienced SLPs/SLTs or clinically untrained listeners. Implications for service delivery are discussed. What this paper addsWhat is already known on the subjectChildren's productions of individual sounds, like /k/, become gradually more adult‐like over the course of development. For a child who has a [t] for /k/ error, this gradual development means that children's productions become progressively less like /t/ and more like /k/ over development. Phonetic transcription does not capture this gradual development. In contrast, studies have shown that continuous ratings of children's speech (such as rating productions on a scale anchored by the text "the 't' sound" at one end and "the 'k' sound" at the other end) can capture this gradual development.What this paper adds to existing knowledgeTo determine continuous ratings are clinically feasible, we must first determine whether clinical experience affects people's use of continuous rating scales to rate children's speech. We conducted an on‐line speech perception experiment in which 81 speech‐language pathologists/speech and language therapists (SLPs/SLTs) and 20 non‐SLPs/SLTs rated 60 productions by children on continuous rating scales. The 60 stimuli included many sounds that had been independently verified to be intermediate productions (i.e., a target /k/ that was neither completely /k/‐like nor completely /t/‐like). Non‐SLPs/SLTs and less‐experienced SLPs/SLTs rated those intermediate sounds with intermediate ratings (i.e., somewhere on the midpoint of a continuous scale). In contrast, more‐experienced SLPs/SLTs were more likely to rate those sounds as instances of endpoints (i.e., as either /k/ or /t/).What are the potential or actual clinical implications of this work?This finding suggests that clinical experience is paradoxically associated with a reduced tendency to use the entire range of responses on continuous rating scales. This finding suggests that we must better understand the cause of this reduced tendency, so that clinicians at all levels can use continuous rating scales equally effectively. [ABSTRACT FROM AUTHOR]

Background: Loss of medullary serotonin (5‐hydroxytryptamine) neurons has been linked to respiratory disturbances in multiple system atrophy (MSA). Broader 5‐hydroxytryptamine dysfunction may contribute to additional motor/nonmotor symptoms in MSA. The objective of this study was to compare brain 5‐hydroxytryptamine1A receptor binding between MSA and healthy controls. Secondary objectives were to compare 5‐hydroxytryptamine1A receptor binding between MSA and Parkinson's disease (PD) and to assess potential associations with motor/nonmotor symptoms in MSA. Methods: 2′‐Methoxyphenyl‐(N‐2′‐pyridinyl)‐p‐18F‐fluoro‐benzamidoethylpiperazine positron emission tomography was performed in matched MSA patients (n = 16), PD patients (n = 15), and healthy controls (n = 18). Results: 2′‐Methoxyphenyl‐(N‐2′‐pyridinyl)‐p‐18F‐fluoro‐benzamidoethylpiperazine distribution volume ratios were lower in MSA patients versus healthy controls in several brain regions including the caudate, raphe nuclei, thalamus, and brain stem. Distribution volume ratios were also lower in brain stem and amygdala in MSA versus PD. Moderate associations were found between 2′‐methoxyphenyl‐(N‐2′‐pyridinyl)‐p‐18F‐fluoro‐benzamidoethylpiperazine distribution volume ratios and fatigue, pain, and apathy in MSA. Conclusion: Our results demonstrate 5‐hydroxytryptamine dysfunction in several brain regions in MSA, which may contribute to fatigue, pain, and apathy. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

J Clin Hypertens (Greenwich). 2012;14:773-778. ©2012 Wiley Periodicals, Inc. Postmenopausal women are at greater risk for hypertension-related cardiovascular disease. Antihypertensive therapy may help alleviate arterial stiffness that represents a potential modifiable risk factor of hypertension. This randomized controlled study investigated the difference between an angiotensin receptor blocker and a calcium channel blocker in reducing arterial stiffness. Overall, 125 postmenopausal hypertensive women (age, 61.4±6 years; systolic blood pressure/diastolic blood pressure [SBP/DBP], 158±11/92±9 mm Hg) were randomized to valsartan 320 mg±hydrochlorothiazide (HCTZ) (n=63) or amlodipine 10 mg±HCTZ (n=62). The primary outcome was carotid-to-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Both treatments lowered peripheral blood pressure (BP) (−22.9/−10.9 mm Hg for valsartan and −25.2/−11.7 mm Hg for amlodipine, P=not significant) and central BP (−15.7/−7.6 mm Hg for valsartan and −19.2/−10.3 mm Hg for amlodipine, P<.05 for central DBP). Both treatments similarly reduced the carotid-femoral PWV (−1.9 vs −1.7 m/s; P=not significant). Amlodipine was associated with a higher incidence of peripheral edema compared with the valsartan group (77% vs 14%, P<.001). BP lowering in postmenopausal women led to a reduction in arterial stiffness as assessed by PWV measurement. Both regimens reduced PWV to a similar degree after 38 weeks of treatment despite differences in central BP lowering, suggesting that the effect of valsartan on PWV is mediated through nonhemodynamic effects. [ABSTRACT FROM AUTHOR]

Compared with other plant expression systems used for pharmaceutical protein production, alfalfa offers the advantage of very homogeneous N-glycosylation. Therefore, this plant was selected for further attempts at glycoengineering. Two main approaches were developed in order to humanize N-glycosylation in alfalfa. The first was a knock-down of two plant-specific N-glycan maturation enzymes, β1,2-xylosyltransferase and α1,3-fucosyltransferases, using sense, antisense and RNA interference strategies. In a second approach, with the ultimate goal of rebuilding the whole human sialylation pathway, human β1,4-galactosyltransferase was expressed in alfalfa in a native form or in fusion with a targeting domain from N-acetylglucosaminyltransferase I, a glycosyltransferase located in the early Golgi apparatus in Nicotiana tabacum. Both knock-down and knock-in strategies strongly, but not completely, inhibited the biosynthesis of α1,3-fucose- and β1,2-xylose-containing glycoepitopes in transgenic alfalfa. However, recombinant human β1,4-galactosyltransferase activity in transgenic alfalfa completely prevented the accumulation of the Lewis a glycoepitope on complex N-glycans. [ABSTRACT FROM AUTHOR]

Describes the case of a 29-year-old woman with contact allergy to the antiseptic decyl glucoside after body piercing. Presenting signs and symptoms; Past medical history; Diagnostic procedures; Treatment; Outcome.