A home-based exercise intervention for caregivers of persons with dementia: study protocol for a randomised controlled trial

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Repurposing Proteostasis-Modifying Drugs to Prevent or Treat Age-Related Dementia: A Systematic Review

Background: Dementia has a significant impact on quality of life of older individuals. Impaired proteostasis has been implicated as a potential cause of dementia, that can be therapeutically targeted to improve patient outcomes. This review aimed to collate all current evidence of the potential for targeting proteostasis with repurposed drugs as an intervention for age-related dementia and cognitive decline.Methods: PubMed, Web of Science and Embase databases were searched from inception until 4th July 2017 for studies published in English. Interventional studies of repurposed proteostasis-modifying drugs in Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body disease, vascular dementia, and cognitive aging, in either animal models or humans with change in cognition as the outcome were included. The SYRCLE and Cochrane tools were used to assess risk of bias for included studies.Results: Overall 47 trials, 38 animal and 9 human, were isolated for inclusion in this review. Drugs tested in animals and humans included lithium, rapamycin, rifampicin, and tyrosine kinase inhibitors. Drugs tested only in animals included Macrophage and Granulocyte-Macrophage Colony Stimulating Factors, methylene blue, dantrolene, geranylgeranylacetone, minocycline and phenylbutyric acid. Lithium (n = 10 animal, n = 6 human) and rapamycin (n = 12 animal, n = 1 human) were the most studied proteostasis modifying drugs influencing cognition. Nine of ten animal studies of lithium showed a statistically significant benefit in Alzheimer's models. Rapamycin demonstrated a significant benefit in models of vascular dementia, aging, and Alzheimer's, but may not be effective in treating established Alzheimer's pathology. Lithium and nilotinib had positive outcomes in human studies including Alzheimer's and Parkinson's patients respectively, while a human study of rifampicin in Alzheimer's failed to demonstrate benefit. Microdose lithium showed a strongly significant benefit in both animals and humans. While the risk of bias was relatively low in human studies, the risk of bias in animal studies was largely unclear.Conclusion: Overall, the collective findings support the hypothesis that targeting proteostasis for treatment of dementia may be beneficial, and therefore future studies in humans with repurposed proteostasis modifying drugs are warranted. Larger human clinical trials focusing on safety, efficacy, tolerability, and reproducibility are required to translate these therapeutics into clinical practice

The interplay between helicity and rotation in turbulence: implications for scaling laws and small-scale dynamics

Invariance properties of physical systems govern their behavior: energy conservation in turbulence drives a wide distribution of energy among modes, observed in geophysical or astrophysical flows. In ideal hydrodynamics, the role of helicity conservation (correlation between velocity and its curl, measuring departures from mirror symmetry) remains unclear since it does not alter the energy spectrum. However, with solid body rotation, significant differences emerge between helical and non-helical flows. We first outline several results, like the energy and helicity spectral distribution and the breaking of strict universality for the individual spectra. Using massive numerical simulations, we then show that small-scale structures and their intermittency properties differ according to whether helicity is present or not, in particular with respect to the emergence of Beltrami-core vortices (BCV) that are laminar helical vertical updrafts. These results point to the discovery of a small parameter besides the Rossby number; this could relate the problem of rotating helical turbulence to that of critical phenomena, through renormalization group and weak turbulence theory. This parameter can be associated with the adimensionalized ratio of the energy to helicity flux to small scales, the three-dimensional energy cascade being weak and self-similar

Update on the LLRF operations status at the European XFEL

The European XFEL (EuXFEL) is a free-electron laser in the X-ray range for users. Its high availability is one of the key aspects of the machine. In 2022, it entered in the sixth year of operation. The EuXFEL linac is based on the TESLA superconducting RF technology, operating at 1.3 GHz with an RF pulse length of 650 $\mu$s and a repetition rate of 10 Hz. The LLRF system is based on the MicroTCA standard and relies on a high level of automation. In this contribution, we review the LLRF operation at the EuXFEL and the development of new tools and features to improve the monitoring and extend the usability of the LLRF system.Comment: Talk presented at LLRF Workshop 2022 (LLRF2022, arXiv:2208.13680

Virulence potential of Candida albicans isolated from oral cavity of patients with chronic renal failure on hemodialysis

Objective In patients with chronic renal failure (PCRF), the frequency of colonization of the oral cavity by yeasts of genus Candida spp. is high compared with healthy individuals. These yeasts have virulence factors that may contribute to the persistence of colonization and the development of these infections. The aim of this study was evaluate aspects of virulence from Candida albicans isolated from oral cavity of PCRF on dialysis. Methods This study was initially conducted with 49 clinical samples of C. albicans. The virulence factors assayed were produce of biofilm, germ tube, determination of adherence in oral epithelial cells and evaluation of resistance to the antimicrobial action of neutrophils and mononuclear cells. Results All isolates were highly efficient in forming biofilms on poly- styrene microplates, where 94% of the samples formed 4 + biofilm. Used as a screening test, of which three isolates were selected with different degrees of ability to form biofilm to assess other indicators of virulence. Overall, the isolates exhibited different characteristics regarding the virulence factors analyzed. It was also observed that the hypophosphorous acid (HOCl), production, one of leading inflammatory mediators with fungicidal action, also varied especially when the neutrophils, and not mononuclear cells, were stimulated with different samples. (Figure 1). Conclusion Therefore, our results indicate that C. albicans, is not only the most common species in the oral cavity of CRFP on dialysis, but also it presents the main virulence attributes, which reinforces the importance of monitoring of these patients towards the prevention of fungal infections

Effect of Semicore Orbitals on the Electronic Band Gaps of Si, Ge, and GaAs within the GW Approximation

We study the effect of semicore states on the self-energy corrections and electronic energy gaps of silicon, germanium and GaAs. Self-energy effects are computed within the GW approach, and electronic states are expanded in a plane-wave basis. For these materials, we generate {\it ab initio} pseudopotentials treating as valence states the outermost two shells of atomic orbitals, rather than only the outermost valence shell as in traditional pseudopotential calculations. The resulting direct and indirect energy gaps are compared with experimental measurements and with previous calculations based on pseudopotential and ``all-electron'' approaches. Our results show that, contrary to recent claims, self-energy effects due to semicore states on the band gaps can be well accounted for in the standard valence-only pseudopotential formalism.Comment: 6 pages, 3 figures, submitted to Phys. Rev.

Stress relaxation in SSC collared coils and their component materials

Previous work, reported at last year's meeting, has been continued. One model section of an SSC outer coil has had it's stress relaxation measured for nearly two years. In addition, the stress relaxation of SSC cable without insulation has been measured. Kapton insulation alone has been studied both in creep and stress relaxation. Creep has been measured parallel to the plane of the film. These measurements are dependent on internal stresses that may be present in the film and on the moisture content of the film. They indicate that any measurements of coil relaxation are not likely to be repeatable if these factors are not controlled. The measurements on Kapton film alone are being done at different temperatures to obtain a time-temperature shift factor so that measurements at one temperature may be used to predict relaxation at any other temperature. 12 refs., 8 figs

Anxiety, depression, and comorbid anxiety and depression: Risk factors and outcome over two years

Background: This study aimed to determine: (1) the prevalence of depression, anxiety, and depression associated with anxiety (DA); (2) the risk factor profile of depression, anxiety, and DA; (3) the course of depression, anxiety, and DA over 24 months. Methods: Two-year longitudinal study of 20,036 adults aged 60+ years. We used the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale anxiety subscale to establish the presence of depression and anxiety, and standard procedures to collect demographic, lifestyle, psychosocial, and clinical data. Results: The prevalence of anxiety, depression, and DA was 4.7%, 1.4%, and 1.8%. About 57% of depression cases showed evidence of comorbid anxiety, while only 28% of those with clinically significant anxiety had concurrent depression. There was not only an overlap in the distribution of risk factors in these diagnostic groups but also differences. We found that 31%, 23%, and 35% of older adults with anxiety, depression, and DA showed persistence of symptoms after two years. Repeated anxiety was more common in women and repeated depression in men. Socioeconomic stressors were common in repeated DA. Conclusions: Clinically significant anxiety and depression are distinct conditions that frequently coexist in later life; when they appear together, older adults endure a more chronic course of illness

Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis(1.).

Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We compared Tp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM