Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight ...junctions (TJs) were compromised and linked to disease status.
TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology.
Severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 correlating with abundant arteriolar Aβ
deposition were identified in MCI and AD patients. Retinal claudin-5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO-1 defects correlated with cerebral pathology and cognitive deficits.
We uncovered deficiencies in blood-retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aβ
deposition suggests a common pathogenic mechanism of failed Aβ clearance via intramural periarterial drainage.
OBJECTIVE:We investigated longitudinal changes in iron concentration in the subcortical gray matter (caudate nucleus, globus pallidus, putamen, thalamus) of patients with clinically isolated syndrome ...(CIS) and definite multiple sclerosis (MS) and their relation to clinical and other morphologic variables.
METHODS:We followed 144 patients (76 CIS; median Expanded Disability Status Scale EDSS 1.0 interquartile range (IQR) 0.0–2.0; 68 MS; median EDSS 2.0 IQR 1.0–3.3) clinically and with 3T MRI over a median period of 2.9 (IQR 1.3–4.0) years. Iron concentration was determined by R2* relaxometry at baseline and last follow-up.
RESULTS:At baseline, subcortical gray matter iron deposition was higher in MS compared to CIS. In CIS, R2* rates increased in the globus pallidus (p < 0.001), putamen (p < 0.001), and caudate nucleus (p < 0.001), whereas R2* rates in the thalamus decreased (p < 0.05). In MS, R2* rates increased in the putamen (p < 0.05), remained stable in the globus pallidus and caudate nucleus, and decreased in the thalamus (p < 0.01). Changes in R2* relaxation rates were unrelated to changes in the volume of respective structures, of T2 lesion load, and of disability.
CONCLUSIONS:Iron accumulation in the basal ganglia is more pronounced in the early than later phases of the disease and occurs independent from other morphologic brain changes. Short-term changes in iron concentration are not associated with disease activity or changes in disability.
Rab GTPases control vesicle movement and tethering membrane events in membrane trafficking. We used the 38 human Rab GTPase activating proteins (GAPs) to identify which of the 60 Rabs encoded in the ...human genome function at the Golgi complex. Surprisingly, this screen identified only two GAPs, RN-tre and TBC1D20, disrupting both Golgi organization and protein transport. RN-tre is the GAP for Rab43, and controls retrograde transport into the Golgi from the endocytic pathway. TBC1D20 is the ER-localized GAP for Rab1, and is the only GAP blocking the delivery of secretory cargo from the ER to the cell surface. Strikingly, its expression causes the loss of the Golgi complex, highlighting the importance of Rab1 for Golgi biogenesis. These effects can be antagonized by reticulon, a binding partner for TBC1D20 in the ER. Together, these findings indicate that Rab1 and Rab43 are key Rabs required for the biogenesis and maintenance of a functional Golgi structure, and suggest that other Rabs acting at the Golgi complex are likely to be functionally redundant.
Für Pflegekräfte ist es plausibel, dass gute Arbeitsbedingungen dazu führen, dass die Pflegearbeit gut bewältigt werden kann. Und für sie ist es einleuchtend, dass gute Pflege einen positiven Effekt ...auf die Zufriedenheit von Patientinnen und Patienten hat. Überraschend ist, dass dies in Deutschland wissenschaftlich noch nicht hinreichend belegt ist. Deshalb soll dieser Zusammenhang in dem dreijährigen Forschungsprojekt „HALTgeben“ in einer Längsschnittstudie untersucht werden. Angesichts des aktuellen Fachkräftemangels in der Pflege legen die Partner des Vorhabens großen Wert auf den Transfer der Ergebnisse in die Praxis. Der Beitrag skizziert die Ziele und Instrumente des Projektes.
Für Pflegekräfte ist es plausibel, dass gute Arbeitsbedingungen dazu führen, dass die Pflegearbeit gut bewältigt werden kann. Und für sie ist es einleuchtend, dass gute Pflege einen positiven Effekt ...auf die Zufriedenheit von Patientinnen und Patienten hat. Überraschend ist, dass dies in Deutschland wissenschaftlich noch nicht hinreichend belegt ist. Deshalb soll dieser Zusammenhang in dem dreijährigen Forschungsprojekt „HALTgeben“ in einer Längsschnittstudie untersucht werden. Angesichts des aktuellen Fachkräftemangels in der Pflege legen die Partner des Vorhabens großen Wert auf den Transfer der Ergebnisse in die Praxis. Der Beitrag skizziert die Ziele und Instrumente des Projektes.
The extend of lung disease remains the most important prognostic factor for survival in patients with cystic fibrosis (CF), and lack of adherence is the main reason for treatment failure. Early ...detection of deterioration in lung function and optimising adherence are therefore crucial in CF care. We implement a randomized controlled trial to evaluate efficacy of telemonitoring of adherence, lung function, and health condition in combination with behavior change interventions using innovative digital technologies.
This is a multi-centre, randomized, controlled, non-blinded trial aiming to include 402 patients ≥ 12 years-of-age with CF. A standard-of-care arm is compared to an arm receiving objective, continuous monitoring of adherence to inhalation therapies, weekly home spirometry using electronic devices with data transmission to patients and caring physicians combined with video-conferencing, a self-management app and professional telephone coaching. The duration of the intervention phase is 18 months. The primary endpoint is time to the first protocol-defined pulmonary exacerbation. Secondary outcome measures include number of and time between pulmonary exacerbations, adherence to inhalation therapy, changes in forced expiratory volume in 1 s from baseline, number of hospital admissions, and changes in health-related quality of life. CF-associated medical treatment and care, and health care related costs will be assessed by explorative analysis in both arms.
This study offers the opportunity to evaluate the effect of adherence interventions using telemedicine capable devices on adherence and lung health, possibly paving the way for implementation of telemedicine in routine care for patients with CF.
This study has been registered with the German Clinical Trials Register (Identifier: DRKS00024642, date of registration 01 Mar 2021, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024642 ).
The surface‐assisted synthesis of gold–organic hybrids on Au (111) and Au (100) surfaces is repotred by thermally initiated dehalogenation of chloro‐substituted perylene‐3,4,9,10‐tetracarboxylic acid ...bisimides (PBIs). Structures and surface‐directed alignment of the Au–PBI chains are investigated by scanning tunnelling microscopy in ultra high vacuum conditions. Using dichloro‐PBI as a model system, the mechanism for the formation of Au–PBI dimer is revealed with scanning tunnelling microscopy studies and density functional theory calculations. A PBI radical generated from the homolytic C‐Cl bond dissociation can covalently bind a surface gold atom and partially pull it out of the surface to form stable PBI‐Au hybrid species, which also gives rise to the surface‐directed alignment of the Au–PBI chains on reconstructed Au (100) surfaces.
Stable gold‐organic hybrids can be prepared on single crystal gold surfaces via a surface assisted coupling reaction between chloro‐substituted perylene‐3,4,9,10‐tetracarboxylic acid bisimides (PBIs) and surface gold atoms in an ultrahigh vacuum environment. Participation of surface gold atoms in the coupling reaction leads to the oriented alignment of the Au–PBI chains on reconstructed Au (100) surfaces.
Positron emission tomography (PET) myocardial perfusion imaging (MPI) can be used to evaluate left ventricular (LV) volumes and function. We performed a head-to-head comparison of LV function and ...volumes obtained simultaneously using 13N-ammonia-PET and cardiac magnetic resonance (CMR), with the latter serving as the reference standard.
In this prospective study, 51 patients underwent 13N-ammonia-PET MPI and CMR using a hybrid PET/MR device. Left ventricular end-systolic volumes (LVESV), end-diastolic volumes (LVEDV), stroke volumes (LVSV), ejection fractions (LVEF), and segmental wall motion were analyzed for both methods and were compared using correlational and Bland-Altman (BA) analysis; segmental wall motion was compared using ANOVA. The agreement between 13N-ammonia-PET and CMR for LVEF was good, with minimal bias (− .6%) and narrow BA limits of agreement (− 7.9% to 6.8%), but 13N-ammonia-PET systematically underestimated LV volumes, with high bias in LVESV (− 11.2 ml), LVEDV (− 28.9 ml), and LVSV (− 17.5 ml). Mean segmental wall motion in 13N-ammonia-PET differed significantly among the corresponding normokinetic (6.6 ± 2 mm), hypokinetic (5.1 ± 2 mm), and akinetic (3.3 ± 2 mm) segments in CMR (P < .01).
LVEF and LV wall motion can be accurately assessed using 13N-ammonia-PET MPI, although LV volumes are significantly underestimated compared to CMR.
We present a comprehensive investigation of the Berezinskii-Kosterlitz-Thouless transition in ultrathin strongly disordered NbN films. Measurements of resistance, current-voltage characteristics, and ...kinetic inductance on the very same device reveal a consistent picture of a sharp unbinding transition of vortex-antivortex pairs that fit standard renormalization group theory without extra assumptions in terms of inhomogeneity. Our experiments demonstrate that the previously observed broadening of the transition is not an intrinsic feature of strongly disordered superconductors and provide a clean starting point for the study of dynamical effects at the Berezinskii-Kosterlitz-Thouless transition.
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